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use mefenamic acid for perimenstrual prophylaxis of
menstrually related migraines, with treatment starting 2 days
prior to the onset of flow or 1 day prior to the expected onset of
the headache and continuing for the duration of menstruation.
Metoclopramide has been shown to have efficacy for both
the pain and nausea associated with migraine. safely used in
Topiramate is second line prophlaxis for migraine after
Oral contraceptive pills are contraindicated in women with
migraine with aura, especially if the aura involves more than
just simple visual aura, if there are additional stroke risk
factors, or if the aura begins after the initiation of oral
Tension-type headache
is distinguished from migraine by the fact that patients
with tension headache are not disabled and can carry out
activities of daily living in a normal, expedient manner.
Medication overuse headache
headache for more than 15 days per month and the use of
acute headache medication on more than 10 days per month.

Trigeminal neuralgia.
affects the right side of the face five times more frequently
than the left.
The number of attacks may vary from one a day up to a
hundred per day, and patients are typically asymptomatic in
between attacks
Trigeminal neuralgia is a disease of middle-to-late age
We should evaluate for secondary causes of Trigeminal
neuralgia if it
o occur in a young patient
o associated with any physical signs as reduced corneal reflex
and reduced sensation in the mandibular and maxillary division
of the trigeminal
secondary causes of Trigeminal neuralgia
o multiple sclerosis,
o posterior fossa tumors, and
o vascular or aneurysmal compression of the trigeminal nerve.
Usual treatment for trigeminal neuralgia would be a
titrated dose of carbamazepine, with addition of gabapentin or
amitriptyline if needed.
The disorder may cease spontaneously after 6-12 months.
The trigeminal autonomic cephalalgias

Disease Duration Frequency Treatment

Cluster headache 1 hour 1-3/day
prefer to be mobile, because resting causes worsening of the
1. verapamil
2. Prednisone is the most appropriate treatment for episodic
cluster headache.
Paroxysmal hemicrania 15 minutes 11/day indomethacin
SUNCT syndrome 60 seconds 30-200/day lamotrigine
Migrain > 3hours Resting in a dark, quiet room results in
Thunderclap headache
is head pain that begins suddenly and is severe at onset.
TCH might be the first sign of
o subarachnoid haemorrhage,
o unruptured intracranial aneurysm,
o cerebral venous sinus thrombosis,
o cervical artery dissection,
o acute hypertensive crisis,
o spontaneous intracranial hypotension,
o ischaemic stroke,
o retroclival haematoma,
o pituitary apoplexy,
o third ventricle colloid cyst, and
o intracranial infection.
CT of the head without enhancement is the most sensitive
test for subarachnoid hemorrhage.
A lumbar puncture is necessary if CT scan results are
If results of both the CT scan and lumbar puncture are
normal, neurovascular imaging is indicated in these patients
and should include magnetic resonance or CT angiography (or
Vertebral artery dissection
Typically presents with
o neck or head pain,
o Horner's syndrome,
o dysarthria,
o dysphagia,
o decreased pain and temperature sensation,
o dysmetria,
o ataxia, and
o vertigo.
Magnetic resonance angiography is a sensitive diagnostic
test for vertebral artery dissection as a cause of stroke.
If MR angiography negative and suspicion is still high, 4
vessel cerebral angiography can be arranged.
Where there is no evidence of sub-arachnoid haemorrhage,
anti-coagulation is the management of choice to prevent
thromboembolic sequelae as a result of the dissection
Subclavian steal syndrome

is associated with retrograde flow in the vertebral artery

due to a proximal subclavian artery stenosis.
Neurological symptoms are precipitated by vigorous
exercise with the arm above the head, such as painting a wall,
they are in fact related to reduced blood flow.
The diagnosis is often confused with transient ischaemic
attacks or epilepsy.
Duplex ultrasound and magnetic resonance angiography
are the investigations of choice.
Endarterectomy and stenting are common surgical
methods involved in relieving symptoms associated with this
Subarachnoid hemorrhage
CT brain imaging within the first 48 hours is approximately
95% sensitive at identifying SAH.
However, a normal CT scan does not exclude SAH and a
lumbar puncture should be performed if the CT scan is negative
and SAH is still suspected.
Since bilirubin is undetectable in the cerebrospinal fluid
(CSF) until 12 hours after the onset of symptoms, a lumbar
puncture should be delayed until after this time unless
meningitis is suspected.
Lumbar puncture is most sensitive in the initial period (12
hours after the onset of symptoms and up to 14 days later).
Bilirubin may be detected in CSF by spectrophotometry
visual inspection for the yellow discoloration
(xanthochromia).from 12 hours up to 2 weeks
Evidence clearly indicates that visual inspection is not a
reliable method.
CSF spectrophotometry detects the presence of both
oxyhaemoglobin and bilirubin because either one or both of
these pigments may contribute to xanthochromia following
SAH. CSF supernatant is scanned
CSF may be of this
Appearance Clear Clear
Opening pressure 17 cm H20 (NR 4 - 18)
CSF white cell count 0 cells/mL (NR <5)
CSF red cell count 4 cells/mL (NR <5)
CSF protein 0.40 g/L (NR 0.15 - 0.45)
Xanthochromia screen Negative by visual inspection
CT angiography and four vessel angiography would be the
next management step for those with a confirmed diagnosis of
An MRI brain scan is inferior to CT imaging in SAH.
MR angiography is less sensitive
Focal neurologic symptoms 3 to 7 days after a
subarachnoid hemorrhage may be due to vasospasm with
cerebral ischemia.
patient should receive adequate analgesia, balancing pain
relief against interfering with Glasgow coma scale measurement
If the diagnosis is not confirmed, oral nimodipine is not
Use of steroid for all intracranial bleeds remains unproven, and
in the absence of major shift cannot be recommended.

CSF Examination in Subarachnoid hemorrhage

The gold standard method is by CSF spectrophotometry,
which must be requested at the time of sending the CSF to the
the CSF has to be spun down immediately (thus removing
any acute red cells that are contaminants from the LP
The CSF can then be analysed by spectrophotometry for
evidence of prior bleeding.
If sending CSF to the lab overnight, it can be spun down,
then stored for analysis the next morning.
When blood enters the CSF by SAH or by traumatic tap it
will haemolyse to form oxyhaemoglobin. This is seen as an
absorption peak on the spectrophotometry.
The conversion of oxyhaemoglobin to bilirubin occurs only
in the presence of haemoxygenase, which is found only in
macrophages, the arachnoid membrane and the choroid
Bilirubin causes a second absorption peak on the
downward slope, the oxyhaemoglobin peak. This bilirubin peak
on spectrophotometry cannot be caused by a traumatic tap and
indicates a SAH (unless a traumatic tap has been preceded by a
previous traumatic tap more than 12 h before, or the serum
bilirubin or CSF protein is elevated).

Spectrophotometry can detect both oxyhaemoglobin and

bilirubin. Oxyhaemoglobin produces an absorption peak at
413415 nm, bilirubin when detected alone produces a peak
at 450460 nm.

Extra cranial vertebral artery dissection

stroke in young people (less than 40 years old).
The onset of severe occipital pain usually caused by trivial
About 85% of patients develop focal neurological signs due
to ischaemia of the brain stem or cerebellum.
o vertigo, dysarthria, ataxia, nausea and vomiting nystagmus
o intention tremor
o Tone, power, reflexes and sensation are all may be normal
The commonest neurological manifestations are lateral
medullary dysfunction
Infarction of the cervical spinal cord
o occlusion of the anterior spinal artery
o Weakness in shoulders Abduction

o Knee flexors were 2/5 on both sides.

o All limbs were flaccid and the tendon reflexes were
universally absent.
o Both plantars were upgoing.
o Pinprick was impaired over both shoulders;
o but joint position sense and vibration were intact for all the
EhlersDanlos syndrome and fibromuscular dysplasia
are risk factors.
Axial MRI images show a double lumen in the dissected
Treatment is anticoagulation
Extracranial carotid artery
Neck pain
haematoma in the neck as a mass
Examination findings may include the following:
o Ipsilateral partial Horner syndrome (32-82% of patients in
various series)
o Ipsilateral cranial nerve palsies, particularly cranial nerves 9,
10, 11, 12 more often than the"5, 6, 7 nerves" in up to 12% of
o Audible bruit (up to 20% of patients)
o Gold standard for diagnosis of carotid dissection is contrast
o Other, non-interventional methods are more commonly
performed when it is suspected
duplex scanning and
magnetic resonance angiography
Fine computed tomography neck cuts can also make
the diagnosis in cases where there is significant haematoma.
Carotid dissections more rarely involve intracranial vessels
and the neck pain in this case makes it likely to be extracranial.
The main complications are completed stroke, usually from
thrombus formation associated with the damage to the
endothelium. It is for this reason that anticoagulation is often
advised if not otherwise contraindicated

Occlusion of anterior inferior cerebellar artery

o lateral inferior pontine infarction.
8th nerve vertigo, vomiting, horizontal and vertical
nystagmus, tinnitus.
7th nerve A lower motor neuron facial weakness
parapontine reticular formation,,,,paresis of conjugate lateral

o cerebellar ataxia
o Horners syndrome (descending sympathetic) and
o rarely deafness (cochlear nerve or nucleus)
o impaired pain and temperature over the half of the body
"spinothalamic tract" involvement.
Benign intracranial hypertension
Headache, which occurs in almost all (9294%) cases.
worse in the morning, generalized in character and throbbing
10% of cases are free of headaches.
nausea and vomiting.
worse by coughing and sneezing.
pain may also be experienced in the neck and shoulders
pulsatile tinnitus
abducens nerve palsy "double vision"
rarely, the oculomotor nerve and trochlear nerve facial
Bilateral papilledema, "transient visual obscurations",
episodes of difficulty seeing that occur in both eyes but not
necessarily at the same time.
Long-term untreated papilledema leads to visual loss, leads
to optic atrophy
o Neuroimaging Should be done first CT or MRI "MRI brain is
better than CT brain to look for cerebral venous thrombosis",
rules out mass lesions. In IIH these scans may be normal,
although small or slit-like ventricles and "empty sella sign"
(flattening of the pituitary gland due to increased pressure) may
be seen. An MR venogram to exclude the possibility of cerebral
venous sinus thrombosis.
o Lumbar puncture is performed to measure the opening
pressure,Occasionally, the pressure measurement may be
normal despite very suggestive symptoms. This may be due to
the fact that CSF pressure may fluctuate over the course of the
day. If the suspicion remains high, it may be necessary to
perform more long-term monitoring of the ICP by a pressure
Ischemic stroke
The preferred treatment of intravenous rtPA,within 3
hours from stroke onset "even patient has AF"
o Blood pressure lowered and stabilized (systolic <185 mm Hg,
diastolic <110 mm Hg)
o In a patient with ischemic stroke treated with recombinant
tissue plasminogen activator (rtPA), systolic blood pressure
should be kept below 180/105 mm Hg for 24 hours after rtPA
treatment; intravenous labetalol or nicardipine can best achieve
this goal.
o rtPA is not contraindicated if warfarin taken if INR less than
or equal to 1.7
o No seizure with postictal residual neurologic deficits
o Platelet count of 100,000/L (100 109/L) or greater
and plasma glucose level of 50 mg/dL (2.8 mmol/L) or greater

To maximise benefit thrombolytic therapy should not be

given if
The neurological deficit is mild
The time from onset is more than three hours
There is evidence of major stroke on CT and
The patient has uncontrolled hyperglycaemia more than 25
Other contraindications include
PT should be less than 15s
Platelet count less than 100
BP more than 185/110 mmHg.
Aspirin is indicated for acute ischemic stroke in patients
who are not eligible for rtPA,
Aspirin (160 to 325 mg/d) administered within 48 hours of
stroke onset results in a small but significant reduction in the
risk for recurrent stroke during the first 2 weeks after the stroke
and improves outcome at 6 months.
For patients with acute stroke who receive thrombolysis,
aspirin should be withheld in the emergency department and
for 24 hours after rtPA administration.
Although long-term anticoagulation is an effective
treatment for prevention of cardioembolic stroke in patients
with atrial fibrillation, acute anticoagulation with heparin has
not been shown to be beneficial in patients with acute ischemic
Intra-arterial administration of rtPA is indicated for
selected patients with acute stroke who have major intracranial
artery occlusion within 6 hours of symptom onset and who are
not otherwise candidates for intravenous administration of
In a patient with stroke, dysphagia screening "water
swallow test" should be performed before food, oral medication,
or liquids are administered. a patient with stroke should be
given nothing by mouth (kept NPO) until a swallowing
assessment is conducted.
Elevated blood pressure is common at the time of initial
stroke presentation, even among patients without chronic
Rapid lowering of blood pressure may further impair
cerebral blood flow and worsen the ischemic injury.
Elevated blood pressure often will resolve spontaneously or
improve gradually during the first few days after a stroke.
The threshold for acute blood pressure lowering in patients
with acute stroke who are eligible for thrombolysis is 185/110
mm Hg. In such a setting, preferred agents include intravenous
infusions of labetalol or nicardipine.
The PROGRESS trial showed that BP reduction (using
perindopril and indapamide) after "not in acute stage"
ischaemic stroke reduces the risk of further events even in
patients with normal blood pressure.
The Heart Protection Study showed that treatment with
simvastatin 40 mg reduces the risk of stroke and other vascular
events in high-risk patients (previous ischaemic stroke,
coronary or peripheral vascular disease, diabetes) even if the
cholesterol level is normal <3.5mmol/l

Carotid endarterectomy is the gold standard of surgical

therapies for patients with Internal "not External" carotid
stenosis 50-70% , it cannot be performed in
o stenosis that is difficult to access surgically (above the C2
o medical conditions that greatly increase the risk of surgery,
o other specific conditions, such as
radiation-induced stenosis or
restenosis after carotid endarterectomy.
Recent NICE guidance suggests that in people with acute
non-disabling stroke or TIA, who have symptomatic carotid
stenosis of 50-99% , should be considered for endarterectomy
Combination of carotid angioplasty and stenting is
alternative to Carotid endarterectomy in above conditions
Cerebral venous sinus thrombosis
signs and symptoms of intracranial hypertension, such as
o headache,
o Bilateral papilledema
o visual problems; homonymous hemianopsia,
o focal neurologic findings as unilateral hemiparesis
o seizures , fluent aphasia
mental status changes, stupor, and coma.
Major risk factors
o thrombophilia,
o pregnancy,
o oral contraceptive use,
o Dehydration
o malignancy,
o sepsis, and
o head trauma.
The absent delta sign on CT scan implies a filling
defect in one of the venous sinuses, although often in this
condition the CT scan is normal.
Magnetic resonance venography can readily detect
obstruction of the venous sinuses by a thrombus and the
damage to the brain caused by the resultant increased pressure
Treatment anticoagulation + Rehydration if dehydrated
Chiari malformation as a cause of syncope
central nervous system syncope due to intermittent
obstructive hydrocephalus.
This presents with sudden pressure headache which builds
up over a few seconds before losing consciousness.
Signs and symptoms of subdural hematoma
A history of recent head injury
Loss of consciousness or fluctuating levels of
Headache (either constant or fluctuating)

Weakness or lethargy
Nausea or vomiting
Loss of appetite
Personality changes
Inability to speak or slurred speech
Ataxia, or difficulty walking
Altered breathing patterns
Hearing loss or ringing ringing
Blurred Vision
Deviated gaze, or abnormal movement of the eyes
Neurologic examination may demonstrate
o mental status changes,
o hemiparesis,
o papilledema,
o hyperreflexia or reflex asymmetry,
o hemianopsia, or
o third or sixth cranial nerve dysfunction.
Hereditary haemorrhagic telangiectasia
Presents with epistaxis, and
Arteriovenous malformations
o brain "stroke"
o lung "hemoptysis"
Do not confuse HHT with Wegener's granulomatosis which also
present with epistaxis, hemoptysis but NO stroke as
Neurological involovement is occasionally sensory neuropathy
(10%) and rarely mononeuritis multiplex
Nystagmus Nystagmus duration Imbalance Vomiting Hearing
Peripheral Severe Nystagmus
Horizontal, torsional Never vertical inhibited by fixation does
not change direction with gaze to either side Usually< 1 minute
fades after a few days
Mild to moderate able to walk
DixHallpike Latency of symptoms 15 seconds May be severe
Central Mild Nystagmus
vertical, horizontal, or torsional not inhibited by fixation of eyes
may change direction with gaze Usually>1 minute
may last weeks to months Severe unable to stand
DixHallpikeNo Latency of symptoms Variable Rare
NO Tinnitus
Disease Type Duration Auditory symptoms
Benign paroxysmal positional vertigo Peripheral
Repositioning procedure Epley manoeuvre Medications not
Vestibular neuronitis Peripheral Days

No Vestibular suppressant medication

Labyrinthitis Peripheral Days Yes
Menieres disease Peripheral Hours Sensitivity to noises
Yes Sense of pressure in the ear low-salt diet and diuretics
Acoustic neuroma
Peripheral months
Perilymphatic fistula
Peripheral Seconds
Hallpike manoeuvre
is the standard clinical test for benign positional vertigo.
The finding of classic rotatory nystagmus with latency and
limited duration is considered pathognomonic.
A negative test result is meaningless except to indicate that
active canalithiasis is not present at that moment.
If no nystagmus is observed, the procedure is then repeated
on the other side.
Long-term medical therapy is not the treatment of choice
Epley manoeuvre Canalith repositioning, carries a
high chance of relieving symptoms. Most practitioners claim
symptom relief in 97% of patients after two treatments.

Down-beat jerk nystagmus

is a rarity caused by lesions around the foramen magnum
(e.g. meningioma,cerebellar ectopia).

MRI is superior to CT for detection of epileptogenic lesions.
CT is the imaging modality of choice for new-onset seizures
only when there is a suspicion of an acute cerebral hemorrhage
or when a contraindication to MRI is present
Continuous EEG monitoring is indicated for patients who
remain unresponsive after resolution of clinical status
epilepticus to distinguish nonconvulsive status epilepticus from
a postictal state.
Risk of recurrence after a first unprovoked seizure
o partial seizure
o Todd paralysis,
o status epilepticus on presentation,
o age greater than 65 years,
o abnormal findings on neurologic examination.
Juvenile myoclonic epilepsy,,, Lifelong drug treatment is
usually necessary to avoid relapses in patients who achieve
seizure-free status on medication.
Juvenile myoclonic epilepsy linked to chromosome 6
Lamotrigine is an alternate option to carbamazepine if a
woman is considering starting a family, as the risk of

teratogenicity is less compared to carbamazepine

Levetiracetam, gabapentin, and pregabalin
o are the preferred choices in patients with significant liver
o are renally excreted, the dosage may need to be lowered in the
presence of renal insufficiency.
o are preferred for those patients patients who have undergone
organ transplantation because of the lack of significant drug
Video EEG is the gold standard investigation used to
differentiate non-epileptic attacks from epileptiform events
Epilepsy in elderly
Elderly patients may be particularly sensitive to the
cognitive, motor, and coordination side effects of phenytoin,
even if the serum phenytoin level is in the therapeutic range.
Gabapentin, lamotrigine, and carbamazepine are equally
effective at controlling partial onset seizures in the elderly, but
gabapentin and lamotrigine are better tolerated.
Discontinuing antiepileptics
Those with no structural brain lesion,
no epileptiform or focal abnormalities on EEG,
a sustained seizure-free period "2 years"
no abnormalities on neurologic examination.
Factors that have been shown to increase the risk of seizure
recurrence on discontinuation of therapy include
older age,
use of multiple anticonvulsants
Seizures while on therapy
history of myoclonic or tonic clonic seizure,
previous abnormal imaging
previous abnormal EEG.
Partial seizure with secondary generalization.
This type of seizure is characterized by sensory, motor,
autonomic, or psychic (dj vu, depersonalization)
phenomena with or without altered awareness at onset followed
by generalized tonic-clonic activity
Nonconvulsive status epilepticus
a range of conditions in which electrographic seizure
activity is prolonged and results in nonconvulsive clinical
Arrange 24 hour EEG monitoring
intravenous lorazepam
Pseudoseizure (non-epileptic attack).
Violent shaking, resistance to passive eye opening and
normal vital signs
rapid post-ictal recovery,
attacks in public places and lack of injury.
Urinary incontinence can occur
tongue biting is rare.
Suddenly becoming anxious, breathing fast then suddenly
dropping to the floor
Past medical history of anxiety and depression

Simple observation is the appropriate management in this

Pseudoseizures are commonly misdiagnosed as true
seizures and treated inappropriately with anti-epileptic drugs.
MERRF (myoclonic epilepsy and red ragged fibres).
generalised myoclonus (60%),
cognitive decline
encephalopathy (EEG findings of generalised slow waves)
short stature (10%),
optic atrophy (20%),
sensorineural hearing loss
impaired glucose tolerance.
CSF lactate increased
Multiple sclerosis
If facial nerve palsy occur it is of UMNL not LMNL,,,so
Bells palsy is against MS
Oligoclonal bands in CSF may be negative in multiple
sclerosis and may be positive in other diseases,,,It is important
to remember that if they are detected it needs to be established
whether or not they are present in the serum, as they may
reflect systemic and not central nervous system inflammation.
It is for this reason that a serum sample must be taken when
cerebrospinal fluid (CSF) is sent for oligoclonal band analysis
Lhermitte's sign, an electric shocklike sensation
down the neck, back, or extremities occurring with neck flexion,
is a helpful clue to a cervical spinal cord disorder.occure in MS
and other diseases as Cervical spondylotic myelopathy
Primary progressive multiple sclerosis (MS); no treatments
have been shown to affect the disease course. Therefore,
Physical therapy for evaluation and treatment of spasticity and
back pain are most appropriate
Beta interferons, glatiramer acetate, and natalizumab, are
only appropriate for relapsing-remitting disease.
Three or more relapses per year preclude any continuation
of the interferons or glatiramer acetate injections (as the
objective behind using them is to reduce relapse frequency).
Mitoxantrone therapy is of modest benefit in slowing
progression of secondary progressive or severe
relapsingremitting multiple sclerosis.
The primary concern about mitoxantrone therapy is the
risk for cardiotoxicity.
Women taking immunomodulatory treatment for multiple
sclerosis should use effective contraception, or if they want to
become pregnant, stop therapy several months before
attempting to conceive.
Relapses resolve more rapidly with intravenous
methylprednisolone therapy than oral prednisolone
Plasma exchange therapy in attacks of multiple sclerosis
that are unresponsive to corticosteroids
Amantadine reduce MS-related fatigue.

Neuromyelitis optica
o Transverse myelitis " severe paraparesis".
o optic neuritis.
o often associated with serum autoantibodies or other
autoimmune diseases, and has a predilection for the optic
nerves and spinal cord with relative sparing of the brain
o can be distinguished from MS by the NMO-IgG autoantibody
Criteria for commencing beta-interferon therapy.
more than two separate episodes within the last two years
more than 18-years-old, and
Can walk more than 100metres
Contraindications to beta-interferon are
History of severe clinical depression
Uncontrolled epilepsy
Hepatic dysfunction and
Prognosis of multiple sclerosis
o Onset with optic neuritis;
o one year or more duration of first remission;
o onset before the age of 40 years.
o There was no association with sex.
o Onset with pyramidal symptoms
o extent of white matter lesions on MRI and subsequent clinical
deterioration is well documented.
Optic neuritis
In acute ON, the optic disc may appear normal since two
thirds of cases of ON are retrobulbar. However, the optic nerve
may become pale over time.
In case of ON without any clinical signs and symptoms of a
systemic disease ,,, blood tests and CSF examination are of little
MRI can be used to assess inflammatory changes in the
optic nerves and helps exclude structural lesions.
Intravenous methylprednisolone therapy followed by an
oral prednisone taper speeds recovery of visual acuity in optic
Acute disseminated encephalomyelitis is usually readily
distinguishable from multiple sclerosis (MS) by the presence of
certain clinical features, including the following:
o History of preceding infectious illness or immunization
o Association with constitutional symptoms and signs such as
o Prominence of cortical signs such as mental status changes
and seizures
o Comparative rarity of posterior column abnormalities, which
are common in MS
Benign fasciculations
are relatively common in patients who have undergone a
period of very strenuous exercise, and are also seen after an
alcohol binge.
the prognosis of this condition is entirely benign.
Benzodiazepines are generally ineffective in the

management of benign fasciculations, but carbamazepine and

phenytoin are effective
Parkinson's disease
The presence of these suggest alternative condition other
than Parkinson disease
o symmetric signs and symptoms (tremor and rigidity)
o postural tremor
o early falls,
o rapid progression,
o poor or waning levodopa response,
o dementia,
o early autonomic failure
o ataxia.
Pramipexole is a non-ergoline dopamine agonist indicated
for treating early-stage Parkinson's disease and restless legs
A potential adverse effect of dopamine agonist therapy is
the development of compulsive behaviors, such as pathologic
gambling, shopping, and hypersexuality.
Corticobasal degeneration
is a cause of adult-onset parkinsonism,Parkinsonplus
usually unilateral initially but can progress to affect both
rigidity and bradykinesia,
there may also be myoclonus,
apraxia or a
dystonia of a limb.
A particularly characteristic feature of CBD is the
development of an alien limb phenomenon, where a
limb, usually an arm, appears to move on its own.
Cortical sensory loss is also seen
there is sometimes a supranuclear gaze palsy.
cognitive impairment that may include a progressive nonfluent aphasia. difficulties with speech ,,had some word-finding
difficulties and his speech was at times effortful with the
occasional wrong word
There is no curative treatment
Disease Falls Autonomic Ataxia Tremor Other
Parkinson NO NO NO Common Asymmetrical stiffness
Multiple system atrophy Early Common postural hypotension
impotence Common cerebellar NO Shy-Drager syndrome
increased tone brisk reflexes Cerebellar sign intention tremor
ataxic dysarthria. bradykinesia
Progressive supranuclear palsy Early
Repeated abrupt falling without any evidence of ataxia NO
NO postural hypotension
MRI may show midbrain atrophy Impaired down gaze limited
upgaze Blepharospasm and involuntary eye closure
Pseudobulbar palsy slurred speech, impaired swallowing.

