GENERAL NEUROLOGY 1.

INSTINCTIVE REFLEXES AND THEIR CHANGES An involuntary and nearly instantaneous movement in response to a stimulus - Occur through reflex arc a. Receptor : receives stimuli b. Afferent pathway : transmit impulse to center c. Center d. Efferent pathway : transmit impulse to effector e. Effector : glands,muscles - 2 types of reflexes Conditioned reflex - Reflex is learned/acquired throughout life

Unconditioned reflex - Reflex is genetically determined and possessed by all human Center : Spinal cord

Center : cerebral cortex

Ie. Seeing,smelling,thinking about lemons leads to salivation. Only occur in adults,dont occur in newborns whos never tasted lemons before (NB: role of experience in its development)

Normal Physiological reflexes Light reflex Corneal reflex The change of pupil diameter in response to dark or light A protective reflex where when the cornea is lightly touched, the eye will blink When the back of the throat is lightly touched, contraction of pharyngeal muscles lead to its spasm and regurgitation Lightly beat the carpal-radial part of the handfingers will be flexed Lightly beat biceps contraction and flexion of arm Lightly beat triceps antiflexion of arm Light beat the patellar tendon just under the patella contraction of quadriceps femoris;kicking movement

Gag reflex

Carpal radial reflex

Biceps reflex Triceps reflex Knee reflex

Achilles reflex Plantar reflex Skin reflex Anal reflex Cremaster reflex

Tapping on the Achilles tendon causes antiflexion of foot Irritation of the olantar surface of foot causes flexion of toes Irritation of abdominal skin with needle causes contraction of muscles Irritation of anogenital region causes contraction of sphincters Irritation of inner thigh causes cremaster muscle contraction

Pathological reflexes 1. Of the extremities Extensors Babinsky - Irritation of plantar surface of foot extension of the big toe and fanning out of the other toes Opennheim - Pressing the shinbone while moving downward causes extension of leg Gardon - Pressing the calves muscle causes extension of leg

Flexors Rosalimo - When tips of toes are lightly beat using the hammer,knocking movements are seen Bekhterev - When dorsal surface of foot are beat,knocking movements are observed Zhukovskii - When plantar surface of foot are beaten,knocking movement are observed

2. Oral automatism (N in infants during 1st year of life and old person >90 yrs old) 1. Habitkovi reflex I. When the lips are lightly beat with a finger,the lips form a shape resembling an elephants trunk 2. Marinesko-Radovichi /Palmar mental reflex II. Irritation of the palm causes contraction of the mental muscles 3. Nasolabial reflex III. Whenthe tip of the nose is touched lightly, a sudden backward movement of the head, arching of the back, and extension and stretching of the limbs occurs 4. Sucking reflex IV. Lightly tapping the tip of the lip causes sucking movement 5. Grasping reflex V. When an object is placed in the palm,the patient involuntarily grasp it

2. CORTICOSPINAL TRACT: ANATOMY,SIGNS OF LESION,TOPICAL DX 1st neuron (upper motor neuron) Tract begins in the precentral gyrus of the cerebral cortex. In the 5th layer of the cortex where the giant pyramidal (Betz) cells are located Axonx of Betz cell continue as the corona radiate to the capsula interna where the fibers are gathered The fibers then travel downward to the medulla oblongata where crossing of fibers occur at the pyramids I. 85% pass to opposite side II. 15% continue on same side The fibers that cross over end in the tr. Corticospinalis lateralis The fibers that continue on the same side end in the tr. Corticocpinalis medialis NB: Partial crossing over enables double innervation of certain muscles which are essential for survical (ie. Intercostal muscles)

3 qualities of movement: I. Speed Assessment : ask patient to do something rapidly Results : Normal : Decr speed II. Strength 1. Assessment : ask patient to hold DRs finger as tightly as he can : ask patient to flex his arm,try to antiflex it 2. Results : 5 points -fully normal strength : 4 points -can fulfill contraction,but weak : 3 points -can move,but can fulfill contraction : 2points -can move in vertical direction :1 point -can move in horizontal direction : 0 point -no movement at all III. Volume/Amplitude 3. Asessment : ask pt to fulfill full movement Ie Move arms upward,forward,downward (observe inability to fulfill full range of movement)

Motor dysfunction is manifested by I. Paresis : decrease of movement II. Plegia/paralysis : full absence of movement Types of affections: I. Monoparesis : 1 arm or 1 leg affected II. Hemiparesis : L arm n L leg OR R arm n R leg III. Paraparesis : both arms OR both legs IV. Triparesis : 3 extremities affected V. Tetraparesis : all 4 extremities affected

Central paresis 1. Hyperreflexia 2. Patho reflexes 3. Hypertonia like a flexed knife 4. Atrophy 5. Patho synkinesia

Peripheral paresis Hyporeflexia/Areflexia

Hypotonia/Atonia Hypotrophy/Atrophy

like a flexed knife : movement is hard to initiate

3. CORTICONUCLEAR TRACT Some of the fibers from the pyramidal tract branch off as they pass through the midbrain. They ended up innervating the motor nuclei of the cranial nerves. These nuclei are responsible for mediating voluntary movement of cranial musculature The nuclei are : CN V (masticatory muscles) : CN VII (mimic muscles of face) : CN IX (muscles of pharynx) : CN X (muscles of soft palate,pharynx,larynx) : CN XI (m. trapezius,SCM-holding head and neck) : CN XII (movement of tongue)

1. CN VII - Only contralateral corticonuclear (c/n) fibers terminate in the nuclei of the neurons innervating the lower half of face - Facial motor neurons innervating the upper half of face receives bilateral corticonuclear innervation - As a result : Lesion of c/n tract rostral to the nuclei -> facial paralysis of lower half of face on contralateral side (Central facial palsy) Lesion of nuclei or facial nerve itself -> all ipsilateral facial muscle paralysis (Peripheral facial palsy) 2. CN III,IV,VI Receives predominantly c/n innervation from the contralateral frontal and parietal eye field The innervation is indirect,occurring through an interneuron loc in reticular formation and from the vertical and horizontal gaze centers in midbrain and pons

3. CN XI - C/n innervation received is mostly uncrossed. - As a result : Lesion of c/n tract -> ipsilateral paralysis of trapezius n SCM

4. CN XII Receives bilateral innervation of c/n tract,the neurons innervating m. genioglossus receives predominantly crossed innervation - As a result : C/n tract lesion -> deviation of tongue when protruded contralateral to Side of lesion -

4. PERIPHERAL MOTOR NEURON.ANATOMY.SIGN OF LESIONS.TOPICAL DX 2nd motor neuron (lower motor neuron)

The cell bodies of the lower motor neurons (LMN) are located in the ant horn of the SC They receives voluntary impulses from the pyramidal tract Their axons leave the SC through the ant root They transmit impulse to voluntary muscles

Functions 1. Muscle tone - A spontaneous local axon stretch reflex. - The length of any skeletal muscle is always shorter than the distance between its origin and point of insertion ; muscle is in a condition of constant slight stretch - The stretch is a stimulus for the muscle spindles that send impulses to the post horn cells,which in turn stimulate the anterior horn cells ; prod continuous subtetanic muscle contraction (muscle tone) - Important for I. Nourishment of muscles II. Body posture - In case of lesions: I. UMN lesion Loss of inhibition of reflex incr muscle tone (spasticity) below level of lesion without wasting of muscle II. LMN lesion Interruption of reflex arc decr muscle tone (flaccidity) at the level of lesion,with muscle wasting 2. Reflexes (refer Q1)

5. ANATOMY AND PHYSIOLOGY OF CONDUCTORS OF SURFACE SENSITIVITY,SYNDROMES OF LESIONS

Superficial sensitivity includes: 5. Pain Assessment 6. Temperature Assessment

: Irritate skin with needle on symmetrical points on the body.Compare R n L : Use the metal and rubber part of hammer

Pain Unpleasant sensation that plays an important protective function

1. Pathogenesis of pain: 1. Nociceptive receptors receive stimuli from different inflame. mediators (Subs P,bradykinin,PG) 2. The 1st neuron transmit the impulse to the 2nd neuron (interneuron) loc in the post horn of SC, 3. The interneuron act like a gate which set a threshold for pain stimuli.Only stimuli that exceed a certain threshold will reach hypothalamus 4. The fibers cross over to opposite side to ascend as the tr. Spinothalamicus to the thalamus etc. Antinociceptive system : Prevent or control pain 1. endorphin 2. interneuron 3. reticular formation

Types of pain Nociceptive Pain that results from stimulation of nociceptors Relieved by: 1. NSAIDS 2. Steroids 3. Opiates Neuropathic Pain that occur due to problem with structures of NS Relieved by: Anticonvulsants

Syndromes of lesions: 4. Asthesia - anesthesia (no sensation),hypoesthesia (decr sensation),hyperesthesia (incr sensation) 5. Hyperpathia/Allodenia : feeling of pain even with non-noxious stimulation (electric-like) 6. Paresthesia : sensation without stimulation (prickling,needles pain)

6. ANATOMY AND PHYSIOLOGY OF CONDUCTORS OF DEEP SENSITIVITY,SYNDROMES OF LESIONS

The axons of the 1st neuron dont go to the grey matter of the SC,but instead,they enter the Fasciculus Gracilis et Cuneatus I. Fasc Cuneatus- upper extremities II. Fasc Gracilis lower extremities The fibers then ascend upwards to the medulla oblongata where the nuclei are located. The axons of 2nd neurons cross over to the opposite side and they ascend upward to the thalamus The axon of the 3rd neuron ends in the postcentral gyrus

Deep sensitivity -includes : Touch - assessed using a brush applied on the skin of symmetrical points : Proprioreception - assessed by asking pt to close eye.lightly flex or antiflex toe.ask which toe n direction Syndromes of lesions: 1. Sensitive ataxia : loss of coordination in the dark (N coordination during daytime) - Assessment : Romberg test Feet together,arms held forward.1st open eye (N),close eye (abnormal shift)

7. SYNDROME OF HALF TRANSVERSAL LESION OF SPINAL CORD (BROWN SEQUARD SYNDROME) The loss of sensation and motor functions caused by half transversal lesion of the spinal cord. - Etiology : tumor,ischemia,trauma,hematoma - Characterized by: I. 2 ipsilateral signs Motor Deep sensitivity II. 1 contralateral sign S/f sensitivity - Example: A R-sided lesion of the SC will produce R-side central paralysis below level of lesion R-side loss of tactile sensitivity below level of lesion L-side loss of temperature and pain sensitivity 2/3 segment below level of lesion

Pathophysiology: - Dissociation of sensitivity is caused by damage of the I. Tr corticospinalis lat - loss of motor function (ipsilateral) II. Post columns (Fasc gracilis,cuneatus) - loss of deep sensitivity (ipsilateral) III. Tr spinothalamicus lat - loss of s/f sensitivity (contralateral) (because crossing of fibers oocur in the SC)

8. SYNDROME OF TRANSVERSAL LESION OF SPINAL CORD AT DIFFERENT LEVELS

Cervical

1. Central tetraplegia 2. Conductive type of anesthesia (lower than level of lesion) 3. Central dysfunction of sphincters (hypertonia) - no urination,no defecation (spasm) *Prob w breathing,a bp,HB 1. 2. 3. 4. Peripheral paraparesis of upper extremities Central paraparesis of lower extremities Conductive anesthesia (lower than C4,T1) Central paresis of organs

Cervical enlargement

Thoracic

1. Lower central paraparesis 2. Total conductive anesthesia lower than level of lesion 3. Central paresis of organs 1. Peripheral lower paraparesis 2. Total anesthesia 3. Central paresis of inner organ 1. 2. 3. 9. No prob with motor function! Total anesthesia of anogenital zone Peripheral paralysis of sphincter (atonia/hypotonia) Uncontrolled urination/defecation

Lumbar enlargement

Conus medularis

Cauda equina

1. Peripheral paraplegia (affect peri nerves of legs) 2. Total anesthesia (radical/segmental type) 3. No prob of int organs

Some important points to localize level of lesion in thoracic segments: L. mamillaris T6 L. umbilicalis T10 L. inguinalis T12

9. CN I :Olfactory nerve. Course of olfactory conductors. Signs of lesions. -f(x): smell -sensory nerve. -has 3 neurons: Bipolar cells of epithelium: located in nasal cav. at upper margin of superior nasal concha & opposite nasal septum. Axons of bipolar cells form filia olfactoria & extend thru openings in lamina cribrosa to olfactory bulb 2nd neuron forms olfactory tract: they go to primary cortical olfactory centre (eg. Olfactory triangle, septum pellucidum, ant perforated ant substances) Axons of 3rd neuron runs to corpus callosum & finish at temporal lobe(hippocampus, hyrus dentatus)
Bipolar cells of olfactory epi olfact bulb 1 cortical olfactory centre corpus callosum temporal lobe

-for smelling investigation: Ask patient to close his eyes and smell. Use substances familiar to patient (eg. Soap, spices, coffee etc). Dont use too strong subs because can irritate termination of trigeminal n. -clinics: Anosmia : absence of smell Hyposmia: decrease of smell Hyperosmia: intensification of smell Dysosmia: perversion of smell Smell hallucinations occur when temporal lobes r irritated (eg. due 2 tumors, hematoma etc) Kakosmia: perceiving odor nuisances when they r absent. (Always smell bad odor) NB! Usually, for NEURO DIS : unilateral failure of smell (anosmia) For ENT dis: bilateral disturbances (hyposmia due to mucus prob)

10. Visual analyser. Anatomy, physiology. Signs of lesion of spinal cord at different level CN II : opticus n. = sensory Anat: Retina: Internal of retina get light from external field of vision (temporal vision). External of retina get light from internal field(nasal vision) Optic n. pass thru optic canal and enters cranial cavity At diencephalon, optic n. join the contralateral nerve, forming optic chiasm. At optic chiasm: optic fiber from nasal of retina cross, thus forming crossed fibre optic fiber from temporal of retina doesnt cross. Therefore: right tr. contains: right temporal & left nasal fiber , & left tr. contains left temporal & right nasal fiber Distal to chiasm, fiber system is called optic tract. Optic tr.goes to lat geniculate body. Some pass pulvinar of thalamus From lat gen body, optic radiation (Gratiolet) goes to post limb of internal capsule, then to calcarine fissure (at medial surface of occipital lobe). Calcarine div into 2 parts: Upper quadrant of cuneus: take info from lower quadrant of retina Lower quadrant of cuneus(or gyrus lingualis) : from upper quadrant of retina

RETINAOPTIC NERVEoptic canalOPTIC CHIASMOPTIC TRACTLATERAL GENICULATE BODYOPTIC RADIATION (GRATIOLET)posterior limb of internal capsCALCARINE FISSURE (OCCIPITAL LOBE)

NB! There are also medial fibers which go to medial geniculate body. These fibers contain optic reflex tract.

Lesion:

SITES OF LESIONS Optic n. Crossed part of optic chiasm Uncrossed part of optic chiasm Right optical tract Left optical tract Optic radiation Gratilet/ all occipital cortex on right side Right cuneus Right gyrus lingualis Irritation of occipital optical cortex

SIGNS blindness of corresponding eye(amaurosis) Bitemporal hemianopsia Binasal hemianopsia Homonymous left-sided hemianopsia, absence of light reflex, stagnant optic papilla of left side Homonymous right-sided hemianopsia, absence of light reflex, stagnant optic papilla of right side Left-sided hemianopsia with safe light reflex Vision loss in lower quadrant of left eye Vision loss in upper quadrant of left eye Visual hallucination (simple figures like triangles, squares)

11. Occulomotor cranial nerve. Anatomy, f(x), signs of lesions -Motor nerve -innervates 5 external & 2 internal muscles of eyes

1. Oculomotor nerve nucleus(paired) located at sup colliculi in midbrain. Somatomotor fibers arise from it. The nerve runs through roof & lateral wall of cavernous sinus. It enters orbit thru sup orbital fossa. There, nerve divide into: superior branch: supplies levator palpebrae superioris m. , superior rectus m. inferior branch: supplies inferior rectus m., medial rectus m., inferior oblique m. 2. Nucleus of Persia (unpaired), which located next to middle third of oculomotor nuclei is important in convergence. 3. Preganglionic parasympathetic visceromotor fibers form Edinger-Westphal nucleus. They pass via ciliary ganglion and synapse it. Postganglionic fiber enter sclera to eyeball & supply: Ciliary m. Puppilary sphincter m.
Muscle Levator palpebrae superioris Superior rectus Inferior rectus Lateral rectus Medial rectus Superior oblique Inferior oblique Innervation Oculomotor nerve Primary function Secondary function Tertiary function

Oculomotor nerve Oculomotor nerve Abducens nerve Oculomotor nerve Trochlear nerve Oculomotor nerve

Elevation of the superior (upper) eyelid Elevation Depression Abduction Adduction Intorsion Extorsion

Intorsion Extorsion

Adduction Adduction

Depression Elevation

Abduction Abduction

lesions: -restrictions of eyeball movement upwards,downwards and inwards. Outwards movement is normal. -ptosis: lowering of upper eyelids (d2 paralysis of levator palpebrae m) -mydriasis: pupil dilatation (normal pupil diameter: 2-4cm) -failure of convergence & accomondation: Normally, in convergence, medial recti muscles adduct both eyeballs as object come close. Accomondation is adaptation to near & distant vision. o In near vision: ciliary m. contract, lens convex. Pupillary sphincter contracts, pupil narrowen. -strabismus divergence if lift up upper eyelids. Patient feels diplopia (double vision) which intensifies when looking up, down, inwards. It decreases when looking outwards. -exophthalmus : protrusion of eyeball out of eye-socket (d2 decrease eye m. tonus)

12. Trochlear & abducens nerves. Anatomy, functions, signs of lesion. Refer Q11 Trochlear nerve. CN IV -motor nerve, smallest cranial n. - nucleus at midbrain at level inferior colliculi nerve leave brain stem on its dorsal surface run thru sup orbital fissure orbit innervates SUPERIOR OBLIQUE MUSCLE (for downwards & inwards eye movements) -lesions: Diplopia while looking downwards (symptoms of staircase) No strasbismus Abducens nerve. CN VI - motor nerve -nucleus (at pons in the floor of rhomboid fossa) sup. orbital fissure orbit LATERAL RECTUS MUSCLE. -f(x): abduct the eye ( provide outwards eye movement) -lesions: Diplopia which becomes stronger while looking outwards Strabismus convergence the eye of damaged side looks inwards

13. Trigeminal nerve. Anatomy, functions, signs of lesions -CN V : mixed nerve, largest cranial n. -Great sensory nerve of head & face. Motor nerve of muscles of mastication Anat: Nerve leave pons as sensory root (major part) & motor root (minor root). Then, it passes anteriorly over petrous bone to trigeminal impression. Sensory fibres: has 2 parts: 1. Pontine nucleus (principal nuscleus): contain fibre of tactile & proprioceptive sensibility. It terminates in pontine nucleus 2. Spinal nucleus : contain fibres of pain & temperature Mechanism:

Motor fibre: from motor nucleus it runs in front & medial to sensory root beneath trigeminal ganglion foramen ovale join mandibular nerve -Gasserian ganglion (a.k.a trigeminal ganglion & semilunar ganglion) gives off :

1. Ophthalmic n. (sensory) a. Leave brain thru sup orbital fissure b. Branches: n.frontalis, n.nasociliaris, n.lacrimalis c. Innervates frontal & sphenoid sinuses, dura mater of brain, skin of forehead, internal corner of eye, dorsum of nose, eyeball, ant part of hair, upper eyelid 2. Maxillary n. (sensory) a. Leave brain thru foramen rotundum b. Branches: n.infraorbitalis, n.zygomaticus, n.palatinus major et minor c. Innervates upper lip, wing of nose, lower eyelids, external corner of eye, maxillary sinus, teeth of upper jaw & lower gum 3. Mandibular n. (mixed) a. Leave brain thru foramen ovale b. Give off: n.lingualis, n. alveolar inf, n.auriculotemporalis(temporomandibular joint), n.masticatorius c. Sensory innervation to lower lip, lower cheek, skin of chin, lower jaw, lower teeth & gums, sensation of ant 2/3 of toungue d. Motor innervation: ant belly of digastric, mylohyoid, tensor palate & m. of mastication: temporalis, masseter, lat & medial pterygoid

LESIONS Ophthalmic n Maxillary n Mandibular n

Trigeminal ganglion Sensory root (Major part) Motor root (Minor part) Spinal nucleus

Principal nucleus

Lesions: SYMPTOMS pain & total anesthesia in area of innervation. Corneal & supraorbital reflexes are absent pain & total anesthesia in area of innervation total anaest, paralysis of mastication m., absence of mandibular reflex on damaged side. If ask pt open mouth, lower jaw move to affected side. If lesion is double-sided, we observe loose-hanging lower jaw total anest, pain & peripheral paralysis of mastication m. on damaged side total anaest on affected side peripheral paralysis of mastication m. on damaged side Absence of pain & temperature sensation on damaged side. o If upper part of nucleus is damaged, sensation is absent in perioral area of face. o If lower part of nucleus is damaged, no sensation in peripheral part of face no tactile and proprioceptive sensation on affected side o To check it: form fold on patients cheek and lift it. Patient closes his eyes and tell if he feels this shift

14. Innervation of mimic muscles and signs of its disturbances CN VII Facial nerve. -Mixed nerve. Motor part supplies muscle of face expression & 4 muscles [platysma, post belly of digastric m., stapedius, stylohyoid] Sensory: receive taste sensation from ant 2/3 of tongue Autonomic: lacrimal gl, submaxillary & subligual gl. Anat: refer picture. Facial nerve nucleus n. bends around CN VI at internal genu exit from medulla at lower border of pons pass through internal acoustic meatus enter facial canal* at petrous bone, it bends and form external facial genu ; where, here lies geniculate ganglion leave skull through stylomastoid foramen terminal branches at parotid gland innervates all m. of face except m. masseter Facial n. runs together with intermediate nerve (n. of Vrisberg). *In facial canal, facial n. gives off: 1. Greater pertrosal nerve: innervates lacrimal, nasal and palatal glands o Damage causes: dryness of eyes 2. Stapedius n. : innervates stapedius m. in middle ear o Damage causes: hyperacusia(noices, crackles in ears) 3. Chorda tympani: innervates ant 2/3 of tounge o Damage causes: loss of taste on ant 2/3 of tongue

Damage of facial n.: Prosoplegia: paralysis on of face. Face resemble half mask No folds on forehead Patient cannot knit his brow, blink, close eyes(lagophthalmos, hares eye) Attempt to close eyes result in rotation of eyes upwards so that we can see sclera(Bells symptom) Patient cannot whistle, blow out candle When patient in coma, can determine prosoplegia by these symptoms: Symptom of sail : patient blows up his cheeks Symptoms of racket: absence of symmetry of oral fissure Levels of facial n. lesion: PERIPHERAL PARALYSIS LESIONS Nucleus

SIGNS Peripheral paralysis unilateral side, half-mask Asymmetry of face: on affected side eyebrow is lower, palpebral fissure is widened d2 paralysis of orbicular muscle of eye, nasolabial fold is smoothed Pt cannot knit his brows, close eyes(lagopthlmos, hairs eye) Bells symptom- uncovering of sclera when pt attempts to close eye Rocket symptom- when pt attempts to bare his teeth, angle of mouth on affected side doesnt change its position Before nerve enters facial canal Dryness of eye Hyperacusia Loss of taste on ant 2/3 of tongue After greater petrosal nerve & Prosoplegia before stapedius n Hyperacusia Loss of taste Watering of eyes (instead of dryness of eyes) after stapedius n. & before chorda Prosoplegia tympani Loss of taste Watering of eyes after leaving stylomastoid foramen Prosoplegia Watering of eyes CENTRAL PARALYSIS Nucleus facial n. take impulse from corticonuclear tr. It has 1 pecularities: Upper part of nucleus has 2sided innervation, while lower part take impulse from contralateral corticonuclear tr. Therefore, in central paralysis: symptoms of affection of lower part of face on contralateral side Lowering of angle of mouth Smoothening of nasolabial fold etc

Lower motor nucleus lesion (peripheral) Nuclear/ infranuclear. Affecting facial motor nucleus/ the nerve itself Paralysis of m. of upper & lower half of face on the same side of lesion Paralysis affect voluntary, emotional & associative movement Flaccid with hypotonia & hyporeflexia Present Hemiplegia on opposite site of facial paralysis

vs Site of lesions Extent of paralysis Emotional movement Types of paralysis Bells palsy Motor manifestations

Upper motor nucleus lesion (central) Supranuclear. Affecting pyramidal tr above facial nucleus Paralysis of lower half of face on the opposite side of lesion Paralysis involves voluntary movement only Spastic with hypertonia & hypereflexia Absent Hemiplegia on same side of facial paralysis

BELLS PALSY (EXTRA NOTES) Acute paralysis of face, d2 n-suppurative inflm of facial n. usually unilateral, recurrent, familial. Etio: vascular ischemia, 2ry to neutropic virus(eg HZV), autoimm Clinical Pic: history of exposure to air draught, more of female, onset with acute pain behind ear CM: lower face(obliteration of naso-labial fold, deviation of mouth to healthy side + dribbling of saliva, accum of food behind cheek, cannot to blow cheek, cannot to show teeth properly). Upper face: cant to raise eyebrow+absence of wrinkle of forehead, cant close eyes, when pt attempts to close eyes his eyeball rolls upwards(Bells phenomenon) Impairment of taste 2/3 ant of tongue on same side. Affections of emotional fibers

15. Glossopharyngeal nerve. Anatomy, physiology, signs of lesions -CN IX: mixed n. -Fibers of sensory innervate middle ear & parts of tongue and pharynx -Fibers of motor innervate m. of pharynx -behind the olive, it emerges from medulla immediately above vagus n. thru jugular foramen -it consists of 4 nuclei: N.ambigus: motor innervation to pharynx m., stylomastoid m. etc Inferior salivary nucleus: visceroefferent(secretory) fiber which innervate parotid gland Grey wing nucleus: viscerosensory fiber which innervates pharynx, epiglottis, soft palate Nucleus solitarius: taste fibre. Taste for posterior 1/3 of tongue -lesions: a) Loss of taste on post 1/3 of tongue b) Anesthesia of pharynx & soft palate c) Mild chocking while swallowing

16. Vagus nerve. Anatomy, physiology, signs of lesions -CN X : mixed n. [motor & sensory], autonomic [parasympathetic] -it has motor,exteroceptive sensory, visceromotor, viscerosensory & taste fibers sensory: from thoracic & abdominal viscera, from skin over external auditory meatus motor: to soft palate, pharynx & larynx autonomic fibres: parasympathetic fibers to heart(inhibitory), GIT, bronchial tree(secretory & motor) -the fibres leave just behind olive, combine into nerve trunk, and leave skull thru jugular foramen -nerve fibers arise from following nuclei: a) Nucleus ambigus: gives off motor fibers to larynx, epiglottis, upper part of esophagus b) Grey wing nucleus: gives off sensory fibers to meninges, pharynx, larynx, trachea, bronchi, lungs, GIT c) Dorsal nucleus of vagus n.: gives off visceromotor fibers to smooth muscle of internal organs -Lesions: 1-sided lesion of -hanging down of soft palate on affected side vagus nerve -uvula deviated to contralateral side -dysphagia (disturbance of swallowing) -dysphonia (hoarseness of voice 2-sided lesion -aphonia -aphagia -liquid food runs out of nose -rhinulolia voice has nasal twag -disturbances of respiratory & CVS -Palato-pharyngeo-laryngeal paralysis : resulting in bulbar palsy is manifested by: Bulbar symptoms: dysphagia, dysarthria, dysphonia, nasal regurge Ipsilateral loss of palatal & pharyngeal reflex -Tachycardia & constipation

17. Hypoglossal and accessory nerves. Anatomy and physiology, sign of lesion Hypoglossal nerve (CN XI) Anatomy The fibers that form the CN XI are formed by lower motor neurons located in the upper segments of the spinal cord. This cluster of neurons = spinal accessory nucleus is located in the lateral horn of the spinal cord. CN XI consists of 2 parts : cranial part & spinal part Cranial part arises from lowest part on nucleus ambiguus in medulla oblongata. (cont.from lat horn) Spinal part arises in the ventral grey matter of the upper 5 cervical segments. Ascends alongside the SC and passes thru foramen magnum. Then, these 2 parts join & exists as accessory nerve thru jugular foramen.

Physiology CN XI is a purely motor nerve supplying m.sternocleidomastoid & m.trapezius Supranuclear connections act on the ipsilateral sternomastoid (turning the head to the contralateral side) & on the contralateral trapezius. This result in : -head turning away from the relevant hemisphere during seizure -hear turning towards relevant hemisphere during cerebral infarction Unilateral lower motor neuron weakness produce a lower shoulder on affected site (trapezius) and weakness in turning head to the opposite side (sternocleidomastoid).

Sign of lesion Peripheral paralysis a)1 sided lesion = pt x turn head to contralateral side, cant lift arm/shoulder of same side b)2 sided lesion= dangling head, pt head lies on breast (dt m.trapezius) = x shrug both shoulders Central paralysis Doesnt exist bcoz of 2 sided innervations of accessory nerve. Hypoglossal nerve (CN XII) Anatomy The nucleus lies in the floor of IV ventricle & fibers pass ventrally to leave the brain stem lateral to the pyramidal tract and then, it passes thru canalis hypoglossus. It spirals behind the vagus nerve and passes between the internal carotid artery and internal jugular vein lying on the carotid sheath. After passing deep to the posterior belly of the digastric muscle, it passes to the submandibular region to enter the tongue.

4. CN XII 5. IV ventricle 10.pyramidal tract Physiology CN XII is a purely motor nerve which supplies intrinsic muscle of the tongue except m.palatoglossus which is innervated by CN X (vagal nerve). Sign of lesion Since each nucleus is bilaterally innervated, a unilateral supranuclear lesion will not produce sign or symptoms. Bilateral supranuclear lesion result in thin pointed (spastic ) tongue which cant be protruded.

Peripheral paralysis a)lesion of nerve trunk -dysarthria -deviation of the tongue to the affected site when putting it out -atrophy of tongue muscles & fasciculation b)lesion on CN XII -same as above + fibrillary tremor of tongue Central paralysis -lesion of corticonuclear tract = deviation of tongue on contralateral side.

