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NEUROPATHOLOGY

Emphasizes the unique character of the nervous system and the biological attributes that it shares with other tissues.

NS the most complex structure in the body

Interconnected with different organs & capable of rapid communications

CENTRAL NERVOUS SYSTEM


CELLS OF THE NERVOUS SYSTEM DEMYELINATING DISEASE CONGENITAL MALFORMATION TRAUMA CIRCULATORY DISORDERS CSF INFECTIOUS DISEASE SPONGIFORM ENCEPHALOPATHIES NEURONAL STORAGE DISEASE METABOLIC NEURONAL DISEASES VITAMIN DEFICIENCIES DEGENERATIVE DISEASES NEOPLASIA

CELLS OF THE Nervous System


I.
I.

NEURONS
Mature neurons do not divide The human body loses neurons aging process Neurons cannot regenerate axons Not efficiently remyelinated after injury
ANATOMY OF NEURONS

Nuclei centrally located, round, contain nucleolus Cytoplasm - abundant and the ribosome-studded endoplastic reticulum forms prominent basophilic granules Nissl bodies
Cytoplasmic pigment Substantia nigra Locus ceruleus Rich in neurofilaments

CELLS OF NERVOUS SYSTEM


ANATOMY OF NEURONS
Dendrites branching projections in the cell body
Best demonstrated by Silver impregnation

Axon may or may not have myelin sheath

REACTIONS OF NEURONS
Some are reversible Others forecast cell death

NEURONAL REACTIONS TO INJURY


1. CHROMATOLYSIS
Swell Imbibe fluid Nissl substance is displaced centrifugally and becomes marginated near the plasma membrane Nucleus assumes eccentric position Reversible except when the axonal transection closely approximated the body May signal serious metabolic disturbance poliovirus

NEURONAL REACTION TO INJURY


2. ATROPHY 3. NEURONOPHAGIA

Gross: reduction in brain Injuries that kill neurons weight or selective decrease abruptly create cellular debris in mass of specific region which elicits phagocytosis Huntington disease Process of aggregation of caudate nucleus inflammatory cells about a dead neuron coupled with Cell shrivels & become phagocytosis hyperchromatic - disappear

NEURONAL REACTION TO INJURY


4. INTRANEURONAL INCLUSIONS Nuclear & Cytoplasmic inclusions appear in neurons : viral encephalitides and degenerative diseases

CELLS OF THE NERVOUS SYTEM


II. ASTROCYTES
Star-shaped cells, also neuroectodermal in origin ANATOMY Fibrillary astrocytes white matter

Protoplasmic astrocytes the gray matter


Rounded nucleus 7-10 m in diameter Homogenous chromatin pattern

ASTROCYTIC REACTION TO INJURY


ATROGLIOSIS (GLIOSIS)

Multiply in and about localized sites of tissue injury


Proliferation of fibrillary astrocytes is induced over a period of several days Glial scar cell processes

Astrogliosis marks certain generalized disease states Capricious Gliosis


General Paresis Tertiary syphilis Pick disease

Disease that progress with little attention by astrocytes


Creutzfeldt-Jakob disease
Alzheimer disease

ASTROGLIOSIS
This section of a brain with Krabbe's disease shows severe This section of a brain with Krabbe's disease shows severe astrogliosis (black arrows) and globoid cells around blood vessels (blue arrows).

ASTROCYTIC REACTION TO INJURY


Fibrillary astrocytes
Prone to neoplastic transformation
Responsible for dominant family of gliomas

Protoplasmic astrocytomas
uncommon antecedents of cancer

ASTROCYTIC REACTION TO INJURY


Corpora amylacea
Appear within the brains of all aged persons with predilection for the subpial and subependymal regions Spherical, 5-20 nm amorphous structures with basophilic and argentophilic staining affinities, which are composed of carbohydrate and protein Light microscope: extracellular E microscope: within glial processes of astrocytes

CELLS OF NERVOUS SYSTEM


III. OLIGODENDROGLIA
Myelin-producing cells of the CNS and are related to astrocytes both are neuroectodermal in origin Have dark rounded nuclei which resembles those of lymphocytes Thin rim of cytoplasm surrounds the nuclues

CELLS OF THE NERVOUS SYSTEM


IV. EPENDYMAL CELLS
Single layer of ependymal cells cuboidal or flat- lines: the four ventricular chambers Aqueducts of sylvius Central canal of the spinal cord Filum terminale Modulate fluid transfer between the CSF and the cells of nervous system

EPENDYMAL CELLS
During gestation, some viral infections target the ependymal cells: Aquiductal stenosis Congenital hydrocephalus Ependymomas exophytic masses protruding into a ventricle (4th ) Also constitute a common intramedullary tumor of the spinal cord and filum terminale

CELLS OF NERVOUS SYSTEM


V. MICROGLIAL CELLS
Microglia often contains Phagocytic elements of the CNS lipofuscin, dense bodies, & accounting for 5% of all glial multivesicular bodies cells

Gray matter: appear as isolated cells or as neuronal or vascular satellites White matter: predominantly perivascular

MICROGLIAL CELLS
ANATOMY: By H&E: hyperchromatic, elongated nuclei surrounded by a thin rim of cytoplasm. With Silver: linear form appears with fine lateral projections

MICROGLIAL REACTION TO INJURY


PATTERNS OF REACTIONS:
Focal microglial nodules Diffuse microgliosis

MICROGLIAL NODULES formed by microglia and astrocytes and characterize viral, rickettsial and protozoal infection REACTIVE MICROGLIA exhibit a prominent elongated nuclues: rod cells
With necrosis, they become distended by lipid droplets and other cellular debris: gitter cells

CONGENITAL MALFORMATIONS
A congenital anomaly is the result of an interruption in the proper completion of a single developmental sequence