symmetrical stiffness Initially there are vague changes in

Lewy bodies Dementia yes Less "postural hypotension" NO NO
Visual hallucination Cognitive impairment Neurolyptic
Multiple system atrophy
Neuroimaging may be normal in MSA.
Hyperintensity of the lateral margin of the putamen in T2weighted MRI is a characteristic
MRI can help to exclude cerebrovascular diseases.
Fluoride F 18 fluordeoxyglucose dopa positron emission
tomography (PET) imaging can be used to differentiate between
MSA and Parkinsons disease, with reduced putaminal F 18
fluorodeoxyglucose in the MSA.
Autonomic function testing is useful in evaluation of the
distribution and severity of parasympathetic and sympathetic
Sphincter electromyography is useful for demonstrating
hyperreflexia of detrusor in MSA
Dementia with Lewy bodies
fluctuating encephalopathy,
visual hallucinations
Deterioration with haloperidole,,,, haloperidole also
deteriorate Parkinson disease
Affected patients have a central cholinergic deficiency.
Cholinergic augmentation with a centrally acting
anticholinesterase agent such as donepezil, galantamine, or
rivastigmine is likely to alleviate the inattention, hallucinations,
and fluctuating encephalopathy.
In patients with predominant parkinsonian features,
dopamine agonists can be used, although improvement is
usually short-lived
an acetylcholinesterase inhibitor, may cause mild peripheral
cholinergic side effects, including increased vagal tone, with
bradycardia, and occasionally atrioventricular block.
CreutzfeldtJakob disease
Rapidly progression of dementia to memory loss,
personality changes and hallucinations
with myoclonus
motor signs Limb weakness and rigidity
Cerebellar signs ataxia Nystagmus
rigid posture,
EEG showing periodic sharp waves in two-thirds of
A positive CSF 14-3-3 protein
MRI. Normal or can show a characteristic signal change in

the putamen and caudate. MRI is vital in excluding other

diagnoses, in comparison to the findings in variant CJD in
which increased signal in the pulvinar may be seen
Variant CreutzfeldJakob disease
Presents with behavioural and psychiatric disturbances
Rapid cognitive decline in a young person with
myoclonic jerks
cerebellar ataxia
Cerebrospinal fluid (CSF) may reveal elevated 14-3-3
All cases to date are homozygous for methionine at PRNP
codon 129.
This disease can be diagnosed by detection of characteristic
PrP immunostaining and PrPpc on tonsil biopsy demonstrated
by western blot.
The tonsil biopsy obviates the need for brain biopsy.
Hashimotos encephalopathy
subacute diffuse encephalopathy
neuropsychiatric signs (confusion, apathy, memory
myoclonic encephalopathy,
movement disorder (akineto-rigid extrapyramidal signs),
positive antithyroid autoantibodies comparable with
Hashimotos thyroiditis, typically with a euthyroid state.
EEG is abnormal in most,
other etiologies such as infectious, metabolic, toxic,
vascular, neoplastic, and paraneoplastic causes need to be
Women appear to be more affected than men and the
condition is usually steroid responsive.
Frontotemporal dementia
The age of onset is normally between 45 and 60 years
a positive family history in up to 50%
There are three cardinal syndromes:
o Frontal variant frontotemporal dementia which presents
mainly with behavioural disturbance (decreased motivation,
impulsiveness, disinhibition and loss of social skills are all
o Semantic dementia which presents with a fluent aphasia and
difficulty naming objects due to a loss of semantic knowledge
o Progressive non-fluent aphasia which presents with speech
production difficulties.
Overlap between the syndromes is seen.
Patients often develop a sweet tooth or other changes in
Problems with planning and judgment may cause them to
lose their job.
There is currently no treatment for the underlying
Radiation-induced leukoencephalopathy
is a subcortical process affecting white matter and
characterized by the triad of

o gait apraxia,
o dementia, and
o urinary incontinence.
may occur months to years after radiation and
is more common after whole-brain compared with focal
brain irradiation.
Huntington's disease,
Wilson's disease
drugs (neuroleptic agents, levodopa, dopamine agonists,
anticholinergic agents),
infections (Sydenham's chorea),
systemic lupus erythematosus
This is a serologic blood test used to detect antibodies
against antideoxyribonuclease B ,,is produced by group A
This test is used to document a previous streptococcal
infection in those who are suspected of having poststreptococcal disease (for example acute glomerulonephritis,
rheumatic fever).
Anti-basal ganglia antibodies
appears to be a potentially useful diagnostic marker in
post-streptococcal neurological disorders
Westphal variant of Huntingtons disease
presentation in youth
with associated Parkinsonian symptoms.
a sudden decline in academic performance, changes in
behavioral problems,
brief, "shock-like" spasms of certain muscles or muscle
groups (myoclonus); progressively impaired control of
voluntary movement (ataxia); and dystonia
The family history of suicide is of relevance
may be associated with behavioural features of the disease
HD is inherited in an autosomal dominant pattern with
complete penetrance.
CT scan of brain show Gross atrophy of the caudate nucleus
and putamen on both sides is the characteristic
The gene for HD is on the short arm of chromosome 4,
which contains CAG repeats (coding for glutamine).
Wilson disease and Neuropsychiatric complications
Most patients have cirrhosis.
The most common presenting neurologic feature is
asymmetric tremor
o parkinsonian
o pseudosclerotic group had tremor resembling multiple
o Dystonic,,,hypertonicity associated with abnormal limb

o chorea associated with dystonia.
Psychiatric features include
o Depression, poor concentration and "personality change"
o emotional lability, to cry very easily
o disinhibition, and
o self-injurious behavior
o Behavioral
o Affective
o Schizophrenic like
o Cognitive
Kayser-Fleischer rings are observed in up to 90% of
individuals with symptomatic Wilson disease and are almost
invariably present in those with neurologic manifestations.
Restless legs syndrome
consists of abnormal sensations in the legs and restlessness
relieved by movement.
check serum iron levels. Oral iron therapy can alleviate
symptoms and is recommended if serum ferritin levels are
lower than 45 to 50 ng/mL (45 to 50 g/L).
treated with dopamine agonists,
unilateral involuntary flinging movements of the proximal
upper limbs.
The lesion is in the contralateral subthalamic nucleus of
In the elderly the usual cause is a vascular event such as a
whereas in younger patients the aetiology may be infectious
or inflammatory.
Hemiballismus patients require treatment both for the
underlying aetiology and for the movements themselves.
anti-ballismus therapy.
o Dopamine receptor blocking agents have been shown to
suppress choreic and ballistic movements.
o neuroleptic drugs such as haloperidol are started at low doses
and titrated as tolerated until the movements are controlled.
o Catecholamine-depleting agents such as tetrabenazine may be
considered when long-term therapy is required.
Tourettes syndrome
multiple tics, including sniffing, snorting, involuntary
vocalisations. Some patients display repetitive and annoying
motor behaviour.
An attention deficit hyperactivity disorder and
obsessivecompulsive traits are associated
Intelligence does not deteriorate.
Treatment Dopamine receptor blocker"D2" like haloperidol
is an effective treatment
Streptococcal infection has been implicated
Essential tremor
First-line medications used to treat essential tremor
include propranolol, primidone, gabapentin, and topiramate
Clonazepam is considered a second-line
Friedrichs ataxia

autosomal recessive
mentation is normal.
progressive spinocerebellar ataxia
loss of vibration sense
bilateral extensor plantars indicate pyramidal tract
dysarthric speech,
bilateral optic atrophy.
Progressive muscular wasting and weakness
Sensorineural deafness,
oculomotor disturbance in the form of jerky pursuit,
retinitis pigmentosa.
diabetes mellitus,
pes cavus,
equinovarus deformity and scoliosis
Nerve conduction study reveals either
o low amplitude or absent sensory nerve action potentials.
o Motor nerve conduction velocities are usually normal.
Alzheimer dementia
Speech dysfunction
visuospatial skills difficulties.
The presenilin-1 mutation is specific for early-onset
familial Alzheimer dementia. autosomal dominant mutation
Frontotemporal dementia and Alzheimer dementia are
sometimes difficult to distinguish on clinical grounds alone
Rivastigmine is licensed for the treatment of both mild to
moderate dementia of Alzheimer type, and mild to moderate
dementia associated with Parkinsons disease.
NICE guidance for treatment of Alzheimer's disease (AD).
Treatment with drugs for dementia should be initiated in
mild to moderate AD whose MMSE is between 10-20 and
supervised only by a specialist experienced in the management
of dementia.
Repeating the cognitive assessment every six months
assesses benefit.
Up to half the patients given these drugs will show a slower
rate of cognitive decline.
The drug should be discontinued in those thought not to be
In those who are responding, drugs should be stopped once
the MMSE score is less than 10.
Memantine is not recomended as a treatment option for
patients with moderately severe to severe AD except as part of a
clinical trial.
memantine for moderately severe to severe
Alzheimers disease. NICE Guide

Pick's disease
Frontal lobe dementia
progressive changes of personality and behaviour.

Apathy and depression,, sometimes laughing or crying

Appetite had increased,,, developed a sweet-tooth
and ate little else except boiled sweets
disinhibited and was easily distractible with marked
deficiencies in attention and calculation and naming.
4050% of cases have an affected family member.
A subgroup of patients with frontotemporal dementia have
symptoms and signs of motor neurone disease.
o impaired swallow,
o speech has a nasal quality
o an impaired swallow with tongue fasciculations
o proximal limb weakness difficulty getting out of his chair and
Memory and speech are usually intact.
Visuospatial function was preserved Performance in an
MMSE is often surprisingly high, and more formal
neuropsychological testing may be required to establish the
typical cognitive deficits
Neuroimaging usually shows a unilateral atrophy of the
frontal lobe.
There is no effective treatment at present.

Binswanger's disease
"Subcortical arteriosclerotic encephalopathy"
is a form of multi-infarct dementia caused by damage to
the white brain matter.
The average age of onset is between the fourth and seventh
decades of life, and 80% of patients have a history of
This disease is characterized by loss of memory and
intellectual function and by changes in mood
Patients also show progressive motor, cognitive, mood, and
behavioral changes over a period of 5-10 years.
early-onset urinary incontinence
gait disturbances
Patients may be apathetic or abulic.
Tumour at the foramen of Monro
Deterioration in his mental capacity
marked perseveration.
Ataxic gait
Bilateral papilloedema.
Ocular movements were full and the rest of the cranial
nerves were normal.
bilateral palmomental reflexes,
tone, power and reflexes were all intact.
There is obstruction between the lateral ventricles and
third ventricle, A CT scan of the brain showed dilated lateral
ventricles with normal-sized third and fourth ventricles.

Normal pressure hydrocephalus

The gait "Parkinsonism"
o Apraxia falls
o bradykinetic,
o broad based,
o shuffling.
The urinary symptoms
o urinary frequency,
o urgency, or
o frank incontinence. occurs late in the disease process
compared to Binswanger's disease where incontinence is a
relatively early feature.
The dementia
o prominent memory loss
o Deterioration in concentration and immediate memory
o Frontal and subcortical deficits
marked perseveration
deficiencies in executive function and naming
bilateral palmomental reflexes
decreased attention, inertia, and bradyphrenia.
CT scan of the brain showed dilatation of all the ventricles.
The presence of cortical signs such as aphasia or agnosia
should raise suspicion for an alternate pathology such as
Alzheimer disease or vascular dementia.
Fronto-temporal dementia
gait ataxia is extremely unusual in fronto-temporal
MELAS Mitochondrial myopathy, encephalopathy, lactic
acidosis, and stroke ,,,Early symptoms may include
muscle weakness and pain,
Recurrent headaches, migraine , fever and confusion
loss of appetite, vomiting, and
extrapyramidal movements,
autonomic dysfunction
Most affected individuals experience stroke-like episodes
beginning before age 40.
Hemiparesis reflexes are brisk and the plantar response
was extensor.
Vision loss
Glucose intolerance Diabetes
short stature,
proximal myopathy, progressive weakness in legs proximal
muscle wasting of the thighs and arms
MRI scan brain shows multiple cortical lesions and have
predominance for the occipital lobes.
May start with attacks of migraine with aura or

Subcortical transient ischemic attacks or

Strokes and upgoing planter
Mood disorders between 35 to 55 years of age.
The disease progresses to subcortical dementia associated
with pseudobulbar palsy
urinary incontinence.
Leukoencephalopathy on MRI.
DNA testing for the notch-3 gene mutation confirms the
CADASIL can be differentiated from MELAS by
o the absence of extra neurological features,
o normal lactate
o rareness of cortical lesions on MRI imaging.
Whipples disease
caused by a Gram-positive bacillus, which resides
predominantly in the gut.
Hyperpigmentation and lymphadenopathy are usual
Neurological manifestations include
o slowly progressive memory loss and
o supranuclear ophthalmoplegia where superior gaze is
restricted Bells phenomenon is elicitable.
o Nystagmus,
o ataxia,
o myoclonus and
o seizures and
o highly characteristic oculomasticatory movements complete
the clinical picture.
MRI of the brain may or may not reveal enhancing focal
The diagnosis is made mainly by PAS staining of
o an intestinal (jejunal) biopsy
o PAS-positive material in the CSF.
Treatment consists of a course of penicillin and
streptomycin followed by ceftriaxone or trimethoprim
sulphamethoxazole for 1 year.

Wernicke encephalopathy
The typical clinical triad of ataxia, areflexia, and
ophthalmoplegia "lateral gaze nystagmus' is seen in only 19%
Nystagmus "Horizontal"
ophthalmoplegia, especially of the lateral rectus muscles
impaired horizontal eye movements with preserved pupillary
absence of any upper motor neurone focal signs
gait ataxia,
Stupor and coma
hypotension and

Conditions associated with Wernicke encephalopathy

o alcohol abuse,
o cancer,
o hyperemesis gravidarum,
o prolonged total parenteral nutrition,
o postsurgical status (particularly gastric bypass), and
o glucose loading (in a predisposed patient).
The diagnosis remains a clinical one in patients with one or
more of the classic features of mental status change, gait
impairment, and ocular signs.
Measurements of serum thiamine level and erythrocyte
transketolase activity lack specificity
treatment with intravenous administration of thiamine
Wernicke's encephalopathy
Korsakoff's amnestic syndrome
Recent onset of memory difficulties,
mild impairment of attention and concentration
lack of ability to reason
Confabulation It consists of the creation of false memories,
perceptions, or beliefs about the self or the environment
Peripheral neuropathy
A history of burning or lancinating distal extremity pain
and examination findings showing only sensory loss suggest a
small-fiber peripheral neuropathy, which is most frequently
associated with diabetes mellitus and impaired glucose
Carpal tunnel syndrome
Mild to moderate symptoms a trial of conservative therapy
using wrist splints is indicated.
Patients with mild to moderate symptoms who do not
respond to wrist splinting should be considered for
corticosteroid injection.The initial response rate to
corticosteroid injections at or near the wrist is 70%. The
duration of response is quite variable, however, and patients
often require repeat injections or, ultimately, carpal tunnel
Gabapentin and other medications used to treat
neuropathic pain are typically not indicated in carpal tunnel
Carpal tunnel surgery should be considered in patients who
have not responded to conservative therapy and in patients
with moderate to severe signs or symptoms
Multifocal motor neuropathy (MMN)
is an autoimmune neuropathy associated in 80% of cases
with an elevated anti-GM1 ganglioside antibody
slowly progressive, asymmetric motor, predominantly
distal weakness developing over years in isolated limb.
Depressed reflexes
Weakness usually starts in a distribution of a single
peripheral nerve with unilateral wrist drop, foot drop, or grip

without sensory involvement.

Cranial nerves are rarely affected.
It is an important differential diagnosis of motor neurone
disease as it is potentially treatable.
Treatment with IV immunoglobulin may be very effective
in some patients. Cyclophosphamide is also used on a long term
Chronic inflammatory demyelinating polyradiculoneuropathy
chronically progressive or relapsing symmetric
sensorimotor disorder duration of symptoms to be greater than
8 weeks
weakness, numbness, tingling, pain and difficulty in
loss of deep tendon reflexes
There may be atrophy of muscles,
fasciculations (twitching) and
loss of sensation.
The patient may present with a single cranial nerve or
peripheral nerve dysfunction.
Autonomic system dysfunction can occur; orthostatic
dizziness, problems with bowel and bladder functions, and
cardiac problems.
CIDP is clinically similar to Guillain-Barre syndrome
except that it follows a chronic progressive course.
CSF Show increase protein
1. a reduction in nerve conduction velocities b;
2. the presence of conduction block or abnormal temporal
dispersion in at least one motor nerve;
3. prolonged distal latencies in at least two nerves;
4. absent F waves or prolonged minimum F wave latencies in at
least two motor nerves.
Sural nerve biopsy
First-line treatment for CIDP is normally either
o oral prednisolone or
o intermittent intravenous immunoglobulins:
o evidence suggests they are of equal efficacy in the short term,
and they have not been compared in the long term.
Fabry disease
Small vessel stroke
Painful peripheral neuropathy
Renal disease
Skin stigmata and
Myocardial infarction
Refsums disease
autosomal recessive
sensorimotor peripheral neuropathy.
defective alpha oxidation of phytanic acid
sensorineural deafness,
cerebellar ataxia
pes cavus.
Retinitis pigmentosa cause Night blindness and visual

Cardiac conduction abnormalities and cardiomyopathies

Epiphyseal dysplasia causes shortening of the fourth toe.
Serum phytanic acid levels are elevated.
Treatment is by dietary restriction of foods containing
phytanic acid.
Phytanic acid is present in a wide variety of foods including
dairy products, fish, beef and lamb
Vitamin B12 deficiency
Neurologic signs of vitamin B12 deficiency may manifest in
the absence of hematologic signs of vitamin B12 deficienc
The neuropsychiatric manifestations could present without
the classical spinal cord and peripheral nerve involvement.
o Irritability, recently sold his car at an unusually cheap price.
o become hostile if made to realise his mistakes.
o awake at night and sleep most of the day.
o recent memory was impaired.
o bilateral pale optic discs.
o Gait was ataxic and mildly spastic
SACD has been described in operating room personnel who
are exposed chronically to nitrous oxide. Such chronic exposure
to the gas leads to the interference with methionine synthetase,
a methylcobalamin-dependent enzyme.
In SACD, the serum level of B12 is less than 100 pg/ml and
increased levels of methyl malonic acid (normal range 73271
nmol/l) and homocysteine (normal range 5.416.2 nmol/l)
are more reliable indicators of intracellular cobalamin
A two-stage Schilling test is another reliable indicator of
B12 deficiency but it recently been supplanted by measurement
of antibodies to intrinsic factor and parietal cells.

Treat metastatic epidural spinal cord compression.

intravenous corticosteroids followed by
decompressive surgery and
radiation therapy.
There is no role for chemotherapy in the immediate
treatment of epidural spinal cord compression.
Spinal cord compression
An urgent MRI spine is essential. The whole spine should
be imaged because multiple bone metastases are possible.
Immediate high-dose steroids: this has been shown to
improve overall outcome by reducing mass effect.
An urgent neurosurgical review should also be sought.
Surgery is the best option for a single site of metastases
Radiotherapy for multiple sites.
Further imaging by radio-isotope bone scan will be
required to determine whether there are any metastases at
other bony sites.
Pamidronate is only used to correct hypercalcaemia from
malignancies and bone pain secondary to osteoporosis.
Chemotherapy would be indicated in chemosensitive
tumours such as lymphoma.
Autonomic dysreflexia

is a syndrome of massive imbalanced reflex sympathetic

discharge occurring in patients with spinal cord injury (SCI)
above the splanchnic sympathetic outflow
Hypertension An antihypertensive agent with rapid onset
and short duration (nifedipine) is administered for elevated
blood pressure.
erythema (more likely in upper extremities)
headaches and blurred vision.
Mortality is rare with AD, but morbidity such as stroke,
retinal hemorrhage and pulmonary edema if left untreated can
be quite severe.
Spinal artery infarction
symptoms evolve over minutes.
acute onset of thoracic back pain,
Usually lower limb affected not upper limbs
CSF normal
Spinal shock
o flaccid tone bilaterally, paraplegia, with areflexia and absent
plantar responses
o dissociated sensory loss ,,loss of pain and temperature
sensation below the level of injury, with relative sparing of
position and vibratory sensation
o bladder
Central cord syndrome, i.e. syringomyelia,
LMN weakness in the arms greater than UMN weakness in
the legs, and
dissociated pain and temperature loss in the arms.
Neuralgic amyotrophy "Brachial neuritis'
It usually proceeded by viral upper respiratory tract
Pain around the shoulder is the presenting symptom that is
usually very severe.
As the pain starts resolving, weakness begins and usually
affects the muscles innervated by the upper brachial plexus (C56).
o biceps and supinator jerk are both depressed
o Weakness of shoulder abduction and elbow flexion
o Sensation was reduced to all modalities over the deltoid
Treatment is conservative. It is usually a self-limiting
condition (improvement over weeks to months).
Anterior cord syndrome secondary to cervical disc herniation at
In the upper limb there is
o lower motor neuron (LMN) signs at the level of C5/C6 as
evidenced by absent biceps/supinator jerks and weak elbow
flexion, and
o UMN signs below this level (brisk triceps jerk, positive
Hoffman's sign, weakness of handgrip, wrist extension, elbow
o Spinothalamic disruption affecting C6-T1 bilaterally reduced

pain and temperature sensation affecting the thumb, middle,

ring, little finger and medial forearm bilaterally.
o Intact dorsal colomn Vibration and light touch were intact
In the lower limb there is
o upper motor neuron (UMN) weakness and
o evidence of spinothalamic disruption
C5 radiculopathy secondary to disc protrusion
Acute onset pain at the base of the neck and shooting pain
affecting the lateral aspect of his arm to the elbow
weakness of biceps and deltoid muscles "weakness of
shoulder abduction"
depression of the biceps and supinator reflexes, which are
supplied by C5/C6.
triceps reflex appeared intact.
diminished sensation over the deltoid, over the upper
lateral aspect of the arm
some nuchal rigidity on testing neck movements.
Lateral disc protrusion
o Lateral flexion to the left appeared to bring on the left sided
shooting pain.
o Lower limb examination was entirely normal.
central disc protrusion
o leading to cord compression and spastic leg weakness.
Axillary nerve injury.
This nerve arises from the posterior cord of the brachial
plexus and supplies the teres minor and deltoid muscles.
It may be involved in
o dislocations of the shoulder joint
o fractures of the neck of the humerus,
o serum and vaccine induced neuropathies.
o paralysis of abduction of the arm between 15o and 90o,
o wasting of the deltoid muscle and
o slight impairment of sensation over the outer aspect of the
Treatment is conservative
Ulnar neuropathy
wasting of the dorsal interossei of the right hand,
clawing of the right little finger and partial clawing of the
ring finger.
Tone and reflexes both appeared normal,
weakness of adduction and abduction of the fingers
Sensory impairment over the palmar and dorsal aspects of
the little finger, with the medial aspect of the ring finger not
extending beyond the wrist.
L2, L3 root Lesion:
weak hip flexors and quadriceps
knee jerks affected
radicular pain/paraesthesia over anterior aspect of the
thigh, groin and testicle
L4 root Lesion
weak quadriceps, tibialis anterior and posterior
knee jerks affected

radicular pain/paraesthesia over the anteromedial aspect of

the leg
L5 root Lesion
weak hamstrings, peroneus longus, extensors of all toes
no tendon reflexes affected
radicular pain/paraesthesia over the buttock, posterolateral
thigh, anterolateral leg and dorsum of the foot
S1 sacral root:
weak plantar flexors, extensor digitorum brevis, peroneus
longus, hamstrings
ankle jerks affected
radicular pain/paraesthesia over the buttock, back of thigh,
calf, lateral border of the foot
Diabetic Lumbosacral Plexopathy
Asymmetrical pain in the hip, buttock, or thigh.
Proximal weakness in quadriceps, hip adductors, and
iliopsoas muscles is characteristic.
Patients may have underlying distal symmetrical
polyneuropathy (DSPN).
Significant recent weight loss frequently is reported.
Proximal lower limb muscle weakness and wasting are
characteristic. The patient has particular difficulty getting up
from a squatting position.
Minimal sensory loss is observed.
The knee-jerk reflex is absent, with commonly preserved
ankle jerks; however, ankle jerks also may be absent with
underlying distal symmetrical polyneuropathy.
Upper lumbar plexus lesion
weakness of hip flexion
weakness of adduction of the thigh and extension of the leg
with anaesthesia over the anterior thigh and leg.
Lower plexus lesions
weaken the posterior thigh and foot muscles.
Lesions affecting the entire plexus
will affect all muscle groups causing weakness or paralysis
of the leg, areflexia and anaesthesia from the toes, to involve the
perianal area.
Sciatic nerve palsy (L4,5,S1,S2,S3)
Supplies the hamstrings "back of thigh" and all muscles
below the knee
weakness of knee flexion " wasting of the hamstrings"
No weakness of knee Extension "Knee reflex is normal
which is supplied by femoral nerve for quadriceps muscles"
Foot droop "failure of ankle dorsiflexion"
Loss of ankle reflex
Sensory examination reveals reduced sensation to all
modalities over the whole of the right lower leg and back of
involvement of thigh adduction, flexion and anaesthesia

over the anterior thigh would go against a sciatic nerve palsy

o trauma or fracture to the hip or pelvis.
o ill-placed intramuscular injections
o following hip surgery.
o Other causes include
neurofibromas or
nerve necrosis secondary to infection or diabetes.
Femoral neuropathy (L2-4)
hip weakness, knee extension and anaesthesia over the
anterior thigh,
but would not explain weakness of the foot.
In Polymyositis Deep tendon reflexes may be impaired or
absent if weakness is severe
Guillain-Barre syndrome
Back pain occurred at rest radiating to both legs
Fever should not be present, and if it is, another cause
should be suspected.
Ascending symmetrical progressive weakness and
numbness affecting initially the legs and extending to involve
the upper limb.
with or without numbness or tingling.
bulbar weakness, dysphagia
Facial weakness is also commonly a feature, but eye
movement abnormalities are not commonly seen in ascending
GBS, but are a prominent feature in the Miller-Fisher variant
Areflexia bilaterally
Sensory loss, if present, usually takes the form of loss of
position sense
Sensory loss to all modalities bilaterally may occur
loss of autonomic function is, manifesting as
o wide fluctuations in blood pressure,
o resting tachycardia
o Bladder dysfunction
CSF findings
o Often normal at the onset of symptoms in GBS
o May be elevated protein level
o CSF white cell count is usually normal,,,
o A sustained increased white blood cell count may indicate an
alternative diagnosis such as infection.
o the major importance of a lumbar puncture is to exclude
other diagnoses due to infections or neoplasms
Nerve conduction studies help in the diagnosis but again
can be normal early on in the disease
EMG may demonstrate evidence of denervation
anti-GM1-ganglioside antibodies: found in 30% and
generally reflect worse prognosis
The most important aspect of initial management is
o monitoring of respiratory function
o monitoring of autonomic function
o initially IV immunoglobulin
o bedside four hourly monitoring of her forced vital capacity.
o Plasma exchange could be considered if the patient had

significant respiratory compromise

o prophylactic anticoagulation and stockings
o monitoring for cardiac arrhythmias
o steroids are of no benefit
Disease Age presentation Reflex Other Investigation
Lambert-Eaton proximal upper and lower limb weakness
Absent Autonomic neuropathy
NO ptosis, NO diplopia 1. Antibodies to voltage-gated calcium
channel receptors
2. electrodiagnostic studies
Myasthenia gravis Normal Normal sensory 1. EMG
Inclusion body myositis Distal upper and proximal lower limb
weakness Normal 1. Muscle biopsy
2. creatine kinase can be normal
Guillain-Barr syndrome. Weakness of distal lower
extremity, with stocking-glove sensory loss Absent sensory loss
1. EMG demyelinating
2. CSF
Pupillary abnormalities do not occur in myasthenia gravis.
Lambert-Eaton myasthenic syndrome
proximal upper and lower limb weakness,
Autonomic symptoms occur in up to 75% of patients and
o dry mouth,
o constipation,
o blurred vision,
o sluggish pupillary reflexes
o postural hypotension
o impaired sweating.
o erectile dysfunction),
proximal muscle weakness (legs greater than arms)
absent reflexes that return after brief
Dr albarwari, May 13, 2011