18.Bulbar and Pseudobulbar paralysis Bulbar paralysis (true) = peripheral paralysis Paralysis of bulbar nerves : CN IX, CN X, CN XII Symptoms :1)Dysphonia -D/o of phonation -CN XII damage causes palate descent -Rhinolalia nasal sound of voice -CN X damage will affect vocal cord causing hoarse voice 2)Dysphagia -disorder of swallowing -tongue and esophagus arent working -hard food will go to trachea, soft (liquid) food will go to/back thru nose 3)Dysarthria -disorder of speech. Inability of tongue to articulate due to lesion in CN XII -vowels and consonants cant be dictate -however, patient still can write and understand what he wants to say 4) Atrophy muscle of tongue in lesion of CN X , fibrillation of tongue Areflexia reflex of swallowing & soft palate reflex are lost *This syndrome is typical for bulbar form of amyotrophic lateral sclerosis eg: diphtheria polyneuropathy Pseudobulbar paralysis = (central paralysis) Is the result of bilateral lesion of corticonuclear tract (affect CN IX, CN X, CN XII) Symptoms :1)Same as bulbar symptoms , dysphagia, dysphonia, dysarthria BUT without atrophy of tongue and fibrillation of tongue 2)Pharyngeal and soft palate reflexes are Normal or Increase 3)Pathological reflexes (reflexes of oral automatism) are present. For example:- atsvatsaturovs (nasolabial) reflex -lip reflex -sucking reflex -palmomental reflex 4)compulsive weeping (crying) & laughing during conversation (involuntary) * This syndrome is typical for vascular lesion of brain (atherosclerosis), infectious allergic process (encephalitis, intoxications, hypoxia of CNS)

19.Cerebellum. Anatomy, physiology, sign of lesions Anatomy -also known as little cerebrum -located in posterior cranial fossa -consists of 2 hemispheres which is connected by vermis(worm) -hemisphere is made of white mater (consists of pathways) and grey mater(consists of nucleus where it has tract that connect cerebellum to brain & SC, also connect hemisphere to each other). -cerebellum connects with brain thru 3 peduncles Inf : has spinocerebellar tract & has connection with vestibular nuclei Mid: fibers from pons that arise fr pontine nuclei & form the continuation of corticopontine tracts Sup : efferent fibers sys. to red nucleus & thalamus -it carries impulses from CN III nucleus, vestibular nucleus and connects pyramidal & extrapyramidal system. Function -organ for balance -regulate/ support muscle tone -coordination & fine synchronization of body movement -coordinate activity of agonist, accessory & antagonist muscles to serve smooth, precise & efficient execution of movement Signs of lesion 1) Hypotonia of muscles 2) Intention tremor (intensia) - Can be access during finger nose test (tremor increase, as finger reach nose) - Knee-heel test 3) Cerebellar Ataxia -ataxic step/sailor steps -resembles the manner of drunken man (walk with widely spread leg) 4) Fall -romberg test = patient either walk to the side / fall & balance with spreading their legs

5) Speech disturbances -cerebellar diarthria / scanning speech -speak like singing/ speak words separately -speech loss its facility, become explosive & scanning -vocal cord coordinated with respiration 6) Nystagmus -horizontal usually -jerking of eyes during abduction. -it can be horizontal, vertical, rotator, complex, small, middle, large, swinging, congenital, acquired 7) Megalographia -big handwriting, not on 1 line, s/times small & big letter not in line -cant write alphabet precisely 8) Asynergy of Babinski -ask pt to lie on bed with cross hand. Then, ask pt to get up from the bed. Normal : leg is not lifted Patho: leg is lifted 9) Missing -ask pt to touch the hammer, then, touch it with closed eyes, pt cant remember the position of the hammer. 10) Dysmetria -incorrect amplitude or velocity of a planned movement -pt may open fingers excessively while grasping a small object / raise leg too high while attempting to go upstairs -cant raise hand in 1 position for a long time 11) Adiadohokinesia /disdiadohokinesia -disorder in pronation & supination of hand -ask pt to make alternate opposite mvmnt, pt cant perform quickly & properly * in lesion of vermis = both side will be affected *in lesion of hemisphere = symptoms will be seen on ipsilateral to the side of lesion bcoz cerebellum has 2 crossings

20.Striatal system. Anatomy, physiology & signs of lesions Refresh Striatal system & pallidal system are parts that make the extrapyramidal system. Extrapyramidal sys. is the basal ganglion consists of nuclei of gray matter. These includes :-Substantia nigra -Red nucleus -Lentiformis nucleus (Putamen + Globus pallidus) -Light blue corpus It is connected with many other systems : pyramidal, cerebellum, vestibular nucleus,oculomotor nucleus Function of extrapyramidal system -prepare for muscle mvmnt -keep the balance btw antagonist and agonist muscle -automatisation of mvmnt action 1st automatisation occur in childbirth ( sucking, rasping, fixates eyes at 1 place, etc..) -fine & accurate mvmnt Anatomy of striatal system It is made by nucleus caudate & putamen Main mediators : Acetylcholine, Norepinephrine Functions It contra to the pallidum sys. Answers for slow mvmnt. Slow & accurate mvmnt

Signs of lesion Hypotonic hyperkinesia -patient cant control the mvmnt. Lesion of striatal sys. increase/excess the mvmnt a)tic = contraction of m.orbicularis oculi/oris. It can be physio.(eg: stress). Usually 1 sided b)blepharospasm = tonic contraction of m.orbicularis oculi (both eyes) -frequent close & open the eyes. Seen in people who works with computer. -may lead to fxal blindness c)hemifacial spasm = eyes & mouth are pull to 1 direction d)oromandibular dystonia = mvmnt of mouth (mouth open , smiling etc..occur suddenly) e)cervical dystonia=hypertonus of m.sternocleidomastoideus of 1 side. Head always turns to 1sd f)athetosis = slow, worm-like mvmnt. Occur usuall in distal part (fingers) g)hemibolism = hand mvmnt always move like throwing a ball h)ballerina foot i) 3 fingers symptoms j) torsal dystonia body move in a circle, like an a pivot point - body will freeze accor to last pose k)general muscle dystonia l)ambulatory spasm of foot

*All symptoms disappear during sleep

21. Pallidal system. Anatomy, physiology & sign of lesion Anatomy & physiology Answers for fast movements Mediators : dopamine =exert inhibitory influences on cholinergic interneurons of striatum Signs of lesion Hypertonic hypokinesia (Parkinsonism) Tremor (rest tremor) on distal part, more at the side of affection. It could be:

-banker hand mvmnt -pronation-suppination mvmnt =rare -After that, tremor of proximal part can be seen (bird flapping) & jaw tremor -max at rest , high amplitude, low frequency Hypertonic of the muscle

-like dental ring (mvmnt like gear in the watch) -plastic/spastic (not sure which term is correct) -corkwheel type -diffuse/rigid type (air pillow phenomena) Ask pt to sleep on a pillow, then pull away the pillow, we can see pts head remain in air, it didnt fall -rigidity of trunk = pt x turn neck, so turn the whole body Bradykinesia /hypokinesia

-begin usually in mimic muscles = mask like face, amimic face -talk w/o emotion(soft & monotonous speech), no wrinkles of expression on face -walk slowly, dragging walk like shuffling = feet on floor, to walk pt drag their feet -old man pose,bend forward, hand adducted. In hemilesion, 1 side sway, another not. -propulsion = 2 types : lateral or retro. Micrographia = due to paucity of movement Vegetative disturbances

-hypotrichose, hypersalivation, gastroparesis, atony of intestines, impotency, orthostatic HPT Psyhic disturbances

-depress, suicidal Bradyphrenia

-slow thinking dementia Freezing phenomena

-difficult to initiate mvmnt and to stop mvmnt *all symptoms subsides during sleep *refer more to parkinsonism syndromes to get the brief explanation Pallidal system vs Striatal system Balance of pallidal & striatal system is achieved at age of 25-30 YO. But, dpns on sev factors: -genetic -any diseases that we have -trauma of NS in any period of life -medicine -toxic factor = alcohol, narcotics, smoking,poisoning B4 25 YO, pallidum predominant = during this age, we are active, (byk suka) After 50 YO, striatal predominant = mvmnt become slower, move calm, need more rest After 70 YO, symptoms of Parkinson become physiological

22. Internal capsule. Thalamus. Anatomy, physiology & signs of lesion INTERNAL CAPSULE Anatomy & physiology -composed of compact of strip of fibers of white mater -it has a boomerang-shaped structure - this area of white matter separates the caudate nucleus and the thalamus from the lentiform nucleus. - contains both ascending and descending axons (carries information down towards the body, and up towards the brain cortex) -It consists of axonal fibres that run between the cerebral cortex and the pyramids of the medulla. -it consists of 1 genu & 2 limbs (ant. Limb & post. Limb ) A ) anterior limb of the internal capsule contains: 1) Frontopontine (corticofugal) fibers project from frontal cortex to pons 2) Thalamocortical fibers (part of the thalamocortical radiations) connect the medial and anterior nuclei of the thalamus to thefrontal lobes (these are severed during a prefrontal lobotomy). B) genu contains corticobulbar fibers, which run between the cortex and the brainstem. C) posterior limb of the internal capsule contains:

corticospinal fibers, sensory fibers (including the medial lemniscus and theanterolateral system) from the body and a few corticobulbar fibers.

*Other fibers within the internal capsule

The retrolenticular part contains fibers from the optic system, coming from the lateral geniculate nucleus of the thalamus. More posteriorly, this becomes the optic radiation. Some fibers from the medial geniculate nucleus (which carry auditory information) also pass in the retrolenticular internal capsule, but most are in the sublenticular part. The sublenticular part contains fibers connecting with the temporal lobe. These include the auditory radiations and temporopontine fibers.

Signs of lesion Consists of 2 syndromes:1)total capsule syndrome = ant, post & genu are affected Symptoms : hemiplegia/hemiparesis, hemianaesthesia, hemianopsia ( of contralateral side) + central paralysis of CN VII & CN XII 2)partial capsule syndrome = only post limb affected Symptoms: hemiplegia/hemiparesisi,hemianaesthesia, hemianopsia of contralateral side *in internal capsule affection we can see both sensory & motor problem *hemiparesis = weakness of 1 side of body *hemiplegia = severe than hemiparesis. It is total paralysis of arm, leg & trunk of 1 side of body THALAMUS Anatomy & physiology -Located btw brain cerebral cortex & midbrain -Paired, medially placed, deep egg-shaped nuclear structures that form part of the lateral wall of the 3rd ventricle -Composed of multiple nuclei, which receive input from many cortical and subcortical structures. Have 146 nuclei which can be divided into 4 groups:= ventral, anterior, posterior, median -gateway to cerebral cortex. =Sensory input, other than olfaction, relays through the thalamus before reaching the cortex. =All output to the cortex from the cerebellum and basal ganglia relays through the thalamus. =The thalamus also relays limbic input to the cortex -It is also the main pain reception & centre of 1o emotional -Due to its multiple functions, damage to the thalamus can cause many problems, including sensory abnormalities, visual-eld decits, and behavioral changes -Lesions to the sensory area can cause numbness on the contralateral body and face

Signs of lesion Symptoms :1)prolapse -(contralateral side) total hemianaesthesia, hemiataxia, hemianopsia-due to lesion of genicullar body 2)irritation -severe pain (thalamic pain, very intense pain which can be relieve only by narcotics) -laughing/tearing (crying) w/out reason *thalamic syndrome = Pejenne-Rouss vascular syndrome *please refer also from your own notes for additional info.

23. Speech and its disturbances (aphasia & dysarthria) APHASIA A disorder of speech in which pt has trouble in understanding the speech (in absent of hearing problem), or in the thought & word finding processes speech. There is a defect in comprehension &/or expression of language. Types of aphasia It dpns on the localization of the lesion 1.Wernickes aphasia/sensory aphasia,receptive aphasia,fluent aphasia -caused by lesion in the post. Portion of sup.temporal gyrus = wernickes area -characterized by copious speech that is not intelligible bcoz of incorrect word & syllable choice -pt doesnt understand what he is saying or what is said to him (impair comprehend written&spoken words but not speech = prob in understanding the speech, but not in speaking) -ex: if pt is hungry,he will speak volumes but not able to convey the simple message(tht he wants to eat) -if lesion involved surrounding cortex, contralateral sensory loss or homonymous visual defect may occur 2.Brocas aphasia/motor aphasia,expressive aphasia,non fluent aphasia -caused by lesion of inferior portion of left frontal gyrus & its underlying white mater -pt understand speech but speech production is distorted -difficulty with speech fluency & organization & the sentences have few words (telegraphic speech) -unlike fluent aphasia, pt with brocas aphasia can understand the speech (what they & others are saying) and can convey the idea -ex:if pt is hungry, he might communicate his plight by saying hungry.eat -if lesion involved surrounding cortex, pt may also hv upper motor neuron right facial & hand weakness 3.Conduction aphasia -it is lesion that interrupts the connection btw Wernickes & Brocas area (Arcuate fasiculus) -CPx = Inability to repeat what is said

-fasiculus often involved with lesion in Brocas or Wernickes area so pt with this type also may not able to repeat 4.Global aphasia -large lesion affecting both speech area & their connections leaving the pt mute & unable to comprehend the speech -there is also an asso. dense contralateral hemiplegia DYSARTHRIA Result from the disruption of muscular control due to lesion either the CNS or PNS. There is interruption of the transmission of messages controlling the motor movements for speech. In this condition, it involves the problem with the transfer of info. from NS to the muscles thats why dysarthria is classified as neuromotor d/o CNS Lesions Damage of pyramidal tract causes spastic dysarthria. Lesion of substantia nigra causes hypokinetic dysarthria Disruption of feedback loops involving the cerebellum causes ataxic dysarthria PNS Lesions Damage to any part of PNS that serves the muscles of speech cause flaccid dysarthria Types of dysarthria 1.Spastic dysarthria -caused by bilateral UMN lesion & produce speech which is harsh & strained in character -range of mvmnt, tongue strength, speech rate and voice onset & time for stops are reduced -increase in syllable & word duration and increase voicing of voiceless stops 2.Extrapyrimidal dysarthria -2o to lesion of basal ganglion & can be seen in Parkinsons syndrome -speech has low volume, no change in pitch & may be distorted tremor 3.Ataxic dysarthria -can be seen in cerebellar lesion

-the speech has irregular rate, range & volume -it may be explosive in character -pt tend to place equal & excessive stress on all syllable soken -before this it is term as scanning speech 4.Hyperkinetic dysarthria -unpredictable contraction of the muscles of articulation producing speech that is distorted in terms of pronunciation, articulation and volume -can be seen in dzs producing excessive mvmnt eg: chorea and dystonia 5.Flaccid dysarthria -result from damage to LMN (cranial Nn.) that involved in speech -If CN X is damaged, voice will be affected as this Nn innervates intrinsic musculature of the larynx, vocal fold is paralyzed -monopitch & monoloudness may both result from vocal fold paralysis -associated characteristics:=Muscles affected by flaccid paralysis may begin to atrophy or loss mass over time =Lack of innervations may cause fasciculations or twitching of muscles fibers =These mvmnt are esp visible in tongue; its surface may dimple as if worms were moving beneath skin

24.Agnosia, Apraxia. Their kinds AGNOSIA Disturbances of recognition affecting a particular sensory modality that cannot be explained by a deficit of elementary perception, attention, or cognition Types 1. 2. 3. 4. Visual agnosia Pt has N visual acuity , yet cannot recognize an object on sight & must feel it in order to name it. Lesion lies in the visual association cortex (area 18 & 19) of both hemispheres Optic aphasia = lesion of the fiber pathway linking the visual association cortex to the speech area leave the pt still able to recognize an object & demo its use but unable to name it or the activities for wic it is use Special form of visual agnosia 1.colour agnosia -inability to recognize color -produce by lesion of ventromedial portion of the left occipital lobe -need to distinguish from inability to name colors (color anomia) 2.prosopagnosia -inability to recognize familiar faces & usually complex structure of other kind as well -produce by lesion of the inferior portion of the temporal & occipital lobe of right side or both side 3.simultanagnosia -disturbance of global recognition, despite a preserved ability to recognized details -produced by bilateral parietal or parieto-occipital lesion & in milder form, by left occipital lesion Examination for visual agnosia -by showing objects & pictures to be named Visual agnosia Tactile agnosia Finger agnosia/autotopagnosia Anosagnosia

-if pt cant name it, ask pt demo the use of the object -task of sorting different colour color agnosia =pt with color anomia can perform this task, pt with color agnosia cant -for prospoagnosia test with picture of pts relatives Tactile agnosia Inability to recognize an object by touch despite intact primary somatic sensation & despite the preserved ability to recognize & name the object on sight Due to lesion of contralateral parietal lobe Finger agnosia / autotopagnosia Finger agnosia -Deficit in orientation to ones own body that is confined to the fingers -When examiner touch one of the pts finger, pt cant state which finger was touched -Due to lesion at the junction of the left parietal & occipital lobe Autotopagnosia -Inability to name a part of ones own body after the examiner touches it or inability to point to it after the examiner name it Anosagnosia Failure to recognize ones own neurological deficit Affected pt behave as if they were not blind, deaf ,hemiparetic or other impaired as the case may be. They will also minimize the deficit or even actively deny it APRAXIA -acquired disturbances of the execution of sequential mvmnts or activities, in the absence of 10 disturbances of motor or sensory fx, coordination, comprehension or attention -inability to make skilled mvmnt with accuracy -apraxic pt can carry out certain mvmnts or activities spontaneously while being unable to carry out the same mvmnt or activities on command or in imitation of examiner. Types

1.ideomotor apraxia -inability to carry out an individual mvmnt or activity 2.ideational apraxia -inability to carry out activities involving multiple steps 3.facial apraxia 4.limb apraxia Test for facial apraxia -ask pt to blow out a candle, stick his tongue out, lick the lips, drink thru the straw,snap his fingers, make a hissing sound. Test for limbic apraxia -ask pt to salute, thumb his nose or shake his fist at the examiner, mimic mvmnt eg:tooth brushing, haircombing, hammering in a nail Test of ideamotor leg apraxia -ask pt to kick a ball, climb over an obstacle Test for ideational apraxia -folding a latter -putting it in an envelope -sealing the envelope *bilateral ideomotor apraxia is practically always the result of left-hemisphere lesion & its usually accompanied by aphasia *ideational apraxia is often accom by disturbances of spatial orientation, processing & planning and is usually encountered as a component of dementia.

25. AUTONOMIC INNERVATION OF EYE.SIGN OF DISTURBANCES Nerves that innervates the eye: Sensory: N.opticus, N.trigeminus(1st branch- n.opthalmicus) Motor : N.oculomotorius , N.trochlear, N.abducens Sympathetic nerve N.OPTICUS Damage of optic nerve bilndness of corresponding eye (amourosis) Damage of crossed part(optic chiasma- hypophisis tumor) bitemporal hemianopsia Damage of uncrossed part of chiasma- increased ICP) binasal hemianopsia Damage of R optical tracthomonymus L side hemianopsia,no light reflex, stagnant optic papilla on L side Damage of L optical tract vise versa of the R damage Optic radiation(R) damage L side hemianopsia, preserved pupillary reflex(arch not Damaged) Lower part optic radiation damage(R) vision lost at L upper quadrant Upper part optic.rad. damage(R) vision lost in lower L quadrant Damage gyrus lingualis(R) L upper quadrant vision lost Damage of cuneus (R) L lower quadrant Irritation occipital lobevisual halliucination N.OCULOMOTORIUS 1.restriction in eyeball movement All eye muscle dont work except troclear and abducens. Eye doesnt move UP, DOWN, INWARD, only move OUTWARD strabismus divergence 2.ptosis Upper eyelid lowered (m.levator palpebrae superior not working) 3. Mydriasis Pupil dilation (> 2-4 mm) Caused by dmage of nucleus Edinger Westpall sphincter Pupilla X function difficult to see near objects, X accomodation 4.failure of convergence and accomodation 5.diplopia double vision (failure of foveation) 6 exophtalmus N.TROCLEAR

Damage diplopia (m.obliiquous superior failure) X strabismus N.ABDUCENS Diplopia (double vivion) Convergence strabismus Restricted eye movement( eye dont move laterally, stops at midline) N.TRIGEMINUS( N.OPTHALMICA) Pain and total anaesthesia at site of innervation Absent of corneal and surpaorbiatal reflex SYMPATHETIC FIBRE INNMERVATION Upper eyelid: smooth muscle fibre for m.levator palpebrae superior innervated by sympathetic postganglionic fibre from superior cervical sympathetic ganglion Division of sympathetic nerve fibre paralysis the smooth muscle ptosis Iris: smooth muscle fibre circular sphincter pupiila Radiating dilator puppila Sphincter (parasympathetic fibre frm nucleus Edinger Westpall of oculomotor nerve) Dilator (postganglionic fibre from superior cervical sympathetic ganglion) Sympathetic : pupil (dilates), ciliary muscle (relaxes) Parasympathetic :pupil (constricts), ciliary muscle (contract)

26. RESEARCH OF CSF.MENINGEAL AND HYPERTENSIVE SYNDROME. o o For diagnosis or exclusion of infectious or demyelinating disease of brain,meninges,spinal cord or nerve root, subarachnoid hemorrhage, carcinomatous and sarcomatous meningitis. Obtained by lumbar puncture

Indication: Imaging studies fail to detect acute bacterial meningitis CT negative subarachnoid hemorrhage

Contraindication: Absolute: Clinical sign of intracranial hemorrhage Platelet count under 5000 Relative: Anticoagulation Platelet count 5000-20000 Lumbar paraspinal abscess or other infection Lumbar puncture risk: Transtentorial/transforaminal herniation (if intracranial pressure is dangerously elevated) Clinical worsening of paraparesis (if there is partial block in CSF flow) Epidural,subdural,subarachnoid hemorrhage Lumbar puncture: first the patient is usually placed in a left (or right) lateral position with his/her neck bent in full flexion and knees bent in full flexion up to his/her chest, fetal position. Patient can also sit on a stool and bend his/her head and shoulders forward. The area around the lower back is prepared using aseptic technique. Appropriate location is palpated, local anaesthetic is infiltrated under the skin and then injected along the intended path of the spinal needle. A spinal needle is inserted between the lumbar vertebrae L3/L4 or L4/L5 and pushed in until there is a "give" that indicates the needle is past the ligamentum flavum. The needle is again pushed until there is a second 'give' that indicates the needle is now past the dura mater. When needle has pierced the dura mater it has also traversed the thinner arachnoid membrane and is now in the subarachnoid space. The stylet from the spinal needle is then withdrawn and drops of cerebrospinal fluid are collected. The opening pressure of the cerebrospinal fluid may be taken during this collection by using a simple column manometer.

 The procedure is ended by withdrawing the needle while placing pressure on the puncture site. The upright seated position is advantageous in that there is less distortion of spinal anatomy which allows for easier withdrawal of fluid. It is preferred by some practitioners when a lumbar puncture is performed on an obese patient where having them lie on their side would cause a scoliosis and unreliable anatomical landmarks. Patient anxiety during the procedure can lead to increased CSF pressure, especially if the person holds their breath, tenses their muscles or flexes their knees too tightly against their chest

Normal CSF: a) Colous b) Cell c) Smell - colourless - lymphocyre (0-5) -none

d) Protein - 0.033 g/l e) Glucose 1.30-3.20 mmol/l f) Chloride 120-140%

g) Pressure- lying 180-220 mmh20 -sitting200-320 mmh20

Meningeal syndromes: 1) General infection syndrome Nausea, vommiting,malaise, fatigue, dizzy 2) General cerebral syndrome headache, confusion,photophobia Meningeal syndromes: Rigidity of neck muscle Kerning sign positive when the thigh is bent at the hip and knee at 90 degree subsequent extension in the knee is painful (leading to resistance). Brudzinski: The symphyseal sign, in which pressure on the pubic symphysis leads to abduction of the leg and reflexive hip and knee flexion. The cheek sign, in which pressure on the cheek below the zygoma leads to rising and flexion in the forearm. Brudzinski's reflex, in which passive flexion of one knee into the abdomen leads to involuntary flexion in the opposite leg, and stretching of a limb that was flexed leads to contralateral extension. angles, and

 Meningeal pose

In kids: Meningeal cry (continuous monotonuous cry) Lessaq sign when holding baby,head upward,leg flexed

3) CSF changes Colour yellow ,cloudy Cell increased (neutrophil bacterial ... lymphocyte viral) Pressure increased

Hypertension syndrome: Hypertensive encephalopathy Disturbance of brain function due to acute elevation of blood pressure, whether/not patient previously suffered from chronic arterial hypertension Signs headache, nausea, vomitting, visual disturbances, confusion, stupor, focal neurological deficit, focal/generalised epileptic seizure Retinoscopy: retinal swelling and papillary edema, vasospasm of small arteries Eclampsia: special type of hypertensive encephalopathy caused during pregnancy

27. SYNDROMES OF PARIETAL LOBE LESION Definitions The parietal lobe is where peripheral sensory information registers in the cerebral cortex. Functions at this cortical area include both perception and interpretation of sensory information. With parietal lobe lesions, the ability to interpret peripheral sensory information is most likely to be affected, although the primary sensory modality itself may also be impaired. Anatomy The parietal lobe extends from the central sulcus anteriorly to the imaginary parietal-occipital fissure posteriorly, above the temporal lobe. There is a parietal lobe in each hemisphere, and one is not completely a mirror image of the other, especially at the functional level. Over the convexity, each lobe shows three parts: the post central gyrus, the superior parietal lobule and the inferior parietal lobule. The inferior lobule includes theangular and the supramarginal gyri. From the medial aspect, the parietal lobe contains the post-central gyrus part of the paracentral lobule, part of the cingulate gyrus, and the precuneus.

Physiology The dominant lobe is particularly important for perception, interpretation of sensory information, and the formation of the idea of a complex meaningful motor responses to the stimuli (whereas the frontal lobes are important for the execution of the act.). Particularly, the supramarginal gyrus and the angular gyrus of the dominant inferior lobe are concerned with language, mathematical operations, and body image. The non-dominant lobe is especially important for visual-spatial functions. impairment of tactile sensation impairment of proprioception, i.e. postural sensation and sensation of passive movement sensory and visual neglect syndromes, i.e. inability to pay attention to things in certain parts of the person's sensory or spatial environment. This can be as extreme as denial of a limb. loss of ability to read, write or calculate (dyslexia, dysgraphia, dyscalculia) loss of ability to find a defined place (geographical agnosia)

Location of the Lesion Post-Central Gyrus , Dominant or Non-Dominant (the post central gyrus is also known as the Anterior Parietal Lobe)

Superior Parietal Lobule, Dominant or NonDominant

Inferior parietal lobule, Dominant or Nondominant Dominant inferior parietal lobule

Non-dominant inferior parietal lobule

Impairments 1. Postural sensation (proprioception) 2. Appreciation of passive movement (kinesthesis) 3. Tactile sensation 4. Two point discrimination 5. Agraphism 6. Astereognosis 7. Sensory +/- visual inattention 8. High sensory thresholds 1. Balint Syndrome cannot reach for objects (optic ataxia) 2. trouble with spatial processing 3. poor visual guidance of hands, fingers, eyes, and limbs, head (hard time catching a ball) 4. poor tactile recognition 5. poor knowing of limb position 6. hard time directing movement in space (trouble flying a kite) 7. hard time distinguishing left from right 1. Sensory extinction 2. Astereoagnosia 3. Dysgraphaesthesia 1. Acalculia 2. Agraphia 3. L-R confusion 4. Finger agnosia 5. Conductive aphasia, Wernicke's receptive dysphasia 6. Alexia/Dyslexia 7. Gerstmann's syndrome 1. Geographical agnosia 2. Phonagnosia 3. Amusia 4. Constructional apraxia 5. Asomatognosia 6. Anosognosia 7. Spatial neglect 8. Neglect of contralateral limb 9. Disappreciation of three dimensional sense 10. Dressing apraxia 11. anosagnosia (denial of illness)

Optic radiation deep in either parietal lobe Definitions amusia - inability to recognize and process music. anosagnosia (denial of illness) anosdiaphoria (indifference to illness)

1. Contralateral homonymous inferior quadrantanopia

asomatognosia (loss of knowledge or sense of ones own body usually right side problem) astereognosia (cant tell what things are by feeling them) asymbolia for pain (absence of normal reaction to pain) autotopagnosia (inability to localize or name body parts usually on the left side) dysgraphaesthesia - inability to recognize letters or numbers written on the hand. phonagnosia - inability to recognize familiar voices receptive aphasia Patient can not understand the spoken or written word. This condition is suggested when the patient is unable to follow commands or questions. Speech is usually fluent but disorganized. The Wernickies area is likely affected Syndromes Angular gyrus - If dominant side: can copy writing but not write from dictation; poor spelling; naming still usually possible; word blindness so unable to read out loud or to follow written commands Gerstmanns syndrome Dominant inferior parietal lobe dysfunction, specifically involving the angular gyrus. Patient presents with acalculia, left-right confusion, agraphia, and finger agnosia. Balint's Syndrome - Bilateral parietal dysfunction causing inability to voluntarily control the gaze (ocular apraxia), inability to integrate components of a visual scene (simultanagnosia), and the inability to accurately reach for an object with visual guidance (optic ataxia).

28. SYNDROME OF CONSCIOUSNESS DISTURBANCES. DDX OF DESTRUCTIVE AND METABOLIC COMA. Consciousness : State of awareness of self and surroundings Etiology Coma or impaired consciousness may result from structural disorders, which typically cause focal damage, or nonstructural disorders, which typically cause diffuse damage .But causes are usually thought of as structural or diffuse.

Common Causes of Coma or Impaired Consciousness Cause Examples Focal Structural disorders Brain abscess Brain tumor Head trauma (eg, concussion, cerebral lacerations or contusions, epidural or subdural hematoma) Hydrocephalus (acute) Intraparenchymal hemorrhage Subarachnoid hemorrhage Upper brain stem infarct or hemorrhage Nonstructural disorders Seizures (eg, nonconvulsive status epilepticus) or a postictal state caused by an epileptogenic focus Diffuse Metabolic disorders Diabetic ketoacidosis Hepatic encephalopathy Hypercalcemia Hypercapnia Hypoglycemia Hyponatremia Hypoxia Myxedema Uremia Wernicke's encephalopathy

Infections

Other disorders

Drugs

Encephalitis Meningitis Sepsis Diffuse axonal injury Hypertensive encephalopathy Hyperthermia or hypothermia Sedatives Other CNS depressants

Eyeabnormalities: Pupils may be dilated, pinpoint, or unequal. One or both pupils may be fixed in midposition. Eye movement may be dysconjugate or absent (oculomotor paresis). Homonymous hemianopia may be present. Other abnormalities include absence of blinking in response to visual threat (almost touching the eye), as well as loss of the oculocephalic reflex (the eyes do not move in response to head rotation), the oculovestibular reflex (the eyes do not move in response to caloric stimulation), and corneal reflexes.

Autonomic dysfunction: Patients may have abnormal breathing patterns (Cheyne-Stokes or Biot's respirations) or hypertension with bradycardia (Cushing's reflex). Abrupt respiratory and cardiac arrest may occur. Motor dysfunction: Abnormalities include flaccidity, hemiparesis, asterixis, multifocal myoclonus, decorticate posturing (elbow flexion and shoulder adduction with leg extension), and decerebrate posturing (limb extension and internal shoulder rotation). Other symptoms: If the brain stem is compromised, nausea, vomiting, meningismus, occipital headache, ataxia, and increasing somnolence

TYPES Level of arousal Cognitive and affective function dementia delusions Confusion Inattentiom

Differentiating Toxic-Metabolic Coma from Structural Coma When the history is available, the patient's underlying illnesses and medications, or the setting in which they are found, often help guide the physician to the appropriate cause The time course of the illness resulting in coma can be helpful. Generally, structural lesions have a more abrupt onset, whereas metabolic or toxic causes are more slowly progressive The response to initial emergency therapy may help differentiate metabolic or toxic causes of coma In general, structural lesions have focal features or at least notable asymmetry on neurological examination. Toxic, metabolic, and psychiatric diseases are characterized by their symmetry

State of consciousness Patients with metabolic problems often have milder alterations in arousal, typically with waxing and waning of the behavioral state Patients with acute structural lesions tend to stay at the same level of arousal or progressively deteriorate Toxins may also cause progressive decline in level of arousal

Respiration Deep, frequent respiration most commonly is due to metabolic abnormalities, though rarely it is caused by pontine lesions or by neurogenic pulmonary edema secondary to acute structural lesions Funduscopic examination Subhyaloid hemorrhage or papilledema are almost pathognomonic of structural lesions Papilledema due to increased ICP may be indicative of an intracranial mass lesion or hypertensive encephalopathy Papilledema does not occur in metabolic diseases except hypoparathyroidism, lead intoxication, and malignant hypertension

Pupil size The pupils usually are symmetrical in coma from toxic-metabolic causes. Patients with metabolic or toxic encephalopathies often have small pupils with preserved reactivity. Exceptions methyl alcohol poisoning, which may produce dilated and unreactive pupils late in the course of toxic or metabolic coma if hypoxia or other permanent brain damage has occurred. In terminal asphyxia the pupils dilate initially and then become fixed at midposition within 30 minutes

Pupil reactivity Pupillary reactivity is relatively resistant to metabolic insult and usually is spared in coma from drug intoxication or metabolic causes, even when other brainstem reflexes are absent. Exceptions Hypothermia may fix pupils severe barbiturate intoxication may fix pupils neuromuscular blocking agents produce midposition or small pupils glutethimide and atropine dilate pupils

Ocular motility Asymmetry in oculomotor function typically is a feature of structural lesions Spontaneous and reflex eye movements Roving eye movements with full excursion are most often indicative of metabolic or toxic abnormalities Reflex eye movements normally are intact in toxic-metabolic coma Exceptions: rarely in phenobarbital or phenytoin intoxication rarely deep metabolic coma from other causes

Muscle tone Muscle tone usually is symmetrical and normal or decreased in metabolic coma Structural lesions cause asymmetrical muscle tone. Tone may be increased,normal, or decreased by structural lesions Any toxic-metabolic cause of coma may be associated with focal features; however, such features most often are observed with barbiturate or lead poisoning Hypoglycemia hepatic encephalopathy hyponatremia

Differentiating Psychiatric Coma from Metabolic or Structural Coma In the patient with true stupor or coma, passive eyelid opening is easily performed and is followed by slow, gradual eyelid closure. The malingering or hysterical patient often gives active resistance to passive eye opening and may even hold the eyes tightly closed. It is nearly impossible for the psychiatric or malingering patient to mimic the slow, gradual eyelid closure. The pupils normally constrict in sleep or (eyes-closed-type) coma but dilate with the eyes closed in the awake state. Passive eye opening in a sleeping person or a truly comatose patient (if pupillary reflexes are spared) results in pupillary dilation. Opening the eyes of an awake person produces constriction.

Roving eye movements cannot be mimicked and thus also are a good sign of true coma during cold caloric testing, the eyes do not tonically deviate to the side of the caloric instillation, and the fast phases are preserved, stupor or true coma is essentially ruled out Blinking also increases in psychiatric and malingering patients but decreases in patients in true stupor.