CONGENITAL MALFORMATIONS

I. NEURAL TUBE DEFECTS (DYSRAPHIC STATE)


-Refers to the defective closure of the dorsal aspect of the vertebral column

A. SPINA BIFIDA
An NTD that is most common in the lumbosacral region Spina Bifida occulta: restricted to the vertebral arches; asymptomatic; dimple or small tuft of hair Meningocoele: more extensive bony and soft tissue defect permits protrusion of the meninges as a fluid-filled sac. The lateral aspect of the sac are characteristicaly covered by skin, whereas the apex is usually ulcerated

SPINA BIFIDA

Meningomyelocoele: refers to a more extensive defect that exposes the spinal canal and causes the nerve roots, particularly those of the cauda equina to be entrapped in subcutaneous scar tissue
Characteristically, the spinal cord appears as flattened, ribbon-like structure

Rachischisis: the spinal column is converted into a gaping canal, often without a recognizable spinal cord

SPINA BIFIDA
PATHOGENESIS:
Failure of closure of the neural tube Maternal Folic acid deficiency

CLINICAL FEATURES:
Absence of symptoms occulta Lower limb paresis or paralysis Sensory loss Rectal & vesicle incontinence - meningomyelocoele

NEURAL TUBE DEFECTS


B. ANENCEPHALY
Congenital absence of all or part of the brain 0.5 2.0 / 1000 births with Female predominance Stillborn or die within 1st few days of life

ANENCEPHALY
PATHOGENESIS:

Closure of the anterior neuropore


Disturbed angiogenesis PATHOLOGY: Absence of the cranial vault & the cerebral hemispheres are represented by a discoid mass or highly vascularized poorly differentiated neural tissue - cerebrovasculosa

MALFORMATION OF SPINAL CORD


SYRINGOMYELIA:

Pathology: A Tubular cavitation (syrinx) extends for variable distances along the entire length of the spinal cord which may or may not communicate with the central canal damage to the spinal cord due to the formation of a fluid-filled area within the cord Cause: Trauma, ischemia, tumors Syringobulbia Variant where slit-like cavities are located in the medulla

ARNOLD-CHIARI MALFORMATION
The brainstem & cerebellum are compacted into a shallow, bowl-shaped posterior fossa with a low positioned tentorium Usually associated with lumbosacral meningomyelocoele PATHOGENESIS: Meningomyelocoele serves to anchor the lower end of the spinal cord and that the downward growth of the vertebral column creates traction on the medulla

ARNOLD-CHIARI MALFORMATION
PATHOLOGY:

The caudal aspect of the cerebellar vermis is herniated through an enlarged foramen magnum and protrudes as a tongue on the dorsal aspect of the cervical cord, often reaching the level of C3 to C5
The herniated tissue is bound in position by thickened meninges and shows pressure atrophy with depletion of Purkinje and granular cells

The brainstem is also displaced caudally

CONGENITAL HYDROCEPHALUS

Excessive amount of CSF in varied location and have many causes


Congenital Atresia of Aqueduct of sylvius most c0mmon cause
Midbrain multiple atretic channels Aqueduct stenosed by periaqueductal gliosis : transplacental transmission of viruses known to induce ependymitis

DISORDERS OF CEREBRAL GYRI


- Associated with mental retardation Polymicrogyria presence of small and excessive gyri Pachygyria the gyri are reduced in number and unusually broad Lissencephaly The cortical surface of the cerebral hemispheres is smooth or only lightly furrowed
Almost all patients with Lissencephaly (92%) shows deletion in the region of LIS1 gene on chromosome 17p13.3

DISORDERS OF CEREBRAL GYRI


PATHOGENESIS Gyral malformations arise from disturbances in neuronal migration, a highly patterned event of the trimester of embryonic development Primitive neurons move centrifugally from the germinal mantle to populate the cortex Number of neurons and their positions in the cortex determine factors in the redundancy of the cortical mantle which initiates the infolding that creates sulci

DISORDERS OF CEREBRAL GYRI


Heterotopia a focal disturbance in neuronal migration that leads to nodular collections of ectopic neurons white matter Associated with: mental retardation seizures Migrational disturbances is associated with: Maternal alcoholism

CONGENITAL DEFECTS ASSOCIATED WITH CHROMOSOMAL ABNORMALITIES


Derangements of larger chromosomes Incompatible with sustained intrauterine life

Affected fetuses are aborted

DOWN SYNDROME

Trisomy 21 mental retardation, distinctive facial features, and a variety of anomalies Weight of the brain is moderately reduced, and the organ is shortened in its anteroposterior dimension

Simple gyral pattern, with disproportionately slender superior temporal gyri

TRISOMY 13-15
1 per 5000 births; > female

Congenital deformities involve:


brain, facial features, and extremities The complex is dominated by holoprosencephaly, arrhinencephaly, microphthalmia, cyclopia, low-set ears, harelip, and cleft palate Extremities exhibit polydactyly and rocker bottom feet

TRISOMY 13-15
HOLOPROSENCEPHALY refers to a microcephalic brain that features an absence of the interhemispheric fissure Horse-shoe shaped cerebral hemispheres Common ventricular chamber The base of the ventricular chamber is formed by the bilobed structures of the caudate nuclei and thalami Rarely compatible with life beyond a few weeks or months

TRISOMY 13-15

ARRHINENCEPHALY The absence of the olfactory tracts and bulbs (rhinencephalon) is associated with holoprosencephaly or occurs as a solitary malformation

Agenesis of the corpus callosum is a birth defect in which this structure in the brain is either partially or completely missing. CAUSE: disruption to development of the fetal brain which may be related to chromosome errors, genetic factors, prenatal infections, or other factors related to prenatal environment.