Dr albarwariGuest

Lambert-Eaton myasthenic syndrome
proximal upper and lower limb weakness,
Autonomic symptoms occur in up to 75% of patients and include
o dry mouth,
o constipation,

o blurred vision,
o sluggish pupillary reflexes
o postural hypotension
o impaired sweating.
o erectile dysfunction),
proximal muscle weakness (legs greater than arms)
absent reflexes that return after brief exercise
The diagnosis of Lambert-Eaton myasthenic syndrome precedes the clinical
diagnosis of cancer in up to 50% of affected patients
Nerve conduction test Decremental response at lower rates of stimulation after
repetitive nerve stimulation and incremental response at higher rates of stimulation
Tensilon test may be +ve
Voltage-gated calcium channel antibodies are seen in almost 100% of LEMS
patients with cancer and in more than 90% of individuals without cancer
Management 3,4-diaminopyridine
Myasthenia gravis crisis
Acetylcholine antibodies may be negative
dysphagia requiring nasogastric feeding and/or
severe respiratory muscle weakness necessitating ventilation.
treated with plasmapheresis or IV immunoglobulin.
Seronegative myasthenia gravis
Patients without anti-AChR antibodies
have antibodies against muscle-specific kinase (MuSK). MuSK
are predominantly female, and respiratory and bulbar muscles are frequently
Late onset myasthenia gravis is associated with thymic atrophy as opposed to
thymic hyperplasia.
The most important factor influencing management in this patient is whether
there is impending respiratory muscle weakness.
the patient should be initially commenced on pyridostigmine 60 mg QDS.
If not responding, prednisolone can be cautiously added in small doses to start
with, normally 10-20 mg/day.
High dose prednisolone can lead to paradoxical worsening of myasthenia gravis.
MillerFisher syndrome
Flexor plantar responses
no disturbance of consciousness.
anti-GQ1b antibodies are often positive.
History of viral upper respiratory tract infection
Bickerstaffs brainstem encephalitis
Extensor plantar responses
Disturbance of consciousness.
anti-GQ1b antibodies are often positive.
History of viral upper respiratory tract infection
Botulism can be

o food-borne or
o 3 Days after wound infection or
o from intravenous drug injection.
A descending flaccid paralysis affecting cranial nerves and then spreads towards
the limbs
o Diplopia
o Ptosis
o Facial weakness
o Dysarthria
o Dysphagia
Reflexes are depressed or absent OR normal
sensation is normal
Autonomic features particularly
o Vomiting
o Abdominal pain
o paralytic ileus
o bradycardia
o Dry mouth
o fixed dilated pupils
CSF is normal in botulism.
Diagnosis is by isolating the toxin in the blood, urine or stool.
It is a neuromuscular junction disorder and therefore nerve conduction studies
and EMG are normal.
Botulism can cause a false positive tensilon test result
Repetitive nerve stimulation shows incremental responses, which is diagnostic of
Large doses of botulinum antitoxin can be given intravenously, but are
ineffective once the toxin has bound to an acetylcholine receptor site.
The drug guanidine hydrochloride helps to reduce neuromuscular blockade
o Early administration of IV antitoxin may help reverse paralysis.
o NO role for Intravenous (iv) immunoglobulin
o should be managed in an ITU setting.
Supportive therapy with intubation and ventilation,
respiratory physiotherapy,
nasogastric tube placement and
o Recovery occurs on average between 30 and 100 days after infection;
o severe cases may require ventilation for many months.
Lyme disease
spare the extraocular muscles.
Myotonia dystrophica
Trinucleotide repeats on chromosome 19.
Weakness of the muscles of the face temporalis, masseters and
sternocleidomastoids), neck, and distal extremities are typically involved.
Both hands and wrists were wasted and weak,,, Bilateral foot drop was noticed.
Tendon reflexes were hypoactive
They are prone to recurrent jaw dislocation.
With progressive disease the proximal muscles, bulbar muscles and even the
diaphragm are involved.
Respiratory failure

Progressive dementia,
abnormal immunoglobulins with the risk of increased infections
Myotonia is the hallmark and is characterised by inability to quickly relax a
contracted muscle.
Diagnosis is normally based on
o clinical features with a
o characteristic EMG of myotonic discharges.
o Creatine kinase is generally normal and
o muscle biopsy is non-specific.
The disabling grip myotonia can be treated with phenytoin but should be used
carefully as may have cardiac conduction defects.
KearnsSayre syndrome
mitochondrial diseases
starts before the age of 20 years.
progressive external ophthalmoplegia,
retinitis pigmentosa, increased difficulty seeing at night
cardiac conduction defects and a
cerebellar syndrome. ataxic gait
sensorineural hearing loss
endocrine pathology
Chronic thyroid myopathy (Basedow paraplegia)
is a progressive weakness and wasting of skeletal muscles occurring in
conjunction with overt or masked hyperthyroidism.
The classic signs of hyperthyroidism may or may not be present.
This type of muscle disease presents in middle-aged males more often than
Muscles of the pelvic girdle and thigh are weakened more often, though all
muscles are variably affected.
Tendon reflexes are brisk.
Serum concentration of muscle enzymes is not elevated.
EMG reveals polyphasic potentials.
With successful treatment of hyperthyroidism, muscle bulk and power return to
McArdles syndrome
a type-V glycogen-storage disorder
This disorder is characterised by muscle phosphorylase deficiency.
Symptoms include exercise-induced muscle pain and stiffness with contractures
that subside at rest.
Myoglobinuria can occur.
In normal patients there is a sustained increase in serum lactate after exertion,
but this does not occur in patients with McArdle's.
The diagnosis is confirmed by muscle biopsy, which demonstrates
subsarcolemmal glycogen deposition and central migration of muscle nuclei.

Critical illness myopathy.

Critical illness refers to the syndrome of sepsis and multiple organ failure.
in the intensive care unit,
o either in patients who have difficulty weaning from mechanical ventilation (up to
30% of patients) or
o in patients who have developed severe limb weakness during or after recovery from

critical illness.
Creatine phosphokinase (CPK) is elevated
EMG to exclude other conditions, such as Guillain-Barr syndrome, and
confirm the diagnosis of critical illness myopathy or neuropathy.
EMG reveals myopathic motor unit potentials and fibrillations.
Muscle biopsy reveals loss of myosin filaments.
Most patients recover after several weeks.
Physical and occupational therapy is ideally initiated immediately on recognition
of this syndrome.
It is important to note that this type of myopathy has not been seen after highdose corticosteroid treatment for neurological diseases like multiple sclerosis
Listeria meningoencephalitis
Affects mainly older patients (more than 50 years old)
immunosuppressed (diabetes, excess alcohol, oncology patients).
It produces a mixed picture of
o meningitis and
o brain stem encephalitis. fifth, sixth and seventh cranial nerve palsies with bulbar
The treatment of choice is ampicillin intravenously. Delayed treatment carries a
high mortality.
CSF leucocytosis may occur in
Lyme disease
Partially treated bacterial meningitis.
CSF Finding
Opening pressure 210 mmH20 (NR 50 - 180mm H20)
CSF protein 0.98 g/L (NR 0.15 - 0.45 g/L)
CSF white cell count 140 per ml (NR 5 cells per ml)
CSF white cell differential 90% lymphocytes (NR 60 - 70%)
CSF red cell count 4 per ml (NR 3.8 - 5.6 x 1012/L )
CSF glucose 3.6 mmol/L (NR 3.3 - 4.4 mmo/L)
Subdural empyema
from an infection in the frontal or ethmoid sinuses, less commonly from middle
ear infection.
Streptococci (viridans and non-haemolytic) are the most common organisms,
followed by Staphylococcus aureus, E.coli, proteus and pseudomonas.
Focal lesions may occur as partial seizure "continuous twitching of the hand and
Lumbar puncture may reveal:
Opening pressure 20 cm H2O (518)
Protein 0.85 g/l (0.150.45)
WCC 120 cells/ml (90% lymphocytes)(5)
RCC 3 cells/ml(5)
Glucose 3.4 mmol/l (3.34.4)
MRI is more dependable at demonstrating a collection of pus and meningeal
enhancement than CT scan, and should be arranged urgently.
In the meantime, high-dose intravenous (iv) antibiotics and iv lorazepam should
be given to treat infection and simple partial seizures.

TB meningitis
Subacute onset with confusion;
in a homeless person;alcoholic
Brainstem signs
associated secondary spinal meningitis;
characteristic CSF findings especially the
o very high protein and
o very low glucose.
Low blood sodium of 119 mmol/l is suggestive of SIADH (secretion of
inappropriate antidiuretic hormone).
Spinal arachnoiditis
o weakness and pain of lower limbs
o retention of urine.
o spastic paraparesis with sensory levels of different segments eg, T4, T6, T8, L3
defect while T5, T7, L1, L2 Normal
o confirmed on myelogram (candle guttering appearance) or on MRI
an empirical treatment with four antituberculous (eg rifampicin, INH,
pyrazinamide and ethambutol) drugs is usually started when diagnosis is suspected
on clinical grounds.
Limbic encephalitis
paraneoplastic or
autoimmune disease.
It presents with
o a subacute onset of memory impairment,
o disorientation
o +/ seizures and
o psychiatric disturbances (hallucinations, agitation and sleep disturbance).
o Hypothalamic disease (hyperthermia, weight gain, endocrine dysfunction,
MRI show Medial temporal lobe changes
CSF shows
o raised protein
o oligoclonal bands
o 50% have raised WBC.
A recently described subgroup of patients has
o antibodies to voltage-gated potassium channels.
o 80% have resistant hyponatraemia.
o only 10% had oligoclonal bands.
o This group has shown an improvement with immunosuppressive treatment (IVIg,
plasma exchange, steroids) both clinically and with a decrease in the titre of
voltage-gated potassium channel antibodies.
are often found incidentally during neuroimaging studies.
may be asymptomatic or have subtle signs and symptoms.
Seizure is the most common presentation and is reported in greater than 50% of
symptomatic patients.
Meningiomas characteristically appear on CT scans and MRIs
Treatment . Older adults with small, asymptomatic tumors can be managed
conservatively with observation and serial neuroimaging studies.
Surgical resection is the treatment of choice for younger patients with and
without symptoms and for symptomatic older adults and is curative when complete.
Radiation therapy or stereotactic radiosurgery may benefit patients with
unresectable or rare aggressive meningiomas

Parasagittal meningiomas
may produce seizures may be partial "as rhythmic jerking of the limb" or be
entirely asymptomatic,
Lesions that reach sufficient size may cause spastic paraparesis
Upgoing planter bilaterally
Diagnosis MRI of brain
Brain metastases
are 10 times more common than primary brain tumors,
occur in 20% to 40% of adults with cancer.
The tumors most likely to metastasize are
o lung and
o breast carcinoma and
o melanoma.
Presenting signs and symptoms ,,,local mass effect or increased intracranial
pressure; common symptoms include seizure, headache, behavioral changes
Contrast-enhanced MRI is the diagnostic modality of choice when brain
metastasis is suspected.
o MRI has a higher sensitivity and specificity than CT scanning
o It is safer because MRI contrast does not cause nephrotoxicity, and allergies are
extremely rare.
o normal findings on a CT scan do not exclude the presence of a brain tumor, so a
follow-up MRI would be required.
Meningeal carcinomatosis
is seen in 5% of cases of adenocarcinoma of the breast, lung, gastrointestinal
tract, melanoma, lymphoma etc.
The clinical presentation is variable
o headache,
o sciatic pain,
o cauda equina syndrome,
o multiple cranial nerve palsies,
o confusional state,
o seizures,
o focal neurological deficits and
o poly-radiculoneuropathy.
The diagnosis is established by
o MRI brain with gadolinium
o CSF examinations
identifying tumour cells in CSF using
o cytospin,
o millipore filtering and
o flow cytometry.
It is important to note that several CSF examinations are usually required using
large quantities of CSF,,so if CSF ve it can be repeated
CSF opening pressure is increased and
lymphocytic pleocytosis up to 100 cells/mm3,
elevation of protein, and
low glucose are common findings.
Prognosis The median duration of survival is 6 months.

Foster-Kennedy syndrome
loss of smell.
olfactory meningioma with optic nerve involvement.
optic atrophy on one side with
contralateral papilloedema
due to frontal tumour or tumour within the olfactory bulb compressing the
ipsilateral optic nerve and causing raised intracranial pressure.
Cerebellar pontine angle syndrome
Involvement of cranial nerve V, VI, VII, and VIII.
cerebellar dysfunction
Conus medullaris lesion = UMN+LMN
Cauda equina lesion is a LMN
Conus Medullaris Syndrome Cauda Equina Syndrome
Presentation Sudden and bilateral Gradual and unilateral
Reflexes Knee jerks preserved but ankle jerks affected Both ankle and knee jerks
Radicular pain Less severe More severe
Low back pain More Less
Sensory symptoms and signs Numbness tends to be more localized to perianal area;
symmetrical and bilateral; sensory dissociation occurs Numbness tends to be more
localized to saddle area; asymmetrical, may be unilateral; no sensory dissociation;
loss of sensation in specific dermatomes in lower extremities with numbness and
paresthesia; possible numbness in pubic area, including glans penis or clitoris
Motor strength Typically symmetric, hyperreflexic distal paresis of lower limbs that is
less marked; fasciculations may be present Asymmetric areflexic paraplegia that is
more marked; fasciculations rare; atrophy more common
Impotence Frequent Less frequent; erectile dysfunction that includes inability to have
erection, inability to maintain erection, lack of sensation in pubic area (including
glans penis or clitoris), and inability to ejaculate
Sphincter dysfunction Urinary retention and atonic anal sphincter cause overflow
urinary incontinence and fecal incontinence; tend to present early in course of
disease Urinary retention; tends to present late in course of disease
NO incontinence
Pontine myelinolysis
may occur in Rapid correcting HypoNatremia acute para- or quadraparesis,
dysphagia, dysarthria, diplopia, loss of consciousness, and other neurological
symptoms associated with brainstem damage. The patient may experience locked-in
Serotonin syndrome as in Moclobemide
Serotonin toxicity leads to
Changes in mental status:
o Confusion
o Agitation
o Hypomania (the happy drunk state)
o drowsiness,
o myoclonus,
o Anxiety
o Coma
Systemic changes:
o Tachycardia
o Hypertension
o Nausea

o Salivation
o Rhabdomyolysis
o DIC + Acute renal failure
o Pyrexia
Motor complications:
o Myoclonus
o Hyper-reflexia
o Seizures
o Inco-ordination
o Tremor.
Treatment is supportive and involves
removing the precipitating drugs,
controlling agitation,
administering serotonin antagonists (cyproheptadine or methysergide) and
controlling hyperthermia.
Treatment for hyperthermia includes
reducing muscle over-activity via sedation with a benzodiazepine.
More severe cases may require muscular paralysis with vecuronium, intubation,
and artificial ventilation. Succinylcholine is not recommended for muscular paralysis
as it may increase the risk of cardiac dysrhythmia from hyperkalemia associated with
Antipyretic agents are not recommended as the increase in body temperature is
due to muscular activity not a hypothalamic temperature set point abnormality
Selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome
which typically occurs following abrupt withdrawal of SSRIs.
Symptoms can occur within days and can last months following withdrawal and then
Psychiatric (anxiety, insomnia, mood lability, vivid dreams)
Gastrointestinal (nausea, vomiting) and
Neurological (dizziness, headache, paraesthesia, dystonia, tremor)
Neuroleptic malignant syndrome
o anti-psychotic neuroleptic medication
o patients with Parkinson's disease (PD) who suddenly stop their L-dopa treatment
The mortality is 15-30% if it is not recognised and treated properly.
o confusion,
o hyperthermia,
o muscle rigidity "meningism"
o autonomic dysfunction (dysphagia).
o unstable blood pressure and profuse sweating
Serum creatine phosphokinase may rise up to 60 000 units/l and may lead to
myoglobinuria and Rhabdomyolysis + acute renal failure
Treatment should be started early when consciousness is first altered and
temperature is rising.
Bromocriptine 5 mg tid (up to 20 mg tid) will terminate the condition.
Intravenous dantrolene should be given if the patient is unable to swallow.
Upper brachial plexus injury C5, 6, 7
o idiopathic brachial neuritis,
o irradiation
o trauma (arm jerked downward)
lower brachial plexopathy.C8, T1

o infiltration by malignant tumor,

o cervical rib
o trauma (arm jerked upward)
o C8/T1 root involvement associated with increasing shoulder pain and an ipsilateral
Horner's syndrome
cranial nerves are present 50-70% of cases. facial nerve, optic nerve
Seizures (mostly of the tonic-clonic/"grand mal" type)
Meningitis headache and nuchal rigidity (
spinal cord is rare,
cauda equina symptoms
hypopituitarism: amenorrhoea, diabetes insipidus hypothyroidism or
hypocortisolism (deficiency of cortisol).
Mental and other
depression and psychosis.
Peripheral neuropathy
Weber without lateralization Weber lateralizes left Weber lateralizes right
Rinne both ears AC>BC Normal Sensorineural loss in right Sensorineural loss in left
Rinne left BC>AC Conductive loss in left Combined loss : conductive and
sensorineural loss in left
Rinne right BC>AC Combined loss : conductive and sensorineural loss in right
Conductive loss in right
Progressive multifocal leukoencephalopathy
infection of oligodendrocytes with JC virus, which is a papovavirus found latent
in most healthy adults.
With CD4 counts of less than 100 this virus becomes active leading to
progressive neurological deterioration.
o neoplasm or
o a chronic immunodeficiency state.
o It may also occur in patients receiving immunosuppressive drugs.
o Natalizumab for multiple sclerosis was shown to have led to this disease
Behavioural changes in clear consciousness.
There is absence of fever or depressed conscious level, which would be more in
keeping with lymphoma, HIV encephalopathy or abscess.
Personality changes and intellectual impairment are the initial features that
evolve over several days or weeks followed by
o focal neurological signs
ataxia and
cortical blindness, and visual field defects,
o This is followed by coma and death over 3 to 6 months.
A brain biopsy would be the definitive diagnostic test showing asymmetric foci of
demyelination and intranuclear inclusions containing the JC virus.

There is no effective treatment, but progression can be slowed by initiation of

antiretroviral therapy
Sub-acute sclerosing panencephalitis.
It is recognised to be the result of chronic measles infection. a history of measles
very early in life followed by 68 years of asymptomatic period.
Intellectual deterioration "decline in proficiency in school" is followed by Diffuse
myoclonic jerks "shock like contractions of shoulder muscles " in association with
Focal and generalised seizures and Visual deterioration due to choiroidoretinitis. This
is followed by Pyramidal signs, rigidity Finally the patient lies decorticated followed
by death.
The course of the illness is 1 to 3 years. No effective treatment is available.
Cerebral malaria
symmetrical encephalopathy
no focal signs.
Three negative blood films are required to exclude this diagnosis.
should be considered, even though the patient is taking prophylaxis
Permanent vegetative state (PVS)
is defined as a state of 'wakefulness without awareness'.
The patient breathes spontaneously without mechanical support, is
haemodynamically stable and has cycles of eye closure and opening that resemble a
normal sleeping pattern but the patient is inattentive and unaware of his/her
Patients may have spontaneous movements (moaning, grunting, teeth grinding,
roving eye movements) and may also smile, laugh and cry without any apparent
Although there may be eye movement, the eyes do not track a moving object.
Patients may respond to painful stimuli and
may have myoclonus in response to startling stimuli.
Primitive reflexes may be present.
Posture may become decorticate and
plantar responses are commonly extensor.
The condition typically occurs when there is irreversible damage to the cerebral
hemispheres but
the brain stem remains intact.
Causes include
Head injury
Hypoxic injury (cardiac arrest, carbon monoxide poisoning)
Intracranial infection
End-stage degenerative brain disease (for example, Alzheimer's).
Locked-in syndrome
patients are aware of themselves and their environment but
are unable to respond due to loss of motor and speech function.
The cause is usually either
(1) an upper motor neuron lesion of the descending corticospinal tracts in the
brainstem (often the pons) below the level of the oculomotor nerve nuclei, (for
example, infarction, haemorrhage, tumour, demyelination, head injury, central
pontine myelinolysis after hyponatraemia) or
(2) widespread lower motor neuron disease (for example, polyneuropathy such as
Guillain-Barre syndrome).

Clinically, the patient is unable to speak or move but patients may be able to open
their eyes and may blink in an effort to communicate.
Locked-in syndrome
Usually results in quadriplegia and the inability to speak
lesions in the Ventral pons "not dorsal"
central pontine myelinolysis
Basilar artery "not vertebral" occlusion may cause it
Basilar artery territory cerebrovascular disease
is typically associated with a poor prognosis.
4060% of patients present with motor deficits,
3060% with dysarthria and speech involvement,
5075% with nausea, vertigo and vomiting
40% with headaches
2030% with visual disturbances. This includes
o abducens nerve palsy,
o conjugate gaze palsy,
o internuclear ophthalmoplegia and
o ocular bobbing.
Around 70% of patients presenting with basilar artery territory stroke are
Management includes vigorous control of hypertension and antiplatelet agents.
Phenytoin toxicity typically gives rise to a
Cerebellar-like syndrome.
Nystagmus is present even in mild toxicity.
cause abnormal liver function test
Nystagmus is not a feature of sodium valproate toxicity but can cause nausea and
Gradenigo's syndrome "petrous osteitis"
1st 5 + 6
Retroorbital pain due to pain in the area supplied by the ophthalmic branch of
the trigeminal nerve
Ipsilateral paralysis of the abducens nerve
otitis media.
Other symptoms can include photophobia, excessive lacrimation, fever
Trigeminal nerve and Abducence palsy 5 + 6
The involvement of all the three divisions of the trigeminal nerve suggests that
the lesion has either involved the Gasserian ganglion or its roots and since the
neighbouring 6th nerve is also affected the latter localisation at the petrous temporal
bone is more likely.
Lesions like
o meningiomas,
o schwannomas,
o metastasis, and
o nasopharyngeal carcinoma invading the base of the skull,
o granulomatous infections or
o carcinomatous meningitis would be the likely causes.
Tolosa-Hunt syndrome
3+4+1st 5+6
severe and unilateral headaches
extraocular palsies, usually involving the third, fourth, fifth, and sixth cranial

pain around the sides and back of the eye

Glomus jugulare tumour
Female ,,present between 40 and 70 years of age
A combination of 9th, 10th, 11th nerve palsies "jugular foramen syndrome"
The patient has also developed pulsatile tinnitus
Hearing loss may be conductive or sensorineural; with the latter there may be
Less commonly, the tumours can enlarge sufficiently to cause affect cranial
nerves VII and XII.
Intracranial extension can produce headache, hydrocephalus and raised
intracranial pressure.
Otoscopic examination may reveal a characteristic pulsatile reddish-blue mass
behind the tympanic membrane.
Surgical resection is the treatment of choice, although embolisation and
radiotherapy have been used.
Jugular foramen syndrome
soft palate dropping
deviation of the uvula towards the normal side
loss of sensory function from the posterior 1/3 of the tongue
decrease in the parotid gland secretion
loss of gag reflex
sternocleidomastoid and trapezius muscles paresis
Glomus tumors (most frequently)
Schwannomas (Acoustic neuroma)
Metastatic tumors located at the cerebellopontine angle
Cerebellopontine angle lesion 5,6,7,8th palsy
Causes acoustic neuroma, glioblastoma, lipoma, vascular malformations,
meningiomas, cholesteatomas and hemangiomas.
8th palsy 'buzzing noise' in ear sensorineural deafness Weber's test reveals
lateralisation of the sound to the normal ear. Rinne's test reveals air conduction
better than bone conduction in both ears,
Foramen magnum syndrome
combination of lower cranial nerve dysfunction
associated with long tract signs.
There may be an accompanying occipital headache and neck stiffness and,
on occasion, obstruction of the cerebrospinal fluid (CSF) drainage can lead to

Endotracheal administration of drugs is
no longer recommended
In PPCM,,, Heparin given even before

In acute MI presented with

cardiogenic shock we can give IV
Ventilator-associated pneumonia. It
occurs 48-72 h after admission, and
worsening pulmonary infiltrates despite
negative fluid balance are suggestive of
chest infection. Appropriate management
o fluid resuscitation to achieve optimal
left heart filling pressure, and
o intravenous antibiotics.
o Inotropic support in the form of alpha
agonist is indicated if fluid resuscitation
alone does not improve the blood
Post inferior MI complete HB
o If asymptomatic need NO treatment
o If asymptomatic give atropine if no
response to atropine we can do temporary
Bradycardia,,,The 2010 UK
resuscitation guidelines suggest using
theophylline as a slow intravenous
infusion (100 mg-200 mg).
Bradycardia-induced syncope
o Admit and arrange a 24 hour tape as an
o if cardiovascularly stable no need for
Asystolic cardiac arrests updated
2010 UK resuscitation guidelines no
longer recommend atropine for asystole
Adrenaline alone - repeated doses every 3
to 5 minutes Isoprenaline has no role in
asystolic cardiac arrests
Mobitz type II block in anterior
myocardial infarction treated by
temporary transvenous pacing regardless
of symptoms "not option for Atropin"
Indications for transvenous pacing in
acute MI are:
o asystole
o symptomatic sinus bradycardia or
Mobitz I block not responding to atropine
o Mobitz type II block in anterior
myocardial infarction
o Junctional escape rhythm + wide QRS
o new bundle branch block (BBB) with
first-degree heart block
o an old right BBB with first degree
atrioventricular (AV) block and a new
fascicular block
Syncope + RBBB + left posterior
fascicular block + PR interval is 190

ms,,,,here do not go directly for

permanent pacemaker but Admit for 24
hours and follow up with 72hr - 1 week
holter monitoring for possible episodes of
complete heart block then if CHB present
you can do pacemaker
When a monitored patient develops
VF, and resuscitation and defibrillation
equipment is closely available (as would
be the case on CCU) the recommendation
is to attach the defibrillator and
administer a shock without delay "not do
Praecordial thump"
Praecordial thump is only
recommended if a patient has a witnessed
arrest, is not monitored and/or
immediate defibrillation is not available
(and it should not delay calling for help or
getting a defibrillator).
WPW syndrome with "narrow
complex" presented with palpitation not
respond to adenosine next step give either
IV flecainide or disopyramide "
Amiodarone less effective in
WPW syndrome + AF "broad
complex" best treatment is IV Flecainide
AF + Heart failure can be treated
with Digoxin or b-blocker
Paroxysmal AF + mild Left
venyricular impairment best treatment is
bisoprolol + warfarin
Paroxysmal AF + normal heart need
cardioversion best treatment is flecainide
AF + normal heart need
cardioversion best treatment is flecainide
which is better than sotalol
Patient presented with acute onset
AF. The immediate need would be to rate
control his atrial fibrillation and try and
manage chemical cardioversion WITH
anticoagulation "eg Amiodarone +
Patient with congestive heart failure
and AF the best drug to stabilise the
patient cardiovascularly before the
imminent surgery is Amiodarone not
Patient with Mitral valve stenosis
"not in failure" + AF the best drug to
stabilise the patient is IV Esmolol
Paroxysmal SVT,, best treatment is
adenosine then verapamil then sotalol
Patient with an acute coronary

syndrome and rapid narrow complex

tachycardia ,,,Give her a fast intravenous
(IV) dose of adenosine 6 mg and
repeating it if there is no response "not
give b blocker'
Atrial flutter
o Radiofrequency ablation of typical AFL
has a long-term success rate of greater
than 90%
o Flecainide should not be used as a single
o Flecainide may be used in conjunction
with AV nodal blocking agents, such as a
-blocker or a nondihydropyridine
calcium channel blocker
The treatment for polymorphic
ventricular tachycardia is
o synchronised cardioversion when the
patient is unstable
o magnesium and potassium to correct
any electrolyte imbalances and overdrive
Stent thrombosis usually occurs in
the first two days after the procedure
presented with myocardial infarction
treatment by Intravenous (IV) abciximab
and immediate transfer to Cardiac
Catheterisation L for intracoronary
thrombolytic therapy
In pulseless ventricular tachycardia
the initial shock should be 360 J
VT has RBBB pattern while SVT +
aberrant conduction has LBBB pattern
Verapamil is preferred on
Amiodarone for SVT cardioversion
Patients with prosthetic valve
subacute bacterial endocarditis (usually
with viridans Streptococci) often have
minmal symptoms and there may be NO
Patient with mycoplasma pneumonia
on Amitryptilin give him Doxycyclin "not
Erythromycin" because of QT interval
Flash pulmonary oedema. The most
common cause is
o Myocardial ischaemia."ECG changes"
o Bilateral renal artery stenosis "less
Post MI cardiogenic shock
o Dopamine is CI
o IABP "ballon pump" is indicated
Dyspnea in HOCM
o b-blockade first choice

o but if the outflow gradient is greater

than 50 mmHg, surgical myomectomy is
usually recommended. Unfortunately
surgery does not reduce the risk of
750 ml bottle of 12% wine contains
nine units alcohol,,,more than 50 units
alcohol is excess and need to be reduced
in patient with hypertension
Treatment of overweight, diabetic
patients with metformin, lowers the
relative risk of myocardial infarction (MI)
by 40%, as opposed to treatment with
sulphonylureas or insulin
There is no evidence that
commencing T2Ds on insulin lowers the
risk of MI, even if the HbA1c improves
The presence of a VSD would be
confirmed by detecting a step-up in the
oxygen saturation between the RA and
PA; if there is no step-up, the diagnosis is
probably papillary muscle rupture