INDIVIDUAL NEUROLOGY 1. DISEASES OF PERIPHERAL NERVOUS SYSTEM 1. POLYNEUROPATHIES. FEATURES OF DIPTHERIC, DIABETIC, ALCOHOLIC, LEAD POLYNEUROPATHIES. Syndromes resulting from diffuse lesion of peripheral nerve 3 kinds: A) Wallers degeneration Axon and myelin sheath stimultaneously degenerate Result from gross mechanical trauma neural and connective tissue of nerve destroyed. Poor prognosis B) Primary demyelination First myelin degeneration occur May or may not be followed by axonal degeneration Good prognosis can be followed by prompt degeneration C) Axonal degeneration Primary damage to axonal neuron lead to secondary demyelination Hereditary forms / unknown toxic effect/insufficiency of intracellular energy production Maybe revercible( underline cause can be eliminated)

CLINICAL SIGNS (GENERAL) 1) Acral/distal pain o Spontaneous (paresthesia) or elicited by skin stimulation (dysthesia) o Burning / shocked character 2) Parasthesia o Numbness, tingling,buzzing,stinging,burning or constricting sensations 3) Weakness o Greatest in distal muscles o Paralysis of intrinsic foot muscle(footdrop) or hand muscle (wristdrop) o May become quadriplegic or respiratory dependand 4) Sensory lost o Cutaneous sensory less ( glove & socks) o Maybe superficial or deep sensation o Selective impairment large demyelination position, vibration Small demyelination pain, temperature o Rise in threshold with delayed or hyperreaction 5) ANS involvement

Miosis,anhydrosis, orthostatic HT, sphincter symptoms, impotence, vasomotor abnormality DIABETIC NEUROPATHY Disturbance of glucose metabolism affect peripheral nerve both indirectly (through pathological change in blood vessel supplying nerve) and directly a) Direct- glucose toxic effect on nerve trunk b) Blood supply change-microangiopathy ( decrease nutrition) DM 1 polyneuropathy after 5 years (1st DM diagnosed2nd-polyneuropathy) DM 2 - 1ST polyneuropathy diagnosed 2nd DM ( presenting symptoms: obesity, hypercholesteremia, dyslipidemia, HT) CLINICAL Symmetrical distal glove & socks sensory polyneuropathy (motor function spared) No Achilles tendon reflex (ankle jerk) Unpleasant sensation in feet ( tingling, pain needle sensation > at night) Burning sensation, shooting pain in toes & sole of foot Trophic changes, injury feom trauma,infection, ulceration & joint destruction because pain sensation is lost Deep sensitivity affected (proprioceptive) sensory ataxia Motor dysfunction very rare but will occur if fast treatment not given foot paresis FINDING Hyperesthesia, irritation (needle prick)- sharper in sock area (decrease sensitivity) No ankle jerk Decrease proprioceptive & vibration sense ( teel fork test) Trophic ulcer Polydypsia,polyphagia, polyuria Normal gucose> 11.1 mmol ; fasting glucose > 7.1 mmol TREATMENT Optimum glycemic control Thioctic acid: antioxidant Paresthesia& pain : anticonvulsant (carbamazepam) Vitamins :milgama( B,C,E , complex Sedatives: diazepam Vasodilators Improve circulation: pantoxyfilin, nicotinic acid Improve neuron restoration: B complex( B1, B6, B12) Anticholinesterase drug: motor fuction Physiotherapy: US, laser,plasmophoresis, massage, acupuncture, electrophoresis

ALCOHOLIC POLYNEUROPATHY Direct: direct toxic effect of alcohol Alimentary :no balanced diet ulcervitamin not absorbed (thiamin- B12) Due to metabolic disorder/ toxicosisextend of damage depend on magnitude of alcohol consumption & individual genetics

SYMPTOM Intense neuralgic pain (lower extremity) Muscle cramp Feet sensitive( even slight touch pain) Muscle weaknessprogress to foot/wrist drop No ancle jerk >superficial sensitivity(pain,temp) Intension tremor (lower limb) DM like symptoms: paresthesia, unpleasant sensation Ataxia Initial sensory affection acute decompensation- motor TREATMENT STOP ALCOHOL Improve diet Vitamin : 150 mg B1 Anticonvulsant Thioctic acid good effect for liver vasodilator

recovery slow- frequently incomplete ( can STOP but NO CURE)

DIPHTERIC POLYNEUROPATHY due to infection:Corynobacterium diphtheria toxin corynobacterium diphtheria affects larynx,pharynx,cutaneus wound exotoxinabsorbed in bloodaffect nearest nnerve bulbar syndrome bulbar syndrome: dysphagia, dysphonia, dysarthria,rhinolalia myocarditissymmetric neuropathy

release

SYMPTOMS 1st signpalatal weakness Impaired visual accommodation Paresis of oculomotor and oropharyngeal muscles Sensory polyneuropathy(limb): quadriparesis/ tetraparesis Nerve conduction velocity low Bulbar paralysis After initial symptoms resolved (15th day) Polyneuropathy affects limb:tetraparesis(peripheral) Deep densation lost (proprioceptive,vibration) Cardiomyopathycan die due to heart failure TREATMENT Prevention (immunization)] Antibiotic Prognosis; slow recovery

LEAD POLYNEUROPATHY Symmetric weakness & sensation loss in distal(feet) than proximal Focalweakness of extensor muscle of fingers and wrist Poor motor bilateral arm weakness Infantsencephalopathy Weakness begins in distal muscles innervated by radial nerve (usually bilateral)& radiates to other muscles Sensory symptoms and signs are usually absent Gradual recovery after several month.

2. ACUTE DEMYELINATING POLYRADICULONEUROPATHY. HYENNE-BARR. CLINICAL FEATURES. TREATMENT. GuillainBarr syndrome (GBS) is an acute polyneuropathy, a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom, and some subtypes cause change in sensation or pain as well as dysfunction of the autonomic nervous system. It can cause life-threatening complications, in particular if the breathing muscles are affected or if there is autonomic nervous system involvement. The disease is usually triggered by an infection. Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form of GBS, and the term is often used synonymously with GBS. It is caused by an auto-immune response directed against Schwann cell membranes.

Cause o All forms of GuillainBarr syndrome are due to an immune response to foreign antigens (such as infectious agents) that is mistargeted at host nerve tissues instead, a phenomenon called molecular mimicry. The targets of such immune attack are thought to be gangliosides, compounds naturally present in large quantities in human peripheral nerve tissues. The most common antecedent infection is the bacterium Campylobacter jejuni, followed by cytomegalovirus (CMV ) The end result of this autoimmune attack on the peripheral nerves is damage to the myelin, the fatty insulating layer of the nerve, and a nerve conduction block, leading to muscle paralysis that may be accompanied by sensory or autonomic disturbances. In mild cases, nerve axon (the long slender conducting portion of a nerve) function remains intact and recovery can be rapid if remyelination occurs. In severe cases, axonal damage occurs, and recovery depends on the regeneration of this important tissue. Approximately 80% of patients have myelin loss; in the remaining 20%, the pathological hallmark is axon loss. Guillain-Barr, unlike disorders such as multiple sclerosis (MS) and Lou Gehrig's disease (ALS), is a peripheral nerve disorder and does not in general cause nerve damage to the brain or spinal cord.

o o o

o o

Signs and symptoms symmetrical weakness that usually affects the lower limbs first, and rapidly progresses in an ascending fashion. Patients generally notice weakness in their legs, manifesting as "rubbery legs" or legs that tend to buckle, with or without dysesthesias (numbness or tingling). As the weakness progresses upward, usually over periods of hours to days, the arms and facial muscles also become affected. Frequently, the lower cranial nerves may be affected, leading to bulbar weakness, oropharyngealdysphagia (drooling, or difficulty swallowing and/or maintaining an open airway) and respiratory difficulties. Most patients require hospitalization and require ventilatory assistance for treatment of Type II respiratory failure. Facial weakness is also common.. Sensory loss, if present, usually takes the form of loss of proprioception (position sense) and areflexia (complete loss of deep tendon reflexes), an important feature of GBS Loss of pain and temperature sensation is usually mild. In fact, pain is a common symptom in GBS, presenting as deep aching pain, usually in the weakened muscles, which patients compare to the pain from overexercising. These pains are self-limited and may be treated with standard analgesics. Bladder dysf(x) may occur in severe cases but is usually transient. In severe cases of GBS, loss of autonomic function is common, manifesting as wide fluctuations in blood pressure, orthostatic hypotension (a fall in BP on standing, leading to risk of collapse), and cardiac arrhythmias. Acute paralysis in GuillainBarr syndrome may be related to sodium channel blocking factor in the CSF. Significant issues involving intravenous salt and water admin may occur unpredictably in this pt group, resulting in SIADH, a cause of low sodium levels in the blood.

Diagnosis rapid development of muscle paralysis, areflexia, absence of fever, and a likely inciting event. CSF analysis (through a lumbar spinal puncture) and electrodiagnostic tests of nerves and muscles (such as nerve conduction studies) are common tests ordered in the diagnosis of GBS. In CSF, characteristic findings include albumino-cytological dissociation. As opposed to infectious causes, this is protein level (1001000 mg/dL), w/o an accompanying cell count (absence of pleocytosis). A sustained WBC count may indicate an alternative diagnosis such as infection. Electromyography (EMG) and nerve conduction studies (NCS) may show prolonged distal latencies, conduction slowing, conduction block, and temporal dispersion of compound action potential in demyelinating cases. In 10 axonal damage, the findings include reduced amplitude of the action potentials without conduction slowing. Features required for diagnosis are progressive weakness in legs and often arms and areflexia (the absence of deep tendon reflexes).

Treatment 1) Mechanical ventilation( patient who need aid in breathing) 2) .Intubation - impending failure of the muscles of breathing. 3) plasmapheresis- filtering antibodies out of the blood stream 4) intravenous immunoglobulins (IVIg), to neutralize harmful antibodies and inflammation causing disease 5) Glucocorticoids have not been found to be effective in GBS 6) physiotherapy in helping patients with GuillainBarr syndrome regain strength, endurance, and gait quality, as well as helping them prevent contractures, bedsores, and cardiopulmonary difficulties. 7) Speech and language therapists help regain speaking and swallowing ability, especially if the patient was intubated

3. NEUROPATHY OF FACIAL NERVE. ETIOLOGY, PATHOGENESIS, CLINICAL SIGNS, TREATMENT

Functional disturbance / pathological change in n.fascialis Mononeuropathy Etiology: trauma, autoimmune, bells palsy ( Herpes simplex virus 1), systemic disease (Lyme) PERIPHERAL LESION 1) Facial nerve nucleus Prosoplegia ( paralysis of face), Bells symptm (try closing eye eyeball rotate upward sclera can be seen) Affected side eyebrow lower, wide palpebral fissure Rocket symptom ( asymmetry of oral fissure) 2) Bend before N.petrosus major (before entering canalis fascialis) Prosoplegia Eye dryness (n.petrosus major) Hyperacusia hear low frequency sound,noise,crackles (n.stapedius) No taste anterior 2/3 of tounge (n.chorda tympani)

3) At level of N.petrosus before N.stapedius branch Prosoplegis, hyperacusia, no taste Eye watering (petrosus innervations preserved,bt due to failure of eye closure as orbicularis oculi paralyses watering) 4) After N.stapedis, before chorda tympani Prosoplegia, no taste in tongue (ant 2/3), eye watering 5) After 3 branches Prosoplegia, eye watering CENTRAL LESION Nucleus n.fascialis get impulse from tr.corticonuclearis Upper part 2 side innervations Lower part only 1 contralateral side Central paralysis : o lower part of face get affected (contralateral) o Lowering angle of mouth, nasolabial fold smoothening TREATMENT: Acidi nicotinici (vit B6) Corticosteroid therapy Antocholinesterase( proserine) physiotherapy

4. NEURALGIA OF TRIGEMINAL NERVE. ETIOLOGY, PATHOGENESIS, CLINICAL SIGNS, TREATMENT Trigeminal neuralgia (TN, or TGN), tic douloureux also known as prosopalgia, is a neuropathic disorder characterized by episodes of intense pain in the face, originating from the trigeminal nerve. It has been described as among the most painful conditions known to mankind. In a majority of cases, TN symptoms begin appearing after the age of 50, although there have been cases with patients being as young as three years of age. It is more common in females than males. nerve (V1), the maxillary nerve (V2), and the mandibular nerve (V3). 2. One, two, or all three branches of the nerve may be affected. 10-12% of cases are bilateral (occurring on both the left and right sides of the face). 3. Trigeminal neuralgia most commonly involves the middle branch (the maxillary nerve or V2) and lower branch (mandibular nerve or V3) of the trigeminal nerve,but the pain may be felt in the ear, eye, lips, nose, scalp, forehead, cheeks, teeth, or jaw and side of the face.

1. The trigeminal nerve is a paired cranial nerve that has three major branches: the ophthalmic

Signs and symptoms The disorder is characterized by episodes of intense facial pain that last from a few seconds to several minutes or hours. The episodes of intense pain may occur paroxysmally. (Patients may describe a trigger area on the face so sensitive that touching or even air currents can trigger an episode; however, in many patients the pain is generated spontaneously without any apparent stimulation). It affects lifestyle as it can be triggered by common activities such as eating, talking, shaving and brushing teeth. Wind, high pitched sounds, loud noises such as concerts or crowds, chewing, and talking can aggravate the condition in many patients. The attacks are said by those affected to feel like stabbing electric shocks, burning, pressing, crushing, exploding or shooting pain that becomes intractable. Individual attacks usually affect one side of the face at a time, lasting from several seconds to a few minutes and repeat up to hundreds of times throughout the day. Pain attacks are known to worsen in frequency or severity over time, in some The spread may even affect all divisions of the nerve, and sometimes simultaneously. Cases with bilateral involvement have not indicated simultaneous activity. The following suggest a systemic development: rapid spreading, bilateral involvement or simultaneous participation with other major nerve trunks. (multiple sclerosis or expanding cranial tumor systemic).

Examples of simultaneous involvement include tic convulsive(of the fifth and seventh cranial nerves) and occurrence of symptoms in the fifth and ninth cranial nerve areas.

o o

Outwardly visible signs of TN can sometimes be seen in males who may deliberately miss an area of their face when shaving, in order to avoid triggering an episode. TN sufferers rarely have pain attacks or are awakened due to pain while they are sleeping

Causes The trigeminal nerve -mixed cranial nerve sensory -- tactition (pressure), thermoception (temperature), and nociception (pain) originating from the face above the jawline; m motor -- muscles of mastication, the muscles involved in chewing but not facial expression. The most frequent cause of trigeminal neuralgia is a blood vessel pressing on the nerve near the brain stem. Over time, changes in the blood vessels of the brain can result in blood vessels rubbing against the trigeminal nerve root. The constant rubbing with each heartbeat wears away the insulating membrane of the nerve, resulting in nerve irritation.

superior cerebellar artery - compressing or throbbing against the microvasculature of the trigeminal nerve near its connection with the pons. Such a compression can injure the nerve's protective myelin sheath and cause erratic and hyperactive functioning of the nerve. This can lead to pain attacks at the slightest stimulation of any area served by the nerve as well as hinder the nerve's ability to shut off the pain signals after the stimulation ends.

Short-term peripheral compression is often painless, with pain attacks lasting no more than a few seconds. Persistent compression results in local demyelination with no loss of axon potential continuity. Chronic nerve entrapment results in demyelination primarily, with progressive axonal degeneration subsequently.

o o

A large portion of multiple sclerosis patients have TN, but is not a symptom of MS. Postherpetic Neuralgia, which occurs after shingles, may cause similar symptoms if the trigeminal nerve is damaged.

Management Since triggering may be caused by movements of the tongue or facial muscles, TN must be differentiated from masticatory pain that has the clinical characteristics of deep somatic rather than neuropathic pain. Masticatory pain will not be arrested by a conventional mandibular local anesthetic block Medical The anticonvulsant carbamazepine - first line treatment second line medications- lamkotrigine,phenytoin, sodium valproate Opiates such as morphine and Surgical Only recommended if medical treatment is not effective. there may be pain relief there is also frequently numbness post procedure

Microvascular decompression appears to result in the longest pain relief. Percutaneous radiofrequency thermorhizotomy may also be effective where the nerve first splits into its three divisions.

Three other procedures use needles or catheters that enter through the face into the opening Percutaneous surgical procedure known as balloon compression - helpful in treating the elderly for whom surgery may not be an option due to coexisting health conditions, the best choice for patients who have ophthalmic nerve pain or have experienced recurrent pain after microvascular decompression. Glycerol injections involve injecting an alcohol-like substance into the cavern that bathes the nerve near its junction. This liquid is corrosive to the nerve fibers and can mildly injure the nerve enough to hinder the errant pain signals. In a radiofrequency rhizotomy- electrode heat the selected division or divisions of the nerve. Done well, this procedure can target the exact regions of the errant pain triggers and disable them with minimal numbness.

5. Lumbosacral radiculopathies: An etiology, clinical features, treatment. It is also known as sciatica. Sciatica isa set of symptoms including pain that may be caused by general compression or irritation of one of five spinal nerve roots that give rise to each sciatic nerve, or by compression or irritation of the left or right or both sciatic nerves The pain is felt in the lower back, buttock, or various parts of the leg and foot. In addition to pain, which is sometimes severe, there may be numbness, muscular weakness, pins and needles or tingling and difficulty in moving or controlling the leg. Typically, the symptoms are only felt on one side of the body. Pain can be severe in prolonged exposure to cold weather.

Etiology:
Radiculopathy is caused by compression or irritation of the nerves as they exit the spine. This can be due to mechanical compression of the nerve by - Disk herniation, - Bone spur (osteophytes) from osteoarthritis - From thickening of surrounding ligaments Tumor Infection Scoliosis diabetes which can decrease the normal blood flow to the spinal nerves
Herniated disc with nerve compression - by far the most common cause of radiculopathy Foraminal stenosis (narrowing of the hole through which the spinal nerve exits due to bone spurs or arthritis) more common in elderly adults Nerve root injuries Scar tissue from previous spinal surgery that is affecting the nerve root.

6. Lumbago (Low back pain). An etiology. Pathogenesis of disease. Clinical features. Treatment. Definition: common musculoskeletal disorder affecting 80% of people at some point in their lives. most common cause of job-related disability, a leading contributor to missed work, and the second most common neurological ailment only headache is more common.[1] It can be either acute, subacute or chronic in duration. With conservative measures, the symptoms of low back pain typically show significant improvement within a few weeks from onset Classification
acute (less than 4 weeks) sub acute (412 weeks) chronic (more than 12 weeks)

Etiology: Mechanical Apophyseal osteoarthritis Diffuse idiopathic skeletal hyperostosis Degenerative discs Scheuermann's kyphosis Spinal disc herniation ("slipped disc") Thoracic or lumbar spinal stenosis Spondylolisthesis and other congenital abnormalities Fractures Sacroiliac Joint Dysfunction Leg length difference Restricted hip motion Misaligned pelvis - pelvic obliquity, anteversion or retroversion Abnormal Foot Pronation Seronegative spondylarthritides (e.g. ankylosing spondylitis) Rheumatoid arthritis Infection - epidural abscess or osteomyelitis Sacroiliitis Bone tumors (primary or metastatic) Intradural spinal tumors Osteoporotic fractures Osteomalacia Ochronosis Chondrocalcinosis Tension myositis syndrome

Inflammatory

Neoplastic Metabolic

Psychosomatic Pagets Dzs Depression Oxygen Deprivation

Pathogenesis: They are suspected several pathogenical processes: Most cases are believed to be due to a sprain or strain in the muscles and soft tissues of the back. Overactivity of the muscles of the back can lead to an injured or torn ligament in the back which in turn leads to pain An injury can also occur to one of the intervertebral discs (disc tear, disc herniation) Due to aging, discs begin to diminish and shrink in size, resulting in vertebrae and facet joints rubbing against one another. Ligament and joint functionality also diminishes as one ages, leading to spondylolisthesis, which causes the vertebrae to move much more than they should Pain is also generated through lumbar spinal stenosis, sciatica and scoliosis. At the lowest end of the spine, some patients may have tailbone pain (also called coccyx pain or coccydynia) Others may have pain from their sacroiliac joint, where the spinal column attaches to the pelvis, called sacroiliac joint dysfunction which may be responsible for 22.6% of low back pain. Physical causes may include osteoarthritis, rheumatoid arthritis, degeneration of the discs between the vertebrae or a spinal disc herniation, a vertebral fracture (such as from osteoporosis), or rarely, an infection or tumor.

Clinical features:

Pain in the lower back which does not radiate down the legs (if the pain radiates into the buttock and legs see Sciatica or Piriformis syndrome). Pain may be constant and achey (often associated with muscle spasm), or may be sharper on certain movements/positions (this indicates a more acute injury to a specific structure). Stiffness in the back especially in the mornings. Fever and chills History of cancer with recent weight loss (or unexplained weight loss) Severe trauma Significant leg weakness Sudden bowel and/or bladder incontinence either difficulty passing urine or having a bowel movement, or loss of control of urination or bowel movement Severe, continuous abdominal pain and back pain

General treatment: A short period of rest (e.g. one or two days) Physical therapy and active exercise and stretching Ice and/or heat application for activity related pain relief Appropriate medications for pain relief Rest (in bed if it is really severe). The psoas position is often the most comfortable position (laying on the back with the knees bent up). In gradual onset cases applying warmth such as a warm bath or a hot water bottle may help. In sudden onset cases where there may be tissue damage, cold therapy may be better for the first 2-3 days.

See a sports injury specialist or doctor who can make an accurate diagnosis of the problem.

Specific treatment: Acute Self care For acute cases that are not debilitating, low back pain may be best treated with conservative self-care,] including: application of heat or cold continued activity within the limits of the pain Firm mattresses have demonstrated less effectiveness than medium-firm mattresses
Engaging in physical activity within the limits of pain aids recovery. Prolonged bed rest (more than 2 days) is considered counterproductive Even with cases of severe pain, some activity is preferred to prolonged sitting or lying down - excluding movements that would further strain the back. Structured exercise in acute low back pain has demonstrated neither improvement nor harm Physical therapy can include heat, ice, massage, ultrasound, and electrical stimulation. Active therapies can consist of stretching, strengthening and aerobic exercises. Exercising to restore motion and strength to your lower back can be very helpful in relieving pain and preventing future episodes of low back pain Short term use of pain and antiinflammatory medications, such as NSAIDs or acetaminophen may help relieve the symptoms of lower back pain NSAIDs are slightly effective for shortterm symptomatic relief in patients with acute and chronic low-back pain without sciatica. [ Muscle relaxant for acute and chronic pain have some benefit, and are more effective in relieving pain and spasms when used in combination with NSAIDs

Activity

Physical therapy

Medications

Spinal manipulation

For chronic case

Exercise therapy appears to be slightly effective at reducing pain and improving function in the treatment of chronic low back painTricyclic antidepressants are recommended in a 2007 guideline by the American College of Physicians and the American Pain Society. Antibiotics can eliminate chronic pain when the cause is bacterial infection. In a Danish study, more than half the patients were either cured or much improved after 90 days of daily antibiotics. Acupuncture may help chronic pain however, a more recent randomized controlled trial suggested insignificant difference between real and sham acupuncture. Intensive multidisciplinary treatment programs may help subacute or chronic low back pain. Behavioral therapy Back schools have shown some effect in managing chronic back pain Spinal manipulation has been shown to have a clinical effect equal to that of other commonly used therapies and was considered safe. Manipulation under anaesthesia, or medically-assisted manipulation, currently has insufficient evidence to make any strong recommendations Prolotherapy, facet joint injections, and intradiscal steroid injections have not been found to be effective

7. Cervical radiculopathies (radiculitis and radialgia). An etiology. Clinical features. Treatment. Cervical radiculopathy is the damage or disturbance of nerve function that results if one of the nerve roots near the cervical vertebrae is compressed. Damage to nerve roots in the cervical area can cause pain and the loss of sensation in various upper extremities, depending on where the damaged roots are located. Cervical nerves exit the cervical spine (neck) at each level, C1 C7, (nerves in the neck exit above the designated vertebral level at all levels except the last one; C8 exits below C7 vertebra) and then branch out to supply muscles that enable the shoulders, arms, hands and fingers to function. They also carry sensory fibers to the skin and muscles that provide sensation The most common levels of root involvement in cervical radiculopathy are C6 and C7; high cervical radiculopathies (C2-C4) are less common.

Etiology Damage can occur as a result of pressure from material from a ruptured disc, degenerative changes in bones, arthritis or other injuries that put pressure on the nerve roots. In older people, normal degenerative changes in the discs can cause pressure on nerve roots. In younger people, cervical radiculopathy tends to be the result of a ruptured disc. This disc material then compresses the nerve root, causing pain. Symptoms The main symptom of cervical radiculopathy is pain that spreads into the arm, neck, chest and/or shoulders. A person with radiculopathy may experience muscle weakness and/or numbness or tingling in fingers or hands. Other symptoms may include lack of coordination, especially in the hands.

Patients with cervical radiculopathy typically feel pain, weakness or numbness in the areas served by the damaged nerve. Pain can be in one area only, like the shoulder, or progress along the entire arm. The type of pain also can vary. Certain neck movements, like bending the neck back, side to side, or rotating it, may increase the pain. Treatment It is most important to note that the majority of patients with cervical radiculopathy get better with time and never need surgery, or even any treatment at all. Some patients will have the pain go away quickly over days to weeks, while others take longer. It is also not uncommon for cervical radiculopathy to come back at some time in the future, but again, this problem usually gets better without any specific treatment. Some patients do develop persistant symptoms and require evaluation and treatment for the arm pain or weakness. Nonsurgical Treatment

If you are not getting better, your surgeon will recommend a course of treatment. Treatment for radiculopathy starts with nonsurgical options. Soft Collars. Soft collars allow the muscles of the neck to rest and limit neck motion. This can help decrease pinching of nerve roots with movement. Soft collars should only be worn for short periods of time, because long-term wear can decrease the strength of neck muscles. Physical Therapy. Physical therapy can help with neck muscle stretching and strengthening. Sometimes, traction is also used. Medications.

Nonsteroidal anti-inflammatories (NSAIDS). These include drugs like aspirin and ibuprofen, and may be helpful if the arm symptoms are from nerve swelling. Oral corticosteroids. A short course of oral corticosteroids may also help reduce swelling, as well as pain. Narcotics. These medications are reserved for patients with severe pain that is not relieved by other options. Narcotics are usually prescribed for a limited time only.

Spinal injections. Sometimes, an injection of steroids can be placed near where the nerve is being pinched. This takes advantage of the anti-inflammatory effects similar to oral steroids. The injection may be placed between the laminae (epidural steroid injection), in the foramen (selective nerve injection), or into the facet joint. While steroid injections do not take the pressure caused by a narrow foramen or herniated disk off the nerve, they may lessen the swelling and relieve the pain enough to allow the nerve to recover with more time. Surgical Treatment

There are several surgical procedures for radiculopathy. The procedure that is right for you will depend on many factors, most importantly the type of problem you have.

2. VASCULAR DISEASES OF NERVOUS 1. CLASSIFICATION OF DISTURBANCES OF CEREBRAL CIRCULATION Cerebral vascular

2. HAEMORRHAGIC STROKE. ETIOLOGY, CLINICAL FEATURES, DIAGNOSTIC, EMERGENCY TREATMENT Occurs within the brain substances, but rupture through to the cortical surface may produce associated subarachnoid bleeding. It results from a weakened vessel that ruptures and bleeds into the surrounding brain. The blood accumulates and compresses the surrounding brain tissue.

Etiology: Hypertension Aneurysm Malformation of blood vessels (basis of all hemorrhage, the thinned vessel wall ruptured) Amyloid vasculopathy Neoplasm anticoagulants Coagulation d/o (haemophilia) Drug abuse, vasculitis, trauma Idiopathic

Clinical pictures: Supratentorial hematoma Mass effects: Sudden onset headache followed by rapid of loss cons or gradual deterioration in cons level over 2448 hrs Focal signs: Hemiparesis, hemisensory loss and hormonymous, hemianopia. Third nerve palsy indicates transtentorial herniation Sudden onset of headache with subsequent effects developing either acutely or subacutely Cerebellar and brainstem symptoms and signs (severe ataxia, dysarthria,nystagmus,vertigo, vomiting) Sudden loss of cons, quadriplegia, resp irregularities, pinpoint pupils, pyrexia, dysconjugate eye movement,death.

Cerebellar hematoma

Pontine hematoma

Diagnostics: CT Scan determines the exact site and size of the haematoma and excludes other pathologies Angiography performed immediately if clinical state requires urgent operation, to identify a possible arteriovenous malformation or aneurysm. If negative angiography, a late MRI may demonstrate a cavernous angioma

Treatment: Surgical clipping of aneurysm - decompression, trepanation Without surgery if the hemorrhage complication does not decrease blood below 30mm3 - give anti hypertensive drugs

3. Ischemic stroke. Etiology, pathogenesis, clinical features of diseases, emergency treatment. In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. Etiology and pathogenesis there are several factors that can lead to the ischemic stroke of the brain. As we know, the general complication is that the ischemic happens due to insufficiency of blood supply to the brain, which is caused by: Atherosclerosis Tissue damage or intima of external carotid artery leads to plague formation What is the need of atherosclerosis anyway? Actually, it is for the normalization of blood flow and condition. Normally, if the tissue damage occurs, lipid band form is form to repair the blood vessels. However if the disorder of lipid metabolism happens, the multiple band form occur and cause the obstruction to the blood flow. Reposition of thrombosis happened when the surface of the plague formed, consequently decreases the area of lumen of the vessel. After the plague mass ruptured, it will form emboli. Atherosclerosis Cardiac emboli Cryptogenic factor

Cardiac emboli Any pathological reaction that can cause blood disturbance, and leads to formation of emboli For example: a) valve diseases b) Inflammation of the heart endocarditis c) Arrhythmia Internal carotid artery is first affected, because the lumen is bigger and emboli tend to go there.

Cryptogenic Also known as unknown or unspecific etiology. It may consist: Vasospasm Rheological properties of blood. Properties of the vessel vasculitis (in case of dzs of vessels)

Clinical features and manifestations: Sudden paralysis of a leg, arm or one side of the face Sudden trouble speaking or understanding speech Sudden vision problems, such as blurred or double vision Sudden loss of coordination or problems with balance A severe, sudden headache without apparent cause Sudden numbness, weakness or dizziness weakness or paralysis, usually on one side of your body lack of awareness of one side of your body (usually the left side) loss of sensation on one side of your body difficulty swallowing extreme tiredness and sleep problems problems with speech, reading and writing problems with vision - such as double vision, or partial blindness memory and concentration difficulties difficulty controlling your bladder and bowel movements (incontinence) or constipation behavioural changes

Treatment Etiological treatment Pathological treatment: antiplatelet aspirin give during the first attack of stroke, and throughout the whole life - to prevent recurrent stroke - 3.75 mg/1st day, 75mg on the next day antihypertensive drug to control the blood pressure and vital function of blood increase metabolism and increase collateral circulation Pyracetam (dose dependant drug) Aktovegin Cerebrolysin Mexidol (antioxidant) vasodilators kaventon euphylline

Symptomatical treatment: depends on the symptoms of diseases that appeared.

4.Subarachnoid Hemorrhage. Etiology. Clinical pictures. Diagnosis. Treatment. Intracranial vessels lie in the subarachnoid space and give off small perforating branches to brain tissue. Bleeding from these vessels or from an associated aneurysm occurs primarily into this space. Some intracranial aneurysms are imbedded to the brain tissue, and their rupture causes intracerebral bleeding with or without subarachnoid hemorrhage. Etiology. Head trauma Ruptured aneurysm Age range 40-60 years old

Clinical pictures: Severe headache Loss of consciousness from minutes to hours Seizures Meningeal signs Secondary hydrocephalus (headache, motor function deficiency)

Diagnosis: CT Lumbar puncture Focal meningeal signs Investigation of CSF - increase RBC - Xanthochromia - increase pressure

Treatment: Control the rheologic props of blood [HPT] clopedagril, dipyridamole Diet statin [atherosclerosis] Control the DM, obesity control level of glucose Smoking, alcohol, hypodynamic control

How teenage (girls) get stroke? - through oral contraceptive and smoking plus with liver diseases How teenage (boys) get stroke? - drugs abuse (cocaine) How normal people get stroke? - by drinking excessive energetic drink, esp with alcohol because have sibutramine which predispose to stroke.

5.Transient Ischemic Attack (TIA). Etiology, Pathogenesis, clinical features, and treatments. TIA are attacks are episodes of focal neurological symptoms due to inadequate blood supply to the brain. Attacks are sudden in onset, resolve within 24 hrs o less and leave no residual deficit. These attacks are important as warning episodes or precursors of cerebral infarction Pathogenesis: A reduction of cerebral blood flow below 20-30ml 100g/min produces neurological symptoms. The development of infarction is a consequences of the degree of reduced flow and duration of such a reduction. If flow is restored to an area of brain within the critical period, ischemic symptoms will reverse themselves. TIAs maybe due to: 1. Reduced flow through a vessel (haemodynamic explanation): A fall in perfusion pressure, e.g. cardiac dysarthria associated with localized stenotic cerebrovascular dzs. 2. Blockage of the passage of flow by embolism (embolic explanation): Arising from plaques in aortic arch/extracranial vessels of from the heart Symptomatology of TIA Anterior part of brain (90%) -carotid territory hemiparesis, hemisensory disturbances, dysphasia, monocular blindness Vertebrobasilar territory of brain (7%) - loss of consciousness, bilateral limb motor/sensory dysfunction, binocular blindness, vertigo, tinnitus, diplopia,dysarthria In many cases, it may cause: Deterioration of cons level Homonymous hemianopia of the contralateral side Contralateral hemiplegia Contralateral hemosensory disturbance Gaze palsy to the opposite side eyes deviated to the side of lesion. Examination of neck reveals: absent carotid pulsation at the angle of the jaw with poorly conducted heart sounds along the internal carotid artery.

Treatment: Anticoagulant therapy Heparin Thrombolytics agent associated with rapid recanalisation of occluded vessels. Streptokinase is not used nowadays because of the risk of intracranial hemorrhage.

Specific measures: Decreasing blood viscosity Neuronal rescue Treatment of edema mannitol

Prevention of further stroke attack The recognition of risk factors and their correction to minimize the risk of further events forms a necessary and important step in long-term treatment. Control hypertension Emphasize the need to stop cigarette smoking Correct lipid abnormality Give platelet antiaggregation drugs (aspirin or in selected cases ticlopidine) to reduce the rate of reinfarction Remove or treat emboli source (long term anticoagulation in arterial fibrillation) Treat inflammatory or vascular inflammatory dzs Stop thrombogenic drugs, esp oral contraceptives.