ABSENCE OF CORPUS CALLOSUM regular feature of holoprosencephaly


Associated with seizures Its absence permits the lateral ventricles to drift outward and upward radiographically diagnostic

EPILEPSY
Paroxysmal, transient disturbances in brain function that are expressed as impairment in or loss of consciousness, abnormal motor activity or sensory or mental disturbances
Idiopathic sporadic, hereditary

PATHOLOGY: neuronal loss & reactive gliosis


Affected areas: hippocampus, cerebellum, thalamus and cerebral neocortex

Acquired Seizures: Intracranial tumor, AV mal, Brain scar from penetrating wound

EPILEPSY

A seizure occurs when the message delivery system becomes unbalanced. Under normal circumstances, the neurotransmitter GABA does its part to make sure the system stays in synch by triggering signals in the form of charged particles (A). It causes a large concentration of negatively charged chloride particles (Cl-) to enter the receiving neuron. This tells the neuron to not pass on the message. When there is not enough GABA a person can have a seizure because receiving neurons can be flooded with signals that say "pass on this message." The "go" messages are triggered by a different type of neurotransmitter that promotes message transfer (B). The charged signals they set off are positive. This time, more positively charged sodium particles (Na+) enter the neuron, which tells the receiving neuron to pass on the message.

TRAUMA
I. EPIDURAL HEMATOMA Accumulation of blood between the calvarium & the dura. A result of a blow to the side of the head that fractures the temporal bone

Must be treated promptly

EPIDURAL HEMATOMA
PATHOGENESIS: Fracture of the temporo-parietal bone causing the transection of the branches of the middle meningeal artery (occupy the space between the dura & the calvarium) Temporal bone - one of the thinnest bones of the skull

The initial 4-8 hrs : asymptomatic


The earliest volumetric adjustment displacement of CSF through the aperture in the tentorium

Symptoms: volume of the hematoma 30-50ml.

EPIDURAL HEMATOMA
PATHOLOGY

When the increased ICP exceeds the venous pressure the large venous sinuses are compressed creating cerebral ischemia & hypoxia

Clinical: confusion & disorientation


CUSHING REFLEX: Protective response that augment cerebral circulation and increased oxygenation. The heart slows down to increase ventricular filling & myocardial contraction become forceful > BP systolic is increased

EPIDURAL HEMATOMA
Continued Bleeding > Decline in the level of consciousness > hge & necrosis appear > the regional injury to the reticular formation becomes irreversible >> Death Epidural Hematomas are invariably progressive & when not recognized early & evacuated, becomes fatal in 24-48 hrs.

SUBDURAL HEMATOMA
Accumulation of blood in the subdural space as a consequence of bleeding from torn bridging veins Significant cause of death after head injuries from falls, assaults, vehicular accidents, and sporting mishaps Cerebral hemispheres are immersed in CSF Blood vessels and cranial nerves Free to float in an anteroposterior direction

SUBDURAL HEMATOMA
Venous drainage from the cerebral hemispheres flows upward through veins in the pia Parasagittal region Subarachnoid space

Arachnoid

Traverse the theoretical subdural space Dura sinus

SUBDURAL HEMATOMA
Arachnoid applied to the dura

Dural border cell (DBC)


Arachnoid barrier cell (ABC) Intercellular junctions

SUBDURAL HEMATOMA
Hematomas and hygromas separate the meninges along the path of least resistance Frontal or occipital portion/stationary head Cerebral hemispheres are displaced

Soft cerebral tissues become compact and then recoil; rippled movement in the cerebral parenchyma

SUBDURAL HEMATOMA
Dura skull

Arachnoid cerebrum
Disparate movement of membranes produces shearing effect localized to the Dura Border Cell layer Cortical veins are torn Compression of severed bridging veins initiates thrombosis

SUBDURAL HEMATOMA
Bleeding from outer membrane

Vulnerable to minor trauma


Hyperosmotic state Diaphanous arachnoid Contiguous fibroblastic proliferation Absence of blood in the CSF does not negate the presence of a subdural hematoma

SYMPTOMS: SUBDURAL HEMATOMA


Protean

Stretching of meninges headaches


Pressure on motor cortex contralateral weakness Focal irritation of cortex seizures Impair cognitive function Dementia

Enlarge mass and lethal transtentorial herniation

SUBARACHNOID HEMORRHAGE
Bleeding into the subarachnoid space of any cause

Traumatic head injuries, Cerebral contusion , Laceration


2/3 of cases reflect a pre-existing arterial aneurysm

10% AV Mal is demonstrated

CEREBRAL CONTUSION
A bruise of the cortical surface of the brain as a result of head trauma MECHANISM OF CEREBRAL CONTUSION: The cerebral hemispheres float in the CSF

Rapid deceleration or less commonly acceleration of the skull cause the cortex to impact forcefully into the anterior & middle fossae.
The position of a contusion is determined by the direction of the force & the intracranial anatomy

CEREBRAL CONTUSION

CEREBRAL CONTUSION
A cerebral contusion is basically a bruise of the brain. With trauma, the tissue can become damaged and swollen and blood vessels within the tissue can break, leading to oozing of blood into the tissue. When a traumatic brain injury occurs, the brain moves around inside the skull. Direct impact or the sloshing of the brain and hitting the inner part of the skull can cause this type of injury to the brain. The brain tissue itself is quite fragile and easily injured. With enough force applied to the head, the brain can hit the side of the skull, leading to a cerebral contusion.

CEREBRAL CONTUSION
coup is the primary impact on the head, caused by whatever hit the head during the trauma. When this force is applied, the brain slides back and forth inside the skull, frequently hitting the bone on the other side of the head. contra coup is opposite the side of the initial impact. the most common location for these contusion injuries is in the area of the temporal lobes and lower frontal lobes.