Trifascicular block is a term used for the combination of
right bundle branch block,
left hemiblock (typically left anterior hemiblock) and
long PR interval
o Clinically it means there is extensive disease of the conduction system and, in a
patient such as this, would be an indication for permanent pacemaker

Indications for permanent pacemaker implantation include

third-degree block,
symptomatic Wenckebach phenomenon,
asymptomatic type II second-degree block, and
pauses of >3.0 s.
Symptomatic sinus node dysfunction is an indication for pacemaker placement,
even if the bradycardia occurs as a consequence of drug therapy, if there is no
acceptable alternative.
Type 2 second degree block
most often occurs in the His-Purkinje system; as such this poses a higher risk to
the patient of progression to complete heart block.
syncopal attacks. Optimal management is therefore referral for permanent
Pacemaker syndrome
Occur in VVI
An untimely contraction of the atria caused by retrograde conduction of the

ventricular pacemaker impulse mimics complete heart block and the pounding is the
feeling of atria contracting against a closed tricuspid valve causing cannon waves in
the neck.
The treatment is to upgrade the system to a dual chamber pacemaker; this allows
the atria to sense any retrograde electrical impulse, so inhibiting native atrial
Lead displacement in pacemaker implantation.
The lead can displace through the ventricle into the pericardial space, leading to
pain with features suggestive of pericarditis.
Electrical stimulation of the diaphragm may be experienced as hiccoughs.
A chest X-ray would reveal the displaced lead in most cases.
Sick sinus syndrome, cause episodes of bradycardia and tachycardia. Antiarrhythmics are likely to exacerbate any bradycardia and the treatment of choice
would be a permanent pacemaker. Dual chamber pacemakers are usually used, as
single chamber pacing may be associated with the development of pacemaker
Paroxysmal atrial fibrillation + complete heart block + ejection fraction points
towards impairment of LV function. Management of choice in this case is dual
chamber pacing, She should continue her sotalol to prevent further episodes of atrial
AV Block after inferior MI
no prognostic significance
usually resolves in the first 24 h.
If the patient is haemodynamically stable and asymptomatic, should continue to
be monitored
If symptomatic give atropin
Indications for permanent pacemaker implantation include
third-degree heart block,
symptomatic second-degree block,
asymptomatic type II second-degree block
pauses of more than 3.0 s.
Carotid sinus hypersensitivity
exaggerated response to carotid sinus stimulation.
The diagnosis is only made after ischaemic heart disease or rhythm disturbance
have been reasonably excluded, as in this case.
CSH may be
o predominantly cardioinhibitory (resulting in bradycardia),
o vasodilatory (resulting in hypotension),
o or a mixture of the two.
Cardioinhibitory CSH is usually managed with insertion of a dual-chamber
pacemaker, and
vasodilatory CSH is managed with support stockings, fludrocortisone and

Do not give atropine to patients with cardiac transplants. Their hearts are
denervated and will not respond to vagal blockade by atropine, which may cause
paradoxical sinus arrest or high-grade AV block in these patients

If bradycardia with adverse signs persist despite atropine, consider cardiac

pacing. If pacing cannot be achieved promptly consider the use of second-line drugs
consider giving intravenous glucagon if a beta-blocker or calcium channel
blocker is a likely cause of the bradycardia
Consider using theophylline (100-200 mg by slow intravenous injection) for
bradycardia complicating
acute inferior wall myocardial infarction,
spinal cord injury or
cardiac transplantation
In structurally normal heart with Paroxysmal SVT
Sotalol, a class III anti-arrhythmic agent would probably represent the best
choice of the options given for this man.
An alternative would be a class 1c agent such as flecainide where patients suffer
side-effects such as erectile dysfunction on -blockade or verapamil.
Recurrent atrial flutter (AFL)
Typical AFL is a macroreentrant circuit that rotates counter-clockwise
around the tricuspid valve
Radiofrequency ablation of typical AFL has a long-term success rate of greater
than 90%
Flecainide should not be used as a single agent in patients with AFL. It can
enhance AV nodal conduction, which may cause 1:1 transmission of AFL waves and
result in ventricular fibrillation.
Flecainide may be used in conjunction with AV nodal blocking agents, such as a
-blocker or a nondihydropyridine calcium channel blocker.
VT Treatment
If compromised with a low blood pressure, even though asymptomatic, the
treatment of choice is DC cardioversion.
In pulseless ventricular tachycardia the initial shock should be 360 J
unsynchronised. The rationale for using unsynchronised shock in pulseless VT is to
avoid the slight delay that might occur with synchronised shock.
Pulseless VT has the same protocol as ventricular fibrillation.
In a witnessed VF arrest the guidelines now suggest that
a single DC shock is given (either a single biphasic (150360 J) or monophasic
(360 J) shock) followed by immediate chest compressions (without feeling for a pulse
or reassessing rhythm).
After 2 min of CPR the rhythm should be reassessed and if still VF a further DC
shock should be given. monophasic (360 J)
After a further 2 min of CPR of VF persist iv adrenaline should be given followed
by a further DC shock.
appropriate energy on the defibrillator (150-200 J biphasic for the first shock and
150-360 J biphasic for subsequent shocks)
Despite the fact if there is acidosis, the use of sodium bicarbonate is no longer
recommended as part of the ALS algorithm drawn up by the UK resuscitation council.
It may however still be considered in cases of profound hyperkalaemia or where there
is overdose of tricyclic antidepressants.
Amiodarone 300mg IV is part of the guidelines for the treatment of persistent VF/VT
(with pulse) after three shocks have been given.
Where there is suspicion of hypovolaemia, e.g. after massive blood loss due to
trauma, then IV fluids may be of value.
At core temperatures of less than 30C, treatment of ventricular arrhythmias with
medical therapy is largely ineffective and electrical cardioversion is less effective. For

this reason, a prolonged period of CPR may be required until core temperature is
above 30C. Where available, for a long period of cardiac arrest, cardiopulmonary
bypass may be effective, although practically this would be possible in only a handful
of centres within the UK. Recovery is usually complete for patients with mild to
moderate hypothermia (28C or higher core temperature) and no pre-existing
medical conditions,
severe hypothermia coupled with pre-existing medical illness carries a mortality of
around 50%.
Precordial thump
A single precordial thump has a very low success rate for cardioversion of a
shockable rhythm and is only likely to succeed if given within the first few seconds of
the onset of a shockable rhythm.
There is more success with pulseless VT than with VF.
Delivery of a precordial thump must not delay calling for help or accessing a
It is therefore appropriate therapy only when several clinicians are present at a
witnessed, monitored arrest, and when a defibrillator is not immediately to hand. In
practice, this is likely to be in a monitored environment such as the emergency
department resuscitation room, ICU, CCU, cardiac catheter laboratory or pacemaker
Torsade de pointes
haemodynamically unstable should be treated with electrical cardioversion.
If stable
Magnesium and potassium are first-line
Other therapies include overdrive pacing and
isoproterenol infusion.
supraventricular tachycardia (SVT) + Asthma
Adenosine is contraindicated in asthmatic patients as is beta-blockade with
The safest alternatives would be IV verapamil or iv flecainide in this patient
Vagal manoeuvres or adenosine will terminate almost all AVNRT or AVRT within
seconds. Failure to terminate a regular narrow-complex tachycardia with adenosine
suggests an atrial tachycardia such as atrial flutter (unless the adenosine has been
injected too slowly or into a small peripheral vein).

Wolff Parkinson White (WPW) syndrome.

If the tachycardia has a narrow QRS complex the anterograde limb (the pathway
that conducts impulse to ventricle) is the atrioventricular (AV) node, while the
retrograde limb is the accessory pathway.
1. The delta wave in this case is lost.
2. This type of tachycardia is called orthodromic AV re-entrant tachycardia.
Termination of orthodromic AV re-entrant tachycardia involves
manoeuvres that depress conduction through the AV node such as carotid sinus
massage or a Valsalva manoeuvre;
if not successful then drugs that depress AV nodal conduction like adenosine is
Digoxin and verapamil should be avoided as they may accelerate conduction down
the accessory pathway.
Intravenous flecainide or disopyramide should be used for chemical cardioversion.

Beta-blockers may also be used.

Amiodarone is slightly less effective in achieving cardioversion in this situation
than flecainide.
DC cardioversion should be used early if the tachycardia is causing haemodynamic
If symptoms are recurrent, patients should be referred for Radio-frequency
ablation, which is the definitive treatment.
Atrial fibrillation of Acute onset
The immediate need would be to rate control his atrial fibrillation and try and
manage chemical cardioversion, in which case IV amodarone is an obvious choice.
Digoxin would not encourage reversion to sinus rhythm so would not be the first
choice here.
The likely outcome is the patient reverting back to sinus rhythm within hours.
If the patient does not revert back to sinus rhythm, formal anticoagulation would
need to be instituted.
He would also need to be investigated for the cause of the atrial fibrillation.
Electrical cardioversion may be an option post anti-coagulation and may still be
considered acutely if he remains compromised or his BP worsens
Brugada syndrome
Right bundle-branch block and ST elevation in the right precordial leads
associated with ventricular fibrillation and sudden death
The underlying cause of BrS is a genetic defect in the SCN5A gene, which
encodes the sodium channel controlling the depolarisation phase of the cardiac
action potential.
There are usually no structural abnormalities in Brugada syndrome (BrS)
patients and the disease may be defined as a pure electrical abnormality of
myocardial cells.
BrS manifests with syncope and cardiac arrest typically occurring in the third
and fourth decade of life, and usually at rest or during sleep.
Ajmaline test,,,Ajmaline is a class Ia antiarrhythmic agent. It is often used to
bring out typical findings of ST elevations in patients suspected of having Brugada
syndrome. Intravenous drug testing and electrophysiological testing for diagnostic
An implantable defibrillator is the treatment of choice in these patients,,,it may
remarkably improve quality of life. Studies suggest that the majority of BrS patients
are likely to remain asymptomatic and are at relatively low risk of relapsing.
patients may also be considered for therapy with quinidine, particularly those
who present with "VF storm", with multiple firings of their defibrillator in one day.
Syncope cardiac
The gold standard for diagnosis of an arrhythmic cause of syncope is
documentation of a rhythm disturbance at the time of symptom occurrence.
The choice of monitoring test should be related to the frequency of the
patient with recurrent, infrequent events; therefore, an implantable loop
recorder would be the most likely test to result in a useful finding (either positive or
An implanted loop recorder records patient-activated events and automatically
records bradycardic and tachycardic events; it is, therefore, significantly less prone to
acquisition errors than an event monitor. Implantable loop recorder batteries now
last approximately 2 years.
The implantable loop recorder has repeatedly been shown to be cost effective and
highly likely to result in a useful finding compared with a 24-hour ambulatory
monitor or an event monitor.
External event monitors are of two types:

loop monitors, which are worn and record continuously but only save when the
patient activates the monitor, and
hand-held event monitors, which must be held to the chest to record.
o Loop monitors are useful for syncope because patient activation saves data from a
short period of time (programmable and varying by company) before the monitor is
activated by the patient.
o Hand-held event monitors are not useful for syncope, since the patient cannot
activate the monitor when consciousness is lost.
Syncopy and ventricular arrhythmia
In the setting of a high enough clinical suspicion for syncope caused by
ventricular arrhythmia, it is not necessary to formally document the arrhythmia with
an event monitor before proceeding with ICD implantation, given the extremely high
risk for sudden death in this setting.
In heart failure If the ejection fraction remained low after optimal medical
therapy, the patient would also qualify for ICD implantation for a primary
prophylaxis indication.
Kawasaki disease
The condition is frequently self-limiting
but it is important to recognise, as it causes coronary arterial inflammation
resulting in aneurysm formation (25% of cases) which may present much later in life.
Coronary disease can be prevented with treatment which includes non-steroidal
anti-inflammatory drugs (NSAIDs) and gamma globulin infusion.
Ischemic HD
Patients with peripheral arterial disease have an increased risk of adverse
cardiovascular event and frequently have coexistent coronary and cerebrovascular
atherosclerosis; therefore it is considered a coronary artery disease equivalent. For
this reason an appropriate statin should be commenced. Currently the recommended
target is LDL less than 2.0 mmol/l,
Unstable angina Six-hour troponin T test may still miss some cases of unstable
angina with troponin rise, as such 12-hour testing is recommended. Unless the
electrocardiogram (ECG) changed significantly, IV heparin or IIB IIIA receptor
antagonist therapy would not be indicated.
Recent studies have demonstrated that troponin T assay at the 12 hour stage is
the most effective for cardiovascular risk stratification. If troponin T is normal
(<0.03) at 12 hours it indicates very low forward cardiovascular risk. Mild elevation
in the presence of ECG changes is supportive of a diagnosis of unstable angina and
elevation of troponin T above a level of 0.1 indicates a confirmed myocardial
A normal echocardiogram between episodes of chest pain does not rule out
unstable angina because wall motion returns to normal between ischemic episodes.
However, if patient had no wall motion abnormalities during chest pain, an acute
coronary syndrome is highly unlikely
-Blockers are first-line therapy for unstable angina and NSTEMI unless
contraindications are present.
With ongoing angina, a calcium channel blocker can be added to a -blocker.
However, there is no benefit in substituting a calcium channel blocker for a -blocker
in the absence of significant side effects.
Recent studies have suggested the possibility that angiotensin-converting
enzyme inhibitors may be effective in reducing exercise-induced ischemia.
Recent randomized trials have shown that full-dose low-molecular-weight
heparin is more effective than full-dose unfractionated heparin without an increase in
bleeding events.
However, low-molecular-weight heparin is renally excreted, and if estimated
glomerular filtration rate is below 30 mL/min/1.73 m2, the level of antifactor Xa

activity is increased, resulting in increased bleeding events. Full-dose unfractionated

heparin is, therefore, preferable to full-dose low-molecular-weight heparin in
patients with renal insufficiency.
Acute AMI,,,,,Primary angioplasty where available is the treatment of choice in
this case. A number of studies have demonstrated its superiority over thrombolysis.
If the chest pain was associated with ST depression, then a IIb IIIa antagonist
would be the correct answer.
If angioplasty is not available, then tenecteplase would be the best choice for
Tissue plasminogen activator (TPA) has been shown to achieve better vessel
patency than streptokinase in anterior myocardial infarction.
Stable Angina
Elevated serum high-sensitivity CRP levels are an independent cardiovascular
risk factor for myocardial infarction, stroke, and cardiovascular death, and are
associated with development of metabolic syndrome and diabetes mellitus
In elderly patients Coronary angiography is usually reserved for patients who
remain symptomatic in spite of medical therapy "add b blocker" as it carries
significant risks in this age group
The -blocker dose should be titrated to achieve a resting heart rate of
approximately 55 to 60/min
Ranolazine Ranolazine is indicated for the treatment of Chronic angina.
Ranolazine is believed to have its effects via altering the trans-cellular late sodium
current,,, ranolazine indirectly prevents the calcium overload that causes cardiac
ischemia in rats Unlike other antianginal medications such as nitrates and beta
blockers, ranolazine does not significantly alter either the heart rate or blood
pressure. For this reason, it is of particular use in individuals with angina that is
refractory to maximal tolerated doses of other anti-anginal medications.
Ranolazine is known to increase the QT interval and is contraindicated in
patients with preexisting QT-interval prolongation, liver disease, and in combination
with drugs that prolong the QT interval or are inhibitors of CYP3A4, such as
diltiazem and verapamil.
Ranolazine also prolongs the half-life of digoxin and simvastatin, and these
drugs may require dose reduction.
Coronary angiography would not be indicated until the patient is receiving
maximal medical therapy.
Coronary revascularization is beneficial in patients with chronic stable angina
and the following conditions:
o angina pectoris refractory to medical therapy;
o a large area of ischemic myocardium and
o high-risk criteria on stress testing;
high-risk coronary anatomy, including left main coronary artery stenosis or threevessel disease; and
significant coronary artery disease with reduced left ventricular systolic function.
Medically refractory angina on maximal medical therapy and is not a candidate for
either percutaneous or surgical revascularization
Enhanced External Counterpulsation is a non-surgical treatment for Angina &
Coronary Artery Disease. It is an alternative to bypass surgery and angioplasty. It
works by stimulating the opening or formation of small blood vessels (collaterals) to
create natural bypasses around narrowed or blocked arteries,,,,EECP uses three sets
of pneumatic cuffs wrapped around the lower extremities to The cuffs are timed to
inflate and deflate based on the individual's electrocardiogram. The cuffs should
ideally inflate at the beginning of diastole and deflate at the beginning of systole.
During the inflation portion of the cycle, the calf cuffs inflate first, then the lower

thigh cuffs and finally the upper thigh cuffs. Inflation is controlled by a pressure
monitor, and the cuffs are inflated to about 300 mmHg. When timed correctly, this
will decrease the afterload that the heart has to pump against, and increase the
preload that fills the heart, increasing the cardiac output.[4] In this way, ECP is
similar to the intra-aortic balloon pump Contraindications to EECP include severe
aortic regurgitation and severe peripheral vascular disease.
Spinal cord stimulation involves placement of an electrocatheter within the
epidural space that is connected to a pulse generator and stimulates the spinal cord
region receiving the cardiac nerve fibers. In a placebo-controlled trial, spinal cord
stimulation was shown to reduce angina and improve functional status.
Investigation for chest pain with history of IHD
Exercise stress test should be the first choice stressor for patients with good
effort tolerance.
Myocardial perfusion imaging is indicated in the following situations:
o high clinical suspicion with negative exercise test
o low clinical suspicion with positive exercise test
o borderline or uninterpretable exercise test
o resting electrocardiogram (ECG) precludes stress ECG test eg left bundle branch
block (LBBB).
Ranolazine can be useful in patients with chronic stable angina on maximal medical
Stent thrombosis causing myocardial infarction
Stent thrombosis usually occurs in the first two days after the procedure.
Combined antiplatelet therapy with aspirin and clopidogrel, reduces the risk of
Dual antiplatelet therapy with clopidogrel and aspirin is mandatory following
placement of a coronary stent to reduce sudden thrombotic occlusion of the stent.
Clopidogrel is required for 1 month for bare metal stents and for 1 year for drugeluting stents
This patient should be taken immediately to the Cardiac Catheterisation Lab with
a view to performing
o angioplasty or to
o administer intracoronary thrombolytic therapy to open up the blocked stent.
o Simultaneous use of abciximab (a glycoprotein IIb/IIIa inhibitor) has been shown
to improve morbidity and mortality in acute coronary stent thrombosis
Emergency CABG might be considered if percutaneous intervention fails.
IV thrombolytic therapy is not the optimum therapy in this setting.
Diabetes mellitus and ischemic heart disease
Coronary artery bypass grafting is indicated in patients with
left main coronary artery disease,
severe three-vessel disease with reduced left ventricular systolic function, and
severe three-vessel disease with involvement of the proximal left anterior
descending artery.
o In this setting, surgery would not only relieve angina and improve quality of life,
but it would also prolong life expectancy.
o Patients achieve a significant clinical benefit when the left internal mamillary artery
graft is used as the bypass for lesions within the left anterior descending artery
Enhanced external counterpulsation (EECP) is an acceptable treatment for
patients with medically refractory angina who are not candidates for

Contrast-induced renal dysfunction

About 5% of patients undergoing cardiac catheterisation experience contrastinduced renal dysfunction.
Patients with diabetes and prior renal dysfunction are at increased risk.
Renal impairment increases the risk of accumulation of metformin and lactic
Therefore, metformin should be stopped prior to coronary angiography and
reinstated 48 h after the procedure if renal functions are found to be normal.
Myocardial infarction
ST segment elevation in leads I and aVL is termed as high lateral wall MI and is
usually the result of
o occlusion of the first diagonal branch of the left anterior descending artery,
o though occlusion of other arteries like branches of the left circumflex or a short left
anterior descending artery may cause the same picture.
Low molecular weight heparin (LMWH) is the standard treatment in non-STsegment elevation myocardial infarction (NSTEMI).
Despite the fact that LMWH is said to accumulate in renal failure, reduced dose
LMWH have been shown to be effective in haemodialysis patients, as such it would
still be an appropriate option here.
Management of cardiogenic shock
o circulatory support in the form of vasopressors (IV dopamine) and
o Intra-aortic balloon pump (IABP) and
o reperfusion of the infarct-related artery.
Diabetes and Myocardial infarction
Best Treat with IV insulin for 48hrs then consider restarting oral therapies
The DIGAMI(1) study suggested that using IV insulin for a short period, followed
by S/c insulin therapy was associated with a survival benefit versus conventional
glucose management.
This was not replicated in the later DIGAMI(2) study, where no benefit was seen
from the DIGAMI regime versus conventional treatment of blood glucose.
The majority of clinicians now recommend only a short period of IV insulin
therapy followed by a return to tablet treatment if the HbA1c was adequately
controlled pre-myocardial infarction.
In patients with acute myocardial infarction with reduced left ventricular
function (ejection fraction 40%) and clinical heart failure or diabetes mellitus, and
who were on therapeutic doses of a -blocker and an ACE inhibitor, the addition of
eplerenone reduced total mortality and cardiovascular mortality.
Post MI ventricular arrhythmia
If VT with unstable hemodynamic
o give DC shock Then
o IV lignocaine given as a bolus followed by infusion reduces myocardial automaticity
and hence is the first choice for prophylaxis against a further episode of VT.
o IV amiodarone would be the first choice alternative to lignocaine, especially where
there is persistent hypotension.
Premature ventricular contractions (PVCs) and non-sustained ventricular
tachycardia (NSVT) are common in the early post-myocardial infarction (MI) period.
NSVT is defined as three or more consecutive beats at a rate greater than 100
beats/min that last less than 30 s.
If these do not cause any haemodynamic compromise, treatment is not needed.
Hypokalemia increases the incidence of NSVT as well as VT and ventricular
fibrillation (VF), hence it is prudent to check serum potassium (K+) levels early.
During the GISSI-2 trial it was observed that a serum K+ level of less than 3.6
mmol/l was associated with a two-fold increased risk of VF. Therefore serum K+
should be maintained above 4 mmol/l by oral or intravenous (iv) supplementation in

patients with acute MI.

Concomitant magnesium (Mg2+) deficiency is present in many patients with
hypokalaemia and also makes correction of hypokalaemia difficult. Hence serum
Mg2+ levels should also be checked and maintained above 1 mmol/l.
Antiarrhythmic therapy might be considered if NSVT causes haemodynamic
Electrophysiological studies and implanting a cardiac defibrillator might be
considered if NSVT occurs late (after 48 h) in the course of MI.
Results from the DINAMIT trial showed no benefit from cardioverterdefibrillator implantation early after myocardial infarction. For this reason, patients
with reduced ejection fraction are not candidates for device placement within 40 days
after acute myocardial infarction or immediately after percutaneous or surgical
Rescue angioplasty and emergency coronary artery bypass grafting (CABG)
should be considered if there is evidence of failed thrombolysis or cardiogenic shock.

Right ventricular myocardial infarction

Inferior wall myocardial infarction (MI) is associated in one-third of cases with
right ventricular myocardial infarction (RVMI).
RVMI leads to reduced right ventricle compliance and stroke volume, which in
turn leads to reduced left ventricle filling and low cardiac output.
a pansystolic murmur is most likely to be a function of tricuspid regurgitation
secondary to a hypokinetic dilated right ventricle.
Patients typically present with
o hypotension,
o jugular venous distension and
o clear lung fields in the setting of an inferior or inferoposterior MI
These findings can mimic cardiac tamponade. An echocardiography will be
useful in
o excluding tamponade
o demonstrating right ventricular dysfunction and dilatation.
o It has an added advantage of assessing left ventricular ejection fraction.
Pulmonary embolism (PE) can also have similar physical findings that are
jugular venous distension, hypotension and clear lung fields. However these findings
occurring in a setting of inferior MI make PE less likely.
Treatment of right ventricular infarction includes early revascularization (PCI or
thrombolytic therapy) to restore blood flow to the ischemic right ventricle
Even with successful revascularization, it can take up to 3 days for right
ventricular function to return to normal.
Therapy for hypotension associated with RVMI involves
o boluses of iv saline to improve right ventricular (RV) preload and cardiac output.
o If up to 1.5 l of normal saline do not correct hypotension, invasive haemodynamic
monitoring should be considered to guide further fluid therapy.
o Similarly inotropic support may be considered after adequate fluid resuscitation
has failed.
o Nitroglycerin is contraindicated in patients with right ventricular myocardial
infarction because of the potential for venodilation and hypotension.
o iv Furosemide will reduce RV filling pressure and should be avoided.
iv Heparin in combination with streptokinase does not confer any additional benefit
and is not indicated.
non ST segment elevation myocardial infarction
aspirin and Clopidogrel
Glycoprotein IIb/IIIa inhibitors should be administered in patients with
NSTEMI who are at high risk of death and complications.
The high-risk features include:

o age more than 70 years

o prolonged rest pain
o pulmonary oedema, hypotension or bradycardia
o prior revascularisation
o ST segment changes of greater than 1 mm or ventricular arrhythmias
o elevated cardiac enzymes.
Other pharmacotherapy of NSTEMI includes
o anticoagulation,
o beta-blockers and
o anti-anginals like nitroglycerine
o angiotensin-converting enzyme inhibitors.
Dressler syndrome
usually occurs 1 to 8 weeks after myocardial infarction.
Patients present with malaise, fever, pericardial pain, elevated erythrocyte count
and sometimes may also have pleuritis and pneumonitis.
Results from release of cardiac antigens which then stimulate antibody
production. The immune complexes are then deposited in the pericardium, pleura
and lung.
Treatment involves Aspirin in large doses is effective.
Recurrences can occur, and in such cases colchicine is helpful.
Corticosteroids and non-steroidal anti-inflammatory agents are best avoided in
the first 4 weeks after myocardial infarction as they delay myocardial healing.
There may be accompanying pleural and pericardial effusion and therefore
echocardiography should be done. in the presence of significant effusion or if the
effusion is increasing, heparin should be discontinued.
Anticoagulation can be continued if there is no pericardial effusion, as in such
cases the risk of haemorrhagic pericarditis is low.
Acute pulmonary oedema
The first step
o high-flow oxygen,
o furosemide 0.51 mg/kg intravenous (IV),
o morphine 24 mg IV, and
o sublingual nitroglycerine (GTN).
The second step is dictated by the systolic blood pressure (BP) after initial
o If the BP is >100 mmHg, start IV nitroglycerine 1020 g/min;
o BP of 70100 mmHg, with no signs or symptoms of shock start IV dobutamine
220 g/min;
o BP is 70100 mmHg with signs or symptoms of shock, start IV dopamine 515
o BP is less than 70 mmHg with signs or symptoms of shock, start IV noradrenaline
0.530 g/min.
Flash pulmonary oedema
Rapidly developing pulmonary congestion
The most common cause of flash pulmonary oedema is myocardial ischaemia.
Bilateral renal artery stenosis can also present with a similar clinical picture but is
less common cause, as is acute aortic regurgitation.
Tocolysis-associated pulmonary oedema
Tocolytics are medications administered for the suppression of premature
Acute pulmonary oedema can occur with administration of 2 agonists for

tocolysis in up to 515% of cases.