3. INFECTIONS OF NERVOUS SYSTEM 1. MENINGGOCOCCAL MENINGITIS Primary bact. purulent Infection of meninges from nasopharynx in case of reduces immunity CP 1. Intoxication syndrome : Fever , headache , weakness Back pain , muscle pain , atralgia , myalgia 2. Meningeal syndrome : Confussion , reduce consciousness , stupor , headache meningeal type occipito-frontal Photophobia and phonophobia Neck stiffness ask patient to flexed head touch chin to chest Kernigs sign cant underflex leg Brudenskys sign Upper nuchal rigidity Middle by pushing abd. Can see flex leg. Lower kernigs sign In newborn : Monotomous cry and loudly When we hold babys under arm leg will flex Can observe specific position meningeal position ( apistotonus ) Diagnosis Lumbar puncture at lvl L4 L5 or L3 L4 (take 3 sample ) o CSF is cloudy , increase pressure , cells count maybe more than 1000 ( leucocytes ) ,pus in CSF , elevated protein in CSF , decrease glucose , cell protein dissociation. o 1 tube laboratory diagnosis , 2nd bact. Culture , 3rd put in dark place for 24 h(to check present of fibrin mass +ve sign for TB meningitis ) 15% of cases of meningitis but w/o meningeal sign must fulfill lumbar puncture If present CP with ve lab diag. is called meningism Check for 2 inf. Chest x-ray , sinus x-ray , skull x-ray , petrous views.

Treatment Etiological: Antibiotics cephalosporins , ampicillin , aminoglycoside Pathogenetic : Steroids 4 day regime of DEXAMETHASONE 10mg Q.I.D Desintoxification iv infusion of phys. Sol + rheambovin / - colloids and crystalloids Symptomatic : Anti-convulsant Anti pyeretic Analgesic Anti-emetic Sedative

2. SECONDARY PURULENT MENINGITIS.ETIOLOGY.CLINICAL FEATURES.TREATMENT Secondary inf. Of meninges caused from other associated dzs (otitis , sinusitis , pneumonia , mastoiditis, trauma) , mainly caused by bacteria :- strep , staph , pneumococci , This is because all this organs share same venous outflow in 1 sinus. Dzs usually acute and hidden by 1 associated dzs . CP (same as meningococcal meningitis ) Diagnosis In CSF increase neutrophils and pressure All other sign are the same Check for 2 inf. Chest x-ray , sinus x-ray , skull x-ray , petrous views. Treatment Treat 1 cause of dzs eg : otitis and sinusitis

3. ACUTE SEROUS MENINGITIS. ETIOLOGY.CLINICAL FEATURES.TREATMENT Inflammation of meninges can be classified into :a) Infectious Viral i. Enterovirus ii. Mumps iii. Herpes simplex virus iv. EPV v. HIV Non-typical bact. i. Spirochetes b) Non infectious Tumor * Common features in viral infections 1. Viral meningitis is milder and occurs more often than bacteria meningitis 2. 70% of infections occur in children < 5 y.o 3. Usually characterized by signs of meningeal irritation 4. Symptoms may disappear within 2 weeks with x residual complications * The most often pathogenic agents 1. Enteric virus (echo,coxsackie V) 2. HSV, epstain barr V, CMV 3. Epidemic Parotiditis (mumps) V 4. Tick-borne encephalitis V 5. More rare agents: adenovirus, HIV most epidemic forms of meningitis, encephalitis or myelitis due to infections with enterovirus and togavirus (transmitted by tick); from forest or kindergarden region. neurological disease due to members of other group V usually occur sporadically and as isolated instances that complicate V infections of other organs and system common biological properties of members of a specific virus group may dictate how they attack CNS and type of disease that they produce most dangerous is herpes encephalitis > attack temporal lobe

* CSF changes # CSF findings in 3 acute viral syndrome ( viral meningitis, encephalitis, myelitis) are usually similar, consisting of: 1. pressure (lesser than purulent) 2. Cell count: pleocytosis ( dt lymphocytes) of varying degree 200-500 but not until 1000s 3. Moderate protein content : up until 1-1.5 g/l 4. Normal sugar content ( only in virus but in TB, sugar ) 5. Clear color; but may be pearl-liked color * Diagnosis 1. Knowledge of seasonal occurrence and of whether an illness is occurring in an epidemic setting 2. The etiological diagnosis can be made by a combination of: virus isolation (inoculation of blood, nasopharyngeal washings, feces, CSF, tissue suspension intosusceptible animals or tissue culture ) serological test amplification of viral nucleic acids 3. Tissue and fluids to b used for virus isolation studies shud b frozen unless they can b immediately transferred to lab 4. Serological tests : applicable to all known acute viral disease of the CNS Serum removed in the 1st few days of illness serves as the control Serum withdrawn in 3-5 weeks after the onset of the illness is used to determine whether antibody have dev. 5. Any material used for viral isolation can also b used for amplification of viral nucleic acid by PCR 6. Identification is then made by the use of complimentary probes (hybridization) * Treatment 1. HSV : acyclovir (zavirax) 2. VZV : acyclovir, famciclovir (famvir), foscarnet sodium (foscavir) 3. CMV : ganciclovir sodium ( cytovene), foscarnet 4. HZV : reverse transcriptase and protease inhibitor

4. TUBERCULAR MENINGITIS.CLINICAL FEATURES, DIAGNOSTIC, TREATMENT * Infection of meninges caused by mycobacterium TB spread for another site in the body * Primary focus infection usually in LUNGS but can b lymph gl, bones, nasal sinus, GIT or any organ in the body * Risk factors: history of pulmo. TB, excessive alcohol use, AIDS and other disease that compromise immune system * The onset of meningeal symptoms may coincide with sign of acute military dissemination * TB meningitis differs from that caused by most other common bacteria in that: 1. Course is more prolonged 2. Mortality rate 3. CSF changes are acutely less severe 4. Treatment less effective in preventing sequelae * Course 1. Subacute 2. Chronic * Stages 1) Prodromal stage: headache, fever, burst of irritability, nocturnal wakefulness, anorexia, loss of weight 2) Early stage: sign of infections ( fever, irritability), sign of irritation of meninges (severe headache, vomiting, neck stiffness, kernigs and brudzinskis) 3) Late stage: irritability is gradually replaced by apathy, confusion, lethargy, and stupor and coma Papilledema, CN damage, Focal neurological sign, convulsion, hi temp, ptosis, squint # TB meningitis is base meningitis where it damages 2nd cranial nn (optic nn)

* Following test help diagnose TB Meningitis 1. CSF with lympho, protein, glucose Lymphocytes 600-800 in 1mm3 Protein 0.9-1.5 g/l may be to 5-10 g/l Glucose 0.15-0.3 g/l 2. Spinal fluid (CSF) stain +ve for mycobacteria 3. CSF culture growing in TB 4. CSF +ve for M. TB PCR 5. +ve skin test for TB ( 30-50% cases) 6. Brain or meningeal biopsy showing in TB

* Treatment 1. Isoniazid 2. Riphampycin 3. Pyrazinamide # for 2-3 months, then isoniazid + riphampycin during next 7 months * Miyasnikobs >> treatment 1. Send to infectious hospital 2. Lumbar puncture b4 antibiotics 3. Antibiotics: 3rd generation cephalosporin (ceftriaxone, cefotaxime)

5. MAIN PRINCIPLES OF DDX OF MENINGITIS Types meningcoccal normal Stages acute Lumbar puncture (result) Cloudy (purulent) Decrease cells Predominant polymorphonuclear leucocytes(2000-10000) Increase protein Decrease sugar +ve result meningococcal culture Cloudy (purulent) Decrease cells Predominant polymorphonuclear leucocytes(2000-10000) Increase protein Decrease sugar +ve result meningococcal culture Transparent , colourless , increase pressure , pleurocytosis with lymphocytes , decrease protein , sugar norm Increase pressure Cloudy Moderate pleucytosis 25500cells/m3 Increase protein Decrease sugar -ve serological test No growth in culture medium Fibrin net after 24h duration 4-6w

Secondary purulent

Purulent dzs of sinuses , ears , rhinitis , otitis , pneumonia pus in body

Acute , may be hidden by other dzs

4-6w

Acute serosa

normal

acute

10-14d

TB

tuberculosis

subacute

6-12mon

6. HERPES SIMPLEX ENCEPHALITIS [HSE]. A PATHOGENESIS, CLINICAL FEATRUES, TREATMENT. Encephalitis: inflammation of the brain tissue/ parenchyma. Peculiarities Can occur at any age [childadult] Both sex Any time of year [non seasonal] Course: acute, severe Etiology Herpes simplex virus [HSV] has 2 antigenic type [HSV-1, HSV-2] 1. HSV-1 -more common -infect children older than 3 months and adult -HSE usually LOCALIZED at temporal and frontal lobe 2. HSV-2 -less common -infect neonates -inflammation of the brain parenchyma is GENERALIZED -HSE acquired at the time of delivery Pathogenesis -how HSV enter brain is unknown and unclear but has some theory o o o o Primary or initial infection by HSV-1 usually occur early in life through asymptomatic infection of mouth and throat. HSV-1 enter sensory nerves in the throat and moves into trigeminal ganglia virus then stay in latent form there Reactivation of virus from its latent form can occur due to change in immune system [ex stress]-yet it still unclear Virus enter brain trough retrograde transmission [from trigeminal ganglia go backward to spinal cord and the upward into brain]

-70% of HSE is lethal due to severe brain edema and severe viral aggression [lethal outcome within 1 week] Clinical Features 1. General infections (GI) -Fever, chills, increase temperature (38-40) -headache, fatigue -myalgia, malaise

2. General Brain Symptoms (GB) -Severe Headache -nausea, vomiting -irritation -dizziness/vertigo -change level of consciousness [stuporsupor] 3. Meningeal Signs [M] I. Nuchal rigidity -patient supine, then passively flex neck -+ve sign: neck cant touch chest II. Kernings sign -patient supine, flex the knee -then try to extend -+ve sign: cant xtend due to muscles contraction Brudzinskis sign -3 part: uppernuchal rigidity : lowerkerning sign :middle press kower abdomen

III.

lead to flexion of the leg

IV.

Meningeal sign in newborn Meningeal cry : non stop crying,monotonous Lasegue sign : hold baby under armpitflex leg Meningeal position: opisthotonus [hyperextension of the body, flex leg and arm]

4. Focal neurological sign -depend on place of focal lesion -ex : hemiplegia,focal seizures, ataxia, hemisensory loss, psychotic disturbance (hallucination, disturbed memory attention) etc If focal sign+ all other signs r present: it is encephalitis NOT meningitis (meningitis no focal sign) Diagnosis 1. Lumbar puncture [CSF] - Pressure increase -protein increase neutrophils pleocytosis (neutrophil+lymphocyte) -cells countleukocytosis [mostly lymphocytosis] -glucoseNormal or reduced -HSV can be confirmed by identification of virus in CSF by polymerase chain reaction [PCR]

2. MRI -reveal focal lesion on 1st week of disease 3. CT 4. EEG : may show periodic-slow wave complexes arising from 1/both temporal lobes Treatment 1. Etiological tx o Antiviral therapy -Acyclovir IV 30mg/day divided into 3 daily doses at least 10 days [maybe up to 21days] -Amantadine 2. Pathogenetic tx o Desintoxication therapy -plasmaphoresis -physiological solution infusion 3. Symptomatic tx -depend on symptoms appear -eg : paralysis o General paralysis treatment i. Medicamentous -vit B -nicotinic acid -drug which increase metabolism of the brain actovegin -drug which increase neurotransmission prozevir ii. Non medicamentous -massage -warm procedure -acupuncture -physical exercise

prevent muscle atrophy

7. EPIDEMIC ENCEPHALITIS. ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT IN ACUTE AND CHRONIC STAGE OF DISEASE.

Etiology and Pathogenesis -unknown etiology, but presumed cause by virus -in US, most common cause of epidemic encephalitis is; ARBOVIRUSES (arthropod-borne virus) -is a virus that transmitted to people through bite of arthropods usually mosquitoes, fleas or ticks -epidemic occurs in people only PERIODICALLY -when population of mosquitoes/fleas/ticks increase and they tend to biting usually during warm weather -infection spread from arthropodsperson Never person person This diseases occur as an epidemic from 1917-1928 Now epidemic encephalitis not so significant no cases/very rare During epidemic, millions of people died worldwide Its affect all ages, sexes, races and occupations. This disease also known as sleeping sickness/ encephalitis lethargy/economo encephalitis

Clinical features -epidemic encephalitis cause diffuse degenerative and disseminated inflammatory changes in CNS and its covering -2 stages : acute and chronic Acute stage -1st sign typically sore throat, fever, headache -then progress into more alarming symptomsdouble vision/diplopia, severe weakness -then most victims undergo episode of tremors, strange bodily movement, intense muscles pain, delay mental response -change in behavior psychosis, hallucination -increase drowsiness and lathergy -dysomnia (disorder in sleep) Excessive sleep -pathological sleep continues sleep (sleepy) -lethargic sleep like coma Insomnia -sleep <5 hours in 24hours -last normally 14 days months

 Virus of epidemic encephalitis live in 4th ventricle in brain which is close to limbic system Cause problem with appetite, sleeping (dysomnia), emotion change etc Chronic stage -associated with subcortex disturbances and lead to disturbance of pallidal system -progressively, symptoms of Parkinson develop Postencephalitis Parkinsonism Tremor bankers hand (proximal pronation and suppination) Hypokinesia- muscle of face amimic, like mask, cant smile Rigidness cogwheel like - additional symptoms Micrographia smaller handwriting Slow gait/movement Vegetative insufficiency hypotrichosis (abN hair pattern-reduce), hypersalivation, gastroparesis Psychological disturbance decreased attention, emotional disturbance, dementia -the parkinsonian syndrome that develop after epidemic encephalitis can be distinguished by Occur at early age Unusual features -grimace -torsion spasm -myoclonus -bizarre posture and gait

Treatment Acute stage o Symptomatic therapy for dysomnia 1. If increased sleep nootropic, ginseng, caffeine 2. If decreased sleep nootropic, zolpidem o Anti-inflammatory and immunosuppressant drug 1. Glucocorticoid- dexamethasone

Chronic stage o Treatment of parkinsonism 1. Dopamine derivatives : Nakom, Madapor tablet 250mg 2. Anti cholinergic agent : Parkopan, Cyclodor

8. SPINAL EPIDURAL ABSCESS. AN ETIOLOGY, CLINICAL FEATURES, DIAGNOSTICS, TREATMENT. Is an accumulation of purulent material in epidural space within spinal cord and can mechanically compress the spinal cord. Etiology -infection may reach spinal epidural by 3 ways 1. Direct extension from inflammation process of adjacent tissue such as furuncles of skin most common decubitus ulcerosis carbuncle 2. Hematogenous metastases through blood from infection elsewhere in body (septic route) Eg; from tonsils, lungs, dental abscess, urinary tract infection 3. Perforating wound in spinal surgery, lumbar puncture -the abscess usually not cause direct infection to spinal cord, but it compress it

Risk factors 1. DM 2. Chronic diseases 3. Immunosuppressive therapy 4. Heroin abus Clinical features -symptoms develop suddenly after several days or weeks infection of skin or other part of body 1. Focal severe back pain : usually the 1st and presenting sign 4 sequential phase: 2. Malaise, fever, headache 1. Localized back pain 3. Radicular pain 2. Radicular pain and 4. Muscular weakness and paralysis of leg if not treated paresthesia 5. Neck stiffness 3. Muscular weakness, sensory 6. Kernigs sign loss, sphincter dysfunction 7. Local sign : erythema and swelling in area of back pain 4. paralysis 8. Local percussion: tenderness over spine

 Diagnosis 1. Laboratory diagnostics -leucocytosis -increased ESR 2. Radiograph of spine -not routinely indicated -but may show osteomyelitis or abscess 3. Myelography(use contrast medium) followed by spinal CT 4. MRI -choice procedure -more sensitive 5. Lumbar puncture -usually contraindicatedrisk of introducing purulent material to subarachnoid space -but can exclude meningitis 6. CSF characteristics -xanthochromic or cloudy appearance -normal or increased pressure -pleocytosis; increased cell count -increased protein content -glucose is usually normal 7. Sample from blood and infected are cultured Differential diagnose 1. Acute or subacute meningitis 2. Acute poliomyelitis it 3. Infection polyneuritis 4. Acute transverse myelitis 5. Multiple scelrosis 6. Epidural hematoma

clinical and myelography use to differentiate

Treatment Surgical drainage by laminectomy 1. Antibiotics should be administered before and after operation 2. Surgery may be not necessary for certain cases but epidural aspiration for culture are useful for antibiotics sensitivity test

9. MYELITIS. AN ETIOLOGY, CLINICAL FEATURES, TREATMENT. -Inflammation of the spinal cord Etiology can be 1. Primary -infection enters spinal cord through hematogenous route 2. Secondary -spreading from other diseases -eg : infectious mononucleosis can cause transverse myelitis Infectious agents can be: 1. Neurotropic virus -enteroviruses,retrovirus, cytomegalovirus -herpes virus, poliovirus 2. Bacteria -treponema pallidum -mycobacterium tuberculosis 3. Fungi, protozoa -rare 4. Neuroallergic post-vaccination reaction -caused disseminated encephalomyelitis Several types of myelitis 1. Acute disseminated encephalomyelitis 2. Myalgic encephalomyelitis a.k.a chronic fatigue syndrome 3. Poliomyelitis 4. Transverse myelitis inflammation restricted to a few segments 5. Disseminated myelitis inflammatory foci located at several segments of spinal cord 6. Diffuse myelitis extensive area of the cord is inflamed in continuity Clinical features -course : acute, subacute, chronic 1. General infections symptoms -fever, chills -myalgia, malaise -weakness 2. Focal signs of lesions of spinal cord -depend on level of lesions -most common cervical, thoracic

-it can be: intense pain at lesions, paresis, sensitivity of conductive disorder, dysfunction of pelvic organ -clinical features also can be classified into I. Acute focal myelitis II. Acute disseminated myelitis III. Subacute necrotizing myelitis I. Acute focal myelitis 1. Start with sharp pain and general weakness 2. Fever, chills 3. Paresthesia of leg numbness rapid loss of movement complete paralysis 4. If thoracic spinal cord affected : lower paraplegia with loss of sensitivity of conductive type : paralysis from flaccid spastic 5. Middle segment spinal cord : Brown-sequard syndrome 6. Lower segment of spinal cord : retention of urine and feces, weakness of sphincter II. Acute disseminated myelitis -there are numbers of foci of inflammation in diff segment wic affect both with and grey matter. 1. Increase patellar reflex 2. Absence of Achilles reflex 3. Presence of pathological reflex 4. Motor, sensory disorder 5. Disorder of pelvic organs 6. Disorder of deep sensitivity III. Subacute necrotizing myelitis -a disorder of lower spinal cord in adult males resulting in progressive paraplegia Treatment 1. Etiological treatment -depend on the causes -antiviral drug, broad spectrum antibiotic 2. Symptomatic treatment -glucocorticoid; dexamethasone -antipyretics -anticholinesterase; for urine retension -general treatment of paralysis; if paralysis appear -vitamin B1, B6, B12 Poor prognosis

10. MULTIPLE SCLEROSIS AND DISSEMINATED ENCEPHALOMYELITIS. AN ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT. Is a chronic disease that begins mostly in young adult and is characterized pathologically by multiple areas of CNS white matter inflammation, demyelination and glial scarring (sclerosis). Clinical Course Benign symptoms free Rapidly progressive and disabling Relapsing and remitting symptom -1st recovery full -later neuro disability increase gradually Incidence and epidemiology -age of onset 20-30years old -symptoms rarely begin before 10 yrs and after 60 yrs -in women 3 times higher Etiology -cause is unknown 1. Genetic susceptibility - non monogenous or multifactorial disorder -genes found in MS patient -no familial history of MS 2. Immunology -evidence in peripheral blood, CSF of patient Autoimmune mechanism -CSF: pleocytosis, especially in acute phase Perivascular lymphocyte and microphage infiltration 3. Virus -role of environmental exposure -viral encephalitis demyelination -herpes simplex, rubella, EBV etc 4. Physical trauma -can precipitate/aggravate disorder 5. Vaccination -as a trigger for 1st attack

 Pathogenesis Lesion of brain is based on main thing that cause demyelination and plague formation. Myelin is a covering that protect axon from degeneration Attack of antibody against own myelin destroy the myelin sheath Myelin can be restored by Schwann cells [remyelination of axon] Healthy nerve conducted impulse normal and fast o 70-100 m/s [myelinated] o 4-7 m/s [n-myelinated] Demyelinated nerve conduct poorly *Demyelination : non-specific reaction of CNS to the damage : eg due to ischemia, viral infection : in MS chronic course and changes Pathology 1. Gross appearance of brain Normal it affect white matter Evidence of atrophy widening of sulcus 2. Cross- section Irregular grey areas Irregular pink areas (acute lesion) -especially in white matter of periventricular regioin [spot/hole in white matter] -also in cerebellum, brainstem plague 3. Cortex shrunken, pia arachnoid thicken sometime 4. Lesion of brain tend to group around lateral and 3rd ventricle -size: pin head whole lobe (varies) 5. Zone of demyelination in optic nerve, cerebellum, brainstem Clinical features 1. Dissemination in time and space Exacerbation or relapse followed by remission Length: several monthsdecades Multiple attack (time) Symptoms may indicate > 1 point of lesion (space) No classic form of multiple sclerosis exist But, we have areas involved > often 1) Optic chiasm 2) Brainstem 3) Cerebellum 4) Spinal cord (esp lateral and posterior column) Type of MS 1) Brainstem 2) Cerebellar 3) Cerebral 4) Spinal

2. Retrobulbar neuritis Most common, ~70% Not all cases of retobulbar neuritis is MS, but 70% are MS Symptoms 1) Suddenly blurred vision, diminished visual acuity in 1/ both eyes -lesion of CN II -period last several days 1/2 weeks -with spontaneous remission/recovery (faster by taking drugs, PE, physiotherapy) 2) Weakness 3) Paresthesia 4) Ataxia 5) Vertigo 6) Bladder dysfunction 3. Sharko triad Sign of cerebellar lesion 1) Nystagmus 2) Scanning speech (n-fluent) -jumping from 1 word to another 3) Intention tremor -when patient want to do something Can also be 1) Hemianesthesia 2) Retrobulbar neuritis 3) Problem with gait and speech 4) Problem with internal organ (stool, urine) Several attack & several points of lesion suspect MS Diagnosis 1. No special test (no specific enzyme etc) 2. Depend on multiple signs and symptoms with multiple remission and relapse 3. Base on ability to demonstrate -history -neurologic examination -Laboratory test -existence of lesion at different part of NS 4. Most valuable is MRI -can demonstrate fresh and old lesion by using contrast -fresh : accumulate contrast -old : not accumulate contrast -multiple white matter lesion 90% -point of demyelination (perivascular, subcortical, cerebellum) -distribution and nature of lesion *normal person: up to 5 points of demyelination, each 3mm -most important MRI matching with clinical pictures and abnormality

5. CSF -gamma globulin -lgG -oligoclonal Ig -simple, non invasive, useful of producing evidence 6. Cortical Evoked Response - from visual, auditory, somatosensory stimulation -simple, non invasive - maybe useful to provide evidence when clinical data unclear Criteria for Clinical Diagnosis 1. Clinically Definite MS Consistent course [relapsing-remitting course] At least 2 attacks separated by at least 1 month Slow or stepwise progressive course of at least 6 months Documented neurological sign of lesion in > 1 site of brain and spinal cord white matter Onset between 10-50 years No better neurological explanation 2. Probable History of relapsing remitting symptom but sign not documented and only 1 current sign commonly associated with MS Documented 1 attack with signs of > 1 white matter lesion, good recovery No better neurological explanation 3. Possible History of relapsing and remitting symptom without documented sign Objective sign insufficient to establish > 1 lesion of central white matter No better neurological explanation Useful Classification 1. Clinically definite MS 2. Laboratory supported definite MS -1 attack several points -1 point several attacks 3. Clinically probable MS -1 lesion : seen in MRI

 Differential diagnosis 1. Lyme diseases Especially in endemic areas A chronic CNS infection by Borrelia Cause spastic paraparesis, cerebellar lesion signs and cranial nerve palsy. MRI and CNS findings can be similar to MS Differential diagnosis based on history of acute attack -rash of Lyme disease -history of bitten by ticks Flu-like onset of disease Find antibody to Borrelia antigen in blood serum or CSF 2. 3. 4. 5. 6. HIV Syphilis Herpes Simplex infection Paraneoplastic symptoms esp in older patient Subacute combined degeneration -excluded by measuring serum vit B6 level

Course and Prognosis Clinical Course varies 1. Clinically silent -found on autopsy 2. Malignant *Marburgs type+ -very rapid -2 months (onsetdeath) Types 1. Relapsing Remitting -exacerbation followed by variable extends of improvement (full recovery neurological deficit) -benign course 2. 2 progression 3. 1 progression -no remission after 1st attack -keep getting worse

 Prognosis -no reliable clinical prognosis is available 1. Good Prognosis -minimal disability in 5 years after onset -complete remission of the symptoms -age 35 or less at onset -only 1 symptom in the 1st year -acute onset of the 1st symptom and brief duration of exacerbation -onset with optic neuritis 2. Poor Prognosis indicator -polysymptomatic onset -cerebellar sign of ataxia and tremor -corticospinal tract sign -disability in 50-55 years -after 10 years, 70% of patients cant work sphincter dysfunction spastic paraparesis memory dysfunction Death from MS is rare, usually patient die due to COD bronchopneumonia Cardiac failure Malignancy Septicemia (after decubitus ulcer, UTI) Suicide Management -before recommendation of treatment 1. Inform family and patient about diagnosis -tell the truth, find best way to make patient accept the diagnosis 2. Disease should be explained in understandable term and realistic with best possible prognosis 3. Reevaluate patient every 3-6 months -if good treatmentsee patient each year 4. Give realistic goal of therapy

-Treatment 1. No Etiological treatment 2. Pathogenetic treatment I. Treatment of Acute Attack 1. Methylprednisolone lg -IV infusion daily -for pulse therapy -3-5 days -followed by oral prednisolone 80mg daily for 4 days -then slowly decreased the dose 2. Plamaphoresis -remove immune complex 3. Cytostatics -last choice II. Prevention of New Attack 1. B-IFN -change activity of immune system decrease ability to produce antibody against own myelin -example -Betason -Rebit -Avonex 2. Glatiramer acetate -copaxone (polymer of amino acid) is myelin like structure act as false area for attack of antibody so can prolong period of remission

Very expensive + Side effect (Flu-like, headache etc)

3. Symptomatic treatment -depend on symptoms appear -example: 1. Spasticity: Baclofen 2. Cerebellar symptoms: propanol, clonezepam 3. Diet therapy: provide with good amount of protein

11. POLIOMYELITIS. AN ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT, PREVENTIVE MEASURES. -Is an acute viral infection diseases that cause inflammation of grey matter of spinal cord and can lead to partial or full paralysis. Etiology and Pathogenesis -cause by Poliovirus -route of transmission: fecal-oral, oral-oral -virus is transmitted through contaminated food and water then multiples in intestine through hematogenous or lymphogenous pathway virus invade spinal cord. -virus spread by 1. Person-person contact 2. Contact with infected mucus/phlegm from nose/mouth 3. Contact with infected feces -incubation period from 5-35 days [average 7-14 days] -risk factors: 1. Low immunity against poliovirus 2. Travel to area that has experienced polio outbreak 3. Immune deficiency 4. Malnutrition Clinical Features -can be divided into I. Subclinical infection symptoms II. Non paralytic poliomyelitis symptoms III. Paralytic poliomyelitis symptoms i. Spinal ii. Bulbar iii. Bulbospinal I. Subclinical infection symptoms 1. Malaise, general discomfort 2. Headache, Slight fever 3. Sore throat 4. Nausea, vomiting II. Non paralytic poliomyelitis symptoms [last 1-2 weeks] 1. Pain/ stiffness of back, arm, legs, abdomen 2. Muscles tenderness, spasm, stiffness 3. Neck pain and stiffness 4. Slight fever, headache, irritability, fatigue, vomiting, diarrhea, skin rash/lesions with pain

III. Paralytic poliomyelitis 1. Spinal polio -most common form -virus invade motor neuron of anterior horn cells of spinal cord inflammation of nerve cells damage of motor neuron ganglia muscles no longer receive stimuli from brain or spinal cord - we can see : o Muscle weakness o Muscle atrophy o Peripheral paresis paresis can occur in both sides of body but more often ASYMMETRICAL o Absent deep tendon reflex o Sensation of paralyzed leg not affected o Fever, muscle pain -the extend of spinal paralysis depend on region of s.cord affected cervical/thoracic/lumbar 2. Bulbar polio - ~2% cases -virus invade and destroy nerve within bulbar region of brainstem -bulbar region: is a white matter pathway that connect cerebral cortex to brain stem. -it affects cranial nerves. Symptoms appear depend on nerve affected o Glossopharyngeal nerve -partially controlled swallowing, tongue movement and taste -cause difficulty in swallowing, talking o Vagus nerve -send signal to heart, lungs, intestine -cause abnormal respiratory rate, depth, rhythm respiratory arrest -circulatory failure o Accessory nerve -control upper neck movement -cause difficulty in chewing o Trigeminal, facial nerves -innervate cheeks, tear duct, gums, facial muscles -cause facial weakness, double vision 3. Bulbospinal polio o ~ 19% of cases o Have both spinal and bulbar symptoms

o o

Virus affect upper part of cervical spinal cord [C3-C5] and cause paralysis of diaphragm Nerve affected: Phrenic nerve - innervate diaphragm to expand lungs -innervate muscles for swallowing -destroying of this nerve difficult to breathe or impossible to breathe without ventilator -affect swallowing and heart function Paralysis of arms, legs

Diagnosis 1. Paralytic poliomyelitis -maybe clinically suspected if: Acute onset of flaccid paralysis in 1/> limbs + decreased or absent tendon reflexes in affected limbs + without sensory or cognitive loss 2. Lab test -blood test : Antibody of poliovirus -stool sample or take swab from pharynx -CSF: increased no of WBC (lymphocytosis) : increased protein Treatment - No etiological treatment - Aim: symptomatic treatment 1. Antibiotics -prevent infection in weakened muscles, UTI etc 2. Analgesics 3. Long term rehabilitation -physical therapy, massage etc 4. Nutritious diet Preventive measures 1. Vaccination

12. RHEUMATIC CHOREA. ETIOLOGY, CLINICAL FEATURES, TREATMENT. Rheumatic fever is an acute inflammation complication of group A streptococcus infection causing arthritis, carditis, subcutaneous nodule, erythema marginatum and chorea . Joint, heart, skin, CNS is affected. CNS lesion can caused -CHOREA MINOR/SYDENHAM CHOREA/RHEUMATIC CHOREA - Clinical Features Occur in 10% of children May developed along with other manifestation but more frequently it arises after other manifestation appeared. Onset is insidious, maybe preceded by inappropriate laughing or crying Chorea consists of rapid and irregular jerky movement which may begin in hand but often become generalized involving head and neck. Associated motor symptoms include: 1. Loss of fine motor control 2. Weakness 3. Hypotonia 4. Obsessive compulsive behavior Usually last for several month and resolve completely in most patient 1/3 patient may have recurrent especially women during pregnancy [chorea gravidarum] In patient with rheumatic fever in anamnesis, it usually begin in 1st trimester It resolve spontaneously before or after delivery The most important thing is correct diagnosis o If it is sure a result of previous RF NO TREATMENT required o Without anamnesis RF can coz severe complication during pregnancymust treat!