PENETRATING WOUNDS
Causes: Bullets / knives enter the cranium with variable velocities Seizures threat Collagenous tissue

Fibroblasts

SPINAL CORD INJURIES


Morbidity paraplegia or quadriplegia Penetrating wounds stab wounds, bullets Indirect injury vertebral fractures, fracturedislocations, subluxation of spine HYPEREXTENSION INJURY tears spinal ligament HYPERFLEXION INJURY impact forces on vertebral body down upon the underlying one

SPINAL CORD INJURY


We can divide SCI into two categories - complete and incomplete.

A complete injury means that there is no function below the level of the injury (no sensation and no voluntary movement) and both sides of the body are equally affected. An incomplete injury means that there is some functioning below the primary level of the injury. One limb may be able to be moved more than the other, the person may be able to feel parts of the body that cannot be moved and there may be more functioning on one side of the body than the other.

SPINAL CORD INJURIES

SPINAL CORD INJURIES


Concussion of spinal cord mildest injury
Transient and reversible disturbance of spinal cord

Contusion of spinal cord more severe trauma


Myelomalacia Hematomyelia

Lacerations and transections of the spinal cord penetrating wounds


Irreversible; complete loss of function

SPINAL CORD INJURIES


The vertebral column in an adult typically consists of 33 vertebrae arranged in five regions: Seven (7) cervical vertebra twelve (12) thoracic vertebra five (5) lumbar vertebra five (5) fused sacral vertebrae four (4) fused coccyx vertebrae
In adults the vertebral column is approximately 72-75cm in length and serves to: Protect the spinal cord and spinal nerves Support the weight of the body Provides a partly rigid and flexible axis for the body and a pivot point for the head

Play an important role in posture and motion (movement from one place to another)

CIRCULATORY DISORDERS
VASCULAR MALFORMATION

FOUR MAJOR CATEGORIES:


AV-MAL most common & w/ greatest significance Evolves during embryonic dev as a result of a focal absence of a capillary bed which direct communication between cerebral arteries an veins Located in the cerebral cortex & the contiguous underlying white matter Enlarges recruitment of the tributary vessels

VASCULAR MALFORMATION
CAVERNOUS ANGIOMA: Less common Formed by large vascular spaces compartymentalized by prominent fibrous walls Asymptomatic Intracranial bleed, Epilepsy focal neurological disturbances
dilated, thickened blood vessels lacking elastic lamina and without intervening brain parenchyma

VASCULAR MALFORMATION
TELANGIECTASIA : Focal aggregate of uniformly small vessels with intervening neural parenchyma may initiate seizures but rarely ruptures

VENOUS ANGIOMA: Focus of a few enlarged veins distributed randomly in the spinal cord or brain asymptomatic

ANEURYSMS
Weakness in arterial walls exploited by intravascular pressure

CAUSES:
Developmental Defects gives rise to Berry Aneurysm (saccular medial defect)

Atherosclerosis
Hypertension associated with lipohyalinosis of cerebral arterioles and induces Charcot-Bouchard aneurysm Bacterial infection leads to mycotic aneurysm Trauma causes Dissecting Aneurysm

http://emedtravel.files.wordpress.com/2011/11/inform ation_about-brain_aneurysm.jpg

BERRY ANEURYSM
PATHOGENESIS:

The consequence of arterial defects that originate during the embryonic development when the bifurcation of the artery creates a Y-shaped configuration
The muscle layer of the parent vessel & that of the 2 branches are separate and may fail to interdigitate adequately across the notch of the Y. PATHOLOGY: a point of muscular weakness bridged only by endothelium, the internal elastic membrane & a slender coating of adventitia Increase Pressure > internal elastic membrane degenerates & fragments > endothelium yields >Saccular aneurysm formed by adventitia

BERRY ANEURYSM
> 90% - Carotid system: At the union of

Ant. Cerebral & ant. Communicating A


Complex of the int. carotid - post comm.- Ant. Cerebral- ant. Choroidal A

Trifurcation of the middle cerebral A


CLINICAL: Rupture results in life threatening subarachnoid hge with a 35% mortality during the initial hge

BERRY ANEURYSM

BERRY ANEURYSM
CLINICAL: Rupture results in life threatening subarachnoid hge with a 35% mortality during the initial he Sudden severe headache heralds the onset of subarachnoid he & maybe followed by coma Patients who survive for 3-4 days manifest progressive decline in consciousness attributed to arterial spasm & consequent cerebral ischemia & infarction

Survivors re-bleed & prognosis is worse

ATHEROSCLEROTIC ANEURYSM
Caused by atherosclerosis localized in the major cerebral vessels (vertebral, basilar,& internal carotids)

Fibrous replacement of the media & destruction of the internal elastic membrane weakens the arterial wall & permits aneurysm dilatation
Characteristically fusiform

& as they enlarge, the vessel elongates


Rarely ruptures Major complication is Thrombosis

Pontine infarction often sequelae of aneurysm in the basilar A

MYCOTIC ANEURYSM
Infections of arterial walls result from septic emboli with origins in an infected heart valve Emboli - Carotid circulation - lodges in a branch of Middle Meningeal Artery at the origin of the short penetrating carotid vessel -- bacteria proliferate inflammation - destroys the integrity of the arterial wall - aneurysm - rupture (seen as intracerebral or subarachnoid hge) - bacteria / microorganism released - cerebral abscess or suppurative meningitis

CEREBRAL HEMORRHAGE
Spontaneous no trauma / vascular anomaly / consequence of long-standing hypertension Strokes or apoplexy include occlusive cerebrovascular lesions ( infarcts) HYPERTENSIVE INTRACEREBRAL HEMORRHAGE ORDER OF FREQUENCY:
Basal ganglia-thalamus 65% Pons 15% Cerebellum 8%

CEREBRAL HEMORRHAGE
HYPERTENSIVE INTRACEREBRAL HEMORRHAGE Charcot-Bouchard aneurysm formed by the weakening of the wall