It usually occurs after 24 h of administration of these agents.
The chest X-ray reveals pulmonary infiltrates and normal heart size.
Concomitant use of corticosteroids that are often administered for lung
maturation have also been implicated as risk factor for development of tocolysisassociated pulmonary oedema.
Treatment involves stopping the tocolytics, oxygen and careful volume control.
Ventricular free wall rupture
Autopsy studies reveal that ventricular free wall rupture occurs about 10 times
more frequently than postinfarction ventricular septal rupture, occurring in about
11% of patients following acute myocardial infarction.
Ventricular rupture and cardiogenic shock are now the leading causes of death
following acute myocardial infarction, and together account for over two-thirds of
early deaths in patients suffering their first acute infarction.
Coronary stents re-stenosis
Studies have shown that in patients with type-2 diabetes, coronary stents are
liable to re-stenosis at a rate of 4050% by the end of a 6-month follow-up period.
Drug eluting stents have been shown to reduce the relative risk of re-stenosis by
around 80%, but only where dual anti-platelet therapy with clopidogrel and aspirin is
continued for at least 1 year.
Whilst there is evidence that both rosiglitazone and pioglitazone both reduce instent re-stenosis, rosiglitazone is not recommended in patients who have a history of
previous myocardial infarction
Risk factors for torsade de pointes include:
congestive heart failure,
digitalis therapy,
subclinical long-QT syndrome,
baseline QT prolongation,
severe hypomagnesaemia,
severe alkalosis and
recent conversion from atrial fibrillation.
Female sex is a powerful predictor of the risk of torsade de pointes in patients
with congenital and acquired long-QT syndromes. How or whether variability in the
expression of genes that determine normal cardiac electrophysiology explain the sexdependent risk of torsade de pointes is not yet clear.
Ventricular tachycardia (VT)
If secondary to digoxin toxicity and unstable haemodynamically. In the setting of
digoxin toxicity DC cardioversion is not used unless all other measures have been
exhausted because it is unusually unsuccessful. The most useful drugs in this setting
are lidocaine and phenytoin. Amiodarone and procainamide may increase digoxin
levels and should be avoided.
Prolonged QT Interval
Six mutations (LQT16) have been identified in association with the
RomanoWard syndrome.
LQT1 and LQT2 mutations make up around 87% of cases of RomanoWard
syndrome and are associated with cardiac potassium-channel gene mutations.
JLN mutations (JervellLange-Nielsen syndrome) tend to be associated with

Although sudden death usually occurs in symptomatic patients, it happens with

the first episode of syncope in about 30% of the patients.
LQT4 is associated with paroxysmal atrial fibrillation.
Studies have shown an improved response to pharmacologic treatment with a
lowered rate of sudden cardiac death in LQT1 and LQT2 compared with LQT3.
Triggering events are somewhat different by genotype.
Patients with LQT1 usually have cardiac events preceded by
o exercise or swimming.
o Sudden exposure of the patient's face to cold water is thought to elicit a vagotonic
Patients with LQT2 may have arrhythmic events after
o an emotional event,
o exercise, or
o exposure to auditory stimuli (eg, door bells, telephone ring).
Patients with LQT3 usually have events during night sleep.
Diagnosis is based upon the QTc (corrected QT interval), although this may be
within the normal range at rest; hence, Holter monitoring is recommended.
Genetic testing for known mutations in DNA samples from patients is becoming
accessible in specialized centers.
Identification of an LQTS genetic mutation confirms the diagnosis. However, a
negative result on genetic testing is of limited diagnostic value because only
approximately 50% of patients with LQTS have known mutations. The remaining half
of patients with LQTS may have mutations of yet unknown genes. Therefore, genetic
testing has high specificity but a low sensitivity.
Beta-blockade is seen as the treatment of choice for most cases of long QT
syndrome, which is thought to work through reducing adrenergic demand. Betablockers decrease sympathetic activation from the left stellate ganglion. Betablockers also decrease the maximal heart rate achieved during exertion and thereby
prevent exercise-related arrhythmic events that occur in long QT syndrome.
Implantable defibrillators are also used in the management of these patients.
The activity of the left stellate ganglion is greater compared to the right stellate
ganglion in normal individuals. Animal and human studies have shown that right
stellectomy or primary increase in the output of the left stellate ganglion increases
the QT interval.
Patients who experience ventricular arrhythmias or aborted sudden cardiac
death despite beta-blocker therapy should have an implantable cardioverter
defibrillator (ICD) in addition to beta-blockers.
Left stellate cardiac ganglionectomy is an invasive procedure and results in
Horners syndrome. It is performed in patients who have symptoms despite betablockers and have frequent shocks with ICD.
Dual chamber pacing might be beneficial in subset of patients with long QT
syndrome type 3.
Management of drug-induced long QT syndrome is to
o stop the precipitating drug,
o correction of any electrolyte disturbance like hypokalaemia or hypomagnesaemia
o treatment of associated ventricular arrhythmia.
o First-line pharmacological therapy for drug-induced long QT syndrome is
intravenous magnesium sulphate 2 g administered as bolus over 12 min, followed
by another bolus in 15 min if required, or continuous infusion at a rate of 520

Prosthetic valve thrombosis (PVT)

May resulting in shock.
This complication occurs in 0.03 to 5.5% annually with equal frequency in

bioprosthesis and mechanical valves.

It is more common in mitral prosthesis and with subtherapeutic
The best diagnostic modality is transoesophageal echocardiography; however
transthoracic echocardiography is the initial choice in sick patients, and if adequate
visualisation is not obtained TEE can be done.
Thrombolytic therapy for patients
o pulmonary oedema or
o hypotension.
o right-sided PVT should be treated with thrombolytic agents
surgery In
o stable patients,
o is a better option for left-sided PVT, while
Serial echocardiography should be performed, and if the response is inadequate
repeat thrombolytic therapy can be given.
Complications of prosthetic valves include
structural valve deterioration, symptoms of heart failure with significant valve
valve thrombosis,
pannus formation, is a slowly growing fibrous overgrowth fixed on the
prosthesis, causing valve dysfunction
prosthesis mismatch may occur when the inserted valve prosthesis is too small
relative to patient size, recreating the outflow obstruction present preoperatively. The
main hemodynamic consequence is persistence of significant transvalvular gradients
through what is otherwise a normally functioning prosthesis.
Mild hemolytic anemia is common in patients with prosthetic heart valves, but
can be more severe in up to 10% to 20% of patients.
o Hemolytic anemia is more common in those with paravalvular regurgitation and
with mechanical valves.
o Clinical features include fatigue, anemia, new murmur, and, in more severe cases,
jaundice and heart failure.
o Most cases of hemolytic anemia are subclinical, identified only by laboratory data.
o Symptomatic hemolytic anemia can usually be treated with oral iron and folate
replacement, although more severe cases may warrant blood transfusion or
recombinant human erythropoietin
Anticoagulation for the pregnant patient with a mechanical valve prosthesis
when the dose of warfarin is less than 5 mg daily, the risk of embryopathy
decreases to below 10%.So Continue warfarin, adjusted to INR
Aortic stenosis
severe aortic stenosis
o An absent aortic component of S2,
o a long and late-peaking systolic murmur,
o a sustained apical impulse
An overestimation of the severity of aortic stenosis can occur due to large
volumes of blood passing over the valve at high velocities, which occurs in aortic
Aortic valve replacement is not performed in asymptomatic patients because of
the increased surgical risk

Patient with severe left ventricular (LV) dysfunction, and calculated valve area in
such patients can be falsely low because low cardiac output reduces the valve opening
It is important to distinguish patients with true severe aortic stenosis (AS) with
secondary LV dysfunction from those who have a falsely low calculated aortic valve
area because of low cardiac output.
An important method of distinguishing between the two conditions is to assess
the haemodynamics after increasing the cardiac output by dobutamine infusion
during echocardiography or cardiac catheterisation.
Patients with truly severe AS manifest an increase in transaortic pressure
gradient while the valve surface area remains the same during dobutamine infusion;
while those with falsely low calculated valve area manifest an increase in calculated
valve surface area.
Dobutamine echocardiography is also important to assess LV contractile reserve.
Patients who have 20% or more increase in stroke volume after dobutamine infusion
have a much better prognosis after surgery compared to those who do not have LV
contractile reserve.
Aortic stenosis with acutely ill elderly patient with heart failure
The ultimate treatment is valve replacement but in a patient who is acutely
unwell, a valvuloplasty is used as a bridging procedure.
An aortic balloon pump would improve the cardiac failure and also increase
coronary perfusion, and is necessary in such a high-risk procedure.
Noradrenaline has no place here as it can worsen the left ventricular failure as
raising the afterload may cause the ventricle to fail further. Milrinone, a
phosphodiesterase III inhibitor, appears to be useful in moderate ventricular
dysfunction with small doses of adrenaline. This increases the cardiac output as well
as raising the mean arterial pressure.
Microcytic anaemia and severe calcific aortic stenosis
This is Heydes syndrome
The treatment is to replace the valve after blood transfusion " No further gastroendoscopies are needed", as the mechanism is thought to be due to destruction of von
Willebrands factor as the platelets traverse the stenosed valve resulting in
bleeding per rectum.
several gastric endoscopies and colonoscopies in search of an underlying cause of
his anaemia may be done with ve results
The investigation of choice after valve replacement is mesenteric angiography as
the bleeding vessels are poorly visualised on colonoscopy. This would look for the
presence of angiodysplasia, which may be associated with aortic stenosis. Resection
of the diseased bowel has also been described as a treatment
Mitral stenosis
Clinical markers consistent with severe mitral stenosis are
transmitral pressure gradients greater than 10 mm Hg,
enlargement of the left atrium,
mitral valve area less than 1.5 cm2, and
pulmonary pressures greater than 50 mm Hg.
Clinical outcome in
asymptomatic or minimally symptomatic patients with mitral stenosis is
excellent (>80% survival at 10 years),
but once patients are symptomatic, 10-year survival is less than 15%.
Morbidity associated with untreated mitral stenosis includes
o pulmonary hypertension,

o right-sided heart failure,

o systemic embolism from atrial fibrillation, and
o valve infection.
In symptomatic patients, percutaneous valvuloplasty is the preferred
less invasive than surgical intervention
avoids the need for lifelong anticoagulation.
o Major complications of percutaneous valvuloplasty include
severe mitral regurgitation (1%-8%)
systemic embolization (1%-3%)
tamponade (1%-2%).
Procedural mortality rate is 1%.
o Valve characteristics that favor successful valvuloplasty include
pliable mitral valve leaflets,
minimal commissural fusion, and
minimal valvular/subvalvular calcification,
o These are contraindications:
severely calcified or
rigid valve leaflets,
concomitant coronary artery or other valve disease requiring surgery.
concomitant mitral regurgitation.
atrial thrombus
In patients under consideration for valvuloplasty, transesophageal
echocardiography is necessary to definitively exclude a left atrial thrombus because of
the risk of thrombus dislodgement and embolization during the procedure.
If thrombus present These patients should undergo mitral valve replacement.
Mitral stenosis with paroxysmal AF
A beta-blocker can be used as first-line treatment, as it might prevent atrial
tachyarrhythmias. It will also slow down the heart rate in sinus rhythm, thus
increasing diastolic time and augmenting cardiac output.
Digoxin is not particularly helpful in paroxysmal AF, and
amiodarone should be reserved for resistant cases.
Mitral regurgitation
Clinical markers that should prompt surgical intervention include
o left ventricular enlargement or dysfunction (end-systolic dimension >40 mm and
ejection fraction <60%),
o new-onset atrial fibrillation,
o pulmonary arterial systolic pressure >50 mm Hg, or
o an exercise-associated increase in pulmonary pressures (increase of approximately
25 mm Hg over baseline).
Otherwise, asymptomatic patients with severe, chronic mitral regurgitation but
normal left ventricular size and function can be reevaluated with periodic 6- to 12month monitoring.
Decompensated rheumatic mitral valve disease in pregnancy
optimization of medical management is preferred over urgent percutaneous
mitral balloon valvuloplasty.
A transthoracic echocardiogram aids in evaluating the severity of mitral stenosis,
pulmonary pressures, involvement of other cardiac valves, and the presence of
concurrent mitral regurgitation.
If the patient can be treated medically and the pregnancy carried to term,
valvuloplasty can be delayed until after delivery to reduce radiation exposure to the

fetus and provide an opportunity to reassess the patient.

With the decrease in volume load, a previously symptomatic pregnant patient
may improve following delivery, delaying or eliminating the need for valvuloplasty.
If despite aggressive medical therapy, the pregnant patient remains severely
symptomatic, however, percutaneous balloon valvuloplasty may be performed
(preferred gestational age >8 weeks) if significant mitral regurgitation is absent and a
left atrial thrombus is excluded by transesophageal echocardiography.
Peripartum cardiomyopathy
Peripartum cardiomyopathy is defined as heart failure with a left ventricular
ejection fraction less than 45% that is diagnosed between 3 months before and 6
months after delivery in the absence of an identifiable cause.
Risk factors for peripartum cardiomyopathy include
age (>30 years at the time of the pregnancy),
race (black, African, Haitian), and the
presence of gestational hypertension.
With a maternal mortality rate of approximately 10%,
Improvement in left ventricular function occurs in about 50% of women with
peripartum cardiomyopathy within 6 months after delivery.
Treatment is the same as for the non-pregnant patient with cardiac failure,
although angiotensin-converting enzyme inhibitors should be avoided.
The mainstay of medical treatment is digoxin and loop diuretics.
Nitrates are generally not recommended during pregnancy. If indicated nitrates
and inotropic support with dobutamine should be used.
Beta-blockers should be added once the patients volume status is optimised.
Patients with PPCM are at risk of thromboembolism due to both hypercoagulable
state of pregnancy and stasis of blood in the left ventricle. Therefore, anticoagulation
with heparin or warfarin is recommended "when left ventricular ejection fraction is
less than 35%". Heparin is preferable in late pregnancy because it has short half-life
and can be discontinued prior to delivery.
Intravenous immune globulin and pentoxifylline have been shown to improve
outcomes in some studies.
Dilated cardiomyopathy
The prevalence of is approximately 1%, and incidence increases with age and
approaches 10% at the age of 80 years.
Annual mortality associated with cardiomyopathy and moderate heart failure is
Signs at clinical presentation include increased jugular venous pressure (JVP),
small pulse pressure, hepatomegaly and peripheral oedema, and functional mitral
regurgitation is often present.
Predisposing factors include
o alcoholism,
o viral myocarditis,
o cocaine abuse, and toxins such as cobalt, lead, phosphorus and carbon monoxide.
Heart failure should be managed with diuretic therapy, sodium restriction and
ACE inhibition.
Crucial to the management of alcoholic cardiomyopathy is cessation of alcohol
Patients who succeed in giving up ethanol often gain rapid improvement in their
Hypertrophic obstructive cardiomyopathy
The disease exists in two major forms:
o a familial one that presents in young patients and has been mapped to chromosome
14q, and
o a sporadic form usually found in the elderly.

Symptoms of cardiac failure respond to medical therapy with

o b-blockade use metoprolol ,,,,BUT Carvedilol has vasodilator properties that could
further lower blood pressure as well as potentially exacerbate outflow gradient.
o but where the outflow gradient is greater than 50 mmHg, surgical myomectomy is
usually recommended.
o Unfortunately surgery does not reduce the risk of arrhythmia.
o Surgical septal myectomy should be considered in patients with outflow obstruction
who are NYHA functional class III or IV and whose symptoms are refractory to
medical therapy.
Patients prone to ventricular arrhythmias may be considered for implantable
Common ECG findings in patients with HOCM include
1. LV hypertrophy,
2. atrial enlargement,
3. ST-T segment abnormalities,
4. right or left axis deviation,
5. PR prolongation,
6. sinus bradycardia with ectopic atrial rhythm and bundle branch block.
7. Ventricular fibrillation is responsible for the sudden death in 80% of these
8. HOCM can also be associated with WolffParkinsonWhite syndrome
Cardiac amyloidosis
most commonly presents as restrictive cardiomyopathy.
The clinical findings are those of right heart failure ie jugular venous distension
and peripheral oedema,
whereas orthopnoea and paroxysmal nocturnal dyspnoea are typically absent.
In more advanced stages systolic dysfunction also occurs.
Postural hypotension can occur as a result of
o poor ventricular filling or
o associated autonomic neuropathy.
Combination of low-voltage electrocardiogram (ECG) and thickened ventricular
walls is one of the characteristic features of cardiac amyloidosis.
The most distinctive feature of cardiac amyloidosis is a sparkling, granular
appearance of the myocardium, but this is a relatively insensitive feature occurring
only in about 25% of cases.
Other echocardiographic abnormalities include dilatation of atria, thickened
interatrial septum, diastolic dysfunction and small-volume ventricles.
Cardiac amyloidosis usually occurs in setting of light chain amyloidosis (AL) and
hereditary amyloidosis, and rarely in secondary amyloidosis.
beta-blocker diuretic combination is not recommended due to an association
with incident diabetes in BP lowering meta-analyses.
Every patiente with type 2 diabetes above 40 years of age should be treated with
a statin unless contraindicated.
Lowering diastolic blood pressure should be gradual and cautious in patients
with coronary artery disease or diabetes mellitus and in those who are older than 60
years, to avoid the possibility of inducing myocardial ischemia. Although lower
systolic blood pressure measurements are associated with better outcomes in
ischemic heart disease, there is inconsistent evidence that excessive diastolic blood
pressure lowering may worsen cardiac outcomes.
accelerated hypertension
o should be admitted to hospital
o Initial treatment can be with ORAL nifedipine or atenolol, escalating to intravenous

therapy with nitrates if there is no effect.

o Sublingual nifedipine should be avoided as it might lead to a sudden drop in blood
pressure, which could interfere with the autoregulatory mechanism of cerebral
perfusion leading to an ischaemic stroke.
Hypertensive encephalopathy with a deteriorating level of consciousness
conscious level.
o condition is too advanced for oral therapy and requires intravenous (iv) blood
pressure lowering therapy with sodium nitroprusside.
o The aim of treatment is to lower blood pressure to around 110115 mmHg
diastolic within 24 h.
o Nitroprusside therapy is usually accompanied by iv furosemide.

How should I manage a woman with chronic hypertension?

Advise the woman that:
She should restrict her dietary intake of salt (sodium)..
Bed rest is not recommended.
For uncomplicated hypertension, keep the blood pressure less than 150/100
mmHg (but diastolic pressure no less than 80 mmHg).
If there is evidence of target-organ damage (for example kidney disease), keep
the blood pressure less than 140/90 mmHg.
Warn about symptoms of pre-eclampsia and that she should seek immediate
advice if she develops any symptoms after 20 weeks' gestation (including during the
postpartum period).
Prescribe aspirin 75 mg daily from 12 weeks' gestation. Explain that this is
believed to help prevent the development of pre-eclampsia.

Acute mountain sickness,

o one manifestation of which is acute pulmonary oedema.
o oxygen would be initiated first, particularly in view of persistent hypoxia
o Nifedipine reduces pulmonary hypertension and is the treatment of choice for
pulmonary oedema in cases where high-flow oxygen is not available.
o Acetazolamide may be of some value in prophylaxis in preventing acute mountain
sickness, but the best prevention is slow acclimatisation.
o Patients may also present with high altitude cerebral oedema, the treatment for
which is dexamethasone. Where available, portable pressure bags are a useful adjunct
to therapy.

Congestive cardiac failure

BNP may be elevated with

heart failure,
acute myocardial infarction
pulmonary embolism.
Obesity is associated with lower BNP levels
BNP levels are higher in the settings of
renal failure,
older age, and
female sex.
A calcium antagonist such as amlodipine precipitates peripheral oedema and

fluid retention and should be withdrawn.

Digoxin is a last resort in patients with no evidence of atrial fibrillation.
A beta-blocker such as bisoprolol offers great prognostic benefit but should be
initiated during a stable stage of the condition.
o Beta-blocker should be initiated in small doses and in stable patients who have little
or no evidence of fluid overload. Once started, patients should be monitored for
worsening of symptoms or fluid retention.
o Patients should be educated about possible worsening of symptoms and to weigh
themselves daily.
o If worsening of symptoms or fluid retention occurs, it should be managed by
increasing the dose of diuretics
o Stopping the beta-blocker is only required if there is
heart block,
hypotension or
severe pulmonary oedema.
o It is better to try and continue the beta-blocker if possible.
For patients intolerant of ACE inhibitors due to hyperkalemia or renal
insufficiency, the combination of hydralazine and a nitrate is a suitable alternative,
with hemodynamic effects of vasodilation and afterload reduction. Treatment with
this combination is also associated with a reduction in mortality
The addition of hydralazine and isosorbide dinitrate to standard medical therapy
is indicated for treatment of black patients with systolic heart failure and New York
Heart Association functional class III or IV symptoms.
Thiazide diuretics should be used very cautiously if there is no satisfactory
diuresis on furosemide alone
Spironolactone combines a good diuretic effect with prognostic benefit. In this
case it will also help raise the patients potassium.
Alpha-blockers and nitrates are alternatives for patients who do not tolerate
first-line agents.
Clinical studies have not demonstrated that the combination of captopril and
valsartan improves survival, and the combination is associated with an increased
incidence of side effects.
Endomyocardial biopsy is recommended in patients with
o new-onset heart failure (<2 weeks) with hemodynamic compromise and
o in those with new-onset heart failure of 2 weeks to 3 months duration
associated with a
dilated left ventricle and
new ventricular arrhythmias,
Mobitz type II second- or third-degree atrioventricular heart block, or
failure to respond to usual care within 1 to 2 weeks.
Heart failure on maximal medical therapy.
Other options
biventricular pacing " cardiac resynchronization"
o ejection is less than 35%,
o there is refractory heart failure
o QRS complex duration >120 ms.
biventricular implantable cardiac defibrillator (ICD)
o if there is evidence of previous ischaemic heart disease and ventricular arrhythmias.
o Current guidelines recommend implantable cardioverter-defibrillator (ICD)
placement in patients with ischemic or nonischemic cardiomyopathy and an ejection
fraction of less than or equal to 35%. ICD placement is, therefore, indicated in this
setting (primary prevention), regardless of symptoms or functional status
Biventricular pacemaker-defibrillator placement
o Approximately 70% of patients who undergo biventricular device placement obtain
a symptomatic benefit, thought to result from mechanical resynchronization

of the timing of right and left ventricular contraction.

o These devices have been shown to improve
ejection fraction,
quality of life, and
functional status,
decrease heart failure hospitalizations and mortality.
A ventricular assist device is an alternative to transplantation. The criteria
o history of cardiogenic shock,
o pulmonary capillary wedge pressure >20 mmHg, and
o either a cardiac index <2.0 l/min/m2 or a systolic blood pressure <80 mmHg
despite maximal inotropic support.
The indications for biventricular pacemaker-defibrillator placement include NYHA
class III or IV heart failure, an ejection fraction less than or equal to 35%, and a QRS
width greater than 120 msec. Approximately 70% of patients who undergo
biventricular device placement obtain a symptomatic benefit, thought to result from
mechanical resynchronization of the timing of right and left ventricular
contraction. These devices have been shown to improve ejection fraction, quality of
life, and functional status, as well as to decrease heart failure hospitalizations and
Hyponatraemia in heart failure
is associated with poor outcomes.
Patients with congestive heart failure (CHF) have decreased cardiac output and
effective blood circulating volume. This results in activation of the
reninangiotensin system and release of antidiuretic hormone (ADH) and
subsequent failure of excretion of ingested water.
Water restriction is the first-line and mainstay of therapy in hyponatraemic
patients with CHF.
Stopping furosemide will not be possible for a patient who has decompensated
heart failure.
Similarly, administration of hypertonic saline is only indicated if there is
neurological manifestation of hyponatremia. Moreover hypertonic or isotonic saline
administration will be poorly tolerated in a volume-overloaded patient.
Lithium can inhibit the action of ADH, but has slow onset of action and
numerous central nervous system and cardiotoxic effect
Endocarditis: initial blind therapy
1. Flucloxacillin (or benzylpenicillin if symptoms less severe) + gentamicin
2. cardiac prostheses present, or if penicillin- allergic, or if meticillin-resistant
Staphylococcus aureus suspected "vancomycin + rifampicin"
Endocarditis caused by staphylococci
1. Flucloxacillin 4 weeks
2. if penicillin allergic or if meticillin-resistant Staphylococcus aureus "vancomycin +
rifampicin" 6 weeks
3. prostheses vancomycin + rifampicin+Gentamicin
Endocarditis caused by streptococci
1. Benzylpenicillin "4wk" + gentamicin"2wk" (if no intracardiac abscess or infected
2. Benzylpenicillin "6wk" + gentamicin"2wk" prostheses

3. if penicillin- allergic or highly penicillin-resistant vancomycin + gentamicin

Endocarditis caused by enterococci (e.g. Enterococcus faecalis)
1. Amoxicillin + gentamicin 4wk
2. Amoxicillin + gentamicin 6 wk prosthetic
3. if penicillin-allergic or penicillin-resistant vancomycin + gentamicin
4. if gentamicin-resistant, substitute gentamicin with streptomycin
Endocarditis caused by haemophilus, actinobacillus,
cardiobacterium, eikenella, and kingella species
(HACEK organisms)
1. Amoxicillin+ low-dose gentamicin
2. if amoxicillin-resistant ceftriaxone + low-dose gentamicin
Candida endocarditis
Risk factors
o Intravenous drug abuse,
o immunodeficiency states and
o indwelling catheters
The aortic valve is the most common valve to be involved.
Optimum management involves
o intravenous (iv) amphotericin for at least 6 weeks and
o early surgery.
o Despite this, recurrences can occur.
Conditions in which surgery should be done for optimum management in the setting
of infective endocarditis include
o congestive heart failure
o organisms that are difficult to eradicate by medical therapy as such
brucella, coxiella,
pseudomonas aeruginosa,
vancomycin-resistant enterococci
o vegetations greater than 1 cm in diameter (which pose an embolic risk),
o recurrent embolisation
o persistent bacteraemia despite appropriate antibiotic therapy
o extension of infection to a extravalvular site "paravalvular extension"
o early prosthetic valve endocarditis (within 2 months)
o Patients with fever and a prosthetic valve should be treated presumptively for
endocarditis unless a clear alternative source of infection is present. Surgery should
not be delayed to complete an antibiotic course if surgical criteria are met
o dehiscence or obstruction of a prosthetic valve.
Bacteroides fragilis endocarditis
is a rare complication associated with colonic resection.
As passage of bacteria to the heart occurs via venous drainage, valve lesions tend
to be right sided but may also occur as here on the left side of the heart. In this case
the mitral valve lesions have lead to mitral regurgitation.
Management of choice is with metronidazole.
The incidence of post-op endocarditis is actually very low because of the use of
peri-operative broad-spectrum antibiotics, normally the combination of a
cephalosporin and metronidazole.
Acute respiratory distress syndrome
may be secondary to a fat embolus in frctures

clinically there may be

o coars

Acute respiratory distress syndrome
may be secondary to a fat embolus in frctures
clinically there may be
o coarse crackles on auscultation of his chest bilaterally.
o jugular venous pressure is raised
o There is no peripheral oedema.
o ECG shows right axis deviation with prominent R waves on leads V1V2.
Initial resuscitation should involve
o high flow oxygen and
o intravenous (iv) fluids to maintain high right ventricular filling pressures.
o Steroid therapy is normally used a little later in ARDS, it can worsen pulmonary
o Continuous positive airways pressure ventilation would help in the management of
the pulmonary oedema.
o It should be noted that diuretic treatment would be strongly contraindicated "even
in pulmonary oedema". This is because the right ventricular output is dependent on
elevated filling pressures. Reducing the preload is therefore not a good idea.
Mitral stenosis
MS with AF
Patients tolerate fast atrial fibrillation very poorly.
o oxygen
o achieve rate control as quickly as possible. This is most quickly achieved with the
use of a short-acting beta-blocker such as esmolol through a continuous infusion This
might seem counter-intuitive in a hypotensive patient, but the hypotension is rate
dependent as the ventricle has no time to fill.
o Digoxin takes a few hours to act whether given orally or intravenously.
o Amiodarone also takes a few hours to act
o Flecainide is contraindicated in patients with structural cardiac abnormalities.
o DC cardioversion should be considered if the patient does not respond quickly.
Aortic regurgitation
All symptomatic patients with severe AR should have AVR.
Asymptomatic patients with severe AR should also undergo AVR if they have
o depressed left ventricular (LV) function (ejection fraction (EF)<50%) or
o if they have severe LV dilatation (end-diastolic dimension >75 mm and end-systolic
dimension >55 mm).
Similarly patients with severe AR undergoing coronary artery bypass grafting or
surgery on the aorta or any other valve should have AVR at the time of surgery.
Vasodilator therapy in the form of angiotensin-converting enzyme inhibitors or
nifedipine should be given to patients who do not have indications for AVR.
Patients with AR require regular echocardiographic follow-up to assess the state
of the left ventricle, as symptoms develop quite late in the course of the disease. so
regular echocardiographic follow-up is required to pick up individuals with early
features of left ventricular failure "dilated left ventricle, an ejection fraction of 50%"
that would benefit from valve replacement.
Acute severe aortic regurgitation is a surgical emergency, necessitating valve
replacement, particularly with symptoms of heart failure.