- Treatment 1 goal : suppress inflammation : relieve of acute symptoms : limit activity especially associated with arthritis, heart failure General treatment of rheumatism 1. Prednisone 2. Penicillin

13. NEUROSYPHILIS. PATHOGENESIS, CLINICAL FEATURES, TREATMENT, PREVENTIVE MEASURES. - A.k.a Neuro Lues, Treponemal infection. - Syphilis is sexually transmitted infection caused by Treponema pallidum. - Neurosyphilis is chronic inflammatory process of CNS due to invasion of Treponema pallidum which occur early in the course of untreated syphilis. - 12 million of adult diagnose every year. Pathogenesis -similar to these rest of body [look explanation below] Clinical features -symptoms appear is time-dependant -classification: 1. 1 2 3 4 2. 2 general categories: I. Early [early involvement of CNS limited to meninges ] 1. Asymptomatic 2. Acute syphilis meningitis 3. Meningovascular syphilis II. I. EARLY Late [parenchymal involvement of CNS] 1. Tabes dorsalis 2. General paresis 3. Optic atrophy

1. Asymptomatic neurosyphilis No changes in NS function Characterized by changes of serological test 2. Acute syphilis meningitis Signs of meningeal irritation Fever is unusual Cranial neuropathies -in descending order [ CN VIIVIII VI II] Maybe self limiting but if untreated : continue and re-expressed later as more severe form of neurosyphilis 3. Meningovascular syphilis Endoarteritis with perivascular inflammation 1. Fibroblastic fibrillation of intima 2. Thinning of media 3. Fibrous and inflammatory changes adventitia (lymphocytic and plasma cell infiltration)

 Luminal narrowing predispose to vascular occlusion, ischemia, infarction Onset after 7 years of initial infection Most common presentation: 1. Stroke syndrome in a relatively young adult 2. Subacute encephalitic prodrome -headache -vertigo -insomnia 3. Psychological changes -decreases memory -emotional changes

II. LATE 1. Tabes dorsalis Slowly progressive degenerative diseases involving posterior column an posterior root of spinal cord Neurological presentation: 1. Loss of pain sensation 2. Loss of peripheral reflex 3. Impairment of vibration and position of sense 4. Progressive ataxia 5. Bladder incontinence 6. Loss of sexual function Tabetic Crisis -lancinating pain [lighting like, appear sudden, spread rapidly] -develop after stress or after exposure in 90% of patient -can be accompanied by visceral crisis (episode of excruciating epigastric pain, nausea, vomiting 3 stages: 1. Pre-ataxia 2. Ataxia 3. Paralysis Characteristic of gait: -tabetic gait (wide base, slappy)

2. General paresis (dementia paralyica) Occur 20-30 years later [after initial exposure to Treponema pallidum] Represent a chronic progressive frontotemporal meningoencephalitis, resulting in ongoing loss of cortical function Onset of psychiatric symptoms is insidious (noticed by family, friend) 1. Loss of ambition at work 2. Memory lapse 3. Irritability 4. Unusual giddiness 5. Apathy 6. Decrease attention to personal affairs 7. Mental changes -stimulating schizophrenia, euphoric mania, paranoia, toxic psychosis 8. Dementia -depression, confusion, some impairment of memory and judgement 3. Optic atrophy Ocular involvement 1. Anterior uveitis 2. Panuveitis 3. Retinitis 4. Retinal vasculitis 5. Vitritis 6. Papillitis 7. Photophobia 8. Dimming of vision Treatment and preventive measure Adequate treatment is based on achieving Treponema level in CNS 1. Penicillin -T.pallidum is highly susceptible -drug of choice for all stages of syphilis Accurate diagnosis of neurosyphilis is imperative Use good and long doses of penicillin

14. LESION OF NERVOUS SYSTEM IN AIDS 1) Cerebral tumors i. Primary cerebral lymphoma ii. Metastatic systemic lymphoma ------ CT/MRI iii. Metastatic Kaposis sarcoma 2) Infections i. Encephalitis CT/MRI ii. Cerebral abscess ----- Antibody tests iii. Meningitis Biopsy 3) Peripheral neuropathy i. Herpes zoster radiculopathy CT/MRI ii. Cauda equina syndrome (cytomegalovirus) ----- Aspiration/ culture iii. Acute reversible demyelination Antibody tests iv. Chronic demyelination 4) AIDS dementia i. Direct HIV infection with demyelination and perivascular chages. Intellectual decline of CT/MRI subcortical type. -----Psychometry 5) Retinopathy i. Cytomegalovirus ii. Toxoplasmosis ------ Fundal exam Antibody tests

6) Myelopathy i. Acute reversible ii. Compression : abscess, systemic lymphoma iii. Ascending : cytomegalovirus, herpes zoster/simplex

----

Spinal CT/MRI Antibody tests

7) Vascular disorders i. Intracranial hemorrhage ------ CT/MRI ii. Cerebral infarction (septic emboli or thrombosis)

4. TRAUMA OF NERVOUS SYSTEM 1. CONTUSION OF BRAIN. CLINICAL FEATURES, DIAGNOSTICS, TREATMENT. Definition : involves macroscopically evident anatomical injury to the brain State of loss consciousness and post- traumatic twilight lost LONGER than concussion
mechanical impact is more severe; in temporal, frontal lobe (suffer d most) but rare in occipital (dt tentorium) traumatic injury of brain with contusion foci in hemisphere, brainstem @ cerebellum is the result of trauma to head sufficient to cause identifiable lesion such as hemorrhage on CT scan These areas of contusion have less mass effect than their apparent size. Most common in regions where sudden head deceleration causes brain to impact on bony prominence

Common loci : i. ii. iii. Clinical features 1. 2. 3. 4. Focal neuro signs from the start, unconscious Heart dysarryhthmia usually follow and accompanied by brain ischemia Lumbar puncture : bloody CSF CT : focus of contusion ( m.b. normal after weeks-months) Orbital gyri, frontal poles Parasagital cortex, lateral portion of brainstem Caudal position of cerebellum (rare)

1 of d variant: Contrecoup Injury The French word describes contusion that occur in 2 sites in brain when head is hit, impact causes brain to bump the opposite site of the skull Damage occurs at the site of impact and on the opposite side of the brain Clinical Criteria: 1. Loss of consciousness (for min, hrs, days depending on severity of contusion) 2. Focal neurological findings depending on which area of the brain is affected 3. Stiffness of neck with +ve Kernig and & Brudzinski signs in the presence of traumatic SubArachnoid Hemorrhage 4. Lingering regress of signs (> 2-3 weeks) Focal neurological signs: 1. Speech and language problem 2. Loss of sensation, hearing, vision, taste, smell 3. Seizures 4. Paralysis + neurological signs combine with change in behavior, emotion and mental disabilities # if present skull fracture diagnose contusion even w/o any neurological signs

Post traumatic complains 1. 2. 3. 4. Epileptic seizures Traumatic anosmia ( in severe case) Focal symptoms : eg : paresis, gait disturbance, dysphasia, vision Post-trauma encephalopathy

2. CONCUSSION OF THE BRAIN. CLINICAL FEATURES, DIAGNOSTICS, TREATMENT

Definition : involves macroscopically evident anatomical injury to the brain + NOT followed by any lasting neurological deficit Histologically : disruption of axonal continuity cause by shearing effect, also seen in MRI
is a brief alterations of consciousness as a result of closed traumatic injury is a mild traumatic brain injury the alterations of consciousness is brief (however, there is no consensus on length of time considered to be 'brief') alterations in consciousness may include confusion, amnesia, or LOC;is not necessary when there is LOC; it is often virtually instanteous (may b latency of few sec) n usually rapid return of function. X gross or microscopic parenchymal abnormalities x or min CT @ MRI abnormalities

Usually contusion of the skull involves concussion of brain

Clinical pictures 1. 2. 3. 4. Impaired consciousness : very brief but m.b gap in the memory of wat has happened Retrograde amnesia : correspond to post traumatic twilight state Vomiting, headache, vertigo, transient mental disturbance As a rule, unconsciousness not last >15mins and twilight state < 1 hour!

Examination Physical examination show NO general medical and neuro deficit Lumbar puncture and EEG : Normal

Postcontusion complaints : arise immediately after concussion and regress spontaneously Headache : usually diffuse and in the morning Arise due to frequent bending and standing up, stress, alcohol, sun If it is more intensive boring headache; think about meningeal scar! Post traumatic migraine Vertigo : n-specific type Lead to instability of gait, when pt wake up/down, or rapid movements Sometimes benign paroxysmal positional vertigo Generalized mental impairment : memory difficulties, irritability, lack of concentration, easy fatigue *all these may last from weeks,months years Treatment i. ii. Bed rest for few days Neurovegetative stabilization therapy

3. PRELUM OF THE BRAIN BY A POSTTRAUMATIC HEMATOMA. CLINICAL FEATURES, DIAGNOSTICS, TREATMENT. The mechanical trauma of a skull causes a prelum (passing or permanent) a cerebral tissue, a tension and shift of its layers, passing sharp rising of intracranial pressure. Shift of cerebral substance can be accompanied by break of a cerebral tissue and vessels, a bruise of a brain. Usually these mechanical disturbances are supplemented with complex biochemical changes in a brain. Depending on, whether it is kept at a trauma an integrity of integuments of a skull and its tightness or they are broken, craniocerebral traumas section on closed and opened. The closed craniocerebral traumas traditionally divide into concussion, a bruise and a prelum; conditionally to them carry also a fracture of base of the skull and cracks of a crest at safety of an integument. The brain concussion is characterized by a triad of attributes: a loss of consciousness, a nausea or a vomiting, an amnesia. The focal neurologic symptomatology is absent. The bruise of a brain is diagnosed when the general cerebral signs are supplemented with attributes of a focal lesion of a brain. The bruise of a brain can arise both in a place of a trauma, and on the opposite party on the mechanism of a coutrecoup. Duration of a loss of consciousness at concussion - in most cases from several minutes up to tens. The prelum of a brain means development of a traumatic hematoma, more often subdural. At more simple there is " a light period ": the patient who has come to consciousness after a while again starts "to be loaded", becoming apathetic, flaccid, and then soporous. The fracture of base of the skull is inevitably accompanied by a bruise of a brain of this or that degree, characterized by penetration of a blood from a cavity of a skull in a nasopharynx, in periorbital tissues and under a conjunctiva, in a tympanic cavity (at an otoscopy cyanochroic painting of a tympanic membrane or its break is found out). The bleeding from a nose and ears can be consequence of a local trauma, therefore it is not a specific attribute of a fracture of base of the skull. In a peer measure " the sign of glasses " also quite often happens consequence of especially local trauma of the face.

4. TRAUMA OF SC
The cervical spine is the most vulnerable segment with the most of injuries occurring at level C5-C6. At the second place is lumbothoracic level. (T12-L1). Spinal cord contusion The clinical effect are divided into two stages: (a) Stage of spinal shock (b) Stage of heightened reflex activity Spinal shock the transient loss off all neurological functions below the level of the spinal cord injury Lasting varying periods (usually 1-2 weeks, occasionally several months and sometimes permanently), the resolution of which yields the anticipated spasticity below the level of the lesion. Spinal shock is due to the complete destruction of the spinal cord or due to edema & other secondary changes that causes the complete loss of function in a few hours. Spinal shock A complete flaccid paralysis with areflexia below the lesion (due to interruption of the pyramidal tract) Loss of sensory qualities below the lesion. Loss of voluntary control of rectum & bladder ( an atonic bladder with overflow incontinence) Atonic bowel (paralysis ileus) loss of genital reflexes and of vasomotor control. Trophic disorder and decubital ulcers below the lesion.

The immediate clinical effect of an acute transverse lesion is dependent on its level. If the injury at or above C3 ( includes atlantoocipital and atlantoaxial dislocation) results in immediate pulmonary and cardiac arrest and death is immediate unless respiration is supported artificially. If the injury is lower,there is loss of all motor, sensory, autonomic & spchinteric functions below the level of lesion. Injuries of the lower most thoracic and upper lumbar spine are in a position to damage the spinal cord, cauda equina @ both. Dynamic After 1 to 2 week, sometimes longer. Spinal pathological reflexes (babinski sign ,flexor, spasms of the legs) and then tendon reflexes begin to appear in parts of the body supplied by the intact but disconnected lower spinal cord segment. Simultaneously bladder tone and gastric and bowel function begin to recover. Gradually the tendon reflex become hyperactive and the bladder becomes spastic.

 But the term spinal shock is often used in two complete different senses. 1)transient loss of all neurological function below the level of the spinal cord injury. 2)hypotension (shock) that follows spinal cord injury and caused by multiple factors: (a) interruption of sympathetic -loss of vascular tone ( vasoconstrictors of skin and internal) below the level of injury. -leaves parasympathetic relatively unopposed causing bradycardia. (b) loss of muscle tone due to skeletal muscle paralysis below level of injury results in venous pooling and thus a relative hypovolemia. (c) blood loss frm associated wounds- true hypovolemia. Spinal cord injury Incomplete lesion Complete lesion No preservation of any voluntary movements,sphincter control and sensation and below the level of injury. Hypotension and bradycardia may also present. In addition there may be priaprism. Spinal shock is potentially reversible variant of complete lesion About 3% of patients with complete injuries on initial exam will dev recovery within 24 hrs. Persistence of complete spinal cord injury beyond 24 hours indicates tht no distal function will recover. Incomplete lesion Any residual motor or sensory function more thn 3 segments below the level of injury. look for sign of preserved long tract function. Signs of incomplete lesion: Types: central cord symptoms brown-sequard syndrome (cord hemisection) anterior cord syndrome posterior cord syndrome:rare spinal injury stable unstable Sensation ( including position sense ) @ voluntary movement in low extremities. Sacral sparing sensation around anus ,voluntary rectal spchinter contraction, voluntary toe flexion. An injury not qualify as incomplete with preserved sacral reflexes. complete lesion

clinically stability is ability of the spine under physiologic loans to limit displacement so as to prevent injuries of irritation of the spinal cord and nerve roots and to prevent incapacitating deformity or pain.

Spine injury (vertebra column injury) 1) craniocervical jxn (atlantooccipital) 2) C 1 3) C 2 4) Subaxial ( C3-C 7 ) 5) Thoracolumbar

Mechanism of injury Vertical compression eg: object falling on to the head or jumping from a height Hinge injury eg: weight falling on back or blow to the forehead Shearing injury eg: fall from a height or road, traffic accident; often occurs in association with a rotational force Spinal Injury 1. Contusion of spine 2. Isolated injury of ligaments with soft disc prolapsed within the spinal canal 3.subflexion and vertebral dislocation 4.fracture or fracture/dislocation Isolated injury of ligaments and / or rupture of the intervertebral disc with soft disc prolapsed within the spinal cord. Middle aged results with hyperextension dislocations that reduce spontaneously immediately may present with no bony abnormality on x-ray. But with rupture of the anterior longitudinal ligament and or intervertebral disc with on MRI or autopsy. Atlanto-occipital dislocation (craniocervical junction dislocation) Is found in 8-19 % of fatal cervical spine injury autopsies. May be neurologically intact, therefore must be ruled out in any major trauma Maybe bulbar cervical dislocation that is due to a disconnection btw medulla oblongata and spinal cord and result in immediate pulmonary and cardiac arrest. May have lower cranial nerve deficit +/- cervical cord injury. Worsening neurological deficit with the application of cervical traction: check lateral cspine film immediately after applying traction. Atlantoaxial dislocation Lower morbidity and mortality than atlanto-occipital dislocation, may be either; (1) rotatory ; usually seen in children after minor trauma. (2) anterior; more ominous.

Anterior atlantoaxial dislocation ; 1/3 of patients have neurological deficits Evaluation CT and MRI are recommended to evaluate the transverse ligament. Rotatory atlantoaxial subluxation May occur spontaneously following major or minor trauma If the transverse ligament is intact, results in rotation without ant displacement. If the transverse ligament is incompetent, there may also be ant displacement with more potential for neurologic injury. Neurological deficits rare. Subaxial ( C3-C7) dislocation Severe flexion injuries in cervical spine can result in locket facet ( sprung facets or jumped facets) with reversal of the normal shingled relationship btw facets ( normally the inferior facets of the level above is posterior to the superior facet of the level below. Fractures Atlas ( C1 ) fracture -acute C1 fracture account for 3-13 % of cervical spine fractures. -more thn half of patients have isolated C1 fractures. Jefferson fracture -named from sir Geoffrey Jefferson -there is bilateral offset of both the right and left lateral masss of C1 relative to the lateral masses of C2 on the open mouth cervical spine view. -the injury is considered stable if the overhand is less thn 7 mm. -no cases of isolated C1 fractures required surgical stabilization of fusion -it is treated with external immobilization for 8-16 weeks. Odontoid fracture -high posterior cervical pain, sometimes irradiating in the distribution of the greater occipital nerve (occipital neuralgia). -paraspinal muscle spasm, reduced range of motion of the neck -tenderness to palpation over the upper cervical spine. -the tendency to support the head with the hands when going btw the upright & supine position (it is a very suggestive findings in the patient with high posterior cervical pain). -paraesthesia in the upper extremities & slight exaggeration of mm stretch reflexes may occur. -myelopathy may develop in pat with no union pyramidal tract insuff due to compression of spinal cord.

Axis C2 fractures -hangmans fracture -mech; hyperextension & axial loading frm diving accidents. - bilateral interarticularis fracture thru the pars interarticularis (isthmus) of the pedicle of C2. There is often anterior subluxation of C2 & C3. -usually stable-neurological deficit are rare. -plain lateral c-spine x-rays show the fraction.

Subaxial ( C3 thru C 7) & thoracolumbar injuries/fractures -to indentify CT criteria of instability of thoracolumbar spine fractures ,denis conceived the 3 column model of the spine. 1)ant column- composed of ant half of disc & vertebral body 2)mid column-post half of disc & vertebral body + posterior longitudinal 3)post column-posterior bony complex (post arch) with interposed post ligamentous complex ( supraspinous & infraspinous lig,facet joints & capsule,& lig flavum),injury to this column alone does not cause instability.

Main types of major fractures 1)compression fracture ( compression failure of anterior column .middle column id intact) 2)brust fracture (pure axial load causes compression of vertebral body & failure of anterior and middle columns) 3)seat belt fracture-flexion causes failure of both posterior and middle columns due to distraction. 4)fracture dislocation-failure of all 3 columns at compression ,tension,rotation or shear subluxation. Minor injuries-fracture of the transverse process, fracture of articular process, pars interarticularis, isolated fractures of spinous process. Stable injury-are minor to minimal to moderate compression factures with intact posterior columns. Other injury hv instability of a variable degree.

Initial management of spinal cord injury 1)initial brief med inspection to suspect of spinal injury. 2)immobilization prior to & during extrication frm vehicle & transport to prevent active @ passive movement of spine. 3)maintain BP 4)maintain oxygenation 5)repeated brief motor exam to identify possible deficit.

Initial brief examination may reveal -tenderness over the spinous process,paraspinal swelling or a gap btw the spinous process indicating rupture of an interspinous ligamernt . -neurogenic paradoxical ventilation ( indrawing of the chest on inspiration due to absent of intercostals function. -bilateral absence of limb reflexes in flaccid limbs, unresponsive to painful stimuli.(it indicates sc damage unless death is imminent fr severe head injury) -painless urinary retention @ priaprism.

Any of the following patients should be treated as having a spinal cord injury until proven otherwise. All victims of significant trauma Trauma patients with loss of consciousness Minor trauma victims with complains referable to the spine ( neck or back pain or tenderness) or spinal cord ( numbness or tingling in an extremity;abdominal breathing ,priaprism)

Spine injury may mask other injury (e.g ; abdominal injury ) below the level of spinal injury.

5. TRAUMATIC LESIONS OF NERVES OF UPPER AND LOWER EXTREMITIES.

In process regeneration of nerves tissue, axon can regrow from the site of injury to periphery as long as continuity of nerve has not been disrupted by injury, or has been restored by surgery Nerves regenerate at speed 1mm per day According to morphology, nerve injuries r 1. Anatomical interval nerve trunk 2. Intratrunk nerve injury

Clinical features 1) Disorder nerve function: movement, sensitivity, vegetative-trophic at innervations site 2) Symptoms of peripheral nerve injury (muscle paresis at site innervational nerve injuries In anatomical interval nerve injury spontaneous regeneration will occur in not more than 1.5months. In no regeneration, must restored by surgery repair to refresh central and peripheral nerve ending

Traumatic Brachial Plexus Palsies Etio : direct trauma (motocycle driver) to shoulder, coz sudden, intense pull on brachial plexus 1) Upper Brachial Plexus Injuries Reflect loss of nerve fibers from C5 & C6 roots Symptoms : weakness of shoulders abductors, elbow flexors and extensor 2) Lower Brachial Plexus Injuries Reflect loss of nerve fibers from T1 & C8 Symptoms : all small muscles of hand are paretic Horners syndrome = ptosis, miosis, enophthalmos, conjuctival injection Treatment 1. 2. 3. 4. 5. 1st: prevention of stiffening shoulder joint proper positioning, passive motion exercises Then active motion exercises If sharp cutting injuries : surgically nerve suture Autogenous nerve transplantation Orthopedic procedures help restore arm function

Femoral Nerve Injuries (L2-L4) Etiology : 1. Surgical trauma (appendectomy) injury under inguinal ligament 2. Hyperextension of hip 3. Hemophilia Symptoms 1. Paralysis of all knee extensors 2. Diminish knee-jerk reflex 3. Weak hip flexion 4. Sensory deficit on anterior thigh Tibial Nerve Injury (L4-S3) Etiology 1. Gunshot wound 2. Femoral fracture 3. Dislocation knees 4. Continuous pedaling movement Symptoms 1. Paralysis of plantar flexors of foot and toe 2. Impaired toe- walking, diminished Archilles reflex 3. Valgus posture of foot (toes maximally flexed) Tarsal Tunnel Syndromes Compression of tibial nerve by flexor retinaculum in region medial malleolus Etiology 1. Ankle sprain 2. Heel fracture Symptoms 1. Painful paresthesia of sole of foot, by walking 2. Sensory deficit of plantar nerves 3. Diminished sweating on sole of foot 4. Weakness muscles of sole Diagnosis 1. Electromyography

5. TUMOR OF BRAIN AND SPINAL CORD 1. CEREBRAL, FOCAL, DISLOCATION SINGS IN TUMORS OF THE BRAIN Tumours of a brain - depending on histological structure of a tumour of a brain share meningiomas, neurinoma of cranial nerves (mainly 8 pairs), metastatic, congenital and other tumours. 1. General cerebral signs (caused by intracranial pressure) the headache vomiting congestive disks of optic nerves

*Depending on histological structure of a tumour and its localization speed of development of the general cerebral and focal signs widely varies. 2. Focal signs (dep on localization of a tumour) i) Tumour of a frontal lobe: change of mentality defects of memory epileptic attacks disturbances of speech (at a lesion of a dominant left hemisphere) an anosmia on the party of a tumour.

ii) Tumour of a parietal local cramps disturbance of sensitivity and movements in an opposite half of body an aphasia at link sided localization.

iii) Tumour of an occipital abaissement of vision in opposite fields of vision visual aura before a convulsive attack.

iv) Tumour of a temporal psychomotor epileptic attacks an aphasia (at a lesion at the left) abaissement of vision in opposite fields of vision.

v) Tumour of a cerebellum: disturbance of equilibrium and coordination of movements a forwardness of attributes of an intracranial hypertensia.

vi) Tumour of a pituitary body neuroendocrinal disturbances a bitemporal hemianopsia augmentation of a turkish saddle.

2. CLASSIFICATION OF BRAIN TUMOR (BYK KOT) -Primary -secondary (metastatic) According to location 1. Supratentorial (semihemisphere) 2. Subtentorial 3. Tumour of pituitary According to the histology, brain tumors may be divided into: Neuroepithelial tumors Astrocytoma Oligodendroglioma Ependymoma Glioblastoma Medulloblastoma Meningeal tumors Meningioma Hemangiopericytoma Tumors of the skull and cranial nerves Tumors of the nerve sheath Schwannoma Neurofibroma Spinal tumors Extramedullary tumors Intramedullary tumors Vertebral tumors Tumors of the sellar region Pituitary tumor Cranioharyngioma Metastatic tumors Parenchymal metastases Leptomeningeal metastases Spinal cord metastases Vascular tumors and malformations Hemangioblastoma

AV-malformations 3. PARACLINIC METHOD OF DX OF BRAIN TUMOR Diagnostic evaluation

Pale skull xray reveal intracranial injury Angiography- exclude atriovenous malformation Positron emission tomography (pet)-measure tumour metab Electroencephalography (eeg)Evoke potential-intraoperative monitoring during surgical resection Csf analysisMri n ct- best method

Clinical diagnosis A) Positive and negative signs Symptoms and signs of tumors may be due to: a) Direct tumor effect and compression to adjacent structures (primary effects) b) Secondary effects of edema, hydrocephalus or increased intracranial pressure Symptoms may be: a) Negative symptoms arise from loss of function (eg: sensory loss, weakness in the limbs) b) Positive symptoms arise from irritation and excitation (eg: seizures and headaches) Specific symptoms of tumors depend on: a) Location of tumors - Tumors located in relatively silent areas (anterior frontal lobe, non-dominant temporal lobe) may be asymptomatic b) Histologic type - Eg: secreting and non-secreting pituitary tumors c) Rapidity of tumor growth - Slowly-growing tumors may be asymptomatic because the adjacent brain may accommodate the mass - Surrounding edema suggests rapid growth and may cause symptoms even when tumor is small B) General symptoms 1)Headache and associating vomiting and nausea 2)Facial pain 3)Plateau waves (periodic fluctuations of ICP) 4)Cushing reflex (rising of blood pressure with bradycardia) 5)Dizziness, vertigo, hearing loss 6)Seizures 7)Alterations in consciousness Headache - occurs as the first symptoms in 35% of patients and develops as late symptoms in other 70% - supratentorial tumors usually produces frontal headaches - tumors in the posterior fossa usually produces neck and occipital pain - some characteristics in primary brain tumors: o morning headaches or those that awaken patient form sleep; pain improves later in the day o headaches that becomes more frequent and increase in severity in weeks or months o headaches that differ from a persons pattern of chronic headache

o headaches associated with papilloedema or focal cerebral signs headache in presence of brain tumors is caused by: o irritation of pain-sensitive structures in the cranium (eg: the meninges, venous sinuses, cerebral arteries, cranial nerves)

Vomiting and nausea - may be due to increased ICP or hydrocephalus - projectile vomiting can also occur (vomiting due to irritation of chemoreceptor trigger zone in the medulla) - vomiting may relieve headache because it is usually followed by hyperventilation which may lower ICP Facial pain - involvement of trigeminal nerve (V) with tumors at the base of skull or nasopharynx - difference with trigeminal neuralgia: tumor pain lasts longer, less likely to be stabbing or piercing and may be accompanied by sensory loss Plateau waves (periodic fluctuations of ICP) - Typically there is abrupt elevation of ICP up to 100mmHg above baseline. The elevated ICP may be sustained for minutes or hours then quickly descending to normal. - clinical manifestations: o headache o nausea and vomiting o leg weakness o other symptoms of incoming herniation - the waves arise with severely increased pressure and is life-threatening - the waves may be triggered by cerebral vasodilation caused by events that lower arterial blood pressure, such as infections and anesthetics Cushing reflex - with severely increased pressure, Cushing reflex may be observed - it consists of rising of blood pressure and bradycardia - increased blood pressure: o activation of sympathetic NS due to ischemia to increase heart rate and contractility to increase cardiac output to ensure blood flow - bradycardia o activation of parasympathetic NS due to stimulation of carotid baroreceptors due to increased BP Dizziness, vertigo and hearing loss may be seen in tumors of the posterior cranial fossa Seizures - occur as the first symptoms in up to 30% of patients; other 70% patients have seizures at some time during the course of the tumor - especially seen in tumors in the rolandic fissure and slow-growing tumors - association between brain tumors and seizures increases with age: o most seizures in children are due to developmental abnormalities or injuries o up to 20% of seizures in adults are due o brain tumors - in adults, a first seizure, particularly if focal, should be evaluated by MRI Alterations in consciousness - vary from subtle personality changes to confusion or coma

most common in frontal lobe tumors also seen in hydrocephalus, gliomas of cerebri, or brainstem herniation

C) Focal symptoms and signs 1) Frontal lobe tumors - personality changes - impaired judgement - abulia - gait abnormalities - urinary incontinence - gaze preferences - appearance primitive reflexes 2) Temporal lobe tumors - tend to cause seizures that may be: o simple olfactory hallucinations o feeling of fear o complex partial seizures - field defects - aphasia 3) Parietal lobe tumors - cortical sensory loss - neglect - anosognosia - hemiparesis - disturbances of depth perception 4) Occipital lobe tumors - visual field changes - visual seizures 5) Thalamic tumors - contralateral sensory loss - cognitive changes - aphasia 6) Brainstem tumors - cranial nerve disturbances - hiccups - vomiting - vertigo - hemiparesis 7) Pineal tumors - signs and symptoms of hydrocephalus - Parinauds syndrome - precocious puberty 8) Intraventricular tumors - usually produces hydrocephalus

Valsalva maneuver or postural changes may worsen CSF flow, leading to: o headches o weakness o syncope there also may be symptoms of hypothalamic or autonomic dysfunction, as well as memory problems

9) Cerebellar tumors - headaches - ataxia - neck stiffness - vertigo - nystagmus - hypotonia - cranial nerve or corticospinal tract sign 10) Tumors of the skull base (commonly affecting cranial nerves) - meningiomas of the olfactory groove causes anosmia - glioma or meningioma with involvement of optic nerve cause unilateral visual loss - pituitary tumor with involvement of optic chiasm causes bitemporal hemianopia - cavernous sinus or brainstem tumors can cause extraocular abnormalities - acoustic neuroma can cause hearing loss or facial weakness - carcinomatous meningitis causes multiple cranial nerve signs which can lead to num-chin syndrome from involvement of the mandibular nerve 11) False localizing signs - may arise from increased ICP - the most common is VI nerve palsy due to compression of abducens nerve - ipsilateral hemiparesis may occur as uncal herniation compresses the contralateral cerebral peduncle - hydrocephalus may cause: o gait abnormalities o bitemporal hemianopia from compression of chiasma opticus o endocrine deficiencies from hypothalamic compression 12) Cranial nerve palsies - III nerve palsy o usually ipsilateral when there is uncal herniation o sometimes may be contralateral o first sign may be dilated pupil - IV nerve palsy o rare, but may be possible due to the nerves long course - VIII nerve palsy o hearing loss o vestibular signs o vertigo o nystagmus

D) Neuro-ophthalmologic Signs 1) Oculomotor problems are common with tumors of the pineal area: a. Parinauds syndrome, which consists of: i. light near dissociation ii. paralysis of convergence iii. paralysis of upgaze b. convergence-retraction nystagmus c. ptosis or lid retraction (Colliers sign) d. setting-sun sign is common in children (downward deviation of the eyes and lid retraction) 2) Papilloedema - rarely occurs as first sign of tumor; usually follows sustained elevation of ICP for weeks or months - it is secondary to transmission of increased ICP along the optic nerve sheath and to blockade of axoplasmic transport - papilloedema due to increased ICP is bilateral - unilateral papilloedema is due to asymmetric swelling of the nerve, may be due to location of the lesion 3) On visual-field testing, the characteristic findings are: - enlargement of the blindspot - constriction of the visual field 4) Foster-Kennedy syndrome - ipsilateral optic nerve atrphy and contralateral papilloedema - usually associated with orbital or skull base tumors that compress the optic nerve 5) Asymmetric herniation may also occlude the posterior cerebral artery, leading to: - homonymous hemianopia, or - cortical blindness

4. ADENOMA OF PITUITARY GLAND. CLINICAL FEATURES, DX N TX. Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas. Symptoms Most pituitary tumors produce too much of one or more hormones. As a result, symptoms of one or more of the following conditions can occur: Hyperthyroidism Cushing syndrome Gigantism or acromegaly Nipple discharge Symptoms caused by pressure from a larger pituitary tumor may include: Headache Lethargy Nasal drainage Nausea and vomiting Problems with the sense of smell Visual changes o Double vision o Drooping eyelids o Visual field loss Rarely, these symptoms may occur suddenly and can be severe. Exams and Tests physical examination- note any problems with double vision and visual field, such as a loss of peripheral vision or the ability to see in certain areas. Endocrine function tests include: Cortisol levels: o Dexamethasone suppression test o Urine cortisol test Follicle-stimulating hormone (FSH) levels Insulin growth factor-1 (IGF-1) levels Luteinizing hormone (LH) levels Serum prolactin levels Testosterone/estradiol levels Thyroid hormone levels: o Free T4 test o TSH test Tests that help confirm the diagnosis include the following: Formal visual field testing MRI of head

Treatment Pituitary tumors are usually not cancerous and therefore won't spread to other areas of the body. However, as they grow, they may place pressure on important nerves and blood vessels. Surgery to remove the tumor is often necessary, especially if the tumor is pressing on the optic nerves, which could cause blindness. Most of the time, pituitary tumors can be removed through the nose and sinuses. However, some tumors cannot be removed this way and will need to be removed through the skull (transcranial). Radiation therapy may be used to shrink the tumor, either in combination with surgery or for people who cannot have surgery. The following medications may shrink certain types of tumors: Bromocriptine or cabergoline are the first-line therapy for tumors that release prolactin. These drugs decrease prolactin levels and shrink the tumor. Octreotide or pegvisomant is sometimes used for tumors that release growth hormone, especially when surgery is unlikely to result in a cure.