Small fusiform aneurysms located on the trunk of a vessel rather than at the bifurcation & are disposed to rupture & he
Onset of symptoms abrupt & weakness dominates

When hge is progressive, Death occurs within period of hours or several days

CEREBRAL HEMORRHAGE
INTRAVENTRICULAR HEMORRHAGE Rupture of a vessel into a ventricle rapidly distends the entire ventricular system with blood. Death : Distension of the 4th ventricle & compression of the vital centers of the medulla

PONTINE HEMORRHAGE
Loss of consciousness reflects damage to the reticular formation overshadows all other specific cranial nerve deficits

Patients rarely survives

CEREBRAL HEMORRHAGE
CEREBELLAR HEMORRHAGE

Abrupt ataxia, accompanied by severe occipital headache and vomiting


Compression of medulla herniation of cerebellar tonsils into the foramen magnum OTHER CAUSES: Leakage from AV-Mal Erosion of vessels by a 1o or 2o neoplasm Bleeding diathesis thrombocytopenic purpura

Endothelial injury by microorganism: rickettsia


Embolic infarction

ISCHEMIA & INFARCTION

Inadequate perfusion of the brain

STROKE
cerebrovascular accident (CVA), a stroke is a potentially fatal event in which part of the brain does not get enough oxygen. It may be due to either a prolonged lack of oxygenrich blood (cerebral ischemia or cerebral infarction) or bleeding into or around the brain (cerebral hemorrhage).

CEREBRAL ISCHEMIA (INFARCTION)


The most common type of stroke occurs when a blood vessel becomes plugged, and it accounts for about 80% of all strokes. The plug can originate in an artery of the brain or it can originate somewhere else in the body, often the heart, where it breaks off and travels up the arterial tree to the brain, until it lodges in a blood vessel.

"traveling clots" - emboli Strokes caused by emboli from the heart are often seen in: people with an irregular heartbeat -atrial fibrillation after a heart attack or heart surgery Ischemic strokes are largely preventable if risk factors are recognized early and managed.

CEREBRAL HEMORRHAGE
Rupture of a blood vessel can produce a bleeding type of a stroke. This is when an aneurysm, or an out-pouching, of a blood vessel in the brain ruptures. Account for about 15-20% of all strokes, but they are the most deadly. The main thing you can do to prevent a cerebral hemorrhage is to control high blood pressure.

PART II

INFECTIOUS DISEASES
MENINGITIS
Leptomeningitis denotes an inflammatory process that is localized to the interfacing surfaces of the pia and arachnoid
CSF excellent culture medium for most microorganisms

Pachymeningitis Inflammation of the dura, a consequence of contiguous infection: Chronic sinusitis / Mastoiditis
Dura substantial barrier to infection & inflammation is usually restricted to the outer surface

meningitis

BACTERIAL MENINGITIS
1. SUPPURATIVE MENINGITIS

Purulent meningitis (suppurative meningitis) is a type of meningitis characterized by a purulent exudate within the subarachnoid space
Most definitive index of meningitis - PMNs

SUPPURATIVE MENINGITIS

SUPPURATIVE MENINGITIS
E. coli prime cause in NBs
Cross-placental transfer: requires IgM

H. influenza maximal in 3mos 3 yrs


Strep pneumoniae
Pts w/ basilar skull fracture; the 2nd most frequent cause of purulent meningitis.

Neisseria meningitides frequents the nasopharynx


Airborne transmission Initial phase bacteremia: fever, malaise, petechial rash Maybe associated with lethal adrenal hges (WaterhouseFriderichsen syndrome

ACUTE SUPPURATIVE MENINGITIS


Severe infection, almost always caused by bacterial infection

Highest peak in Children ; 2nd peak in elderly


Neonate & Children
Group B Strep, E. coli, Listeria

Older infants, Children, Young Adults


Strep. Pneumonia, N. meningitidis

Older Adults
S. pneumoniae, gm rods

Very ill, with fever, headache, prostration, neck stiffness & photophobia

SUPPURATIVE MENINGITIS
PATHOGENESIS: Hematogenous dissemination (Most Common)
From bacteremia

Near organ infected


Sinusitis, Otitis media, Mastoiditis, Brain Trauma

From Congenital Developmental Malformation


Spinal Meningocoele, Paranasal Sinuses Leak, Sinus Tract

Cerebral surgery & lumbar puncture


Iatrogenic

GROSS: Subarachnoid space contains cream colored purulent exudate Secondary thrombosis of the superficial vessels & cerebral ischemic damage, hydrocephalus (impaired CSF Flow)

Brain abscess

MICROSCOPIC

TUBERCULOUS MENINGITIS

TB MENINGITIS

POTT DISEASE TB OF SPINAL COLUMN

Inclusion bodies in viral encephalitides


Herpes simplex (Cowdry Type A)
Cytomegalovirus Rabies Negri bodies Progressive multifocal leukoencephalopathy Subacute sclerosing panencephalitis

Neuron

Neuron or astrocyte Neuron Oligodendroglia

Neuron

CRYPTOCOCCAL MENINGITIS

Cryptococcus neoformans (Fungal) Inhalation of contaminated particulates

Birds excreta inhaled- pneumonitis


bloodstream intracranial compartment Gelatinous cysts brain parenchyma

Amoebic Meningoencephalitis
Naegleria & Acanthamoeba olfactory nerves to cribriform plate intracranial compartment after swimming

SYPHILITIC MENINGITIS
Treponema pallidum - enters the bloodstream from the primary chancre

CSF PROFILE
PROFILE COMMON CAUSES

PURULENT PMNs LOW GLUCOSE INCREASED CHON LYMPHOCYTIC LOW GLUCOSE LYMPHOCYTIC NORMAL GLUCOSE MOD. INCREASED CHON

BACTERIAL

TB, FUNGAL, SPIROCHETAL, SARCOIDOSIS; CA

VIRAL (ASEPTIC)