Severe Aortic stenosis with noncardiac surgery

prophylactic valve replacement is not performed in asymptomatic patients. In
patients with significant aortic stenosis but with good preoperative exercise tolerance,
non cardiac surgical procedures are generally well tolerated
Rarely, valvuloplasty is considered in patients with severe, symptomatic aortic
stenosis who require emergent noncardiac surgery and are not candidates for valve
Percutaneous aortic balloon valvuloplasty is generally not performed for calcific
aortic stenosis because serious complications, including aortic regurgitation and
embolic stroke, occur in more than 10% of procedures, and restenosis occurs within a
year in most patients.
ACE inhibitor therapy is contraindicated in severe AS.
Mitral valve prolapse
Patients under 75 with mitral valve prolapse (MVP) who are in atrial fibrillation
or those who have echocardiographic evidence of left ventricular impairment should
be referred for surgical assessment as early as possible.
A TOE can demonstrate whether the valve is amenable to repair or needs
replacement. This is often performed intra-operatively.
Progressive mitral regurgitation is the most serious complication occurring in
about 15% of patients over a 15-year period.
Acute hemiplegia, transient ischaemic attacks, cerebellar infarcts, amaurosis
fugax and retinal arterioral occlusions all occur more frequently in MVP patients,
suggesting that cerebral emboli are actually quite common in this condition
Pulmonary valve stenosis
The diagnosis of pulmonary valve stenosis is confirmed by transthoracic
Echocardiography with Doppler evaluation determines the severity of pulmonary
stenosis and the degree of right ventricular hypertrophy.
Intervention is recommended when
o the gradient is greater than 50 mm Hg or
o when right ventricular hypertrophy is present.
Systolic doming of the pulmonary valve noted on two-dimensional
echocardiography suggests that the valve is likely amenable to percutaneous
The treatment of choice for pulmonary valve stenosis is pulmonary balloon
Acute pericarditis.
ECG differential diagnosis of acute pericarditis is myocardial infarction and early
repolarisation abnormality.
It can be differentiated from myocardial infarction by
o concavity of ST segment elevation in pericarditis
o localisation of ST segment elevation to infarction
However, these two features do not differentiate acute pericarditis and early
repolarisation abnormality.
The two most helpful differentiating features are
o PR segment depression, which is usually best seen in lead II and V6, and PR
segment elevation in aVR.
o An ST/T ratio greater 0.25 or a T wave amplitude of less than or equal to 3 mm also
has high positive and negative predictive value in diagnosis of acute pericarditis
Between 15% and 30% of patients with apparently idiopathic acute pericarditis

may have recurrent attacks and this is considered to be an autoimmune

Echocardiogram is of little value in the diagnosis of pericarditis. It can be used if
a pericardial effusion or aortic dissection is suspected.
The mainstay of therapy for acute pericarditis is pain relief with NSAIDS like
indomethacin "not paracetol"
Colchicine is useful both in acute episode and to prevent recurrence of
Prednisolone can be considered in patients who fail to respond to non-steroidal
anti-inflammatory drug and colchicine therapy.
Pericardectomy is only indicated once thorough medical therapy has failed.
Pericardial biopsy in patients with recurrent pericarditis without effusion is
unlikely to be revealing and is not needed
Constrictive pericarditis
It is important to consider use of corticosteroids in conjunction with antituberculous therapy early in these patients, as there is some evidence that steroids
may reduce the risk of constrictive pericarditis.
Surgical pericardial biopsy is most likely the investigation to determine the
underlying diagnosis
Pericardial effusion, management
In the absence of cardiac tamponade,
o pericardiocentesis may be indicated if clinical suspicion exists for bacterial,
tubercular, or systemic inflammatory causes of pericarditis.
In patients with an isolated pericardial effusion
o An idiopathic pericardial effusion lasting less than 3 months in a stable patient
requires no specific therapy, but serial echocardiography based on clinical status, is
o Pericardiocentesis is warranted if an effusion persists for longer than 3 months and
may be curative in approximately 50% of patients with idiopathic effusions. In
addition, pericardiocentesis prevents the development of cardiac tamponade.
There is no specific treatment for idiopathic (also called lymphocytic) myocarditis
other than supportive care and standard therapy for heart failure; thus, therapy with
an angiotensin-converting enzyme (ACE) inhibitor such as captopril and a -blocker
such as carvedilol would be appropriate to start
Dilated cardiomyopathy
If secondary to alcohol abuse, Abstinence from alcohol and angiotensinconverting enzyme (ACE) inhibitor therapy are paramount in arresting the progress
of the condition.
Before a diagnosis of dilated cardiomyopathy can be made, any occult coronary
artery disease should be excluded
Restrictive cardiomyopathy
Digoxin is contraindicated in amyloid patients as patients are extremely sensitive
to it. This is possibly due to digoxin binding in the amyloid fibrils.
Hemochromatosis is the only cause of restrictive cardiomyopathy that is
potentially reversible by medication therapy that induces regression of symptoms.
Restrictive cardiomyopathy from iron overload may improve with removal of
iron by chelation therapy in iron-overload states, such as lifelong transfusiondependent anemias.

Iron chelation therapy is indicated only in patients who cannot tolerate

phlebotomy therapy, such as those with significant anemia.
In hereditary forms of hemochromatosis, iron overload is appropriately treated
by phlebotomy. Phlebotomy effectively removes excess iron and circumvents the
need for chelation therapy. However, phlebotomy would not be appropriate for this
patient with acquired hemochromatosis and sickle cell anemia.
Echocardiographic findings evidenced by
o restrictive left ventricular filling without respiratory variation in peak filling
o biatrial enlargement, and
o preserved ventricular systolic function.
Endomyocardial biopsy is positive for iron deposition in this patient, but this
biopsy finding is not invariably present because iron deposition is often
predominantly in the epicardial layer. Thus, a negative endomyocardial biopsy would
not exclude myocardial iron infiltration.
Atrial myxoma
finger clubbing,
normocytic anaemia,
a positional murmur and
intracardiac calcification in the chest X-ray.
The history of fainting spells suggests transient left ventricular inflow
The patient should undergo urgent echocardiography and be referred for surgery
if the diagnosis of myxoma is confirmed, as complete removal is curative.
Primary pulmonary hypertension
young women with worsening breathlessness.
The presence of exertional chest pain (right ventricular angina), Raynauds
phenomenon in combination with the clinical and ECG features of right ventricular
hypertrophy point towards PPH.
Chronic thromboembolic disease and respiratory disease should be excluded
before the diagnosis can be made.
o The patient should be advised against pregnancy.
o Severe pulmonary hypertension in pregnancy has high mortality approaching 50%,
o Patients who opt against termination of pregnancy should be closely followed up
and managed with anticoagulation, oxygen and pulmonary vasodilator therapy like
o Bosentan is teratogenic and should not be used in pregnancy.
o The patients should be advised for contraception in future, but oral contraceptive
pills should not be used for possible increased risk of thrombo-embolism.
Treatment of PPH consists of
o oxygen,
o anticoagulation,
o high-dose calcium channel blockers in patients responsive to acute vasodilator
testing and
o intravenous/nebulised prostacyclin to non-responders. Continuous infusion of
prostacyclin has been shown in prospective studies to improve quality of life and
symptoms related to PPH, exercise tolerance, haemodynamics and survival.
o A combined lungheart transplant is the last resort for those who fail to respond
to any other treatment.
o Anticoagulation, prostacyclin and transplant all confer a survival benefit.
Aortic dissection

central chest pain radiating to the back

Ascending aortic dissection is often associated with
o acute aortic regurgitation,
o myocardial ischemia inferior MI (involvement of the right coronary artery)
o cardiac tamponade or
o hemopericardium, and
o hemothorax or exsanguination.
o Considerable (>20 mm Hg) variation in systolic blood pressure in the arms may be
Descending thoracic aortic aneurysm is more commonly associated with
o splanchnic ischemia,
o renal insufficiency,
o lower extremity ischemia, or
o focal neurologic deficit due to spinal cord ischemia.
The absence of a widened mediastinum on chest X-ray does not rule out
The diagnosis can be further suggested by the finding of aortic regurgitation and
pericardial effusion, or even a dissection flap, in the echocardiogram. This can be
done by the bedside while steps are taken to prepare the patient for theatre, and as
such is much safer than a computerised tomography with contrast in the first
Patients with type A aortic dissection should have emergency surgery because of
the high risk of mortality and complication such as
o aortic regurgitation,
o myocardial infarction and
o cardiac tamponade.
Most patients with type B dissection should be treated medically unless they
have complications such as persistent leak, rupture or compromised blood flow to
renal, mesenteric or limb circulation.
o Beta-blockers are the mainstay of medical therapy, as they
reduce the rate of left ventricular ejection and shear on the aortic wall.
The aim is to reduce blood pressure to 100120 mmHg and the pulse to near
60 mmHg.
o Sodium nitroprusside can be added if blood pressure is not controlled with betablockers but should not be used alone as it may increase rate of left ventricular
ejection. Hydralazine should be avoided for the same reason.

Features that favour oesophageal rupture over aortic dissection include:

The history of onset while eating
Blood pressure equal in both arms
No diastolic murmur
Good peripheral pulses
Presence of a pleural effusion.
Carcinoid syndrome
Markedly elevated HIAA concentrations are typically found and do not reflect a
worse prognosis.
Mild derangement of AST/ALT is typically found and alkaline phosphatase is
often elevated as a consequence of carcinoid infiltration and mild obstruction.
Liver function is usually quite normal despite often heavy hepatic infiltration.
Wheeze, again, is a typical feature as a consequence of the release of vasoactive
compounds such as 5-HT and bradykinin.
Symptoms usually improve following treatment with somatostatin analogues.

Relative youth actually reflects a better prognosis.

Cardiac lesions are not reversible with treatment, deteriorate with time and
frequently require replacement.
Patients with carcinoid heart disease,,,most die of progressive right heart failure
within one year after onset of symptoms.
The prognosis of patients with recognised carcinoid heart disease has improved
over the past two decades [and] may be related to valve replacement surgery
Digoxin Toxicity Indications for administration of Digoxin specific Fab Fragment
o haemodynamic instability
o life-threatening arrhythmias
o serum potassium >5 mmol/l in acute toxicity
o plasma digoxin level >13nmol/l
o ingestion of more than 10 mg digoxin in adults and 4 mg in children
Deep venous thrombosis
Thrombosis involving the popliteal veins are considered to be proximal DVT,
while thrombosis involving veins distal to popliteal veins are considered distal.
Anticoagulation for distal DVT is controversial as the incidence of pulmonary
embolism in such a setting is very low. However, patients with distal DVT should be
followed by serial Doppler studies, if not anticoagulated, because proximal extension
of thrombosis can occur.
Clopidogrel causing thrombotic thrombocytopenic purpura
fever, altered mental status, hemiparesis, anaemia, thrombocytopenia and renal
This disorder can occur in less than 1% of patients receiving clopidogrel or
The peripheral blood smear reveals fragmented RBCs (schistocytes, eg,
spherocytes, segmented RBCs, burr cells, or helmet cells).
While further imaging with MRI would certainly be indicated, cerebral
angiography would not be performed here as a next step, and in any case the low
platelet count would give cause for caution with invasive procedures including
lumbar puncture.

dysbetalipoproteinaemia (type III hyperlipoproteinaemia)
Palmar xanthomas are pathognomonic
It is caused by mutation in apoprotein E,
transmitted as an autosomal recessive trait
usually requires a secondary exacerbating metabolic factor for expression of the
Therefore, secondary causes of hyperlipidaemia such as
o hypothyroidism,
o obesity,
o diabetes mellitus,
o renal insufficiency,
o high-calorie,
o high-fat diet or
o alcohol are often encountered at diagnosis,
Patients are predisposed to peripheral vascular disease and coronary artery
Lipid profile in these patients reveals
o elevated cholesterol and triglycerides while high-density lipoprotein (HDL) is

normal and low-density lipoprotein(LDL) low.

o Definitive diagnosis can be made by lipoprotein electrophoresis or genotyping of
apoprotein E.
Treatment involves
o management of secondary causes
Atrial septal defect should be closed if there is evidence of a
left-to-right shunt with a pulmonary flow to systemic flow ratio that is greater
than or equal to 1.5:1.0,
volume overload of right-sided cardiac chambers, or
symptoms related to the defect.
Atrial septal defect with atrial fibrillation
The patient should be cardioverted to sinus rhythm prior to any intervention to
close the atrial septal defect.
A transoesophageal echocardiogram can give sufficient anatomical data as to the
size and site of the defect.
It is well worth patients undergoing electrophysiological studies prior to any
closure procedure. Any abnormal pathways predisposing to atrial flutter , fibrillation
should be considered for radiofrequency ablation which can be curative.
Cardiac transplantation
Coronary artery disease (transplant vasculopathy) increases in frequency with time
after cardiac transplantation and is present in almost half of all patients by 5 years
after transplantation.
coronary artery disease in a cardiac transplant patient often presents atypically
and may manifest with
new-onset heart failure symptoms,
decreased exercise tolerance,
syncope (usually due to arrhythmias or conduction defects), or
cardiac arrest.
Because transplant-related coronary artery disease is frequently asymptomatic or
manifests with very atypical symptoms, regular screening with coronary angiography
and/or noninvasive stress testing is generally performed,
Traditional risk factors
diabetes mellitus,
immunologic factors
Because the pathophysiology is a diffuse intimal thickening, standard
revascularization methods are frequently not feasible.
There is evidence that statins help prevent and retard progression of transplant
Prognosis is poor once significant transplant vasculopathy becomes
symptomatic, and in appropriate candidates, another cardiac transplantation is a
possible treatment option.
Side effects for cyclosporine include
o hypertension,
o nephrotoxicity,
o hypertriglyceridemia,
o hirsutism,
o gingival hyperplasia, and

o tremor.
o High levels of cyclosporine can cause seizures
-blockers and pregnancy
All available -blockers cross the placenta and are present in human breast milk,
resulting in significant levels in the fetus or newborn.
Therefore, when used during pregnancy, fetal and newborn heart rate and blood
glucose monitoring are indicated.
Adverse fetal effects, have been associated with the use of atenolol, especially
when initiated early in the pregnancy.
o low birth weight,
o early delivery, and
o small size for gestational age
o The World Health Organization considers atenolol (U.S. Food and Drug
Administration [FDA] pregnancy risk category D) unsafe during breastfeeding as it
concentrates in breast milk, resulting in a significant dose to the breast-fed infant
with associated risks for hypoglycemia and bradycardia.
o Metoprolol (pregnancy risk category C) should be considered as an alternative.
Digoxin in pregnancy
risk category C drug.
Although it readily passes to the fetal circulation, no teratogenic effect has been
reported in humans.
Digoxin is often used as a maintenance medication in patients with heart failure
or atrial arrhythmias during pregnancy.
The indications for digoxin are identical to those for nonpregnant patients with
heart failure.
It is recommended for patients with New York Heart Association class III heart
failure to improve symptoms and reduce hospitalization.
It is not indicated in asymptomatic patient.
Diuretics in pregnancy
Diuretics impair uterine blood flow and placental perfusion.
Continuation of diuretic therapy initiated before conception does not seem to
have unfavorable effects.
Maternal use of furosemide during pregnancy has not been associated with toxic
or teratogenic effects, although metabolic complications have been observed.
Neonatal hyponatremia and fetal hyperuricemia have been reported.
Use of diuretics should be limited to the treatment of symptomatic heart failure
with clear evidence of elevated central venous pressure.
Furosemide (pregnancy risk category C)
Central Retinal Vein Occlusion
Patients usually present with painless loss of vision
diffuse retinal hemorrhages in all four quadrants of the retina
as well as dilated, tortuous veins.
cotton-wool spots,
disc edema,
optociliary shunt vessels
neovessels might also be present.
Multiple etiologies should be considered including:
o hypertension,
o glaucoma,
o optic disc edema,
o hypercoagulable states,

o vasculitis,
o drug-induced, and
o retrobulbar compression by tumors or grave's opthalmopathy
left Subclavian steal syndrome
left upper extremity claudication precipitated by exertion
Examination findings include the
o low blood pressure in the left arm compared with the right,
o the diminished left radial and brachial pulses, and
o the systolic murmur in the left clavicular region.
Another possible symptom is syncope or near-syncope due to subclavian steal
syndrome, which occurs in the setting of significant stenosis of the subclavian artery
and retrograde flow in the ipsilateral vertebral artery during upper extremity
Transient ischemic attack in complex ascending aortic atheromas.
The presence of an ascending aortic atheroma of 4 mm or greater in diameter
increases the risk of recurrent stroke.
Treatment either warfarin or antiplatelet
Lyme carditis
is manifested by acute-onset, high-grade atrioventricular conduction defects that
may occasionally be associated with myocarditis.
Carditis occurs in 5% to 10% of patients with Lyme disease, usually within a few
weeks to months after infection.
Cardiac involvement can occur in isolation or with other symptoms of the
Atrioventricular block can present in any degree, and progression to complete
heart block is often rapid.
Atrioventricular block is usually within the node, but sinoatrial and His-Purkinje
involvement have also been described.
Prognosis is good, with usual resolution of atrioventricular block within days to
In some patients, heart block is the first and only manifestation of Lyme disease,
but the diagnosis can be confirmed by a positive IgM and IgG antibody response to B.
burgdorferi. Lyme serologic testing should be considered in any patient with
unexplained high-grade atrioventricular block, particularly in patients with potential
tick exposure living in endemic areas.
Electrophysiology study is not indicated, since it does not provide additional
prognostic information.
The preferred antibiotic regimen is intravenous ceftriaxone until the heart block
resolves, followed by a 21-day course of oral therapy.
Erythromycin is considered a third-line agent for the treatment of Lyme disease,
as it is less effective than penicillin or cephalosporin drugs. However, oral
erythromycin can be used for patients with erythema migrans who are intolerant of
amoxicillin, doxycycline, and cefuroxime.
Most cases of Lyme carditis resolve spontaneously, and neither temporary nor
permanent pacemaker therapy is needed.
Temporary pacing would be required if the patient were hemodynamically
unstable with bradycardia. However, this rarely occurs in the setting of Lyme
Indications for permanent pacemaker placement would include persistent highgrade atrioventricular block.
Tetralogy of Fallot

Women with tetralogy of Fallot have an increased risk of having offspring with
congenital anomalies.
Approximately 15% of women with tetralogy of Fallot have chromosome 22q11.2
microdeletion "DiGeorge Syndrome", which raises the risk of having a child with
congenital heart disease substantially, from 4% to 6% in affected women without the
microdeletion to approximately 50% in those with the microdeletion.

Peripheral arterial disease

A supervised program of regular, repeated exercise to the point of near-maximal
pain significantly increases pain-free walking time and walking distance in patients
with symptomatic peripheral arterial disease.
In patients with class I acute limb ischemia (moderate to severe claudication but
no rest pain, audible venous and arterial Doppler signals),
o antiplatelet therapy along with systemic anticoagulation with heparin is indicated.
Patients with transient sensory deficits and no motor weakness are typically
considered for intra-arterial thrombolytic therapy.
Patient with marked motor and sensory deficits; needs emergency surgical
Patients with anesthesia, paralysis, and loss of vascular flow signals have
irreversible ischemia and prompt amputation is required.
Patients with less dense sensorimotor defects and intact venous flow signals may
obtain limb salvage, but only with immediate revascularization.
Patients without sensorimotor loss and with evidence of intact vascular flow are
more likely to obtain limb salvage, but only with prompt vascular intervention.
Traveler venous thrombosis
There is no evidence for an association between dehydration and travelassociated VTE and so whilst maintaining good hydration is unlikely to be harmful it
cannot be strongly recommended for prevention of thrombosis
Travellers at the highest risk of travel-related thrombosis undertaking journeys
of greater than 3 hours should wear well fitted below knee compression

Recommended goals for management of adults with diabetes are
hemoglobin A1C <7.0%,
preprandial plasma glucose 90-130 mg/dL (5-7.22 mmol/L),
peak (2 hour) postprandial plasma glucose <180 mg/dL (9.99 mmol/L),
blood pressure <130/80 mm Hg,
triglycerides <150 mg/dL (1.69 mmol/L),
HDL cholesterol >40 mg/dL (1.03 mmol/L), and
LDL cholesterol <100 mg/dL (2.59 mmol/L).
Compared with subjects with normoglycaemia, beta cell mass is reduced
By 50% in subjects with impaired fasting glucose
By 65% in subjects with Type 2 diabetes and
Over 90% in subjects with type 1 diabetes.
The suggestion therefore is one of gradual insulin deficiency associated with
increasing insulin resistance.
Gestational diabetes mellitus
Patients with gestational diabetes mellitus have a 50% risk of developing type 2
diabetes mellitus in the 5 to 10 years after the diagnosis of gestational diabetes.