5. ABSCESS OF BRAIN. ETIOLOGY, CLINICAL FEATURES, DX, TX Brain Abscess Incapsulated or free pus in the substance of the brain after an acute focal purulent infection Etiology Classified on the basis of the likely entry point of the infection.( example, brain abscesses arise most commonly as direct extension from cranial infections (mastoid, teeth, paranasal sinuses, or osteomyelitis of the skull), from infections after fracture of the skull or neurosurgical procedures, or as metastases from infection elsewhere in the body) Metastatic seeding from a remote site may cause brain abscess (e.g., arising in the lungs, by bronchiectasis or lung abscess) or less frequently in bacterial endocarditis. Other sources include the tonsils and upper respiratory tract, from which the infection can reach the brain along the carotid sheath, or after urinary tract or intraabdominal infections The infecting organism may be any of the common pyogenic bacteria depending on the site of entry; the most common are S. aureus, streptococci (anaerobic, aerobic, or microaerophilic species), Enterobacteriaceae, Pseudomonas, and anaerobes such as Bacteroides. In infants, gramnegative organisms are most frequent offenders. After penetrating head injury, abscess formation is usually due to S. aureus, streptococci, Enterobacteriaceae, or Clostridium species; S. epidermidis infection follows neurosurgical procedures. In the immunocompromised host, Toxoplasma, fungi, Nocardia, and Enterobacteriaceae are frequently found. Pathology - Pathologic changes in brain abscess are similar to subdural of epidural infection - Four stages of maturation are recognized. W/in 1st 3days, suppurative inflammation of brain tissue is characterized by early cerebritis. The progression from late cerebritis to early capsule formation and final maturation of the capsule takes about 2 weeks Symptoms and Signs - Headache - Pain is dull ache that is not localized - Fever present in less than 50% of patients , many are afebrile - Edema of surrounding brain rapidly increase IP so it will worsen headache, nausea and vomiting are early symptoms. - Sudden worsening of headache with new onset of nuchal rigidity heralds rupture of abscess into ventricular space - Seizures, focal or generalized - Focal signs including altered mental status and hemiparesis. Apathy and mental confusion linked with abscess in frontal lobe. Hemianopsia and apahsia particularly anomia are found when temporal or parietoccipital lobes are involved - Cerebellar abscess will see ataxia , intention tremor, nystagmus

Diagnosis - Suspected clinically when seizures , focal neurologic signs or increased IP develop in a patient with congenital heart disease or with a known acute or chronic infection in the middle ear, mastoid, nasal sinuses, heart or lungs - Can use CT or MRI Investigation - Leukocytosis - Increase ESR - LP is contraindicated because of clear risk of transtentorial herniation - CSF revealed elevated opening pressure and aseptic meningeal reaction - CSF is usually clear but maybe cloudy or turbid - In early unencapsulated abscesses near the ventricular or subarachnoid spaces, the cell count is high, with a high percentage of polymorphonuclear leukocytes. The cell count is normal or only slightly increased when the abscess is firmly encapsulated. The cell count in 34 patients at various stages of the disease varied between 4 and 800 cells with an average of 135 cells/mm 3. The protein content is between 45 and 200 mg/dL. The CSF sugar content is normal. A decrease in sugar content below 40mg/dL indicates that the meninges have invaded by bacteria Treatment - Surgical, including incision and drainage through a burr hole or open craniotomy with marsupialization, packing the cavity, and complete extirpation - current recommended treatment for most brain abscesses is CT-guided stereotactic or free-hand needle aspiration with therapeutic drainage and obtaining diagnostic specimens for culture and special studies, along with appropriate antimicrobial therapy - Choosing the appropriate antimicrobial therapy depends on the ability of the drug to penetrate the abscess cavity and its activity against the suspected pathogen. - Intravenous high-dose penicillin G (10 to 20 million units per day) and metronidazole and also can use ceftriaxone or cefotaxime

6. TUMOR OF SPINAL CORD. CLASSIFICATION. CLINICAL SIGNS OF EXTRAMEDULLAR TUMOR. TX SPINAL TUMORS (Classification and signs, extra- and intradural) Epidemiology Histologic types of spinal tumor and their frequencies: o Neurofibromas (29%) o Meningiomas (26%) o Ependymomas (13%) o Miscellaneous (12%) o Astrocytomas (7%) o Metastatic and other (13%) Spinal tumors occur less often than intracranial tumors in a ratio of 1:4. Men and women are equally affected, except that meningiomas are more common in women. Spinal tumors occur more often in young or middle-aged adults and less often in childhood or after age 60 years old. Spinal tumors appear most often in thoracic region, but other region can be affected too, and multiple lesions are possible too.

Classification of spinal tumors according to its location 1) Intramedullary tumor is inside the spinal cord 2) Extramedullary Intradural tumor is part of the dura mater Extradural tumor is outside the dura mater Symptoms Extramedullary tumors cause symptoms by compressing nerve roots or spinal cord, or by occluding the spinal vessels. Intramedullary tumors cause symptoms from direct interference with the intrinsic structures of the spinal cord from mass effect, edema, or development of syringomyelia.

EXTRAMEDULLARY TUMORS Extramedullary tumors may be: Intradural (18% of all spinal tumors) Extradural (78% of all spinal tumors) The most common intradural tumors are: Meningioma Schwannoma The most common extradural tumors are: Metastasis Myeloma Neurofibroma Lymphoma

 Extramedullary tumors usually involve a few segments of the cord. These tumors cause focal signs by compression of nerve roots. Symptoms: The first symptoms are focal pain and paresthesia, arising from pressure on the dorsal nerve roots Then, sensory loss, weakness and muscular atrophy follow They may extend and affect the spinal cord directly too. Early signs of spinal cord compression are due to interruption in the functions of the pathways that lie at the periphery of the spinal cord: Spastic weakness below the level of lesion Impairment of cutaneous and proprioceptive sensation below the level of lesion Impaired control of the bladder Impaired control of the rectum (less often) Increased tendon reflexes Babinskis sign Loss of superficial abdominal reflexes If untreated, these early symptoms may lead to signs and symptoms of complete transection of the spinal cord Wasting and atrophy of muscles at the level of nerve root lesion Paraplegia or quadriplegia below the level of lesion The severity and distribution of weakness and sensory loss depends on the location of tumors Spinal vessels may be occluded by extradural tumors, particularly: Metastatic carcinoma Lymphoma Abscess Occlusion of spinal vessels causes myelomalacia and signs and symptoms similar to those of severe intradural compression and necrosis of the spinal cord. Occlusion of major components of the anterior spinal artery results in segmental lower motor neuron signs at the appropriate level bilateral loss of pain and temperature sensation upper motor neuron signs below the lesion

Signs of epidural cord compression can occur due to extension of tumors of the vertebral column into the spinal canal persistent neck or back pain, especially when lying in bed gait disorder due to sensory ataxia sometimes, there may be little signs of weakness or sensory loss

7. INTRAMEDULLAR TUMORS OF SPINAL CORD. CLINICAL FEATURES. DX, COURSE, TX INTRAMEDULLARY TUMORS (4% of all spinal tumors) The most common intramedullary tumors are: Neurofibromas Schwannomas Meningiomas Primary intramedullary tumors usually extend over many segments, sometimes involving the whole length of the cord. Therefore, signs and symptoms are more variable than that of extramedullary tumors.

Tumors of the foramen magnum These tumors may extend up into the posterior cranial fossa, or down to the cervical region. Signs and symptoms may be: Signs and symptoms which are typical of dysfunction of the lower cranial nerves (9th, 10th, 11th, 12th). The most common is tumor of the foramen magnum is ventrolateral meningioma which compresses spinal cord at the junction between the cervical segment and the medulla can cause posterior column signs: loss of position, vibratory and light touch perception, more prominent in the arms than in the legs Upper motor neuron signs in all four limbs are seen There may be cutaneous sensory loss in distribution of C2 or the occiput There may be posterior cranial headache or high cervical pain

Cervical tumors Tumors of the upper cervical segments cause pain or paresthesia in the occipital or cervical region neck stiffness spastic tetraplegia or hemiplegia below the level of lesion there may be involvement of the trigeminal nucleus Characteristic findings according to the level involved: C4: paralysis of the diaphragm C5: atrophy and paralysis of the muscles of the shoulder and biceps; sensory level extends to the outer surface of the arm; biceps and supinator reflexes are lost C6: paralysis of triceps and extensors of the wrist forearm is held semiflexed and there is partial wristdrop; triceps reflex is lost; sensory impairment extends to a line running down the middle of arm slightly to the radial side

 C7: C8: T1:

paralysis of flexors of the wrist and of flexors and extensors of the fingers; there is extension of the wrist and slight flexion of the fingers (preachers hand); the sensory level is similar to that of C6 segment, but more to the ulnar side of the arm atrophy and paralysis of small muscles of the hand resulting in clawhand (main-engriffe); Horners syndromem unilateral or bilateral (ptosis, miosis, loss of sweating on the face); sensory loss extends to the inner aspect of the arm and involves the 4th and 5th fingers and the ulnar aspect of the middle finger. lesions rarely cause motor symptoms, because the T1 nerve root normally provides little functional innervation of the small muscles of the hand

Other signs of cervical tumor include: Nystagmus due to involvement of the descending portion of the median longitudinal fasiculus Horners syndrome may be found with lesions in any portion of the cervical cord if the descending sympathetic pathways are affected

Thoracic tumors Clinical localization of tumors in the thoracic region is best made by the sensory level It is not possible to determine the location of a lesion in the upper half of the thoracic segment by testing the strength of intercostal muscles Lesions that affect the abdominal muscles below T10 but spare the upper ones can be localized by the Beevors sign: the umbilicus moves upward when the patient, lying in the supine position, attempts to flex the neck against resistance Abdominal skin reflexes are absent below the lesion Lumbar tumors Lesions in the lumbar region can be localized by the level of the sensory loss and motor weakness Tumors that compress only the L1 and L2 segments cause loss of cremasteric reflexes the abdominal reflexes are preserved the knee and ankle jerk reflexes are preserved too If the tumors affect the L3 and L4 segments and does not involve the cauda equina, the signs are: weakness of the quadriceps loss of patellar reflexes hyperactive Achilles reflexes

Lesions involving the cauda equina cause flaccid paralysis of the legs loss of knee and ankle reflexes If both the spinal cord and cauda equina are involved, there may be spastic paralysis of one leg with an overactive ankle reflex on that side, and flaccid paralysis with loss of reflexes on the other side

8. NEURINOMA OF CAUDA EQUINE. CLINICAL FEATURE. DX, TX Tumors of the conus and cauda equina The first symptoms of a tumor that involves the conus and cauda equina are: pain in the back, rectal area, or both legs, often leading to a diagnosis of sciatica. loss of bladder function impotence As the tumor grows, there may be: flaccid paralysis of the legs with atrophy of leg muscles and foot drop fasciculation may be evident sensory loss may affect the perianal or saddle area and the remaining sacral and lumbar dermatomes loss may be slight or severe that a trophic ulcer develops over the lumbosacral region, buttocks, hips, or heels Signs of increased ICP may be seen with ependymoma of this region

Diagnostic methods a) Plain x-ray b) Diagnostic imaging (CT-scan and MRI) c) Cerebrospinal fluid When there is a complete subarachnoid block, the protein count increases and the CSF may be yellowish in colour The cell count is usually normal, but a slight pleocytosis is found in 30% of patients The glucose content is usually normal, unless there is meningeal spread Cytologic evaluation of the CSF is useful when malignant tumors are suspected Course and prognosis Benign tumors of the spinal cord are characterized by slow progression for years. Intramedullary tumors are generally benign and slow growing. Usually they are discovered only when they have attain a large size in 6 8 years. Extradural tumors are usually malignant (such as metastatic carcinoma or lymphoma), with sudden onset of a severe neurological disorder, with or without pain. Treatment of primary spinal tumors Once the diagnosis of an intraspinal tumor has been made, the treatment is surgical removal of the tumor whenever possible. When the neurologic disorder is severe or rapidly progressive, an emergency is indicated.

Radiotherapy is rarely indicated after total or partial removal of the tumor, but the patient should be observed for recurrence. After radical and extensive surgery, spinal deformities (which may have been present even before the operation) may appear or increase, requiring fixation.

9. EPILEPSY AND CONVULSIVE CONDITION 1. EPILEPSY. ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TX Epilepsy is a gp of d/o charc by recurrent seizures & is common cause of episodic loss of consciousness. There are abnormal recurrent & excessive neuronal discharge + other CNS disturbances. Etilology hereditary abnormal dev of the brain lack of O2 during birth infxn (syphilis-passed transplacentally from mother to fetus) brain tumors severe head trauma cerebral thrombosis/ hemorrhagic (stroke) pathogenesis it result of the alteration of neuronal fx wic is resulting from the selective loss of inhibitory neurons in the damaged region of the brain theremaybe multiplication in dendrite structure of proliferation of dendrite wic synaptic contact & synaptic recognition in a limited area epilepsy is the result of dysfx of a large cell population. Wic initiate a local paroxysmal discharge, probably the result of excessive glutamate or aspartate release & of N-methylD-aspartate receptor (NMDA) xtvt this discharge propagates, from the original site thru an abnormal dendritic network, lacking inhibitory mechanism, recruiting neurons at other sites with emergency of a focal seizure, further propagation lead to generalized seizure. An eplileptc discharge spreading to involve all of brain will result in generalized seizure when discharge not spread, the seizure will be focal or partial In partial seizures, the clinical manifestation is determined by the area of the brain involved.

epilepsy

generalised (grand mal)

partial seizure (focal)

petit mal (absence)

Generalized Few stges:1. Aura (sumtimes) -foul smelling (kakosmia) -vision hallucination -psychological aura -duration from some sec to 2-3 days 2. Falling -pt fall suddenly, quickly -cant protect himself when he fall (injury happens) 3. Tonic -tonic rigidity (all muscles extend) -appearance of acrocyanosis on the face, dilation & prominent exression of the vein -duration from few sec- some min 4. Clonic seizure (contractyion0) -accopanied by foam bubble from the mouth with blood -foam form when pt take deep breath & suddenly expirate it, it is blood bcoz the pt may bite the tounge or buccal area Duration from some min to hours or days 5. Recovery -involuntary micturition & defecation 6. retrograde amnesia -cant remember what had happened

Petit Mal(absence) -short time loss of conscious w/o seizure -externally look like the pt is freezing, stand still & staring at one point. Continue 1-2 sec

Tx. -continuaous tx (no break of drug) -investigation (tanye pt dulu die mkn ape.. siasat laa) -individual tx - Allergy? - Dz of git/ liver dz - Ade ambik ubat lain x? - Duration of dz - Character n frequency of seizure -minimal but sufficient dose -naikan dose sikit2 pahtu tgk effective ke tak nih?? -monotherapy -complex therapy -microcirulation of brain Neuroprotector Osmotic dieretic Vits Drugs for epileptic (sawan) Finlepsy\carbamazepine Depakin Valproid natrii Trigretor

2. FOCAL EPILEPSY. ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT Seizures at this type are caused by a focal abnormality in the brain and are not associated with loss of consciousness or with a generalized tonic-clonic convulsion. Classification Partial (focal, local ) seizures A: simple partial seizures Motor Sensory B: Complex partial seizures ( when partial seizures is accompanied by any degree of impaired conscious level). C: partial seizures evolving to tonic/clonic convulsion. Etiology: Hereditary factor Abnormal development of the brain Lack of oxygen during birth Infection eg:syphilis Brain tumors Severe head trauma Cerebral thrombosis

Clinical picture Simple motor seizures-arise in frontal motor cortex with movement occur in contralateral face, trunk or limbs. Jacksonian motor seizures-march of involuntary movement from one muscle group to the next. Begin from hands or face. After a motor seizures the affected limbs may be weak for some hours before returning to normal( todds paralysis) Patient aware of the movement of the head often attack progress to loss of consciousness n tonic clonic epilepsy. Patients eye n head trun away from the site of focal origin.

Simple sensory seizures

-arise in sensory cortex, usually patient describe paraesthesia or tingling in an extremity or on the face. -a march similar to jacksonian may also occur Complex partial seizures Gustatory or olfactory hallucination lip smacking Patient may experience deja voux phenomena depression

Treatment. -anti epileptic drugs carbamizepine(1st choice) phenytoin valproate phenobarbital

3: DIFFERENTIAL DIAGNOSIS OF EPILEPTIC ATTACK FROM SYNCOPE AND HYSTERIA criteria 1. Character of falling Epileptic attack Rapid n quick Falling associated with trauma + Pupil completely dilated No reaction to light tonic clonic minutes Hysteric attack Falling with stages Not associated with trauma (only cheek or lips) Reaction positive syncope Sudden n quick Fall n may be trauma Reaction slow

2. Bite of tounge 3. Pupil reaction to light

4. Seizure 5. duration

6. Urination

tonic( hyateric arch) Long up to hours, depend on visual. -

Seconds to minutes. -

4: EPILEPTIC STATUS. CLINICAL FEATURES, EMERGENCY AIDS. Definition: it is a long time epileptic seizures more than hours or series of seizures in which between them patient dont recover from loss of consciousness. Precipitating factors Sudden withdrawal of anti-epilleptic drugs Phobic stimulation Hyperventilation Sleep deprivation

Causes of status epilepticus 1. Acute brain insult -stroke -cocaine -Metabolic -meningitis -ac withdrawal of hynotics, alcohol -hypoglycemia -hypoxia 2. Status as first presentation in old age due to tumor Complication A. CEREBRAL COMP Hypoxia, axonal injury, venous thrombosis, inc intracranial hemorrhage. B. CARDIO-PULMONARY COMP Hypotension, hypertension, heart failure, respiratory failure, cardiac arrest C. METABOLIC COMP Hyperpyrexia,hyponatremia, liver failure, dehydration D. OTHERS DIC syndrome, infection, fractures.

Management( emergency aids) Hospitalization n immediate ICU admission -monitoring vital sign -maintain adequate patent airway n ensures oxygen inhalation -establish iv line n take blood sample -IV infusion to correct electrolyte metabolic imbalance - oral airways to avoid tounge bitting -suction of secreation. Cerebral dehydrating. Drug therapy -diazepam-( rapid acting n will cause respiratory centre depression) -phenytoin (long acting with no resp centre depression) - if the fit not stop prescribe Phenobarbital 10 mg /kg IV at rate 50 mg /min -if fit still continue give thiopentone.

10. NEUROSES, DISEASE OF AUTONOMIC NERVOUS SYSTEM 1: NEURASTHENIA. CLINICAL FEATURES, TREATMENT, PREVENTIVE MEASURES.
Neurasthenia is a psycho-pathological term first used to denote a condition with symptoms of fatigue,anxiety, headache, neuralgia and depressed mood

Is a type of neuroses which is manifested by nervous weakness and accompanied by physical asthenia. Psychogenic, conflictogenic neuromental disorder develop when a person cannot find an appropriate answer. Can be of 3 types-hysteria(artistic type) -neurasthenia(mixed type, most frequent type) -obsessive compulsive disorder(mathematics) Often occur in children due to Arguments between parents in which child feel uncomfortable at home. Too much pressure on child eg: Cinderella High expectation on child -their child is the best n is not going to be blame. -the child feel he is the best and not doing any wrong. Etiology Conflict(stress) All changes of environment Positive or negative changes Long term stress Psychogenic in childhood Familial life

Symptom 1. 2. 3. 4. 5. 6. 7. Quick tempered Decrease mood Sleeplessness Apathy Loss of appetite Easily get irritated Lethargy,tiredness, fatique.

Treatment 1. Pharmachotherapy Tranquilizer with anxiolytic effect(alprazalam,grandaxin, atarax) Antidepressant -serotonin selective reuptake inhibitor(fluoxamine, asetalapron) -tricyclic(amytriptyline) combination of antidepressant and tranquilizer. 2. Psychotherapy Therapy of soul Cognitive therapy(talk with patient) Behavioral Linguistic Exposure therapy Change attitude to the circumstances, or change circumstances. Preventive measures 1. Avoid stress 2. Family counseling

2: HYSTERIA, ETIOLOGY, CLINICAL FEATURES, TREATMENT , PREVENTIVE MEASURES.

Hysteria, in its colloquial use, describes unmanageable emotional excesses. People who are hysterical often lose self-control due to an overwhelming fear that may be caused by multiple events in one's past that involved some sort of severe conflict; the fear can be centered on a body part, or, most commonly, on an imagined problem with that body part. -according to lec: hysteria is an emotional imbalance characterize by changes in mood. Their behavior is like actor playing a role. But the involuntary do it( therere not pretending).

Etiology: x sure sgt..tpi etiology rasenye same ngan neuroses sbb hysteria is one of it kn? 1. Conflict(stresss): all changes of circumstances, environment. :positive or negative changes :everyone experience stress, but not all suffers from neuroses. :important to take note about level of stress. >death of relative-high level >changes in work >conflict with colleagues Clinical pictures Hysterical paralysis Hysterical hyperkinetic syndrome Hysterical aphasia Hysterical blindness Hysterical epileptic (grand mal)

Our main task is to differentiate btw hysterical attack n epileptic attack. 1. Hysterical attack /reaction on conflict n stress(always emotional),they need spectators( never happen when patient is alone) 2. Never harm themselves >without uncontrolled urination >without biting tongue 3. level of consciousness:always conscious in hysterical attack > how to check on pt -unconcious:dilated pupil,no light reaction. -cant open her eyes, she closed tightly -to provoke reaction, use cold water, in conscious patient, they wakes up n open eyes, but in unconscious no reaction seen.

Treatment 1. Pharmachotherapy Tranquilizer with anxiolytic effect(alprazalam,grandaxin, atarax) Antidepressant -serotonin selective reuptake inhibitor(fluoxamine, asetalapron) -tricyclic(amytriptyline) combination of antidepressant and tranquilizer. 2. Psychotherapy Therapy of soul Cognitive therapy(talk with patient) Behavioral Linguistic Exposure therapy Change attitude to the circumstances, or change circumstances. Preventive measures 1. Avoid stress 2. Family counseling

3: NEUROSES OF OBSESSIVE CONDITION. ETIOLOGY, CLINICS, TREATMENT Phobia: irritational fear that produce a conscious avoidance of feared subject, activity situation, wic may interrupt social life. Example of phobia Social phobia Agoraphobia( in open space) Claustrophobia( fear to be in a closed space) Cancer phobia Misophobia(fear to be infected)

Anxiety-is the most common feature, consist of two symptom 1. Obsession: intrusive thought ideas, impulse that recur repeatedly ,it cant be controlled even that person know that these thought are irrational. 2. Compulsion: repeated behavior or mental process dat the person is driven to performed over n over even they know that the behavior is irrational.

Symptom Inc heart rate/palpitation Tremor Dyspnea Sweating Paresthesia Dizziness.

Causes: social phobia should be caused by Environmental factors(psychology, trauma) Genetic related Treatment 1. Sel serotonin reuptake inhibitor Eg: fluoxetine, imipramime 2. Aprazolam, buspirone, Phenobarbital 3. Cognitive therapy 4. Psychotherapy: hypnotic, anxiolytics.

4: VEGETATIVE DYSTONIA. ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT N PREVENTIVE MEASURES. Changes in parasymphathetic n sympathetic from the higher suprasegmental vegetative center lead to dev of vegetative dystonia. Definition: psychovegetative complex of symptoms arise from failure of regulation of segmental part by suprasegmental part. Risk factor 1. Psychogenic factor-internal conflict or great fear of something 2. Physiologic-after severe physical exertion, alcohol or drugs intake, or weather changes. 3. Biogenic-pregnancy or abortion or hormonal therapy. Can be Primary affection: independent of other nerve pathway Secondary: result of other organic disorder There are 2 forms of vegetative dystonia Paroxysmal(panic attack) Permanent Paroxysmal(panic attack) Emotional affection disorder. Etiology. 1. 2. 3. 4. After severe physical exertion Deprivation of sleep Poor nutrition Emotional disturbances.

Pathogenesis Arise in background of sympaticotonic condition. Diagnosis Based on clinical evaluation Fear of dying Fear of going crazy Feeling of un reality Depersonalization

Somatic group Chest pain/discomfort Dizziness Chocking Flush n chills Nausea or abdominal distress Numbness or tingling sensation Palpitation, inc heart rate Sensation of shortness of breath Sweating, trembling, shaking

Diagnose require at least 4 symptom together, frequency of symptom is 10 minute n then disappear. Treatment Usually recovers without treatment if change life style Pharmacological treatment 1. Antidepressant Serotonin selective reuptake inhibitor Selective norepinephrine uptake inhibitor Act upon 2-3 w of intake Thats why we combined antidep + benzodiazepine( act on first pill n after 2 w stop benzodiazepine but cont with antidep. 2. Vegetocorrection-balance sympathetic n parasymphatetic Eg: grandacine,teoroligine(neuroleptic),belotrominal Psychotherapy 1. Cognitive psychotherapy( talk with patient) 2. Exposure therapy(diminish fear, reconstructing

Permanent form Progressive vegetative insuff n dysfunction appear during hormonal period(puberty) Functional n organic psychogenic disease, after infection, trauma n rarely constituitonal character Can be Sympaticotonia: dryness of skin, cold extremities, exopthalmus, tachycardia, inc BP Vagotonia; cold n moist skin, sweating, hypersalivation, bradycardia, slowness of movement. Disease develop gradually, occur at rest. Treatment: same with panic attack.

5: MIGRAINE. GENETIC ASPECTS, CLINICAL FEATURES, TREATMENT. Definition: paroxysmal often familial disorder characterized by recurrent intense throbbing headache that affects the head unilaterally or bilaterally alternating n associated with nausea n vomiting. It may preceded by visual, sensory and or motor manifestation. Etiology: Herido family(70%) Females more than males Onset around puberty More in obsessive perfectionistic person

Predisposing factor Stress: mental n physical Exercise Dec sleep Diet: cheese, chocholate, mushroom, chicken pizza etc. Hunger lead to dec glucose inducing migraine attack.

Genetic aspects -70% in 1st relative with history of migraine -increase in relative which have migraine wit aura -have maternal inheritance pattern.

Clinical picture 1. Prodroma:drowsiness, fatique, or hunger may occur several days before attacks 2. Aura: are some symptom that make the patient feel the attacks is coming -visual hallucination-moving stars, flashes of light, hemianopia -others: sensory(numbness of lips or the tounge) :motor(paresis, weakness, paresis, dysphasia) 3. Headache:start at the temple or around the eye n spread to involve the whole side of the head, pulsating. -duration : 2-3 hours or severe enough to involve the whole day and rare to reach status migranus. Pain is relieve when take treatment. -associated symptom: vomiting, photophobia, phonophobia, photosbia

Treatment 1. Vasoconstrictor Rest in dark quite room Avoid or dec risk factor Paracetamol caffein Analgesic( NSAID): voltaren Ergot preparation -tablets( migranile, cafergot) -injection Triptans(sumatriptan, zomitriptan, elitriptan) 2. Prophylactic treatment Avoid precipitating factor Calcium channel blocker to stabilize the blood vessel. (flunarizine) NSAID voltaren or cataflam Antiepileptic.

6. Panic attacks : etiology, pathogenesis, clinical features, diagnostic 7. Disturbances of sleeping and wakefulness 8. Tension headache : etiology, pathogenesis, clinical features, treatment 9. Cluster headache : clinical features, diagnostic, treatment. HEADACHES - a subjective symptom. -according to International Headache Society 1. Primary Headache : no organic/ structural etiology include migraine/ vascular headache, trigeminal autonomic cephalgias (cluster headache) & tension headache, hemicranias continua, exertional headache, hypneic headache, fundaclub 2. Secondary headache : due to underlying structural/ organic disease -headache in encephalitis, meningitis, tumor For DD(x) between primary and secondary we use : A. Screening method i. Plain X-ray -exclude trauma -high ICP -structural congenital anomalies ii. Encephaloechography (EEG) -see oscillation of mid structure -compare both hemisphere *if deviation of mid structure > 3mm = extravolume iii. Neuropthalmological examination -evaluate condition of N. opticus : *edema? Atrophy? -eye fundus = mirror of brain **if no changes, we may suspect benign **if changes present do CT/MRI

B. Pattern of the pain -frequency, intensity, location, duration, characteristic (tingling, dull, throbbing) of pain & factor associated with exacerbation and remission. **we must know : 1. accompanying symptoms 2. preceding condition 3. factor provoking the pain 4. factor relieving the pain TENSION TYPE HEADACHE - most prominent -2 types : Episodic & Chronic -at least must have 2 of following characters : *pressing/tightening ( non-pulsating) *mild/ moderate intensity *bilateral location *no aggravation for climbing stairs/ similar routine physical activity *no nausea/ vomiting *photophobia & phonophobia absent/ only 1 present *20 headache type not suggested/ confirmed # Episodic type : <15 days/month # Chronic type : >15 days/month for >6 months Pathogenesis -complex & multifactorial -muscular, vascular & psychogenic factor -abnormal neuronal sensitivity & pain foci but not abnormal muscle contraction -associated with extroreceptor perception -abnormal level serotonin & low level of serotonin B-endorphin lead to decrease level of antinociceptive system -onset at young adult -more in woman ( M : F = 1 : 1.5) -attack usually start at morning and worsening during day Precipitating Factor -in susceptible individual -stress & hunger -sleep deprivation -uncomfortable stressful position -bad posture -eye strain

Physical Examination -see NOTHING, normal neurological state -some have tender spot, trigger zone in pericranial & cervical muscle Medical Care 1. Pharmacotherapy - abortive therapy ( decrease severe attack) -long term preventive therapy -simple analgesic (ibuprofen, PCM, aspirin) -antidepressant (amitryptilin) 2. Physical Therapy -hot/cold compress -stretching exercises -massage -US therapy -acupuncture -transcutaneous electode nerve stimulator -have a rest & sleep 3. Psychophysical therapy -reassurance -cognitive psychotherapy -relaxation therapy -stress management -biofeedback technique CLUSTER HEADACHE - > in men -no hereditary factor Clinical Picture : * periorbital/ temporal pain *begins w/o warning *reach crescendo in 5 min. *excruciating *deep non-fluctuating & explosive quality *strictly unilateral & affect same sidein subsequent attack *lasts for 30 min to 2 hours *pain lasts for several second but repeatedly *homolateal lacrimation

*red eye, nasal stiffness *lid ptosis & nausea *between attack, alcohol no effective *during pain alcohol increase the pain *pain is unbearable *cant stay quiet *no photophobia/phonophobia *beat wall with the head (pain is very severe) *each day attach start at the same time Treatment - no good abortive therapy Prophylaxis -prednisalone -lytium -ergotamine CRISIS (PANIC ATTACK) -emotional affective d/o -problem to differentiate fear (definite) & anxiety (indefinite) Etiology -after severe exertion -sleep deprivation -poor nutrition -emotional disturbance -stress Pathogenesis -rise on the background of sympathicotonic condition -due to recurrence panic attack accompanied by fear of future attack -cytotherapy + drug Cognitive Symptoms -fear of dying -fear of losing control -feeling of unreality/detachment from self/ depersonalization

Somatic Symptoms -chest pain, discomfort -dizziness -feeling of choking -chills/flush -nausea/abdominal distress -numbness/ tingling sensation -palpitation/ increase HR -sensation of shortness of breath -sweating -trembling/shaking *symptoms peak in 10 min and then disappear *paleness of the skin *lability of arterial BP Once end of panic attack - polyuria Treatment -recover w/o treatment if change lifestyle -psychotherapy (cognitive) -exposure therapy ; to decrease fear -behavior psychotherapy -pharmacological *anti-depressant - serotonin inhibitor -norepinephrin inhibitor -tricyclic inhibitor *benzodiazepam * vegeto-corrector -grandoxine -tiaroligen -beloteminal DISTURBANCE OF SLEEP AND WAKEFULLNESS Sleep disorder or somnipathy is a medical disorder of the sleep patterns of a person or animal [Wikipedia] Types & Symptoms 1. Insomnia -inability to fall asleep or stay asleep at night -waking up earlier than usual

-daytime fatigue -dont fall asleep in inappropriate situations (eg. driving) How to D(x)?? -sleep diary -Epworth sleepiness scale -polysomnogram -actigraphy -mental health exam 2. Sleep Apnea -excessive daytime sleepiness (primary) -some people deny sleepiness but feel fatigued -snoring,snorting and gasping sounds when sleep -restless or unrefreshing sleep -headache in the morning How to D(x) -EEG -EMG -EOG -ECG -nasal airflow -snore microphone Treatment -continuous positive airway pressure (CPAP) -sleep apnea and dental devices -surgery for sleep apnea 3. Narcolepsy -excessive sleepiness during day, alleviated by naps -dreaming during naps and experiencing dream-like hallucinations once fall asleep -loss of muscle control (cataplexy) [eg. Laughing or anger] -unable to move as youre going to sleep or waking up (sleep paralysis) How to D(x) -polysomnography -multiple sleep latency test

4. Restless Leg Syndrome -irresistible urge to move legs shortly after get into bed, in the middle of night or even wide awake duing day -feel better if get up, walk around or rub your leg -creepy-crawly or twitching feeling in calves, feet, thighs or arms -kicking or twitching leg movements during sleep and sometime while awake Treatment -dopaminergic agents -dopamine agonists -benzodiazepines -opiates -anticonvulsants -alpha2 agonists Hypersomnia -abnormal daytime sleepiness -causes : *fatigue *old age *after eating *after alcohol *particular disease (eg. Myotonic dystrophy) Clinical picture -disturbance of vigilance : typical sleep attack even in well rest patients in sleep inducing situations -cataplexy : sudden loss of muscle tone (eg. Eyelids, lower jaw, arm etc) -sleep disturbances : waking attack -rare manifestation : hypnogogic?? Hallucinations Treatment -methylphenidate -clomipramide -eliminate sleep attack B-blockers with high dose of propraolol -tyrosine

Infants may be normal or have such features : Residual neck webbing from the cystic hygroma Shield chest Coarctation Edema of the hands and feet

During childhood Short stature Cardiac murmur

Teenager Primary or secondary amenorrhea or lack of 2o sex characteristic Infertile (mostly) Mentally normal but may have spatial-perceptual abnormalities Women w/o treatment : osteoporosis & CVS disease

C. Mosaic aneuploidy Definition : presence of more cell lines with different karyotypes in single individual Clinical pictures -depends in the specific chromosome involved and the proportions of normal and abnormal cell lines. Autosomal examples a. Mosaic trisomy 8 -mild facial dysmorphism -mentally retarded -fingers with flexion deformaties -deep creases on the palms and soles -fibroblast culture demonstrates mosaicism for chromosome 8 -if suspected skin biopsy b. Sex chromosome example : mosaic Turner syndrome -variable and depends on the proportions of the normal and aneuploid cell lines c. Undiagnosed low level mosaicism

11. MEDICAL GENETICS Q.2 Classification of inheritable diseases -can be classified into three major categories Chromosomal disorders Single gene defects Polygenic or multifactoral diseases Somatic cell genetic defects (addition)