NEOPLASIA
Nueroectoderm Gliomas

Mesenchymal Structures Meningiomas &


Schwannomas Ectopic Tissues Craniopharyngiomas, Dermoid & Epidermoid cysts, Lipomas, Dysgerminomas Retained Embryonal Structures Paraphyseal cysts Metastasis

NEOPLASIA
2 % of all aggressive tumors Frequent in childhood
Gliomas 60%
Astrocytes - Astrocytomas Oligodendroglia- oligodendrogliomas Ependyma - ependymomas

Meningiomas 20% All the others 20% Difficulty: Well-diff Normal Tissue Anaplastic tumors Not resemble nervous tissue

NEOPLASIA: REMINDERS
Benign Vs. Malignant

Requires Qualification when used in reference to gliomas


Age of the Patient & Location

Predictable geographic location


Astrocytic tumors :
Cerebral hemispheres, middle life & old age Cerebellum & pons Childhood Spinal cord in young adults

NEOPLASIA
Oligodendrogliomas
Predominantly involve the cerebrum Adults

Ependymomas
Highest incidence in the 4th ventricle Intramedullary lesion derived from the lining of the spinal canal & filum terminale Lowest incidence Lateral ventricle

Meningiomas Arise from widely distributed arachnoid villi but with preferred sites of origin

NEOPLASIA: SYMPTOMS:
Neurological deficit sensory or motor
Cognitive functions Seizures
Meningiomas Well-diff Gliomas:
Astrocytomas Oligodedrogliomas Gangliomas

Increase intracranial pressure Edema + Mass


Headache Vomiting

TRANSTENTORIAL HERNIATION
Medial aspect of the hippocampus (uncus) herniates into the aperture of the tentorium Interferes with the circultory dynamics of the midbrain & causes a decline in the level of consciousness result of the impaired function of the reticular formation Compresses the 3rd nerve against the edge of the tentorium 3rd nerve palsy FIXED DILATED PUPIL Irreversible Midbrain necrosis & hemorrhage permanent loss of consciousness then DEATH

FORAMEN MAGNUM HERNIATION


Cerebellar tonsils herniate into the Foramen magnum due to increase pressure in the posterior fossa Compresses the cardiac & respiratory centers Death

SUBFALCINE HERNIATION
The cingulate gyrus herniates beneath the falx results in infarction of areas supplied by the pericallosal vessels >> Weakness or sensory loss in the legs

TUMORS FROM ASTROCYTES


1. ASTROCYTOMA
A glioma composed of well-differentiated astrocytes
20% of primary intracranial tumors Frequent location:
Cerebral hemispheres in adults Optic nerve, walls of the 3rd ventricle, midbrain, pons & cerebellum 1st 2 decades of life Spinal cord pred in the thoracic & cervical regions young Adults

FIBRILLARY ATROCYTOMA
Cerebral hemispheres in adults Intermediate dense glial processes The pivotal event in the transformation of normal to neoplastic astrocytes is mutation of the tumor supressor gene p53 on 17p. GFAP immunostain -The protein of these filaments, glial fibrillary acidic protein

ASTROCYTOMA
The fibrillary astrocytoma is the most common histologic subtype of diffuse astrocytoma.

Gemistocytic is the other common subtype, and it has a higher and more rapid rate of progression to glioblastoma

GEMISTOCYTIC ASTROCYTOMA
Abundant eosinophilic cytoplasm the tumor cells can be stellate, spindle-shaped with fiber like processes, or plump with a large eosinophilic cytoplasmic mass (gemistocytic astrocytomas). They spread in a diffuse fashion but may also form microcysts and other tissue patterns.

PILOCYTIC ASTROCYTOMA
GROSS: Circumscribed & Cystic Hypothalamus Cerebellum

Pons

JUVENILE PILOCYTIC ASTROCYTOMA


Sparsely cellular , without anaplasia or mitoses. - biphasic pattern, consisting of cellular and Characterized by abundant fibrillary perivascular areas, alternating with hair-like glial processes & loose microcystic zones.

Occurs in children

typically contains the Rosenthal fibers and eosinophilic granular bodies.

GLIOBLASTOMA MULTIFORMEWHO GRADE IV

Varriegated appearance Necrosis & hemorrhage

GBM

anaplsia

Necrosis and pseudopalisading

GBM
Vascular endothelial proliferation Densely cellular arrays of tumor cells are often arranged in a perpendicular (pseudopalisading) fashion around serpiginous necrotic areas. It has been proposed that these tumor cells are migrating away from a central hypoxic area. GBM is one of the most highly vascular solid tumors.

WHO GRADING SYSTEM


Grade I-Pilocytic astrocytoma
Benign cytological features

Grade II-Low-grade astrocytoma


Moderate cellularity-no anaplasia or mitotic activity

Grade III- Anaplastic astrocytoma


Cellularity, anaplasia, mitoses

Grade IV-Glioblastoma
Same as Grade III plus microvascular proliferation and necrosis

OLIGODENDROGLIOMA
Arise in the cerebral hemispheres of middle-aged adults. They are insidious, slowgrowing tumors and have a mean survival of five years. Oligodendrogliomas are more circumscribed than astrocytomas.

the tumor cells are uniform and have round central nuclei surrounded by a clear space or halo (unstained cytoplasm) which is an artifact of processing.

OLIGODENDROGLIOMAS
Infiltrate the cortex diffusely Traversed by delicate capillaries and have a tendency to calcify, which is helpful in radiological and histological diagnosis EM examination, the tumor cells produce abundant plasma membrane that tends to form concentric layers mimicking myelin Some oligodendrogliomas have an astrocytic component. Such mixed tumors are called oligoastrocytomas. Can be classified: as lowgrade or high-grade based on cellularity, mitotic activity, vascular endothelial proliferation, and necrosis.