Maturity onset of diabetes of youth

MODY3 due to
o HNF1-alpha mutation (Hepatic nuclear factor1).
o MODY3 is the cause of 2% of type 2 diabetes and makes up around 70% of MODY
o It presents most commonly in early adulthood and is associated with severe
hyperglycaemia in some cases and frequent microvascular complications.
o One-third of patients require insulin therapy and around
o one-third may be controlled on oral hypoglycaemic drugs.
o Sulphonylureas would be the initial oral therapy of choice.
o It is linked to a mutation on chromosome 12q24, which is the cause of the HNF1alpha mutation.
Next commonest MODY variant is MODY 2,
o results from a glucokinase mutation leading to altered glucose sensing in pancreatic
beta cells.
o In contrast, 90% of MODY2 patients are controlled on diet therapy alone.
Group B "not A" Streptococcus the commonest cause of cellulites in diabetics
Diabetic ketoacidosis
Patients with diabetic ketoacidosis (DKA) are at increased risk of venous
thromboembolism because of volume depletion, hyperglycaemia and their decreased
conscious level.
As such standard prophylaxis against deep vein thrombosis is an important
component of management.
Whilst phosphate depletion may be a feature of DKA, IV phosphate replacement
is not part of routine management.
Sodium bicarbonate is also not used routinely and is only recommended in
severe acidosis or circulatory collapse as an adjunct to insulin and fluid resuscitation
Hyperglycaemic hyperosmolar state
occurs in older type 2 diabetic patients, some residual insulin production
preventing the development of ketoacidosis, which occurs in type 1 diabetic patients
more commonly.
pH normal
Serum urea elevated
Consequent on the osmotic diuresis due to hyperglycaemia, the patient will be
o very dehydrated.
o Hypotension
o Serum sodium elevated
The initial goal is repletion of extracellular volume. 1-3 litres of normal saline will
start to restore this
Then treat hypernatraemia, 0.45% saline is then given which replaces intra- and
extracellular fluid loss,
5% dextrose should be added when blood glucose reaches 15 mmol/l.
Intensive glycemic control in the ICU
intensive glucose control increased mortality among adults in the ICU: a blood
glucose target of 180 mg or less resulted in lower mortality than did a target of 81 to
108 mg
glucose levels between 140 and 180 mg/dL (7.8 and 10.0 mmol/L) may be
is best achieved in the intensive care unit with an intravenous insulin infusion.
If patient is ready for transfer to a general ward, patient should be transitioned to

an injectable regimen involving long- or intermediate-acting and rapid-acting

insulins. Oral agents can be restarted before discharge
Insulin glargine, the dosage of which is typically adjusted every 2 to 3 days until
optimal glycemic control is achieved, cannot quickly guarantee adequate control
during the 1 to 2 days that this patient is likely to be in the ICU.
Sliding scale, this approach to glycemic control is considered inadequate because
insulin is provided only when hyperglycemia becomes established.
Management of hyperglycemia in the hospital setting
Hospitalized patients frequently experience stress hyperglycemia because of
counterregulatory hormonal surges, which frequently complicate an acute illness.
Therefore, the best next step in managing this patients mild hyperglycemia
is to measure his fasting plasma glucose level (or perform an oral glucose tolerance
test) several weeks after discharge.
Diabetes and Cardiovascular diseases
Studies suggest that diabetes is a coronary artery disease equivalent, i.e. that
cardiovascular risk associated with diabetes is similar to that of patients with
established ischaemic heart disease (IHD).
Therefore evidence from CARDS, HPS, etc. indicates that subjects with diabetes
should receive statin therapy as this significantly reduces cardiovascular events.
Fibrates are more effective on hypertriglyceridaemia
ezetimibe would be associated with an approximate 20% reduction in cholesterol
and diet a paltry 10%.
Statins such as rosuvastatin may reduce cholesterol by as much as 60%.
Diabetes mellitus and Heart failure
The insulin sensitizing drugs metformin and the thiazolidinediones are
contraindicated in patients with advanced heart failure.
Diabetes mellitus and Renal failure
Glycemic control improves spontaneously
Metformin is contraindicated in men with a serum creatinine level greater than
1.5 mg/dL (132.6 mol/L) or women with a level greater than 1.4 mg/dL (123.8
mol/L). When the glomerular filtration rate is reduced, circulating concentrations
of metformin can accumulate, which increases the risk of lactic acidosis.
Sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is frequently used
in patients with chronic kidney disease. Inhibiting the degradation of DPP-IV
increases glucagon-like peptide-1 levels and thereby leads to increased insulin
secretion and decreased glucagon secretion. sitagliptin does not cause hypoglycemia.
Sitagliptin is metabolized in the liver but excreted largely unchanged in the urine, and
the dosage needs to be reduced by 50% to 75% in patients with renal insufficiency.
Diabetic nephropathy
develops in approximately 40% of patients with type 1 diabetes and in 5% to 40%
of patients with type 2 diabetes.
Without intervention nephropathy is likely to deteriorate with the development
of macroalbuminuria. In association with the latter, renal function declines about
10% per year, ending in end-stage renal disease.
Proven interventions in the treatment of nephropathy include ACE inhibitors,
low dietary protein and improved glycaemic control.
The evidence for good glycaemic control in the treatment of microalbuminuria in
patients with type 1 diabetes suggests no clear benefit [DCCT]).
However, meta-analyses of the effects of ACEi on the development of
nephropathy in type 1 diabetics show an albumin excretion rate 50% lower at two
years in treated versus untreated patients.
The evidence for a low protein diet exists for overt proteinuria but not

Diabetic Retinopathy
o Recent UK studies have put the 4-year incidence of maculopathy in type 2 diabetes
patients as high as 10.4%,
o 75% of cases of maculopathy being type 2 diabetes related.
o In type 1 diabetes maculopathy is named as the cause of blindness in 14% of
Immediate ophthalmology referral is recommended for
o proliferative retinopathy (presence of new vessels signifies a 40% risk of blindness
within 2 years if untreated),
o rubeosis iridis,
o vitreous haemorrhage, and
o advanced retinopathy with fibrosis and
o retinal detachment.
Referral within 6 weeks is recommended for
o preproliferative retinopathy,
o maculopathy and for
o any cause of deterioration of more than two Snellen chart lines in visual acuity,
o although the presence of email technology means that a same day opinion should
be obtained from the ophthalmologist.
Routine referral may be considered in some
o cases for cataract surgery or
o in those patients with non-proliferative retinopathy but who have a large amount of
hard exudates and
o circinate formation.
Rubeosis iridis
ocular pain is due to raised intraocular pressure.
Causes include
o Sickle cell disease
o Diabetes mellitus
o central retinal vein occlusion and
o carotid artery occlusive disease.
Diagnosis is with fluorescein angiography to assess extent of retinal ischaemia
and ultrasound.
Progression of rubeosis is thought to be reduced by aggressive management of
the underlying medical cause and reduction of the area of viable retina with panretinal photocoagulation.
Topical steroids and standard treatments for open angle glaucoma are also of
Unfortunately prognosis for this condition is generally poor as many patients
present at a late stage.
Diabetic autonomic neuropathy
early satiety due to gastroparesis,
poor night vision due to pupillary dysfunction, and
urinary incontinence.
Cardiovascular neuropathies
orthostatic hypotension,
absent normal variation of the heart rate with breathing,
tachycardia, and
sudden death.
Patients should thus undergo further testing, such as an exercise stress test, to
exclude exercise-induced silent ischemia.

The treatment of orthostatic hypotension, fludrocortisone and midodrine

,,,,,Patients being treated with these drugs should be closely monitored for supine
hypertension, abnormal potassium levels, and fluid retention.
Postural hypotension
A standing BP of 110 systolic is clearly acceptable,
first step is in stopping diuretics and monitoring his blood pressure over the
subsequent 2-4 weeks.
If he still has significant postural hypotension then the next steps would be to
add elastic stockings, then
Neurogenic bladder
which can manifest as recurrent urinary tract infections and overflow
Measuring postvoid urinary residual volumes or obtaining a bladder
ultrasonogram will determine whether high urinary residual volumes are present.
If they are, prokinetic drugs (such as bethanechol chloride) can be given, or
an intermittent urinary self-catheterization regimen can be initiated.
Regular and complete bladder emptying will help reduce the incidence of urinary
tract infection and possibly reverse or improve the patients renal insufficiency
Anticholinergic agents, such as oxybutynin, inhibit contraction of both the
normal and unstable bladder. Oxybutynin is highly effective in the treatment of
detrusor instability (overactive bladder). However, oxybutynin is contraindicated in
patients with an atonic bladder and would likely exacerbate this patients
Neuropathic ulcer
commonly found on the pressure points of the feet and are painless.
Between 5 and 13% of patients have neuropathy at diagnosis of type-2 diabetes.
Ten per cent of people have absent dorsalis pedis pulses. Therefore, their absence
does not indicate ischaemia.
Venous ulcers are usually found on the gaiter area of the ankle.
Ischaemic ulcers are found on the dorsa or edges of the feet. The feet are cold,
pulseless, and hairless, and the nails are in poor condition.
Infected ulcers are malodorous and often exude pus.
UTI and Diabetes
Candida urinary tract infections (UTIs) occur more commonly in uncontrolled
diabetic patients.
An "Methicillin resistant Staphylococcal aureus" MRSA UTI occurs in patients
with indwelling lines/prostheses.
Escherichia coli strains resistant to ciprofloxacin tend to be seen in elderly
patients, especially those who live in nursing homes.
Necrobiosis lipoidica diabeticorum.
Necrobiosis lipoidica is seen in 0.31% of patients with diabetes and is
more common in females.
Around 4060% of patients with necrobiosis lipoidica have diabetes
presents in young adults or in early middle life.
may precede symptoms and signs of diabetes by several months " Urine dipstick
is negative and a fasting blood glucose is normal"
The lesions are usually managed with
o support bandaging
o Treatments with topical steroids, injectable steroids, skin grafting and camouflage
creams have been used as therapies.
o low-dose aspirin or topical steroids.

Diabetic amyotrophy
uncommon and disturbing condition which is said to usually affect men in their
fifties who have type-2 diabetes.
weight loss, burning proximal muscle pain and weakness. quadriceps wasting.
The condition affects lumbar sacral plexus lower motor neurones.
Presentations may be :wasting of the quadriceps muscles bilaterally with loss of
power. Loss of Knee and ankle jerks some loss of light touch and pinprick sensation
over both feet and ankles. Plantar responses may be flexor or extensor.
EMG shows multifocal denervation in paraspinous and leg muscles.
Prior to making the diagnosis it is important to exclude other causes such as disc
disease or malignancy "MRI spinal cord"
The aetiology of this condition is unknown, but oral antidiabetic agents may play
a part. Transition to insulin therapy is therefore recommended, additionally in this
case it would improve blood glucose control.
Recovery happens over 34 months, but only 50% achieve complete recovery.
Partial or complete resolution occurs with control of hyperglycaemia

best evaluate the patient for insulinoma, a prolonged fast (up to 72 hours) under
strict medical observation is often necessary.
Serum glucose, insulin, C-peptide, and proinsulin levels are measured at 4- to 6hour intervals throughout the supervised fast.
The fast is discontinued once the glucose value falls below 45 mg/dL (2.5
mmol/L) with associated symptoms of hypoglycemia and appropriate blood tests
(measurement of plasma glucose, insulin, and C-peptide levels) are obtained.
More than 95% of patients with insulinoma will have hypoglycemia within 72
Insulin and C-peptide levels will generally be elevated, as will the proinsulin
level, which suggests a greater tumor release of immature insulin.
Once the diagnosis of insulinoma is confirmed biochemically, imaging studies of
the pancreas are obtained, beginning with an abdominal CT scan
Charcots arthropathy
indium labelled white cell scan is the best way to differentiate between infective
causes and Charcots arthropathy.
Charcots is thought to occur due to increased blood flow as a result of
neuropathy. This results in increased osteoclast activity and bone turnover; the foot is
then susceptible to often very minor trauma and destructive changes take place.
joint immobilisation for at least 3 months in an aircast type non-weight-bearing
plaster. This is to allow bone remodelling/repair to occur.
Bisphosphonates are a useful adjunct to the healing process as they reduce
osteoclast activity.
Whilst insulin therapy is likely to improve glycaemic control and slow further
progression of neuropathy, it will not affect recovery of the Charcots joint.

High dose metformin is thought to interfere with the enterohepatic circulation of bile
salts, leading to reduced reabsorption of bile salts from the ilieum

The mode of action of fibrates is to

o enhance lipoprotein lipase activity,
o increase low-density lipoprotein (LDL) receptor-mediated clearance of LDL and
o increase high-density lipoprotein (HDL) synthesis.
o This leads to a corresponding fall in triglycerides due to a fall in very low-density
lipoprotein (VLDL), and a rise in HDL.
o In total, they reduce triglycerides by 20-60%, LDL by 5-25%, and increase HDL by

Diabetes insipidus
Osmolality, plasma 275-295 mosm/kg
Initial plasma osmolarity Initial urine osmolarity Water deprivation urine
Desmopressin urine
Normal 275-295 600 > 600 > 600
Nephrogenic DI >295 <300 No effect <300 No effect <300
Cranial DI >295 <300 No effect <300 > 600
Partial cranial DI >295 <300 300-400 400-600
Psychogenic <275 <300 300-400 400
If initial urine osmolarity >660 it exclude DI
Psychogenic Both the plasma and urine osmolalities are low
During pregnancy sNa and plasma osmolarity are in lower normal level,,,,so DI
can easily be missed in pregnancy so finding Na and osmolarity in upper normal level
is abnormal high
can cause hyponatremia if a person continues to drink without any fluid
restriction, particularly if their fluid intake is excessive
In patients receiving desmopressin who develop severe hyponatremia and a low
urine output, cortisol deficiency should be part of the differential diagnosis.
Cortisol is necessary for the distal nephron to excrete a water load. Thus, cortisol
deficiency may mask diabetes insipidus.
Cerebral salt wasting a syndrome characterized by hypovolemia and hyponatremia,
usually occurs within 10 days of a neurosurgical procedure or disease, particularly
subarachnoid hemorrhage.
is a common late finding after irradiation of pituitary adenomas. radiation
therapy typically does not cause damage to the posterior pituitary
In patients with panhypopituitarism, cortisol should be replaced before other
Post-traumatic Hypopituitarism
a frequency of hypopituitarism in up to 35% to 50% of patients after a motor
vehicle accident or subarachnoid hemorrhage.
The most important hormonal axis to test is the hypothalamic-pituitary-adrenal
axis, and an 8 AM serum cortisol measurement is the best first test to determine
deficiency of this axis.
If the basal cortisol level is equivocal (that is, between 6 and 18 g/dL [166 and
497 nmol/L]), then testing with low-dose (1 g) cosyntropin stimulation may prove
Assessment of the other pituitary axes should eventually be carried out in this
patient, but the results of these tests are not as potentially lifesaving as (and thus are
less critical than) the results of an early morning measurement of the serum cortisol

Growth hormone would be the last hormone assessed once all other deficits have
been tested for and corrected.
If there are three or more pituitary hormonal axes found to be deficient, a low
insulin-like growth factor I level would establish a diagnosis of growth hormone
Symptoms of tiredness, poor concentration and weight gain suggest growth
hormone (GH) deficiency and this is supported by the lowish IGF-1 concentration.
The diagnosis of secondary hypogonadism is established if a patients
testosterone concentration and sperm count are low and serum luteinizing hormone
and follicle stimulating hormone levels are inappropriately normal or low.
A serum free thyroxine (T4) level will indicate thyroid hormone status more
accurately than measurement of the serum thyroid-stimulating hormone level
Prolactin more than 6000 in macroadenoma
Always consider the possibility of pregnancy in reproductive-aged females,
because this is the most common cause of secondary amenorrhea
hypoestrogenism include vaginal dryness, dyspareunia, and a decline in bone
mineral density (ie, osteopenia or osteoporosis).
Dopamine agonists are preferred initial treatment because of their very high
Radiation therapy is rarely performed for prolactinomas because of the high
efficacy rates of dopamine agonists.
Somatostatin analogues have not been shown to have substantial prolactinlowering or tumor-shrinking effects in patients with prolactinomas
surgery is reserved for the few patients who cannot tolerate or respond to
dopamine agonists.
optic nerve compression gives no time to wait. In this situation, dopamine
agonists may be used as an adjunct to surgery.
Severe hypogonadism in a young male with an elevated serum prolactin level
strongly suggests pituitary macroadenoma
In men with massive prolactinomas, irreversible damage to the gonadal axis may
occur that necessitates testosterone replacement therapy, despite normalization of
the prolactin level.
Women with microadenomas
The dopamine agonist bromocriptine has been shown to restore ovulatory cycles
in greater than 80% of women.
A dopamine agonist would be indicated if pregnancy were desired.
Amenorrhea, which implies hypo-estrogenemia and an increased risk for
osteoporosis. Oral contraceptives will supply needed estrogen and, at the same time,
provide contraception if patient not interested in becoming pregnant
oral contraceptive use is safe in women with microadenomas, and there is
minimal risk of tumor enlargement.
For women with prolactinomas, dopamine agonists are stopped once pregnancy
is achieved. There are no documented risks of fetal malformations or other adverse
pregnancy outcomes for these agents
Symptomatic growth occurs in approximately 30% of macroprolactinomas and
3% of microprolactinomas in the second or third trimester, which necessitates
reinstitution of the dopamine agonist, transsphenoidal surgical decompression, or
delivery if the pregnancy is sufficiently advanced
Nonfunctioning pituitary tumors
The increase in prolactin levels due to the hypothalamic or stalk dysfunction
The most appropriate treatment for such an adenoma is surgery.
Nonsecreting adenomas generally do not enlarge and cause symptoms during

Prolactinoma "macroadenoma" during pregnancy

dopamine agonists are stopped once pregnancy is achieved.
Dopamine agonists are reinstituted when breast feeding is completed.
Approximately 30% of patients with macroprolactinomas will experience
clinically significant enlargement of their prolactinomas during pregnancy.
o If this occurs, options include reinstitution of dopamine agonists, surgery, or
delivery, depending on fetal viability.
In contrast, only approximately 3% of women with microadenomas will
experience such enlargement.
Tumor enlargement is due both to the elimination of the dopamine agonist that
had been controlling tumor size and to the stimulatory effect of the high estrogen
status of pregnancy.
Follow-up studies of women who became pregnant after using cabergoline or
bromocriptine have shown no increased risk of fetal malformations, premature
deliveries, or stillbirth. Therefore, the patient is unlikely to encounter any of these
Lymphocytic hypophysitis during pregnancy
a pituitary mass that mimics an adenoma is typically seen on an MRI.
Diffuse enhancement of a symmetrically enlarged pituitary gland on MRI is also
This disorder, which usually develops intrapartum, is a destructive process
thought to have an autoimmune basis.
Adrenocorticotropic hormone (ACTH) deficiency occurs in 65% of patients with
such lesions and is a major cause of death
Thyroid-stimulating hormone deficiency occurs in 60% of patients with this
disorder, and other hormonal deficits are of lower frequency.
The only way to diagnose the lesions of lymphocytic hypophysitis with certainty
is by biopsy,
the size of most lesions decreases after delivery.
Serial visual field testing is indicated. If field defects do develop, surgical
debulking may be necessary.
headache (55-86%),
endocrine dysfunction (66-90%)
o A moderately elevated prolactin up to 3000
o 40% of patients have symptoms of hypothyroidism
o 25% of patients have symptoms of adrenal failure
o 20% have diabetes insipidus (eg, excessive fluid intake and urination).
o 8%of adults complain of decreased sexual drive
o 90% of men complain of impotence, while most women complain of amenorrhea.
o Most young patients present with growth failure and delayed puberty.
visual disturbances (37-68%)
o Optic pathway dysfunction on presentation is noted in 40-70%
Other manifestations hyperphagia and obesity, psychomotor retardation,
emotional immaturity, apathy, short-term memory deficits, incontinence).
Short stature is present in 23-45% and obesity in 11-18%.
Three major clinical syndromes have been described and relate to the anatomic
location of the craniopharyngioma.
o Prechiasmal localization typically results in associated findings of optic atrophy (eg,
progressive decline of visual acuity and constriction of visual fields).
o Retrochiasmal location commonly is associated with hydrocephalus with signs of
increased intracranial pressure (eg, papilledema, horizontal double vision).
o Intrasellar craniopharyngioma usually manifests with headache and

Craniopharyngiomas during pregnancy

less common than adenomas
An MRI would typically show an irregular cystic lesion with an enhancing wall,
not the symmetric sellar lesion
Craniopharyngiomas also cause panhypopituitarism and diabetes insipidus
Acromegaly can be diagnosed by demonstrating an elevated insulin-like growth
factor 1 level in a patient in whom there is clinical suspicion of the disorder.
Transsphenoidal surgical resection is typically the treatment of choice.
In patients with pituitary tumors who are not cured by surgery, hormone levels
often normalize with use of somatostatin analogues.such as octreotide or lanreotide.
These drugs can normalize GH and IGF-1 levels in approximately 50% of patients
when given adjunctively after pituitary surgery. They also commonly decrease tumor
Cabergoline normalizes GH and IGF-1 levels in only 10% to 20% of patients.
When transsphenoidal surgery is unable to cure a patient with a pituitary tumor,
a second surgery, such as craniotomy, does so in only approximately 25% of patients.
Because craniotomy also has substantial morbidity, it would rarely be used in a
patient such as this one.
Radiation therapy may normalize GH and IGF-1 levels, but only after an
extended period of time. With conventional radiation therapy, hormone levels in
approximately two thirds of patients normalize in approximately 10 years; with
gamma knife stereotactic radiation therapy, the time is reduced to 4 years. Neither
type of radiation therapy would have a normalizing effect on these levels within 1
McCuneAlbright syndrome
due to a mutation in a G-protein.
caf-au-lait spots and
endocrinopathies. thyrotoxicosis
There is an increased risk of osteosarcoma and other connective tissue tumours,
precocious puberty the patient is at increased risk of developing breast
the finding of an inappropriately normal level of thyroid-stimulating hormone
suggests a pituitary cause of the hyperthyroidism. patient should undergo MRI of the
pituitary gland to detect a possible thyroid-stimulating hormone (TSH) secreting
Factitious thyrotoxicosis show undetectable thyroglobulin
IV heparin interferes with the thyroid function tests assay on occasions
displacing bound thyroid hormone.
Long-term remission following antithyroid drugs is of the order of 15%, with the
vast majority relapsing. Thus, frequently, radio-iodine is advocated as a primary
treatment - particularly for multi-nodular or toxic solitary nodules. However,
approximately 80% will have long-term hypothyroidism following radio-iodine.
There is no evidence of increased risk of thyroid neoplasia or gastric neoplasia
following radioactive iodine (RAI).
Goitre shrinkage may occur in up to 30% following RAI.
Thyrotoxicosis in patient receiving Digoxin need to increase digoxin dose

Anticoagulated patients developing thyrotoxicosis require Decrease warfarin dose,

Agranulocytosis with carbimazole
less than 1% of cases and
sore throats are very common.
It is not uncommon to see a drop in WCC associated with thionamides, if WBC
and neutrophil counts are normal OR just below normal, the carbimazole continued.
Thyroid storm
require hospital admission to an intensive care unit.
Fever is the most characteristic feature, with the temperature often rising above
41 C.
There may be evidence of organ damage
ECG show a fast AF
Appropriate therapy includes a combination of
o -blockers, propranolol (240-480 mg/d)
o antithyroidal medications, propylthiouracil (>450 mg/d)
o saturated sodium potassium iodide plus
o hydrocortisone therapy,
o cooling of body temperature, and
o treatment of any underlying precipitant "chest infection"
Propranolol and propylthiouracil have the added benefit over atenolol and
methimazole of reducing T4 to T3 conversion.
Graves disease and ophthalmopathy
Graves disease is complicated by Graves ophthalmopathy in approximately 5% to
10% of patients.
Graves ophthalmopathy is an autoimmune disease of the retro-orbital tissues
that may present with proptosis and periorbital edema.
Patients may report irritation in the eyes, tearing, ocular pain, and changes in
vision. Vision loss may occur.
A persistent thyrotoxic or hypothyroid state appears to exacerbate eye disease
activity, so patients should be made euthyroid as soon as possible.
Radioactive iodine should be avoided as treatment in patients with significant
thyroid-associated eye disease but can be used in patients with mild ophthalmopathy
if concomitant prednisone therapy is used.
Orbital decompression surgery is reserved for patients with severe
ophthalmopathy that has not responded to medical treatment.
Hashimoto disease
Patients with Hashimoto disease can have normal thyroid hormone levels but are
at increased risk for hypothyroidism in the future,,so patient should have annual
thyroid function tests.
Myxoedema coma
If associated hypoadrenalism is suspected the immediate management is
If NO hypoadrenalism is suspected the immediate management is IV thyroid
hormone - either T4 or T3
Secondary hypothyroidism
The best way to diagnose central hypothyroidism is by measuring the level of the
peripheral hormone T4. Similarly, thyroid hormone treatment is monitored and
adjusted by measuring free T4 rather than TSH levels.
Progressive loss of pituitary hormones is to be expected after pituitary irradiation
,,,,fatigue and constipation and a recent elevated LDL-cholesterol level
Hypothyroidism while on lithium
Patients who develop hypothyroidism while on lithium therapy may require

levothyroxine therapy. Because the patients bipolar disorder has been well
controlled on his present regimen, the lithium should not be discontinued.
Euthyroid sick syndrome,
particularly common in patients with chronic renal failure
small reductions in both free T3 and free T4 and normal or suppressed TSH
abnormal results on thyroid function tests that often normalize after recovery;
This should have repeat thyroid function tests in 4 to 8 weeks.
neither levothyroxine nor liothyronine is indicated for treatment of the thyroid
function changes seen with such non thyroidal illness.
Thyroid nodule
Fine-needle aspiration is the mainstay in the evaluation of such thyroid nodules
in euthyroid patients and has an excellent sensitivity and specificity for detecting
Ultrasonography is superior to CT in the evaluation of thyroid nodules, except
when there is a goiter with substantial substernal extension.
Thyroid scanning has no role in the initial workup of thyroid nodules because
both benign and malignant nodules tend to be hypofunctional or cold on a
thyroid scan.
Thyroid scanning may be helpful when the thyroid-stimulating hormone (TSH)
level is suppressed to assess for a hyperfunctioning (hot) nodule that does not
require fine-needle aspiration biopsy. Hyperfunctioning nodules are rarely
Thyroid cancer
nodule which is 'cold' on uptake scanning
Thyroid-stimulating hormone suppression by levothyroxine is the standard of
care in patients who have thyroid cancer, with the degree of suppression determined
by the severity of disease
TSH suppression has shown benefit is reducing thyroid cancer recurrence.
Typically, patients with low-risk stage I and II disease have a target TSH level in the
low-normal to just-below-normal range (0.3 mU/L)
Thyroid cancer associated with Graves' disease is not uncommon and usually due
to papillary carcinoma and must be considered in suspicious/expanding nodules
Amiodarone-induced thyrotoxicosis
Amiodarone which inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) so consequently T4 may be elevated and T3 low
Radioiodine uptake scan disting between amiodarone induced thyrotoxicosis
type 1 or type 2
Type 1
normal radioiodine uptake
normal interleukin 6 (IL-6) levels.
amiodarone should be discontinued IF there is alternative
treated with a combination of antithyroid drugs and potassium perchlorate
High-dose antithyroid drugs are needed to treat type 1 AIT as they have less
effect due to the high iodine load.
Type 1 AIT should be treated when stable with either radioiodine therapy or
Type 2
decreased radioiodine uptake on thyroid scan
raised IL-6 levels.
treated with a combination of antithyroid drugs and corticosteroids such as
type 2 AIT may progress to hypothyroidism
The amiodarone need not necessarily be stopped if given for VT

Colour flow Doppler ultrasound can be used to differentiate the two. Blood flow
is increased in type 1 and decreased in type 2.
Radioiodine is not usually effective due to reduced uptake by the thyroid due to
high iodine levels.
In both cases, if amiodarone cannot be withdrawn then total thyroidectomy
should be considered.
Lithium would typically cause low T4 and elevated thyroid-stimulating hormone
Thyroglobulin autoantibodies are present in:
Grave's disease
Hashimoto's thyroiditis
idiopathic thyroid atrophy
De Quervain's thyroiditis - transiently
7% of males, and 15-20% of females without thyroid disease
Antithyroid peroxidase antibodies (previously known as thyroid microsome
autoantibodies) are present at:
high titre, in:
o Hashimoto's thyroiditis
o idiopathic thyroid atrophy
low titre, in:
o Grave's disease
o De Quervain's thyroiditis
o 8% of males, and 10% of females without thyroid disease
High titres of thyroid autoantibodies, particularly to thyroid microsomes, is
associated with increased likelihood of progress to myxoedema as it reflects increased
damage to the thyroid cells
Graves disease and ophthalmopathy
an initial inflammatory phase followed by a fibrotic stage.
If the symptoms are mild patients can be managed with lubricants and eye
For active disease treatment, options include
o orbital decompression,
o orbital radiotherapy and
o glucocorticoids.
There is concern that radio-iodine could exacerbate Graves
Patients with pretibial myxoedema tend to have more severe ophthalmopathy.
Secondary hyperthyroidism
elevated tri-iodothyronine (T3)
elevated thyroxine (T4)
normal TSH.
MRI head scan may be expected to demonstrate a pituitary macroadenoma.
Alpha subunit is also secreted in large amounts and measurement of this should
yield an elevated alphaSU:TSH ratio (usually 1:1).
The diagnosis should be suspected when TSH concentrations are not suppressed
in the presence of hyperthyroidism.
Thyroid in pregnancy
It is a feature of normal pregnancy that T3 , T4 levels show a slight increase in
the first trimester due to human chorionic gonadotrophin (HCG) stimulation.
TSH may be mildly suppressed in up to 13.5% of pregnancies during the first
trimester, and this is considered a normal variant.