Q4. Single Gene Diseases. General Signs. Clinical Example -Single gene d/o are inherited in a simple Mendelian fashion & referred as Mendelian diseases -Accounts about 5-10% of pediatric hospital. It characterized by pattern of transmission in family known as PEDIGREE -4 basic pattern/modes of inheritance : *autosomal dominant *autosomal recessive *X-linked dominant *X-linked recessive Clinical Example & Signs Autosomal dominant inheritance -vertical inheritance -MAY appear in every generation -3 possible genotypes : homozygous normal, homozygous affected & heterozygote -each offspring have 50% affected allele another 50% normal -if unaffected child bear normal allele, then he/she can have normal offspring Familial hypercholesterolemia o Affected gene code on external surface of most body cell & mediate uptake of cholesterol into cell o If gene affected, cholesterol (LDL) cant get into the cell & accumulate in the blood o Patient will have high LDL & coronary heart disease Marfans syndrome o Mutation in gene for fibrillin (main component of extracellular microfibrils) o Affects CT esp. in heart,skeletal system,eyes etc. o Clinical Features : Long & thin extrimities & fingers Bony deformities of spine & sternum Severe near sightedness Dislocation of lens Valvular incompetence (mitral valve prolapsed) Chest protruded Neurofibromatosis (Van Recklinghausem disease) o Brownish spots on skin called CAF AU KIT SPOT o Benign hamartomatous nodules on iris of eye (Lisch nodules) o Cutaneous & subcutaneous neurofibromas o Onset usually during puberty Huntingtons chorea (see question 15)

Autosomal Recessive (see also Q.26) -only individual homozygous -horizontal pattern of pedigree; limited to siblings not for multiple generations -on chances (25%) -male and female affected equally Cystic fibrosis o Causes thick,sticky mucus in lungs & GIT o Common type of chronic lung disease in childe and young adult o Clinical signs No bowel movement in 1st 24 hour 48 hour of life Stools are pale/clay coloured/float Recurrent respiratory infection (eg. Pneumonia, sinusitis Coughing /wheezing Diarrhea o D(x)

Sweat chloride test Fecal fat test CT MRI Lung functional test Upper GIT & small bowel series

Phenylketonuria o Phenylalanine is not properly metabolize & can cause severe mental retardation if not treated o Clinical signs : Skin rashes/eczema Microcephaly Tremor, jerking, seizure Delayed mental & social skill Mental retardation Hyperactivity o D(x) Enzyme assay (from parents) Chronic villus sample to detect fetal PKU PKU screening (blood sample fetal) Sickel cell anemia o Red blood cell normally disc shaped & become crescent shaped o Function abnormally & cause small blood clots o HBs delivers less oxygen to body tissue & break easily o Clinical signs : Develops at birth but symptoms only appear after 4 months of life Paleness Yellow eyes/skin

 o D(x)

Fatigue Dyspnea Tachycardia Delayed growth Ulcer on lower leg Bone pain Abdominal pain

Hg electrophoresis Sickle cell test High bilirubin Decrease Hg Increase WBC Increase serum creatinine

X-linked diseases -caused by mutant genes on X chromosome -fully expressed in male -may or may not be expressed in female if it does X linked recessive (hemophilia A and Duchenne muscular dystrophy) Duchenne muscular dystrophy (DMD) o Weakness in affected boys in early childhood o Wheelchair-bound before the age of 10 years and death most likely about 20 years old due to muscle degeneration o Female is unusually affected o The protein encoded by the DMD gene , dystrophin; large protein involved in contractile apparatus of muscle cells o Other cystoskeletal protein which interacts with dystrophin referred as dystrophinassociated protein complex o Mutation of those genes cause muscular dystrophy of autosomal forms Becker muscular dystrophy (BMD) o Milder form of X-linked muscular dystrophy o Caused by mutations in DMD gene but generally results from mutations or deletions o Translation reading frame is maintained and produce some dystrophin protein with reduced quantity or altered size o Mutation in severe form of DMD result in no dystrophin expression or production of a truncated or nonfunctional protein

4. Monogenic diseases. Their general (common) clinical tags. Clinical examples. 5. Modes of inheritance of monogenic disease. Clinical example. Definition: are the diseases caused by single mutant gene. Inhereted in a simple Mendelian fashion also known as Mendelian diseases Type of disorder : Autosomal dominant Autosomal recessive X-linked Some terminology: Genetic locus- specific position or location on a chromosome Alleles-alternative form of gene, or of DNA sequence, at given locus Homozygous: both alleles are identical Heterozygous: different alleles Compound heterozygote: two different mutant allele at a given locus Double heterozygote: one mutant allele at each of two different loci

Genotype genetic constitution or composition of an individual Phenotype observed result of the interaction of the genotype with the environmental factors Dominant individual with one copy of mutant allele and one copy of a normal expressed in heterozygotes

Recessive Double dose of an abnormal gene Manifest in homozygote

AUTOSOMAL DOMINANT DISEASES Affect adult life more compare to others Pattern of inheretence ; only 1 normal allele and 1 mutant

3 possible genotypes : Homozygous normal Homozygous affected heterozygous

Male and female may transmit the abnormal gene with equal probability Pedigree pattern for an autosomal dominant trait show vertical inheritance Mutant genes with pleiotropic effects (affect several organ systems and functions) shows variable expressivity Penetrance- all-or-none phenomenon that refers to observable expression, or lack of it, of the mutant gene Variable sensitivity- characteristic of autosomal dominant traits

Example of autosomal dominant disease: Marfan syndrome and Neurofibromatosis Marfan syndrome Due to mutation in the gene for fibrillin ( main component of extracellular mircofibrils Affects CT of body, mainly skeletal system,eye and the heart The severity of the manifestations may vary widely Can see the variety in the same family even they carry the same mutant allele Variable expressivity may be due to : Environmental influences Effect of other genes that modify the expression of the mutant gene

Neurofibromatosis 1 a.k.a von Recklinghausen disease Characterized by : brownish spots on the skin called caf au kit spots Benign hamartomatous nodules on the iris of the eye ( Lisch nodules) Cutaneous and subcutaneous neurofibromas Protean manifestation affecting almost all systems; highly vascular plexiform neurofibromas which infiltrate surrounding tissues and cause serious growth abnormalities and deformities

Anticipation Manifestation of dominantly inherited diseases Expressed during earlier age and increasing severity in successive generation Eg. Myotonic dystrophy

Common muscular dystrophy affecting adults Characterized by : Muscle fasting (face neck hands) Myotonia or inability of muscle to relax after contraction Also affects cardiac and smooth muscle Associated with early cataracts, Ig abnormalities and mild mental retardation

AUTOSOMAL RECESSIVE DISEASES Manifest only in individual homozygous for mutant gene Horizontal pattern pedigree ; limited to siblings and not found in multiple generations

Male and female are affected equally The probability two heterozygous individual for the same mutant allele will mate depend on frequency in the population It will be increased if they are related If the mutant gene is common in a population,example : Cystic firosis in white population Tay-Sachs disease among European Jews Sickle cell anemia in African-Americans

7. Multifactorial diseases. Features of their inheriting and preventive maintainance. Definition: refers to the diseases which are associated with the effects of multiple genes in combination with the lifestyle and environmental factors. They often cluster in family,but they dont have clear cut pattern of inheritance. The pattern of inheritance does not fit simple pattern as with mendelian diseases. Clinical examples include hypertension and diabetes mellitus. HYPERTENSION Is a chronic cardiac condition in which the systemic arterial blood pressure is elevated. Blood pressure is considered to be high when it is more than 140/90 mm/Hg. Classification: Primary/Essential hypertension & Secondary or Symptomatic hypertension. Essential hypertension: Is the condition in which the elevated arterial blood pressure is the leading symptoms. Most common type of hypertension (95%). Tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors (multifactorial). Examples of genetic factors:

1. Includes the mutation of different genes. example: Mutation of gene coding for enzymes involved in aldosterone metabolism. Excess aldosterone is secreted from adrenal medulla, absorption of Na & H2O is increased, leading to hypertension. Other example: Mutation in epithelial Na channel protein caused increase in reabsorption of Na at distal renal tubule. Environmental factors: 1. Stress 2. Metabolic syndrome obesity, impaired glucose tolerance, dyslipidemia, hypercoagulation 3. Smoking 4. Lack of physical exercise 5. Heavy Na intake

Secondary hypertension: The high blood pressure is the symptom of other diseases. Main causes:

- Endocrine diseases (conn syndrome, pheochromocytoma, hyperaldosteronism, cushing syndrome) - Renal diseases (renal artery stenosis, chronic glomerulonephritis) - CVS diseases (coartation of aorta) - Drug (steroid, contraceptive) - Pregnancy DIABETES MELLITUS It is defined as metabolic disorders with absolute & relative insulin production deficiency. The person has high blood sugar level (normal range 4.4 6.6 mmol/l). There 2 types of diabetes mellitus, Type I and Type II. Type I DM: Aetiology : Absolute deficiency of insulin production by B-cell of islet of langerhans. Deficiency of insulin may be due to hereditary disorder or destruction of cells by certain factors. In autoimmune mediated, the B-cells are attacked by T-cells, causing their destruction. B-cells also can be destroyed by trauma, tumor, enzymes (pancreatitis), removal of pancreas, etc.

Type II DM High glucose level as a result of insulin resistance. The insulin production is normal or even increased (Relative deficiency). Cause of insulin resistance development : Eating habits intake of large amount of carbohydrates constantly stimulates the secretion of insulin. If this occurs for a long time, the cells will no longer sensitive to insulin.

8. Hereditary sex linked diseases. Capabilities of preventive maintenance of the diseases with the data by mode of inheritance. Examples. Caused by mutant genes on the X chromosome Fully expressed in male May or may not be expressed in female if it does express X-linked recessive (eg. Hemophilia A and Duchenne muscular dystrophy) Duchenne muscular dystrophy (DMD) Weakness in affected boys in early childhood Wheelchair-bound before the age of 10 years and death most likely about 20 years old due to muscle degeneration Female is unusually affected The protein encoded by the DMD gene , dystrophin; large protein involved in contractile apparatus of muscle cells Other cystoskeletal protein which interacts with dystrophin referred as dystrophin-associated protein complex Mutation of those genes cause muscular dystrophy of autosomal forms

Becker muscular dystrophy (BMD) Milder form of X-linked muscular dystrophy Caused by mutations in DMD gene but generally results from mutations or deletions Translation reading frame is maintained and produce some dystrophin protein with reduced quantity or altered size Mutation in severe form of DMD result in no dystrophin expression or production of a truncated or nonfunctional protein Mutation also can occur in genes on the mitochondrial chromosome and nuclear chromosomes Mitochondrial diseases affect energy production in nerve and muscle

9. Prenatal diagnostics. Its role in the primary preventive maintenance genetically of family disease. There are several methods of diagnostic used: 1. Ultrasonography 2. Alpha fetoprotein level measurement 3. Amniocentesis 4. Chorion villus sampling 5. Percutaneous blood sampling Ultrasonography and alpha fetoprotein measurement are used as the screening test for all pregnant woman in the population. ULTRASONOGRAPHY Is the first diagnostics method used for pregnant woman. It is very useful, non invasive, and pain free. Done between 15th to 24th week of gestation. Used to assess gestational age, monitor fetal growth and detect multiple gestation. Also can determine the sex of fetus, presence of anatomic defect (for example any cardiac, kidney, or bladder abnormalities) Fetal echocardiography is specially used to detect congenital heart defects. Spina bifida can be detected by ultrasound and it is the indication for prenatal surgery.

ALPHA FETOPROTEIN LEVEL Indirect type of fetal screening. Mothers blood is taken for the test. In fetus with open neural tube defect, the mothers blood will contained increased amount of alpha fetoprotein. Decrease level of alpha fetoprotein seen in down syndrome and other chromosomal abnormalities. The normal level of alpha fetoprotein can be varied. That is why when we checked the level , use ultrasound to determine the age of the fetus, determine no of fetus, and also measure the weight of mother.

AMONIOCENTESIS It is not a screening test. Done in 16th week of gestation. Done only in woman who needs it, those women whose ultrasonography showed some abnormalities. With local anesthesia, a needle is inserted into the amniotic cavity under the ultrasound guidance, and small amount of amniotic fluid is taken (20ml). the fluid reflects the fetal extracellular fluid composition. The cells from the GIT and epidermis of fetus are found in this fluid. Urine is the main contributor to this fluid. The needle can be inserted transabdominally or transcervically. Should be carried out early enough so that it is useful. Used to decide whether termination of pregnancy is required or not. The fluid can also be analysed for alpha fetoprotein or can be cultured Karyotyping, DNA labeling, cytological examination by FISH also done.

CHORION VILLUS SAMPLING Done from 9th to 12 week of gestation. A fine flexible catheter is inserted into cervix, then into uterus, and by suction small amount of chorion frundosum (placental tissue) is obtained. A catheter may be also introduced transabdominally. Fetal cytothrophoblast are rapidly dividing, it may be examined. Disadvantages: it is not possible to diagnose open neural tube defect, infectious diseases, there is also risk for spontenous abortion.

PERCUTANEOUS BLOOD SAMPLING Done in 18the week of gestation. A needle is inserted into umbilical cord (that is into umbilical vein or artery) and a blood sample is aspirated. Done under the guidance of ultrasound Used to detect isoimmunization, blood incompatibility, and hematologic abnormalities. Blood may be cultured for 24 to 48 h. Risk for abortion is higher than in chorion villus sampling.

10. Moral and deontological problems of medical genetics consultation. 11. Medical genetics consultation: purposes, problem, condition of realization. Definition: medical consultation is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning. This complex process can be separated into diagnostic (the actual estimation of risk) and supportive aspects It is offered by a doctor who is specialized in genetics or by a genetic counselor. This consultation can give people information about these conditions, how they are inherited, which family member may be affected. They also can discuss the care of the patient with genetic disorder and any choices that may be available for them to help reduce the impact of their disorder. Families or individuals may choose to attend counseling or undergo prenatal testing for a number of reasons.

Family history of a genetic condition or chromosome abnormality Molecular test for single gene disorder Increased maternal age (>30-35 years) Increased paternal age (>30-35 years) Abnormal maternal serum screening results or ultrasound findings Increased nuchal translucency measurements on ultrasound Strong family history of cancer Predictive testing for adult-onset conditions Exposure to teratogens Recurrent spontenous abortion

Consultation session structure proposed by Seymour Kessler: 1. 2. 3. 4. 5. Intake phase Initial contact phase Encounter phase Summary phase Follow up phase Intake and follow up phases occur outside the actual consultation session. The initial contact phase is when the counselor and families meet and build rapport. Encounter phase include dialogue between the counselor and client about the nature of screening and diagnostics tests. Summary phase provides all the option and decisions available for the next step.

Detectable conditions Most disorders cannot occur unless both the mother and father pass on their genes, such as Cystic Fibrosis. Some diseases can be inherited from one parent, such as Huntingtons disease. Other genetic disorders are the cause of an error or mutation occurring during the cell division process (trisomy). Testing can reveal conditions that are easily treatable as long as they are detected (Phenylketonuria or PKU). Results from genetic testing may also reveal:

Down syndrome Sickle-cell anemia Tay-Sachs disease Spina bifida Muscular dystrophy Mental retardation

12. Parkinsons diseases. Genetics aspect, clinic, diagnostics, and treatment. - is an autosomal dominant hereditary disorder of extrapyramidal system (defect in chromosome 22). - idiopathic slowly progressive, degenerative CNS disorder characterized by: 1. resting tremor 2. muscular rigidity 3. slow and decreased movement 4. postural instability - onset: 50 years old. Pathology Pigmented neuron of substansia nigra and other dopaminergic cell groups are lost. Degeneration of subcortical nucleus also seen. About 10% of cells die each year. We can see cells with big hook, which are the degenerated neurons.

Clinical picture Slow movement (bradykinesia, hypokinesia, akinesia (difficult to initiate movement)). Resting tremor maximum at rest. Low amplitude but high frequency. Rigidity of joint (Cogweel phenomenon can be seen) Postural instability Micrographia Achyrokinesis absent of synkinesia (walk with still hand) Shuffling gait with small steps.

2 stages of the disease : preclinical and clinical. In clinical stage 80% of substansia nigra already lost. Diagnosis Clinically based on signs and symptoms.

Treatment Carbidopa or Levodopa: these drugs provide dopamine to the body. Body tolerance to levodopa occurs. Therefore need to increase the dose with time. However, prolong use of levodopa is associated with problems like dyskinesia and chorea. Amantadine MAO-B inhibitors Anticholinergic drugs Dopamine agonists Surgery deep brain stimulation. Surgeon put electrode into substansia nigra to stimulate it. Exercise and adaptive measures.

13 . FRIEDRICH ATAXIA : PATHOGENESIS, CLINICAL SIGNS, TREATMENT, PREVENTIVE MAINTENANCE

-

Is an autosomal recesive disorder Mutation of chromosome 9 Most common of hereditary ataxias (50%)

Pathophysiology:
-

dying back phenomena: demyelinating and depleting of nerves, start from periphery and end in ultimate loss of neurons and secondary fibrous gliosis

Onset:
-

Is early : from age 15-18 years, almost always before 20. 95% are wheelchair bound by 45

Causes:
-

Classic FA is the result of gene mutation at the centromeric region of chromosome 9(9q13-21.1), at the site of the gene encoding for 210- amino acid protein frataxin This mutation is characterizes by an excessive number of repeats of the GAA (guanine adenine adenine) trinucleotide DNA sequence in the first intron of the gene coding for frataxin deficiency of frataxin

Clinical features:
-

At onset presenting with gait ataxia: o Typically both extremities affected equally o Is both sensory and cerebellar type tabetocerebellar gait Cerebellar gait constant shifting position to maintain balance Sensory gait due to loss of joint position. patient, wide base stance, uneven and irregular striking of floor by bottom of foot o As diseases progresses, ataxia develop in trunks, legs and arms tremor o The cardinal features are: Progressive limb and gait ataxia develops before the age of 40 years Lower extremity tendon reflexes are absent Evidence of axonal sensory neuropathy is noted Dysarthria, areflexia, motor weakness of the lower extremities, extensor plantar responses, and distal loss of joint position and vibration senses are not found in all patients within the st 1 5 years, but are eventually universal Foot deformity, scoliosis, DM Cardiac involvement: ventricular hypertrophy, systolic ejection murmurs, and third or fourth heart sounds

Diagnosis: Family history:

-

In families with one affected child, the subsequent risk of another affected child is >5%. As in most autosomal recessive disorders, the risk of developing FA is highest following birth from a consanguineous union ( maybe cousion kot) The overall risk of a patient with FA having a child with the condition is approximately 1 in 200, unless consanguinity is involved. If that same patient has a partner who is found to be a carrier of FA, then the risk becomes 1 in2.

other studies:
-

MRI : atrophy of spinal cord with minimal cerebellar atrophy CSF: no abnormalities Echocardiography : ventricular hypertrophy

Treatment:
-

5- hydroxytryptophan (serotonin precursor) : suppress posthypoxic myoclonus Coenzyme Q : antioxidant Others: symptomatic for heart failure, arrhythmias, DM Surgical : for foot deformities and scoliosis.

14. AMYOTROPIC LATERAL SCLEROSIS. ETIOLOGY, PATHOGENESIS, CLINICAL SIGNS, TREATMENT. a.k.a : Lou Gehrigs disease (patients name), Charcots diseas, Motor neuron disease
-

is a form of motor neurone disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input. Is a combination of : - muscle atrophy ( due to loss of spinal anterior horn ganglion cells) Spastitcity with pyramidal tract sign (due to involvement of lateral columns of spinal cord)

Epidemiology:
-

Usually begin at the ages 40-65 Men are 3 times more effected Rarely strikes children and adolescent 2-4 cases / 100 000 per year

Etiology and pathogenesis: 1)sporadic 2) familial of genetic cause : - 20 % of these are due to mutation of 50D1 gene, which encodes enzyme superoxide dismutase. - Some family have autosomal inheritance - some family are afflicted with familial, juvenile, relatively benign form of ALS 3) Exposure to heavy metal - this theory is doubtful because symptoms disappear after not exposed 4) virus or prion - enterovirus : polio - retrovirus : HIV, HTLU-1 - lyme disease - creutzfeldt- Jakob disease 5) alternative theories -autoimmunity - paraneoplastic motor neuron - blood disease 6)Lactate dyscrasia hypothesis Researchers specializing in the neurobiology of aging have proposed a novel molecular model for the pathogenesis of ALS called the lactate dyscrasia hypothesis that involves an adenosine triphosphate (ATP)dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell

Symptoms: 1234Signs: 1- Paresis: proximal or distal, involve multiple muscle group 2- Fasciculation- difficult to detect (can be provoked by tapping muscles or I.V administration of cholinesterase inhibitor 3- Spasticity- not very evident 4- Hypereflexia 5- Pyramidal tract sign 6- Bulbar sign: - slurred speech, dysphagia, flaccid facial paresis - tongue atrophic and show fasciculation 7- Enhanced intrinsic muscle reflexes of face: jaw reflex, nasopalpebral reflxex 8- Involuntary laughing and crying Additional test: 1- Electromyography fasciculations and fibrillation potentials 2- Muscle biopsy muscle atrophy 3- MRI global atrophy of spinal cord and changes of corticospiral pathway Prognosis:
-

Weakness: distal mostly, but can be proximal, unilateral, then progress in intrinsic hand muscle Muscle atrophy Painful muscle cramps Fasciculation

Death within 5 years 50% of patients Death within 1 year 60% with bulbar palsy 6% survive after 10 years, sometimes remission are seen

Treatment:
-

No effective treatment Can only : - relieve symptoms and complications - maintain muscle function and movement - delay paralysis and disability Gene therapy Medical care : palliative Surgical care: tracheostomy Diet : evaluate dysphagia Prevent aspiration

15. HUNTINGTON CHOREA: ETIOLOGY, PATHOGENESIS, CLINICAL SIGNS, TREATMENT o Huntington's disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea. is an autosomal dominant inheritance

Causes, incidence, and risk factors: o o o o Huntington's disease is caused by a genetic defect on chromosome 4. The defect causes a part of DNA, called a CAG repeat(triplet of the Huntingtin), to occur many more times than it is supposed to. Normally, this section of DNA is repeated 10 to 28 times. But in persons with Huntington's disease, it is repeated 36 to 120 times. Expansion of a CAG triplet repeat stretch within the Huntingtin gene results in a different (mutant) form of the protein, which gradually damages cells in the brain, through mechanisms that are not fully understood As the gene is passed down through families, the number of repeats tend to get larger. The larger the number of repeats, the greater your chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages. There are two forms of Huntington's disease. o The most common is adult-onset Huntington's disease. Persons with this form usually develop symptoms in their mid 30s and 40s. An early-onset form of Huntington's disease accounts for a small number of cases and begins in childhood or adolescence.

If one of your parents has Huntington's disease, you have a 50% chance of getting the gene for the disease. If you get the gene from your parents, you will develop the disease at some point in your life, and can pass it onto your children. If you do not get the gene from your parents, you cannot pass the gene onto your children.

Path. Anat: o o o HD affects the whole brain, but certain areas are more vulnerable than others. The most prominent early effects are in a part of the basal ganglia called the neostriatum, which is composed of the caudate nucleus and putamen. Other areas affected include the substantia nigra, layers 3, 5 and 6 of the cerebral cortex, the hippocampus, purkinje cells in the cerebellum, lateral tuberal nuclei of the hypothalamus and parts of the thalamus.

Symptoms Behavior changes may occur before movement problems, and can include: Behavioral disturbances Hallucinations Irritability Moodiness Restlessness or fidgeting Paranoia Psychosis

Abnormal and unusual movements include: Facial movements, including grimaces Head turning to shift eye position Quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts Slow, uncontrolled movements Unsteady gait

Dementia that slowly gets worse, including: Disorientation or confusion Loss of judgment Loss of memory Personality changes Speech changes

Additional symptoms that may be associated with this disease: Anxiety, stress, and tension Difficulty swallowing Speech impairment Symptoms in children: Rigidity Slow movements Tremor

Signs and tests The doctor will perform a physical exam and may ask questions about the patient's family history and symptoms. A neurological exam will also be done. The doctor may see signs of: Dementia Abnormal movements Abnormal reflexes "Prancing" and wide walk Hesitant speech or poor enunciation

A head CT scan may show loss of brain tissue, especially deep in the brain.

Other tests that may show signs of Huntington's disease include: Head MRI scan PET (isotope) scan of the brain

Genetic tests are available to determine whether a person carries the gene for Huntington's disease.

Treatment There is no cure for Huntington's disease, and there is no known way to stop the disease from getting worse. The goal of treatment is to slow down the symptoms and help the person function for as long and as comfortably as possible. Medications vary depending on the symptoms. Dopamine blockers may help reduce abnormal behaviors and movements. Drugs such as amantadine and tetrabenazine are used to try to control extra movements. There has been some evidence to suggest that co-enzyme Q10 may also help slow down the course of the disease, but it is not conclusive.

Depression and suicide are common among persons with Huntington's disease. It is important for all those who care for a person with Huntington's disease to monitor for symptoms and treat accordingly. As the disease progresses, the person will need assistance and supervision, and may eventually need 24-hour care. Complications Loss of ability to care for self Loss of ability to interact Injury to self or others Increased risk of infection Depression Death

16 . HEPATOCEREBRAL DYSTROPHIA: ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES, TREATMENT, PREVENTIVE MAINTAINANCE o o o a.k.a: hepatolentiluar degeneration / Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease. It is treated with medication that reduces copper absorption or removes the excess copper from the body, but occasionally a liver transplant is required

Etiology and pathophysiology o o due to mutations in the Wilson disease protein (ATP7B) gene, on chromosome 13. A single abnormal copy of the gene is present in 1 in 100 people, who do not develop any symptoms (they are carriers) When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage through a process known as Fenton chemistry; this damage eventually leads to chronic active hepatitis, fibrosis(deposition of connective tissue) and cirrhosis. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body but particularly in the kidneys, eyes and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus (together called the lenticular nucleus); these areas normally participate in the coordination of movement as well as playing a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilson's disease.

o o o

Sign and symptoms: Its clinically presented in 2 major groups of symptoms: 1) Liver disease: o May present as tiredness, increased bleeding tendency or confusion (due to hepatic encephalopathy) and portal hypertension - leads to esophageal varices, enlargement of the spleen and accumulation of fluid in the abdominal cavity (ascites). On examination, signs of chronic liver disease such as spider naevi (small distended blood vessels, usually on the chest) may be observed. Chronic active hepatitis has caused cirrhosis of the liver in most by the time they develop symptoms.

About 5% of all people are diagnosed only when they develop fulminant acute liver failure, often in the context of a hemolytic anemia leads to abnormalities in protein production and metabolism by the liver accumulation of waste products such as ammonia in the bloodstream go to brain hepatic encephalopathy (confusion, coma, seizures and finally life-threatening swelling of the brain)

Neuropsychiatric symptoms initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Later on, parkinsonism o o o o o o o Seizures migraine Cognition can also be affected : o o frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) subcortical dementia (may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia). cogwheel rigidity, bradykinesia or slowed movements lack of balance can be with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body).

Psychiatric problems due to Wilson's disease may include: o o o o behavioral changes, depression, anxiety psychosis.

3) Other organs involvement: Eyes: KayserFleischer rings (KF rings) may be visible in the cornea of the eyes, due to copper deposition in Descemet's membrane. Kidneys: renal tubular acidosis, a weakening of bones (due to calcium and phosphate loss), and [1] occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis). Heart: cardiomyopathy (rarely seen) Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), infertility, and habitual abortion

Diagnosis: 1) Liver function test shows: High AST and ALT High bilirubin High PT and PTT low albumin

2) Lab tests may include: Complete blood count (CBC) Serum ceruloplasmin low (< 0.2g/L) Serum copper low (ingat ye, walaupun ini pnyakit related to increase in copper production, but still sikit in blood but increase in urine, bcause the copper not bound to ceruloplasmin, thus go and deposit in other organs) Serum uric acid Urine copper : elevated

3) A slit-lamp eye examination may show: Limited eye movement Rusty or brown-colored ring around the iris (Kayser-Fleischer rings)

4) A physical examination may show signs of: Damage to the central nervous system, including loss of coordination, loss of muscle control, muscle tremors, loss of thinking and IQ, loss of memory, and confusion (delirium or dementia) Liver or spleen disorders (including cirrhosis, splenomegaly, and liver necrosis)

5) Other tests may include: 24-hour urine copper test Abdominal x-ray Abdominal MRI CT scan of the abdomen Head CT scan Head MRI Liver biopsy - for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation Genetic testing

Treatment The goal of treatment is to reduce the amount of copper in the tissues. This is done by a procedure called chelation -- certain medications can bind to copper and help remove it through the kidneys or gut. Treatment must be lifelong. The following medications may be used: Penicillamine (Cuprimine, Depen) binds to copper and leads to increased release of copper in the urine. Trientine (Syprine) binds (chelates) the copper and increases its release through the urine. Zinc acetate (Galzin) blocks copper from being absorbed in the intestinal tract. Vitamin E supplements may also be used. Sometimes, medications that chelate copper (especially penicillamine) can affect the function of the brain and nervous system (neurological function). Other medications under investigation may bind copper without affecting neurological function.

A low-copper diet may also be recommended. Foods to avoid include: Chocolate Dried fruit Liver Mushrooms Nuts Shellfish

You may want to drink distilled water because most tap water flows through copper pipes. Avoid using copper cooking utensils. Symptoms may be treated with exercise or physical therapy. People who are confused or unable to care for themselves may need special protective measures. A liver transplant may be considered in cases where the liver is severely damaged by the disease

17. WERDNIG HOFFMANN SPINAL MUSCULAR ATROPHY : ETIOLOGY, CLINICAL SIGNS, TREATMENT, PREVENTIVE MAINTENANCE what? is an autosomal recessive hereditary disease characterized by progressive hypotonia and muscular weakness. Etiology: The characteristic muscle weakness occurs because of a progressive degeneration of the alpha motor neuron from anterior horn cells in the spinal cord. The weakness is more severe in the proximal musculature than in the distal segments. In certain patients, the motor neurons of cranial nerves (especially the CNV-CNXII) can also be involved. Sensation, which originates from the posterior horn cells of the spinal cord, is spared, as is intelligence. Several muscles are spared, including the diaphragm, the involuntary muscles of the gastrointestinal system, the heart, and the sphincters
st

Actually, there are several type of spinal muscular atrophy, but the question just asks about the 1 type, so yg lain2 types tuh x perlu bace pun xper..

Type

Eponym

Usual age of onset

Characteristics

I: Infantile

Werdnig Hoffmann disease

06 months

The severe form manifests in the first months of life, usually with a quick and unexpected onset ("floppy baby syndrome"). Rapid motor neuron death causes inefficiency of the major bodily organs - especially of the respiratory system - and pneumonia-induced respiratory failure is the most frequent cause of death. Babies diagnosed with SMA type I do not generally live past two years of age, with death occurring as early as within weeks in the most severe cases (sometimes termed SMA type 0).

The intermediate form affects children who are never able to stand and walk but who are able to maintain a sitting position at least some time in their life. The progress is known to vary greatly, some patients gradually grow weaker over time while others through careful maintenance avoid any progression. Body muscles are weakened, and the respiratory system is a major concern. Life expectancy is somewhat reduced but most SMA II patients live well into adulthood.

II: Intermediate

Dubowitz disease

618 months

The juvenile form usually manifests after 18 months of age Kugelberg Welander disease Patients who are able to walk without support at same time, although many later lose this ability. Respiratory involvement is less noticeable, and life expectancy is normal or near normal.

III: Juvenile

>18 months

IV: Adult-onset

Adulthood

The adult-onset form (sometimes classified as a late-onset SMA type III) usually manifests after the third decade of life with gradual weakening of muscles mainly affects proximal muscles of the extremities frequently rendering the patient wheelchair-bound. Other complications are rare, and life expectancy is unaffected.

Now, SYMPTOMS2 ADALAH: The symptoms vary greatly depending on the SMA type involved, the stage of the disease and individual factors and may include: Areflexia, particularly in extremities Marked hypotonia in legs, arms, rib, chest, and bulbar (facial) muscles, limpness or a tendency to flop Difficulty achieving developmental milestones, difficulty sitting/standing/walking Adopting of a frog-leg position when sitting (hips abducted and knees flexed) Respiratory distress, weak cough/cry Bell-shaped torso (caused by using only abdominal muscles for respiration) Difficulty sucking or swallowing, poor feeding Fasciculations (twitching) of the tongue Arthrogryposis (multiple congenital contractures)

Diagnosis: Patient will present hypotonia associated with absent reflexes Electromyogram will show fibrillation and muscle denervation Serum creatine kinase may be normal or increased Genetic testing will show bi-allelic deletion of exon 7 of the SMN1 gene - this is conclusive of the disease.