OLIGODENDROGLIOMAS
Oligodendrogliomas are among the most chemosensitive solid tumors. They show losses of chromosomes 1p and 19q which correlate with increased sensitivity to PVC and temozolomide chemotherapy and longer survival

EPENDYMOMA

EPENDYMOMAS
Predominantly tumors of children and adolescents. Arise most frequently in the 4th ventricle and cause hydrocephalus by blocking CSF flow. Occur anywhere in relation to the ventricular system or central canal The most common primary intra-axial tumors in the spinal cord and filum terminale. Well demarcated from the surrounding brain and spinal cord Grow in an exophytic fashion, protruding into and out of the fourth ventricle. Spinal ependymomas are circumscribed intra-axial masses.

EPENDYMOMAS

Perivascular pseudorosettes

Tubular formation true rosettes

EPENDYMOMA
Microscopically: The tumor cells resemble normal ependymal cells and are arranged in: perivascular formations tubular structures like the central canal of the spinal cord papillary formations An anaplastic version of ependymoma, called ependymoblastoma, is seen infrequently in young children. Most ependymomas are histologically and biologically low-grade, but surgical resection of fourthventricle ependymomas is difficult.

MEDULLOBLASTOMA
10-yr survival rate = 50%

Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum (infratentoria) or posterior fossa in the external granular layer of the neurons Another term for medulloblastoma is infratentorial PNET.
Medulloblastoma is the most common PNET originating in the brain. All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the CSF & freq metastasize to different locations in the brain & spine

MEDULLOBLASTOMA

medulloblastoma

Desmoplastic

External granular layer

MEDULLOBLASTOMA
Second most frequent BT in children after pilocytic astrocytoma. Most medulloblastomas occur in the 1st decade of life. There is a second peak in the early 20s. Its embryonal nature is underlined by its high incidence in infants and children and by its undifferentiated, immature appearance, which resembles developing neural tissue. The term primitive neuroectodermal tumor (PNET), which has been applied to medulloblastoma and other "small blue cell tumors" of the brain, reflects the embryonal nature and undifferentiated appearance of these tumors and their potential for neuronal and glial diffferentiation

MEDULLOBLASTOMA
Gross : medulloblastomas are soft, pink-red, and well demarcated. They can block the fourth ventricle and the aqueduct, causing hydrocephalus.

MEDULLOBLASTOMA
Microscopically: classical medulloblastoma is a highly cellular tumor composed of diffuse masses of small, undifferentiated oval or round cells. Some medulloblastomas show neuronal, glial and other differentiation. Neuronal differentiation is manifested by neuropil and rosette formation. Rosettes are groups of tumor cells arranged in a circle around a fibrillary center. Infrequent mature neurons may also be found in medulloblastomas. Glial differentiation in some tumors is reflected by GFAPpositive cells.

MEDULLOBLASTOMA
Treatment : Prognosis:

begins with maximal resection of the tumor


The addition of Radiation to the entire neuraxis and chemotherapy may increase the disease-free survival

Presence of desmoplastic featres better prognosis


Prognosis is worse < 3 yrs. Old Inadequate resection CSF, Spinal, Supratentorial or systemic spread Intracranial pressure may be controlled with corticosteroid or VP shunt

This combination: 5-yr survival > 90%


Gamma knife radiosurgery for recurrent

NEOPLASM OF MESENCHYMAL ORIGIN


MENINGIOMA Intracranial tumor that arise from the arachnoid villi and produce symptoms by compressing adjacent brain tissue

MENINGIOMA
A meningioma is benign neoplasm that arises from the meninges. The tumor can arise within the intracranial cavity, spinal cord or orbit. PATHOGENESIS:

Arise in one of the 3 settings:


1. Sporadic cases (most common) 2. Iatrogenic cases caused by prior radiation therapy to the cranium 3. In association with a genetic disorder esp neurofibromatosis type 2

MENINGIOMA
Sporadic: loss, partial deletion or mutation of chromosome 22 involving the NF2 locus (22q12) Suggests that inactivation of the putative NF2 tumor-suppressor gene is involved in the genesis of many meningiomas and schwannomas arising sporadically Seizures parasagittal & over the convexity Post-Radiation dose related

GROSS: MENINGIOMA
Meningiomas are circumscribed; They may be attached to the dura, though they do not arise from the dura per se. Usually, they displace brain tissue without invading it. Some meningiomas grow flat on the surface of the brain.

Meningioma: HISTOLOGIC
the most common histological subtypes of meningiomas - have no prognostic significance. Meningothelial meningiomas are composed of diffuse masses of arachnoidal-like cells.

Transitional meningiomas, tumor cells are arranged in whorls with hyalinized and calcified centers that are called psammoma (sand) bodies because they resemble tiny grains of sand.
Fibroblastic meningiomas are composed of fascicles of fiber-like cells with abundant interstitial collagen.

MENINGIOMA

Fibroblastic meningiomas

Transitional meningiomas w/ whorls

MENINGIOMA
Malignant meningiomas are relatively infrequent. They display overt histological anaplasia and increased mitoses and invade the brain. These atypical meningiomas grow more rapidly and are more prone to recur after surgical resection. Some histological types, such as papillary, chordoid, rhabdoid, and clear cell meningioma, also have a more aggressive behavior and are associated with a higher rate of recurrence. Meningiomas of the optic nerve typically affect middleaged women (female: male ratio = 5: 1). This tumor either arises from the meningeal coverings of the optic nerve or from direction extension from the cranial vault.

Manifestations include slowly progressive vision loss, mild proptosis, optic atrophy & optociliary shunt vessels.

SCHWANNOMA
Arise most often in cranial and spinal nerve roots and peripheral nerves but can occur anywhere, including in the brain and in the ventricles. 90% arise in the 8th nerve root (acoustic Schwannoma, cerebellopontine angle tumor) The preferential involvement of the 8th nerve may have to do with chronic exposure to loud noise (acoustic trauma) Most Schwannomas are solitary. Bilateral acoustic or multiple Schwannomas are the hallmark of NF2.

schwannoma

Pons is deformed & pushed laterally

Palisading tissue pattern

SCHWANNOMA
Microscopically they consist of fascicles of spindle cells that are arranged in palisades. Less frequently they form a loose reticular pattern. They are benign, slowgrowing tumors, and cause symptoms by compression. Gross: Schwannomas are extraaxial, circumscribed and encapsulated and range from small and solid to large, irregular, cystic, and hemorrhagic masses. They do not invade, but rather displace the brainstem and spinal cord as they grow

NEUROFIBROMA
Peripheral nerve tumors composed of a mixture of Schwann cells and fibroblasts.
Multiple neurofibromas that involve long segments of peripheral nerves (plexiformfrom a Greek word that means braid- neurofibromas) are characteristic of NF1

They cause a fusiform enlargement of the nerve in which they arise.


Microscopically, their cells are loosely arranged in a wavy pattern.

NEOPLASM DERIVED FROM ECTOPIC TISSUES


CRANIOPHARYNGIOMA

Grossly, they show a mixture of solid and cystic areas.

CRANIOPHARYNGIOMA
Microscopically
composed of sheets of squamous epithelial cells and keratin, set in a loose connective tissue stroma.
FNA CHOLESTEROL CRYSTALS

Islands of keratin often calcify.


Water accumulating in the central portion of the epithelial islands causes them to loosen, creating an appearance that resembles adamantinoma.

TUMORS OF GERM CELL ORIGIN


HEMANGIOBLASTOMAS

are sporadic or familial.


The latter are associated with the von Hippel Lindau disease. Young & middle aged group Found in the cerebellum as a mural nodule within a cyst

Benign Tumor which consists of numerous delicate capillaries set in a background of clear foamy cells.

CEREBRAL LYMPHOMA

Spreading across the corpus callosum

Large cell lymphoma with perivascular infiltration

LYMPHOMAS
Primary cerebral lymphomas are thought to arise from indigenous brain histiocytes (microglia) or from rare lymphocytes that are normally present in the meninges and around vessels. affect immunosuppressed individuals such as patients with AIDS Microscopically, most of them are large, B-cell lymphomas. The tumor cells form dense perivascular sheaths or diffuse masses. Meningeal spread is very common, and some cerebral lymphomas arise in the subarachnoid space. Cerebral lymphomas, like their extracerebral high-grade counterparts, are highly malignant.

METASTATIC TUMORS
Metastatic tumors account probably for the majority of BT. Brain metastases are found at autopsy in 14% to 37% of malignant tumors. In men, the most common primary is carcinoma of the lung, which shows brain metastases in 35% of the cases in women, it carcinoma of the breast, which metestasizes in 21% of the cases.

METASTATIC TUMORS
The tumor with the highest rate of metastasis is melanoma. Meningeal carcinomatosis (diffuse spread of tumor in the subarachnoid space) is seen in 4% to 8% of metastatic BT and is more common with carcinoma of the lung, carcinoma of the breast, and acute lymphoblastic leukemia. The CSF in meningeal carcinomatosis shows: high protein, low glucose, and a few lymphocytes. The often insidious onset of symptoms and the CSF findings suggest mycobacterial meningitis, especially if the primary tumor is too small to be detected. Cytological examination of CSF reveals tumor cells.

THE EFFECTS OF BRAIN TUMORS


The local effects of BT are loss of function (focal deficits) and seizures. The general effects of tumors have to do mainly with increased intracranial pressure. Increased intracranial pressure is caused by: a) the mass of tumor added to the brain

b) hydrocephalus due to obstruction of CSF circulation and


c) cerebral edema, i.e., accumulation of fluid in the interstitial space around the tumor.

A T & TUMORS ????

1. Which of the following(s) is(are) true about childhood meningiomas?


1. They are more likely to behave more aggressive and recur more frequently. 2. 3. They are associated with neurofibromatosis 2 (NF2). They are more likely to be found at infratentorial, intraventricular, or intraparenchymal locations. 4. Meningioms are common tumors in infants and children.

A. 1, 2, and 3 are true. B. 1 and 3 are true.

D. Only 4 is true E. All of the Above

C. 2 and 4 are true.

2. This primary cerebral tumor was removed from an 18 month-old boy. The most likely diagnosis is: A. Ependymoma. B. Choroid plexus papilloma.

C. Pilomyxomoid astrocytoma.
D. Medulloepithelioma. E. Medulloblastoma.

3. Which type of meningioma is most likely to be found in patients under 20 years of age? A. Fibrous meningioma.

B. Transitional meningioma.
C. Secretory meningioma.

D. Chordoid meningioma.
E. Psammomatous meningioma.

4. Which of the followings is not true about optic nerve glioma? A. Optic nerve gliomas in children tend to behave in a indolent, slowing growing fashion.

B. Optic nerve gliomas are associated with neurofibromatosis 1 (NF1).


C. Optic nerve gliomas in adults tend to be non-familial and behave in a benign fashion.

D. Spontaneous regression has been described in childhood cases of optic nerve gliomas.
E. Optic nerve gliomas tend to grow outside the optic nerve and expand the subarachnoid and subdual space.

5. This primary tumor is removed from the cerebellum of a 2 year-old boy. The most likely molecular changes that would associate with this tumor is: A. Isochromosome 17.

B. Deletion of chromosome 22q.


C. t(11;22)(q24;q12) translocation. D. Human homologue of the Drosophilia segment polarity gene (PTCH gene) on chromosome 9q22.3. E. None of the above.