Treatment: There is no known cure for spinal muscular atrophy. Palliative care Care is symptomatic. Main areas of concern are as follows: Orthopaedics Weak spine muscles may lead to development of kyphosis, scoliosis and other orthopaedic problems. Spine fusion is sometimes performed in SMA I/II patients once they reach the age of 8-10 to relieve the pressure of a deformed spine on the lungs. SMA patients might also benefit greatly from various forms of physiotherapy and occupational therapy . Respiratory care Respiratory system requires utmost attention in SMA as once weakened it never fully recovers. Weakened pulmonary muscles in SMA type I/II patients can make breathing more difficult and pose a risk of hypoxiation, especially in sleep when muscles are more relaxed. Impairedcough reflex poses a constant risk of respiratory infection and pneumonia. Non-invasive ventilation (BiPAP) is frequently used and tracheostomy may be sometimes performed in more severe cases; both methods of ventilation prolong survival in a comparable degree, although tracheostomy prevents speech development. Nutritional care Difficulties in jaw opening, chewing and swallowing food might pose SMA patients at risk of malnutrition. A feeding tube can be necessary in SMA type I and more severe type II patients. Additionally, metabolic abnormalities resulting from SMA impair -oxidation of fatty acids in muscles and can lead to organic acidemia and consequent muscle damage, especially when fasting. It is suggested that SMA patients, especially those with more severe forms of disease, reduce intake of fat and avoid prolonged fasting (i.e., eat more frequently than healthy people). Mobility Assistive technologies may help in managing movement and daily activity and greatly increase the quality of life. Cardiology Although heart is not a matter of routine concern, a link between SMA and certain heart conditions has been suggested. Mental health SMA children do not differ from the general population in their behaviour; their cognitive development can be slightly faster, and certain aspects of their intelligence are above the average. Despite their disability, SMA-affected people report high degree of satisfaction from life.

Emerging therapies: Include:

-

Gene therapies Stem cell therapy SMN2 activation SMN stabilization SMN alternative splicing modulation

18. LANDUSY- DEJERIN PROGRESSING MUSCULAR DYSTROPHY : AN ETIOLOGY, CLINICAL SIGNS, TREATMENT, PREVENTIVE MAINTENANCE o o o a.k.a Facioscapulohumeral muscular dystrophy is a usually autosomal dominant inherited form of muscular dystrophy (MD) that initially affects upper body the skeletal muscles of the face (facio), scapula(scapulo) and upper arms (humeral). It is not the same as Duchenne muscular dystrophy and Becker muscular dystrophy, which affect the lower body. Genetic: More than 95% of cases of FSHD are associated with the deletion of integral copies of a tandemly repeated 3.2kb unit (D4Z4 repeat) at the subtelomeric region 4q35 on Chromosome 4 a few cases of FSHD are the result of rearrangements between subtelomeric chromosome 4q and a subtelomeric region of 10q
-

It appears in both men and women and may develop in a child if either parent carries the gene for the disorder. In 10 to 30% of cases, the parents do not carry the genes. Facioscapulohumeral muscular dystrophy affects about 5 out of 100,000 people. It affects men and women equally.

Symptoms: Men often have more symptoms than women. Facioscapulohumeral muscular dystrophy mainly affects the face, shoulder, and upper arm muscles. However, it can also affect muscles around the pelvis, hips, and lower leg. Symptoms can appear after birth, but often they do not appear until age 10 - 26. However, it is not uncommon for symptoms to appear much later in life. In some cases, symptoms never develop. Symptoms are usually mild and very slowly become worse. Muscle weakness of the face is common, and may include: Eyelid drooping Inability to whistle Decreased facial expression Depressed or angry facial expression Difficulty pronouncing words

Shoulder muscle weakness causes deformities such as pronounced shoulder blades (scapular winging) and sloping shoulders. The person has difficulty raising the arms because of shoulder and arm muscle weakness. Weakness of the lower legs is possible as the disorder gets worse. The weakness can be severe enough to interfere with walking. A small percentage of people become wheelchair-bound. Hearing loss and abnormal heart rhythms may occur, but are rare. Signs and tests A physical examination will show weakness of the face and shoulder muscles. High blood pressure may be noted but is usually mild. An eye exam may show changes in the blood vessels in the back of the eye.

Tests that may be done include: Creatine kinase test (may be slightly high) DNA testing Electrocardiogram (EKG) EMG (electromyography) Fluorescein angiography Genetic testing of chromosome 4 Hearing tests Muscle biopsy (may confirm the diagnosis)

Treatment There is no known cure for facioscapulohumeral muscular dystrophy. Treatments are given to control symptoms and improve quality of life. Activity is encouraged. Inactivity such as bedrest can make the muscle disease worse. Physical therapy may help maintain muscle strength. Other possible treatments include: Oral albuterol to increase muscle mass (but not strength) Speech therapy Surgery to fix a winged scapula Walking aids and foot support devices

Expectations (prognosis) Disability is often minor. Lifespan is usually not affected. Complications Decreased mobility Decreased ability to care for self Deformities of the face and shoulders Hearing loss Vision loss (rare)

19. MYASTHENIA. ETIOLOGY, PATHOGENESIS, CLINICAL SIGNS, PRINCIPLES OF TREATMENT o o o o Myasthenia gravis is cuased by a defect of neuromuscular transmission due to an antibody- mediated attack on nicotinic acetylcholine receptors (AchR) at neuromuscular junctions. It is characterized by fluctuating weakness that is improved by inhibitors of cholinesterase nd th Most common in 2 4 decades. It is less frequent before age of 10 or after age 65 years Can be congenital and neonatal

Etiology and pathogenesis: o o o o o o o The postsynaptic membrane is abnormal in MG There is loss of secondary folds, which reduces the surface area available for binding of Ach, and there is decrease in number of Ach receptors- this is due to the blocking of antibodies to the receptors. As a result, there is insufficient number of receptors available to bind Ach to cause depolarization Thus, repetitive stimulation will result in a decrease number of muscles fibers that are able to responds, as each neuromuscular junction reaches a state of receptor insufficiency. Clinically it is presented by a progressive weakness The antibodies actually are produced by the B cell. The autoimmune response maybe arise from the thymus (usually in a patient with thyphomas or hyperplasia of thymus)

Symptoms: Depends on 3 characteristics:

-

Demonstration of the response to cholinergic drugs Electro physiologic evidence of abnormal neuromuscular transmission Demonstration of circulating antibodies to Ach receptors Weakness: o o o o o

From minutes, a single day or longer than that Usually at the end of the day (asthenic syndrome) Prolong variation are termed remission or exacerbation If exacerbation involve the resp. muscles to the point of inadequate ventilations, it is called crisis Distribution of weakness: Ocular muscles ptosis and diplopia Facial and pharyngeal muscles- dysarthtia, dysphagia, and limitation of facial movement Limb weakness with cunjunction with cranial weakness

Signs: o o o o Test: 1) Physical examination Muscle fatigability can be tested for many muscles. A thorough investigation includes: looking upward and sidewards for 30 seconds: ptosis and diplopia Weakness of facial and palpebrae muscles may cuase expressionless facies with drooping eyelids Weakness of ocular muscles may cause papralysis, conjugate gaze, completion opthalmoplegia in one or both eyes, or a pattern resembling nuclear ophtalmoplegia Weakness of oropharyngeal and limbs muscles when present can be detected by the measurement of inspiratory or expiratory rate which maybe abnormal when the symptoms exist Muscular wasting- only in patient with malnutrition due to dysphagia

looking at the feet while lying on the back for 60 seconds keeping the arms stretched forward for 60 seconds ten deep knee bends walking 30 steps on both the toes and the heels five situps, lying down and sitting up completely "Peek sign": after complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show 2) Blood test to find antibodies against Ach receptors 3) electromyography Frequency and proportion of particular abnormal action potential patterns, "jitter" and "blocking," are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit 4) Edrophonium test This test requires the intravenousadministration of edrophonium chloride (Tensilon, Reversol) or neostigmine (Prostigmin), drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors) and temporarily increases the levels of acetylcholine at the neuromuscular junction. In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness 5) Muscle bipsy 6) Chest x ray

Treatment: 1. 2. 3. 4. 5. Anticholinesterase drugs neostagmine, pyridostigmine bromide, mytelase Muscarinic symptoms can be eliminated by atropine (0.4mg) with each dose of pyridostigmine Thymectomy (if after this patient still seriously disabled, give prednisone) Plasmapheresis Prednisolone preparation of patient for thymectomy, for ocular myasthenia patient

20. CHARCOAT- MARIE TOOTH NEURAL AMYOTROPHY : CLINICAL FEATURES, DIAGNOSTICS, TREATMENT, PREVENTIVE MAINTENCE o o o is an inherited demyelinating disease of the peripheral nervous system predominantly characterized by loss of muscle tissue and touch sensation, in the feet, ankles and legs as it progresses over time. As well as in the hands, wrists and arms in various types of the disease. Early and late onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates.

Etiology: o is caused by mutations that cause defects in neuronal proteins o most mutations in CMT affect the myelin sheath, but some affect the axon o most common cause of CMT (70-80% of the cases) is the duplication of a large region in chromosome 17p12 that includes the gene PMP22 o CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap. o . When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test o When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential (CMAP Types: Type 1- autosomal dominant Type 2- autosomal dominant Type 3- autosomal recessive Type 4- autosomal recessive Type 5- x linked

Symptoms: Nerves that stimulate movement (called the motor nerves) are most severely affected. The nerves in the legs are affected first and most severely. Symptoms usually begin between mid-childhood and early adulthood. They may include: Foot deformity (very high arch to feet) Foot drop (inability to hold foot horizontal) Loss of lower leg muscle, which leads to skinny calves Numbness in the foot or leg "Slapping" gait (feet hit the floor hard when walking) Weakness of the hips, legs, or feet

Later, similar symptoms may appear in the arms and hands, which may include a claw-like hand.

Signs and tests A physical exam may show: Difficulty lifting up the foot and making toe-out movements Lack of stretch reflexes in the legs Loss of muscle control and atrophy (shrinking of the muscles) in the foot or leg Thickened nerve bundles under the skin of the legs

A muscle biopsy or nerve biopsy may confirm the diagnosis. Nerve conduction tests are often done to tell the difference between different forms of the disorder. Management: o o o o no current standard treatment The most important activity for patients with CMT is to maintain what movement, muscle strength and flexibility they have Orthopedic surgery or equipment (such as braces or orthopedic shoes) may make it easier to walk. physical and occupational therapy may help maintain muscle strength and improve independent functioning.

Expectations (prognosis) Charcot-Marie-Tooth disease slowly gets worse. Some parts of the body may become numb, and pain can range from mild to severe. Eventually the disease may cause disability. Complications Progressive inability to walk Progressive weakness Injury to areas of the body that have decreased sensation

21. DUSHENNE MUSCULAR DYSTROPHY: AN ETIOLOGY, CLINICAL SIGNS, TREATMENT, PREVENTIVE MAINTENANCE. A recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty walking, breathing, and death. Epidemiology: females (rare, often as carriers) and males. Etiology: mutation in the dystrophin gene, located in humans on the X chromosome (Xp21). The dystrophin gene codes for the protein dystrophin, an important structural component within muscle tissue. Dystrophin provides structural stability to the dystroglycan complex (DGC), located on the cell membrane. Clinical signs: - Muscle wasting (legs and pelvis muscles of the shoulders and neck loss of arm muscles and respiratory muscles. - Calf muscle enlargement (pseudohypertrophy) - Cardiomyopathy (DCM) - Development of congestive heart failure or arrhythmias - A positive Gowers' sign: more severe impairment of the lower extremities muscles. The child helps himself to get up with upper extremities: first by rising to stand on his arms and knees, and then "walking" his hands up his legs to stand upright. - Affected children usually tire more easily and have less overall strength. - Creatine kinase (CPK-MM) levels in the bloodstream are extremely high. - An electromyography (EMG): weakness is caused by destruction of muscle tissue rather than by damage to nerves. - Genetic testing can reveal genetic errors in the Xp21 gene. - A muscle biopsy (immunohistochemistry or immunoblotting) or genetic test (blood test) confirms the absence of dystrophin, although improvements in genetic testing often make this unnecessary.
Diagnosis:

1) Muscle biopsy - A small sample of muscle tissue is extracted (usually with a scalpel instead of a needle) dye is applied that reveals the presence of dystrophin Complete absence of the protein - Not required as often to confirm the presence of Duchenne's. 2) Prenatal tests Chorion villus sampling (CVS) can be done at 1114 weeks, and has a 1% risk of miscarriage. Amniocentesis can be done after 15 weeks, and has a 0.5% risk of miscarriage. Fetal blood sampling can be done at about 18 weeks. Another option in the case of unclear genetic test results is fetal muscle biopsy.

Treatment: 1. Corticosteroids such as prednisolone and deflazacort increase energy and strength and defer severity of some symptoms. 2. beta2-agonists: increase muscle strength but do not modify disease progression. 3. Mild physical activity (swimming, exercise) 4. Physical therapy: maintain muscle strength, flexibility, and function. 5. Orthopedic appliances (such as braces and wheelchairs) 6. Respiratory support 7. Psychological counseling of parents

22. SYRINGOMYELIA AND SYRINGOBULBIA: GENETIC ASPECTS, CLINICAL SIGNS, TREATMENT, PREVENTIVE MAINTENANCE. - Disorder in which a cyst or cavity forms within the spinal cord. - cyst called a syrinx can expand and elongate over time, destroying the spinal cord pain, paralysis, weakness and stiffness in the back, shoulders, and extremities. - cause a loss of the ability to feel extremes of hot or cold, especially in the hands cape-like loss of pain and temperature sensation along the back and arms. These symptoms typically vary depending on the extent and, often more critically, to the location of the syrinx within the spinal cord. - symptoms begin in young adulthood. Signs develop slowly, although sudden onset may occur with coughing, straining, or myelopathy. - Syringobulbia: medical condition when syrinxes or fluid filled cavities affect the brainstem due to congenital abnormality, trauma or tumor growth. - occur as a slit-like gap & affect cranial nerves facial palsies. - Sensory and motor nerve pathways may be affected by interruption and/or compression of nerves.

Two forms of syringomyelia:

1. Congenital - abnormality of the brain called an Arnold-Chiari malformation (most common cause) where the anatomic abnormality causes the lower part of the cerebellum to protrude from its normal location in the back of the head into the cervical or neck portion of the spinal canal. -A syrinx may then develop in the cervical region of the spinal cord. - communicating syringomyelia: connection between the brain and spinal cord in this type of syringomyelia - begin from 25 and 40, worsen with straining or any activity that fluctuate CSF pressure. - also have hydrocephalus (cerebrospinal fluid accumulates in the skull) or arachnoiditis.

2. Acquired - as a complication of trauma, meningitis, hemorrhage, a tumor, or arachnoiditis. - the syrinx or cyst develops in a segment of the spinal cord damaged by one of these conditions. The syrinx then starts to expand. This is sometimes referred to as noncommunicating syringomyelia. - Symptoms may appear months or even years after the initial injury, starting with pain, weakness, and sensory impairment originating at the site of trauma.

Clinical manifestations: Sensory: Sensory disturbances below the level of lesion Motor: Spastic paraparesis with pyramidal tract signs Autonomic: Impaired bowel & bladder functions, sexual dysfunction may develop in longstanding cases Neuropathic arthropathy (Charcot joint)- in the shoulders due to loss of sensory fibres to the joint

Symptoms: Severe chronic pain Loss of sensation in the hands Paralysis or paresis temporarily or permanently Disruptions in the parasympathetic and sympathetic nervous systems: abnormal body temperature or sweating, bowel control issues Syringobulbia: vocal cord paralysis, ipsilateral tongue wasting, trigeminal nerve sensory loss

Diagnosis: MRI CT EMG Lumbar puncture Myelogram

Treatment: Avoid strained physical activities (senile) Analgesics , eg: Tramadol Radiation, eg: tumor Surgery 1. Arnold-Chiari malformation -provide more space for the cerebellum at the base of the skull and upper cervical spine without entering the brain or spinal cord disappearance of the primary syrinx over time as the normal flow of cerebrospinal fluid is restored. - removal of the tumor can eliminates the syrinx.)

Shunt (ventriculoperitoneal shunt ) - in both the communicating and noncommunicating forms - locate the syrinx shunt is placed into it with the other end draining cerebrospinal fluid (CSF) into a cavity usually the abdomen (ventriculoperitoneal shunt) and useful in hydrocephalus. - can arrest the progression of symptoms and relieve pain, headache, and tightness.

23. CLINIC-GENEALOGICAL METHOD, ITS DIAGNOSTIC CAPABILITIES. Genealogy (literally) - pedigree. Genealogical method - a method of family trees studying, eg: tracking of the disease (or trait) in the family or genus and indicating the type of relationships between members of the pedigree. Was first proposed in 1865 F.Galtonom. In medical genetics, this method is called clinical-genealogical, since this is the observation of pathological symptoms through clinical examination techniques.

Objectives: 1. 2. 3. 4. 5. 6. 7. to determine the hereditary nature of the trait to determine the type of inheritance and penetrance of the gene to analyze the linkage mapping of genes and chromosomes to study the linked inheritance to study the intensity of the mutation process to extract the mechanisms of interaction between genes for medical and genetic counseling.

Clinical and genealogical method: For the diagnosis of hereditary diseases and genetic counseling, Allows us to study the heterogeneity of hereditary diseases. S.N. Davidenkov: applied clinical-genealogical method in the study of genetic heterogeneity and clinical polymorphism of neurological diseases. Later these studies were conducted using analysis of family data (N.Bochkov, 1978). Allows for the genetic prophylaxis (prevention of birth of a sick child), and early prevention of clinical manifestations of hereditary diseases.

Ancient usages of genealogical method: 1. Talmud (Jewishs book): described an understanding coupled with X-linked inheritance of hemophilia. 2. XVIII century: P. Maupertuis described the inheritance of a dominant trait polydactyly and correctly analyzed the splitting of the trait in the progeny. 3. XIX century: J. Adams- described dominant and recessive types of inheritance based on empirical analysis of pedigrees. 4. Several doctors described the inheritance of hemophilia and color blindness

24. MYASTHENIA AND CHOLINERGIC CRISISES: CLINICAL SYMPTOMS, FIRST AID. Cholinergic crisis - over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh) because of the inactivity (inhibition) of the AChE enzyme, which normally breaks down acetylcholine. - maybe a consequence of some types of nerve gas, (e.g. sarin gas). - seen in patients with myasthenia gravis who take too high a dose of their anticholinesterase treatment medications - seen in some surgical cases when too high a dose of a cholinesterase inhibitor is given to reverse surgical muscle paralysis. - so, the muscles stop responding to the bombardment of Ach flaccid paralysis, respiratory failure, and other signs and symptoms resembling of organophosphate poisoning - symptoms: increased sweating, salivation, bronchial secretions along with miosis. - may be masked by the concomitant use of atropine along with anticholinesterase inhibitors in order to prevent side effects. - Flaccid paralysis resulting from cholinergic crisis can be distinguished from myasthenia gravis by the use of the drug edrophonium (Tensilon) - Tensilon worsens the paralysis caused by cholinergic crisis, but strengthens the muscle in the case of myasthenia gravis (Edrophonium is an anticholinesterase hence increases the concentration of acetylcholine present). - Cholinergic crisis can be treated with antimuscarinic drugs like atropine. Myasthenic crisis - Life-threatening condition characterized by worsening of muscle weakness, resulting in respiratory failure that requires intubation and mechanical ventilation. - also called myasthenic gravis crisis. - Weakened breathing muscles severe breathing problems lung failure. - Normally, impulses (signals) from your brain travel down through nerves. Nerve endings release a neurotransmitter called acetylcholine that enables the nerves to move the muscles when needed. - MC is the worst form of MG which is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigability caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction and inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors throughout neuromuscular junctions. - When the receptors are blocked, acetylcholine cannot enter the muscle cells.

MYASTHENIC CRISIS Muscle weakness Ptosis Facial diplegia, muscular flaccid No abdominal pain Normal pupils Dysphagia, inability to cough, aspiration Dysarthria Diplopia No urinary problem No GI upset/ hypermotility Diaphoresis (increased sweating) Increased pulse and BP Improve with ChE inhibitors (tensilon test)

CHOLINERGIC CRISIS Muscle weakness Fasciculations Muscular cramping Abdominal pain, abdominal cramps Miosis Bronchial hypersecretion, bronchospasm Salivation Lacrimation, blurred vision Urinary incontinence Diarrhea, emesis (nausea, vomiting) Diaphoresis (increased sweating) Bradycardia, hypotension Worsen with ChE inhibitors (tensilon test)

First aid Airway maneuvers - open the airway by suctioning secretions after positioning the jaws and tongue. - administer high flow oxygen and measure oxygen saturation by pulse oximetry. - if respiration remains inadequate, ventilate by bag-valve mask while preparing to intubate. - in the patient without intact gag reflex, an oral airway maybe placed. Endotracheal intubation - rapid sequence intubation should be modified because depolarizing paralytic agents (eg: succinylcholine) has less predictable results in patients with myasthenia. The relative lack of Ach receptors makes the patients relatively resistant to succinylcholine. - So, higher dose must be used to induce paralysis. Once paralysis is achieved, it may be prolonged. - a rapid onset nondepolarizing agents (eg: rocuronium, vecuronium) is the preferred paralytic agent in this circumstance. Although nondepolarizing agents delay the onset of paralysis, compared to succinysholine, these medications do not results in unwanted prolonged paralysis. - Following paralysis, intubation is accomplished as usual. ABG sampling guides ventilator settings. Once airway is secured, investigation into the cause of myasthenia may be proceeded. In less severely ill patients, oral pyridostigmine can be administered until clinical improvement is seen. The patient should be closely observed and monitored. Reports indicate the thymectomy complete remission of diseases in up to 35% patients.

25. MODES OF INHERITANCE OF SINGLE GENE DISEASES. DANGER OF RELATED DISCARDS IN AUTOSOMAL-RECESSIVE DISEASES. Genetic conditions caused by a mutation in a single gene follow predictable patterns of inheritance within families. Single gene inheritance is also referred to as Mendelian inheritance as they follow transmission patterns he observed in his research on peas.

There are four types of Mendelian inheritance patterns: Autosomal: the gene responsible for the phenotype is located on one of the 22 pairs of autosomes (nonsex determining chromosomes). X-linked: the gene that encodes for the trait is located on the X chromosome. Dominant: conditions that are manifest in heterozygotes (individuals with just one copy of the mutant allele). Recessive: conditions are only manifest in individuals who have two copies of the mutant allele (are homozygous).

Autosomal Dominant Dominant conditions are expressed in individuals who have just one copy of the mutant allele. The pedigree on the right illustrates the transmission of an autosomal dominant trait. Affected males and females have an equal probability of passing on the trait to offspring. Affected individual's have one normal copy of the gene and one mutant copy of the gene, thus each offspring has a 50% chance on inheriting the mutant allele. As shown in this pedigree, approximately half of the children of affected parents inherit the condition and half do not.

Autosomal Dominant Conditions: Huntington Disease acondroplasia (short-limbed dwarfism) polycystic kidney disease

Autosomal Recessive Recessive conditions are clinically manifest only when an individual has two copies of the mutant allele. When just one copy of the mutant allele is present, an individual is a carrier of the mutation, but does not develop the condition. Females and males are affected equally by traits transmitted by autosomal recessive inheritance. When two carriers mate, each child has a 25% chance of being homozygous wild-type (unaffected); a 25% chance of being homozygous mutant (affected); or a 50% chance of being heterozygous (unaffected carrier).

Affected individuals are indicated by solid black symbols and unaffected carriers are indicated by the half black symbols. Autosomal recessive diseases: Cystic fibrosis Tay-Sachs hemochromatosis phenylketonuria (PKU) X-linked Recessive X-linked recessive traits are not clinically manifest when there is a normal copy of the gene. All Xlinked recessive traits are fully evident in males because they only have one copy of the X chromosome, thus do not have a normal copy of the gene to compensate for the mutant copy. For that same reason, women are rarely affected by X-linked recessive diseases, however they are affected when they have two copies of the mutant allele. Because the gene is on the X chromosome there is no father to son transmission, but there is father to daughter and mother to daughter and son transmission. If a man is affected with an X-linked recessive condition, all his daughter will inherit one copy of the mutant allele from him.

X-linked Recessive Disorders: Duchenne muscular dystrophy hemophilia A X-linked severe combined immune disorder (SCID) some forms of congenital deafness

X-linked Dominant Because the gene is located on the X chromosome, there is no transmission from father to son, but there can be transmission from father to daughter (all daughters of an affected male will be affected since the father has only one X chromosome to transmit). Children of an affected woman have a 50% chance of inheriting the X chromosome with the mutant allele. X-linked dominant disorders are clinically manifest when only one copy of the mutant allele is present.

X-linked Dominant Disorders some forms of retinitis pigmentosa Chondrodysplasia Punctata hypophosphatemic rickets

26. CYTOGENETIC METHOD. VALUE DEFINITION OF A KARYOTYPE IN DIAGNOSTIC OF CHROMOSOME DISEASE. THE INDICATIONS FOR ITS REALIZATION. Major advanced facilitated rapid growth of cytogenetic field development technique for examining chromosome in peripheral blood lymphocytes. Standard use for study of human chromosome is by adding small amount of anti coagulated blood into tissue culture. Heme-agglutinin is added to agglutinate RBC and thus stimulate lymphocyte to divide. The dividing lymphocyte is blocked in the mitosis phase and placed in hypertonic buffers. Later preparation of metaphase chromosome and stained it to be observed microscopically for detection of alteration of chromosome numbers and its structure. Technique for radioactive DNA allowing to examine the timing of chromosomal replication. Technique of G-banding: trypsin treatment of chromosomal preparation and as a result a pattern of light and dark bands which is unique for each human chromosome and allows to form KARYOTYPE ARRANGEMENT. Chromosome morphology is defined by position of centromere which divide chromosome onto SHORT ARM (p) and long arm (q). Meta centric: when centromere lies in the middle of chromosome Submetacentric: when centromere lies in distance from center of chromosome Acrocentric: when centromere lies near the end of chromosome SIGNIFICANCE: 1. Allow woman to avoid birth of fetus with genetic disorder (eg: Down syndrome, Turner syndrome) 2. Preparation of family to accept their special child INDICATIONS: 1. Family history of: - chromosome rearrangements - mental retardation of possible chromosome origin where it is not possible to study the affected individuals - relatives with a history of pregnancy losses, a malformed fetus or stillbirth of unknown etiology 2. Couples with: - chromosome abnormality or unusual variants detected at prenatal diagnosis - recurrent pregnancy losses (2-3), stillbirth - primary or secondary amenorrhea or premature menopause - sperm abnormalities - abnormal growth: short stature, excessive growth, micro- and macrocephaly - ambiguous genitalia - abnormal clinical phenotype or dysmorphism - congenital abnormalities - mental retardation - suspected deletion (microdeletion), duplication syndrome

27. MOLECULAR-GENETICAL AND BIOCHEMICAL METHODS OF DIAGNOSTIC OF INHERITABLE DISEASES. THE INDICATIONS FOR THEIR REALIZATION. Guthrie test (Guthrie bacterial inhibition assay) - medical test to detect phenylketonuria - semiquantitative assay is designed to detect blood level of the amino acid phenylalanine. Amniocentesis - removal of a small amount of amniotic fluid at 16th week of gestation (usually 20ml) - the fluid can be analyzed for specific proteins such as -fetoprotein and can be cultured for examination of infectious agents. Chorionic villus sampling - removal of a small amount of chorion frondosum at 9-12th week of gestation - method: passing a fine, flexible, polyethylene catheter through the cervix and into the uterus under US guidance and removing by suction a small amount of chorion frondosum. - disadvantages: not possible to diagnose neural tube defects with slight risk of failure and fetal loss. Percutaneus blood sampling - obtaining fetal blood at 18th week of gestation by inserting a needle into the umbilical cord under US guidance. Ultrasonography (US) - safest, non-invasive and essential in determining anatomical defects and growth of the fetus.

INDICATIONS 1. early recognition of affected in whom a medical intervention will have beneficial effects. 2. genetic screening for identification of individuals at risk of transmitting genetic diseases.

28. PRIMARY AND SECONDARY METHODS OF PROPHYLACTIC OF INHERITABLE PATHOLOGY.

Primary prevention (prevention of the birth of a sick child): Planning childbearing by choosing the optimal reproductive age, which for women is 21-35 years old (over early and late pregnancy increases the likelihood of having a child with congenital disorders and chromosomal diseases) The rejection of procreation in cases of high risk of hereditary and congenital disorders (including the marriages of blood relatives and heterozygous carriers of the abnormal gene). About 20% of all hereditary diseases in every generation are caused by new mutations. Strict control of the content of mutagens and teratogens in the environment.

Secondary prevention: Abortion in the case of a high probability of disease of the fetus or prenatally diagnosed disease. Interrupting only with the consent of the woman and in a timely manner. Termination of pregnancy is clearly not the best, unfortunately, at present it is practically the only suitable in most severe and fatal genetic defects. Tertiary prevention: The correction of pathological manifestations of genotypes achieve a full normalization or reduce the severity of the pathological process. Prevention of hereditary diseases involves a complex of therapeutic measures that can be made in uterus or after birth. Measures are closely related to the treatment of hereditary diseases, and a clear boundary between them.

29. Multifactorial diseases. Gears of their originating. General clinical signs Refer Q7! Disorder that are caused by combination of many genetics and n-genetic factors(environmental factors). 4 groups: 1. Polygenic + only genetic factor (eg. cleft lips, congenital heart dis etc) 2. Genetic + multifactorial dis ( eg. phenylketonuria[genetic]+glycosemia[multifactorial]) 3. Genetic + environmental influences (eg. hypertension, athma etc) 4. No genetic dactors, mostly environment (eg. trauma, burn, accident) CFeatures: the disease defined clinically by: Quantitative traits: eg HPT. It is diagnosed based on BP measurement Qualitative traits: eg. clift palate. It can occur/ doent occur depending on aggregates strength of predisposing factors 1. It is familial but not follow monogenic patterns of inheritance. Like Mendellian traits, autosomal dominant X-link dis 2. It frequently in 1 sex.eg. pyloric stenosis common in males, SLE in female 3. Recurrence risk is same for all relatives who share same proportion of genes. Eg each sibling, child n parents share half od his genes with proband 1st degree relatives 4. Recurrence risk in family decrease as relationship of affected individual become more remote. Eg. recurrent risk of cleft lip with or w/o cleft palate is about 4% 5. Recurrence risk of 1st relatives of an affected individual is approx. equal to square root of freq. of condition in population. Means tht recurrent risk is lower in population exhibing lower incidence in common 6. More common among children of consanguis parent bcoz parents correlated are more likely to share similar dis predisposing genes. Multifactorial dis: 1. DM 2. Cancer :gastrointestinal cancer, lung cancer, breast cancer 3. Coronary artery dis 4. Behavioral disorder/ psychiatric dis 1) DM: Type 1: insulin dependent, juvenile onset - Risk of 1st degree relative -10% - 50% of monozygot twins - Environmental factors: viral inf Type 2: adult onset, n-insulin dependent - Genetic background- monozygot twins 100% - Risk of degree relatives -5% Environmental factors that unmasked presentation of DM: obesity Prophylx maintain body weight, modification of lifestyle 2) cancer: Gene plays major role

Some genetic syndromes predisposing to malignancy & some tumors that follow a strict mendelian inheritance. Breast cancer: -risk for breast cancer in women-9%, but in !st degree relative 2-3 times population risk -if there are two 1st degree relative with bilateral premenoupausal onset, risk increases up to 50% -prophyx: breast self-exam should begin early. Every woman after 35 y.o with 1st relative with breast cancer should do mammogram GI cancer: -genetic constribution: low for esophageal cancer, slightly increase in gastroc cancer, highest in colon caner Presence of colon cancer in 1st degree relatives esp occur at early age should prompt more frequent testing for occurance of blood in stool and sigmoidscopy Lung cancer: -esp bronchial carcinoma -environmental factors smoking -genetic factor also play role -1st degree relative of lung cancer pt hav risk 2-3 higher than in general population 3) coronary heart dis -most frequent cause of morbidity & mortality -monozygous twins 65% 4) behavioral disorder/ ppsychiatric dis -eg. schizophrenia & mood d/o -prophylx: genetic counseling of 1st degree relative, early examination

30.Erbs progressing muscular dystrophy.etiology, CP,prophylactic Def : Erbs muscular dystrophy or Limb-girdle muscular dystrophy is a type of muscular dystrophy that includes Duchenne muscular dystrophy, Beckers muscular dystrophy & large no of rare d/o. Term Limb-girdle is used bcoz the muscle most severely affected are those of the hip & shoulder. Etiology It may be inherited as a dominant, recessive or X-linked genetic defect but usually inherited as an autosomal-recessive trait. The muscle cant properly form the protein needed for N muscle fx Several diff proteins can be affected & the specific protein that is absent or defective identifies the specific type of muscular dystrophy It is a progressively crippling dzs with onset in childhood or adolescence affecting both sexes. Clinical features -mucsle weakness generally symmetric, proximal & slowly progressive -myoglobinuria -pain rarely -myotonia -cardiomyopathy -elevated serum CK -rippling muscles Generally mental fx is not affected Age of onset 10 YO & 30YO Both genders affected equally When it begins in childhood, the progression is faster & more disabling When it begins in adolescence, the dzs is not severe & progresses more slowly Lab test: serum CK level, EMG atypical abN, muscle biopsy (for study) The distal muscle are sometimes affected late in EMD. Over time pt wit EMD loses muscle bulk & strength. Eventually he may need a power wheelchair or scooter, esp for long distances EMD may eventually weaken the heart & lung muscles, leading to illness or death due to 20 d/o

Treatment & Prophylatic 1. Primarily supportive t/m needed. 2. Exercise & physical therapy (eg: stretching) are advised to maintain as much muscle strength & joint flexibility as possible. 3. Assistive devices may be used to maintain mobility & quality of life. 4. Careful attention to lung & heart fx is also required. 5. IV Ig may increases strength in some forms & prevent progressive in others, possibly through the
prevention of fibrosis and inflammation without the secondary weakening caused by corticosteroids.