Thyroid-binding globulin has a twofold increase in concentration during

pregnancy as a result of reduced hepatic clearance and increased synthesis under
oestrogen stimulus.
Patient on oral contraceptive pill has high Total thyroxin because Oestrogen
therapy is associated with elevation of thyroxine binding globulin in the serum,,,
Thus the total serum thyroxine may be misleading in this case, and serum free
thyroxine will confirm whether this patient is hypothyroid or euthyroid.
Thyrotoxicosis in pregnancy
Thyrotoxicosis, of which 85% of cases are due to Graves' disease, there may be
NO goiter
Toxic thyroid adenoma is responsible for a much smaller number of cases of
thyrotoxicosis in pregnancy
propylthiouracil as the primary treatment for toxic thyroid adenoma in
Suppressed TSH with normal free thyroid hormones does not require
A block and replacement regime is contra-indicated as both carbimazole and
propylthiouracil cross the placenta far better than thyroxine and so may induce fetal
If patient on carbimazole and become pregnant the patient should continue
treatment with carbimazole
Both carbimazole at a suggested daily dose of 1020 mg/d and
propylthiouracil (PTU) at a dose of 150 mg bd are acceptable for use in pregnancy,
PTU may be more protein bound and so less is transmitted to the fetus, but
compliance with carbimazole is generally better.
Importantly however there is some controversy that the azole drugs may be
associated with fetal scalp defects, aplastic cutis, and oesophageal atresia.
In patients not controlled at maximal carbimazole, switching of antithyroid
drugs may be appropriate;
In patients who have an adverse reaction to anti-thyroid drugs, poor compliance,
or poor response despite high doses, subtotal thyroidectomy may be required, the
second trimester being the preferred time for surgery.
Relapsed Graves' thyrotoxicosis,with history of previous thyrotoxicosis treated
with anti-thyroid treatment and dysthyroid eye disease, which has now relapsed in
pregnancy.The patient needs to be rendered euthyroid prior to any definitive therapy,
so give propylthiouracil

Postpregnancy thyrotoxicosis Graves' disease OR postpartum thyroiditis

Measurement of TSH-receptor autoantibodies, which are present in more than
90% of patients with Graves' disease but are not present in postpartum thyroiditis,
can distinguish between the two disorders in a patient with postpregnancy
Anti-thyroid peroxidase antibodies will likely be positive in both disorders, and
serum thyroglobulin levels are elevated in both disorders.
Radioiodine uptake will be low in thyroiditis and elevated in Graves' disease;
however, radioiodine is secreted into breast milk, and the isotope most commonly
used to measure radioiodine uptake (131I) has such a prolonged duration of activity
that further breastfeeding is stopped.
Antithyroid drugs are better reserved for confirmed Graves' disease
Hypothyroidism in pregnancy

In patients already on thyroxine when they become pregnant, thyroid function

tests should be assessed at 68 weeks gestation and then at 1620 and
2832 weeks.
Average increase in thyroxine requirements is 2550 g and the increased
need for thyroxine ceases immediately after delivery.
In patients with positive thyroid autoantibodies there is a twofold increased risk
of spontaneous abortion.
In patients who are suboptimally treated for hypothyroidism there is a 21% risk
of pregnancy-induced hypertension.
Maternal hypothyroidism is also associated with increased risk of pregnancy
induced anaemia and postpartum haemorrhage.
Hypothyroidism in pregnancy
Because a fetus depends on maternal thyroid hormone for the first 10 to 12 weeks
of gestation, the thyroid levels of pregnant women with hypothyroidism should be
carefully monitored.
because standard free T4 levels are not as accurate in pregnant patients. The
total T4 level should be kept stable at approximately 1.5 times the normal range, and
the TSH level should be kept in the lower range of normal.
Because of estrogen elevation during pregnancy, thyroid-binding globulin (TBG)
levels increase. However, without an increase in the dosage of levothyroxine, free T4
levels may decrease as more T4 becomes bound by TBG. After delivery, TBG levels
decrease, as do thyroid hormone requirements.
TSH level should be rechecked. If the TSH level is any higher now, an increase in
the levothyroxine dosage is warranted.
Pregnant patients with hypothyroidism may require an increase in their
levothyroxine dosage of approximately 35% to 50% as early as the first trimester.
because undertreatment of maternal hypothyroidism can have a potentially negative
effect on fetal neurocognitive development.
Measurement of the free triiodothyronine (T3) level is not useful in the
evaluation of hypothyroidism because T3 levels typically remain within the reference
range until the point of severe hypothyroidism. This pattern is unaltered by
Subclinical hypothyroidism
Patients with subclinical hypothyroidism who have a serum TSH value above 10
U/mL (10 mU/L) have been shown to have reductions in their LDL cholesterol
concentrations when treated with levothyroxine
Post-partum thyroiditis
develop some 37 months after pregnancy
57% of women and in
3052% of cases anti-TPO antibodies are positive.
Permanent hypothyroidism is said to develop in around 40% of patients, the
frequency is increased in patients with positive anti-TPO antibodies.
Standard treatment for postpartum hypothyroidism is low-dose thyroxine
(around 50 g), with a withdrawal period after 6 months to measure recovery of
thyroid function.
DeQuervain's or subacute thyroiditis
A radio-iodine uptake scan usually shows minimal or zero uptake.
The condition is treated with steroids and/or beta-blockers.
o Mild hypercalcemia are found in approximately 10% of patients with thyrotoxicosis
o suppressed parathyroid hormone levels.

o Thyroid hormone has direct bone-resorbing properties that cause a high-turnover

state; if left untreated, progression to osteoporosis often occurs.
o elevated level of PTH,
o up to 10% become mildly hypercalcemic with PTH levels that are high normal or
slightly elevated.
Serum calcium levels should be monitored in immobilized patients to check for
the development of hypercalcemia of immobilization, which is more likely to occur in
patients with high bone turnover, such as young patients and patients with Paget
Granulomatous diseases involves excess production of 1-hydroxylase, which
converts 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D; corticosteroid
administration diminishes this hypercalcemia.
Malignancy is the most common cause of non-parathyroid hormone
(PTH)mediated hypercalcemia
Malignancy-associated hypercalcemia is differentiated into two forms:
o local osteolytic occurs when tumor growth in the skeleton leads to the release of
calcium by the stimulation of local cytokines ,,multiple myeloma, adenocarcinoma of
the breast and certain lymphomas
o Humoral hypercalcemia systemic effect of a circulating factor produced by
neoplastic cells. PTH-related protein (PTHrP). squamous cell carcinomas, such as
those of the lung, esophagus, or head and neck. PTHrP levels can be measured, but
this is rarely needed to establish the diagnosis of humoral hypercalcemia of
the first step management is aggressive volume expansion with intravenous
normal saline
furosemide should no longer be recommended as part of the management of
Bisphosphonates lower the serum calcium level, with their maximum effect seen
in 2 to 4 days. Their duration of effect is usually several weeks ,,,,Zoledronate appears
to have the longest-lasting effect (1-1.5 months) and a faster onset of action than
other bisphosphonates; it is approved for use in patients with hypercalcemia of
Because of the lag in the onset of effect, bisphosphonates should be combined
with faster-acting therapeutic modalities, such as aggressive volume replacement
with normal saline infusion and possibly calcitonin injections.
calcitonin has a short-lived effect on hypercalcemia because of tachyphylaxis and
therefore should only be used as an interim step.
Cinacalcet is a calcimimetic agent that occupies the calcium sensing receptor and
lowers serum calcium levels in patients with primary and tertiary
hyperparathyroidism associated with chronic kidney disease. It is not effective and
not approved for use in malignancy-associated hypercalcemia.
Increased calcitriol production associated with activated macrophages
(granulomatous diseases and lymphomas) can be diminished by using
corticosteroids. However, prednisone does not lower PTHrP levels and therefore is
not useful in humoral hypercalcemia of malignancy.
Hypercalcemia with low PTH level
The 25-hydroxy vitamin D level is elevated in states of vitamin D intoxication,
1,25-dihydroxy vitamin D level is increased in
o sarcoidosis,
o granulomatous disease, and
o lymphoma.
Malignancy-associated hypercalcemia
The first test should be PTH not PTHrP
PTH low

PTHrP high
Bisphosphonates inhibit osteoclastic bone resorption and are particularly
effective in hypercalcemia of malignancy.
zoledronate, a long-acting intravenous nitrogen-containing bisphosphonate,
induces rapid and long-lasting hypocalcemic response.
Alendronate has a mild hypocalcemic effect but is not potent enough to combat
acute severe hypercalcemia.
Glucocorticoids have classically been used in hypercalcemic states associated
with production of 1,25-dihydroxyvitamin D3, such as lymphoma or granulomatous
Hypercalcemia with normal PTH level
In an asymptomatic patient with mild hypercalcemia and an inappropriately
normal parathyroid hormone level the main differential includes primary
hyperparathyroidism versus benign familial hypocalciuric hypercalcemia.
Familial hypocalciuric hypercalcemia is diagnosed by a urinary
calcium/creatinine clearance ratio <0.01
In familial hypocalciuric hypercalcemia there is hypocalciuria while in primary
hyperparathyroidism there is hypercalciuria
Hungry bone syndrome
severe hypocalcemia and hypophosphatemia
can occur after removal of a parathyroid adenoma in patients with significant
hyperparathyroid bone disease
The associated hypoparathyroidism is usually transient because the healthy
parathyroid glands recover function quickly, generally within 1 week
Treatment with calcium and a short-acting vitamin D metabolite may be
required until the bones heal.
Alkaline phosphatase levels are not elevated in all types of hyperparathyroidism
Although the action of PTH is to increase the renal tubular reabsorption of
calcium, hypercalcemia causes an increase in the filtered load of calcium. This
increase overwhelms the ability of PTH to reabsorb calcium in the renal tubule with
resultant hypercalciuria
Vitamin D deficiency,
characterized by
o hypocalcemia,
o hypophosphatemia,
o increased alkaline phosphatase
o increased parathyroid hormone levels,
o decreased serum 25-hydroxy vitamin D level.
Measurement of 25-hydroxy vitamin D (calcidiol) is more informative than
measurement of 1,25-dihydroxy vitamin D (calcitriol) in most patients with
hypocalcemia because
o vitamin D deficiency causes hypocalcemia and stimulates parathyroid hormone
secretion, which in turn stimulates renal conversion of 25-hydroxy vitamin D to 1,25dihydroxy vitamin D. the 1,25-dihydroxy vitamin D level is influenced more by
parathyroid hormone and phosphorus levels and by renal function.
o Low dietary intake, poor absorption of vitamin D, and lack of production in the skin
will result in a low serum 25-hydroxy vitamin D level.
o This serum level will also be low in patients taking phenytoin, those with nephrotic
syndrome (loss of vitamin Dbinding protein), and those with hepatobiliary
o Whereas 25-hydroxy vitamin D has a long half-life, 1,25-dihydroxy vitamin D is

more short-lived and therefore not a good measure of vitamin D status.

o 1,25-Dihydroxy vitamin D levels will be low despite normal or high 25-hydroxy
vitamin D levels in patients with
renal insufficiency,
deficiency of renal 1-hydroxylase (vitamin Ddependent rickets type 1), or
The serum level of osteocalcin is not a specific marker of vitamin D deficiency
and is not indicated. he level is elevated in disorders that increase the metabolic
turnover of bone, such as Paget disease and osteomalacia.
Secondary hyperparathyroidism due to vitamin D deficiency.
low vitamin D level,
low-normal serum calcium and phosphorus levels,
elevated parathyroid hormone level.
best treated with high-dose ergocalciferol therapy.
Calcitriol, or 1,25-dihydroxycholecalciferol, is a vitamin D3 analogue. It is most
useful in patients with decreased synthesis of calcitriol, as occurs in
hypoparathyroidism and chronic renal failure. Calcitriol therapy would not replete
the body stores of vitamin D because it is given in very low doses because of its
enhanced potency, compared with ergocalciferol, and so is inappropriate treatment
for this patient.
Vitamin D deficiency and primary hyperparathyroidism.
In uncomplicated "without Vit D deficiency" hyperparathyroidism cause
Vitamin D deficiency is common, especially in older patients, and can mask the
severity of primary hyperparathyroidism. In such patients,
the parathyroid hormone level is disproportionately elevated compared with the
serum calcium level, and
urine calcium excretion is often normal
The 25-hydroxyvitamin D level reflects total body stores of vitamin D and is thus
the most appropriate to measure
If the serum calcium level and urine calcium excretion increase substantially
with supplementation of vitamin D Then parathyroidectomy would then be
Parathyroid cancer
is rare and the only feature that may make you suspicious of a cancer rather than
adenoma is the grossly elevated PTH.
Primary hyperparathyroidism management
Parathyroidectomy for patients with asymptomatic primary hyperparathyroidism
and any one of the following four criteria:
1. Serum calcium concentration greater than 11.5mg/dL (2.85mmol/L)
2. Creatinine clearance reduced to less than 60 mL/ min
3. Bone mineral density T score less than 2.5 "osteoporosis" at any site or a previous
fragility fracture
4. Age younger than 50 years
Hypoparathyroidism in alcoholism
Hypomagnesemia in the patient with alcoholism can mimic hypoparathyroidism,
including severe hypocalcemia and hyperphosphatemia.
It causes both suppression of PTH secretion and resistance to PTH action
Measurement of PTH, vitamin D, and phosphate should be done if the
magnesium level is normal in the setting of hypocalcemia.

Tissue resistance to the action of PTH
increased PTH levels
hypocalcemia and
Phenotypically, a short round face, short neck, and short fourth metacarpal bone.
Obesity Dental hypoplasia Soft tissue calcification/ossification.
The diagnosis is confirmed with genetic analysis and with a failure of cyclic
adenosine monophosphate (cAMP) rise following PTH.
Slipped femoral epiphysis is a recognised feature.

phenotypic appearance of pseudohypoparathyroidism but normal calcium and
phosphorus levels because of normal PTH secretion, function, and action.
Familial hypocalciuric hypercalcemia
is a rare autosomal dominant disorder that is diagnosed by a urine calcium to
creatinine clearance ratio of less than 0.01.
Clinical features
Most cases: Asymptomatic (unlike primary hyperparathyroidism)
Hypocalciuria ( Ca excretion rate < 0.02 mmol/L).
Normal to high PTH
Green colored urine
Genetic testing for FHH-associated mutations in CASR
No treatment is generally required, as bone demineralisation and kidney stones
are relatively uncommon in the condition
Oncogenic osteomalacia
Occur in Certain tumours. prostatic carcinoma, and haematological malignancies
such as myeloma and chronic lymphocytic leukaemia
produce a phosphaturic substance.
Clinically, patients present with bone pain and or fracture, profound proximal
myopathy and severe hypophosphataemia, usually accompanied by a marked
reduction in concentration of 1,25-OH vitamin D.
Other abnormalities of renal function such as glycosuria and aminoaciduria may
also be present.
Treatment with vitamin D metabolites and phosphate supplements may result in
some resolution of skeletal symptoms.
In the case of solid tumours, removal of the primary tumour also results in
improvement of symptoms.
Once yearly intravenous infusion of zoledronate is a potent therapy for treating
postmenopausal osteoporosis
Pagets disease
Recent evidence has suggested that limited skeletal survey is superior to bone
scan for the assessment of the disease.
Pagets is present in around 2% of the population over 55 years, this
prevalence increases with age and the disease is also more common in men
Deafness may be a feature in up to half of all patients with skull base
Osteogenic sarcoma is a very rare complication of the disease.
The mainstay of treatment is with bisphosphosphonates.

The goals of therapy in Pagets disease are to normalise bone turnover and
achieve an alkaline phosphatase as a marker of this, in the normal range if possible.
Bisphosphonates have become the mainstay of therapy,
It appears that the more aggressive initial therapy is, then the longer a period of
remission may be achieved.
Alkaline phosphatase, as a non-invasive method, appears to be the best way to
monitor disease activity.
Deafness may occur in up to half of patients with skull base Pagets,
spinal cord compression may also occur.
Rarer complications include hydrocephalus and osteogenic sarcoma. Sarcomas
are found most commonly in the humerus or femur and a rapid increase in pain in
one limb may arouse suspicion, although it may of course just be a marker of
increased disease activity.
Medullary thyroid carcinoma
Important next investigation is Pentagastrin stimulation test NOT Random
Elevated basal levels of calcitonin are seen in pregnancy, carcinoid, pernicious
anaemia, chronic renal failure and thyroiditis.
The pentagastrin test measures calcitonin levels at 2 and 5 minutes however, and
a rise in calcitonin is suggestive of medullary thyroid carcinoma.
Thin skin and loss of subcutaneous fat is a sign of Cushing's disease
Urinary free cortisol,,,, False positive results may be seen, particularly in obesity
or if there is significant alcohol consumption
In patients with renal failure, Urinary free cortisol this test is more likely to give
a false negative the most appropriate test in these circumstances would be an
overnight dexamethasone suppression test
In patients with documented hypercortisolism,
o elevated or normal ACTH levels indicate a pituitary or neoplastic (ectopic) source,
o whereas suppressed ACTH concentrations indicate a primary adrenal source.
Partial suppression of ACTH achieved with high dexamethasone administration,
suggests an ACTH-secreting pituitary microadenoma
MRI findings are normal in 40% to 50% of patients with documented ACTHsecreting pituitary adenomas.
Bilateral petrosal sinus catheterization should be performed in patients with
biochemically established adrenocorticotropic hormonedependent Cushing
syndrome who have negative findings on pituitary MRIs and chest CT scans. the best
way of distinguishing between ectopic and pituitary dependent CS is with inferior
petrosal sinus sampling where a high gradient of ACTH from sinus compared with a
peripheral sample is diagnostic of pituitary dependent disease.
Usually the cause of Cushing's disease is a pituitary microadenoma and this may
not be seen on MR.
CT scan and octreotide scintigraphy should be employed when results of IPSS
suggest an ectopic source.
The most appropriate next step is removal of the pituitary microadenoma by
pituitary adenomectomy.
Bilateral adrenalectomy is an appropriate option in patients with ectopic ACTH
secretion and an occult or metastatic tumor.
Ketoconazole can be used to lower cortisol secretion. However, this drug is used
not as a definitive therapy for hypercortisolism but instead as an interim therapy for
patients with severe Cushing syndrome.

Ketoconazole is also used in patients with recurrent or inoperable ACTHsecreting tumors and is often given as an interim therapy for patients undergoing
radiation therapy because the beneficial effect of radiation treatment may be delayed.
Conventional radiation therapy leads to the normalization of urine free cortisol
production in over 80% of patients, usually within 2 years. Radiation therapy is
reserved for patients who cannot tolerate surgery or as a secondary treatment when
pituitary surgery has failed
Secondary adrenal insufficiency due to exogenous corticosteroids may be
associated with suppression of both ACTH and cortisol levels and with clinical
findings of excess glucocorticoids.
Outcome analyses suggest that pregnant patients with newly diagnosed Cushing
syndrome of all causes should undergo surgery, unless they are near term.
2-day dexamethasone-corticotropin releasing hormone stimulation test would
distinguish pseudo-Cushing's from autonomous glucocorticoid production
Hypogonadotropic hypogonadism with diminished libido and loss of secondary
sexual characteristics
Overnight dexamethasone suppression test
The overnight dexamethasone suppression test is usually used as a screening test
for Cushing's syndrome.
This test has a false-positive rate of up to 212%,
Dexamethasone is primarily metabolised by the cytochrome P-450 system, by
hepatic CYP3A4, an enzyme complex responsible for the metabolism of many
Considerable increases in cytochrome P-450 enzymes can be seen in
o regular smokers and people who
o drink alcohol regularly.
o Several drugs such as phenobarbital, primidone, ethosuximide, carbamazepine and
rifampicin induce the activity of CYP3A4, and can lead to false positive
dexamethasone suppression tests.
Adrenal insufficiency during stress
Major stress give Stress-level dosages of corticosteroids are considered to be 10times the normal daily replacement dosage. equivalent to 100 mg of hydrocortisone
daily, best administered as 25 mg every 6 hours.
Minor stress (such as a common cold), doubling of the oral dosage of
hydrocortisone for 2 days is recommended; for
Moderate stresses (such as a limited surgical procedure), tripling the dosage for 2
to 3 days is adequate.
Once the dosage of hydrocortisone is over 60 mg per day, fludrocortisone is
unnecessary because that dose of hydrocortisone has adequate mineralocorticoid
Adrenal insufficiency with hypothyroidism
Thyroid hormone replacement can worsen symptoms or even precipitate an
adrenal crisis in patients with underlying adrenal insufficiency. Due to increase the
clearance of cortisol
Once adrenal insufficiency is confirmed, glucocorticoid replacement should be
initiated before restarting or adjusting the levothyroxine therapy.
Addisons disease
o hyperkalemia,
o hyponatraemia,
o ureamia,
o hypoglycaemia,
o mild acidosis,

o hypercalcaemia,
o neutropenia,
o lymphocytosis,
o eosinophilia,
o anaemia
o abnormal liver function tests.
o Low aldosterone secretion (leading to salt wasting)
o High plasma renin
o High adrenocorticotrophic hormone (ACTH)
o High lipotropin
o Elevated plasma vasopressin and Angiotensin II.
o Primary hypoadrenalism may also cause mild hypercalcaemia and derangement of
the thyroid function tests.
o autoimmune destruction of the adrenal glands. Adrenal autoantibodies are present
in about 75% of cases.
o The next most common cause is TB.
o Other causes include haemorrhage including
during pregnancy,
sepsis including WaterhouseFriderichsen syndrome from
coagulopathy and
Other causes are
metastases in over 90% in both glands,
HIV and
opportunistic infections associated with AIDS.
Patients present with a variety of symptoms including
o episodic hypertension,
o chest tightness,
o abdominal pain,
o vomiting,
o sweating,
o restlessness, anxiety, pallor and
o weakness.
Symptoms are precipitated by sneezing, stress, surgery and by agents such as
cheese, alcohol and tricyclic antidepressants.
Glycosuria occurs during attacks in 30% of cases.
Tests that help in diagnosis include 24-hour catecholamine measurement,
metaiodobenzylguanidine (MIBG) and CT/MRI of the adrenal glands.
it can also present with severe hypotension from catecholamine-induced
Approximately 10% of tumours are extra-adrenal (sometimes called
paragangliomas), 10% are bilateral and 10% are malignant.
Phaeochromocytomas are associated with a number of syndromes including
multiple endocrine neoplasia (MEN) 2A and MEN 2B.
Diagnosis is made by demonstrating elevated catecholamine levels in a 24-h
urine sample.
A scan with 131iodine-labelled metaiodobenzylguanidine (MIBG) is used in cases
where a tumour is confirmed biochemically but cannot be identified on computerized
tomography (CT) or magnetic resonance imaging (MRI) scanning

Liddles syndrome
hypokalaemic alkalosis
suppressed aldosterone
suppressed renin
an autosomal dominant
mutation in genes mapped to chromosome 16.
This leads to activation of sodium/potassium exchange independent of
circulating mineralocorticoid.
Hypertension and hypokalaemia respond well to amiloride but not
spironolactone, because amiloride acts directly on the sodium channel, whereas
spironolactone acts on the mineralocorticoid receptor
Renal artery stenosis
High renin
High Aldosterone
Secondary hyperaldosteronism

Multiple endocrine neoplasia type 2

hyperparathyroidism due to parathyroid hyperplasia.
The most important is removal of pheochromocytoma. Then , a thyroidectomy
and subtotal parathyroidectomy (removal of 3 parathyroid glands) will be
Pregnancy should be excluded in all patients prior to other evaluations.
Polycystic ovary syndrome is the most common cause of secondary amenorrhea
Laboratory evaluation is
first directed toward ovarian failure,
hyperprolactinemia, A high serum prolactin level requires additional pituitary
evaluation, including MRI.
thyroid disease.
o An FSH greater than 20 mU/mL (20 U/L) suggests ovarian failure.
If the woman is younger than 30 years or has primary amenorrhea, obtaining a
karyotype is often recommended, even if the stigmata of Turner syndrome are not
If the screening laboratory studies do not reveal a diagnosis, the cornerstone of
further evaluation is a progestin withdrawal challenge with medroxyprogesterone
acetate, 10 mg/d orally for 10 days, or micronized progesterone, 200 mg/d orally for
12 days.

o Menstruation with progestin withdrawal indicates normal estrogen production and

a patent outflow tract, which categorizes the amenorrhea as chronic anovulation with
a normal estrogen level.
o The absence of menses with progestin withdrawal indicates a low estrogen level
and/or an anatomic defect. The pelvic anatomy, therefore, should be assessed with
ultrasonography, MRI, or hysterosalpingography.
Polycystic ovary syndrome
PCOS affects 6% of women of child-bearing age and typically presents with
oligomenorrhea and signs of androgen excess (hirsutism, acne, and occasionally
Polycystic ovary syndrome (PCOS) is the most common etiology of hirsutism
with oligomenorrhea. This form of hirsutism normally starts at puberty or several
years later and is slowly progressive. Furthermore, the serum testosterone level in
women with PCOS rarely exceeds 150 ng/dL (5.2 nmol/L)
Insulin resistance is a major feature of the disorder, as are overweight and
obesity, although only 50% of affected women are obese.
Typically, there is a
o mild elevation in testosterone and dehydroepiandrosterone sulfate levels and a
o luteinizing hormone to follicle-stimulating hormone ratio of greater than 2:1.
o Normal oestradiol would be expected in PCOS
o functional hyperprolactinaemia
Diagnosis requires two of the three following features:
1. ovulatory dysfunction,
2. laboratory or clinical evidence of hyperandrogenism,
3. ultrasonographic evidence of polycystic ovaries.
4. transvaginal ultrasound is said to have 91% diagnostic sensitivity for the condition
in experienced hands. The presence of more than eight follicular cysts of less than 10
mm and increased ovarian stroma is sufficient to make the diagnosis.
Normal 17-hydroxyprogesterone level excludes nonclassic 21-hydroxylase
deficiency as a diagnosis. Therefore, corticosteroid (prednisone) therapy is not
Weight loss is the gold-standard treatment for PCOS, and improves ovulation,
androgen levels, hirsuitism and metabolic features associated with insulin resistance.
A loss in weight of only 5% reduces hirsuitism by up to 40%.
In patients with hirsutism and polycystic ovary syndrome who do not wish to
become pregnant, the most appropriate initial therapy after weight loss is oral
contraceptive pill Then spironolactone
Non-classical congenital adrenal hyperplasia
hypogonadotrophic hypogonadism,
low oestradiol
normal concentrations of luteinising hormone (LH) and follicle-stimulating
hormone (FSH)
a slightly raised testosterone concentration and
17-OHP concentration above 33 nmol/l would be diagnostic.
Cushing's syndrome and Amenorrhea
hypogonadotrophic hypogonadism,
low oestradiol
normal concentrations of luteinising hormone (LH) and follicle-stimulating
hormone (FSH)
a slightly raised testosterone concentration
free cortisol could provide useful information.
Pregnancy and Amenorrhea
Very high oestradiol

High prolactin
suppressed luteinising hormone/follicle-stimulating hormone (LH/FSH)

Amenorrhea And adrenal or ovarian tumor

Rapid virilization rapidly developed progressive hirsutism, acne, and a deepened
very high testosterone level. Such a high level (>200 ng/dL [6.9 nmol/L]) need
abdominal and pelvic CT scan.
Functional hypothalamic amenorrhea,
which is usually caused by excessive loss of body weight or fat or excessive
exercise as in anorexia nervosa, is a diagnosis of exclusion includes
o a pregnancy test and
o measurement of serum prolactin,
o thyroid-stimulating hormone, and
o follicle-stimulating hormone
BMI is typically less than 17.
If a functional etiology is still suspected, decreased exercise, improved nutrition,
and attention to emotional needs are helpful adjuncts to restore normal menses and
Low estradiol with normal or low LH FSH
Overweight amenorrhea in young women
PCOS need US of pelvis
Cushing syndrome
hypothyroidism and
hypothalamic disease. there is often a prior history of trauma (or neoplasia) to
the brain. As a result patients can develop excessive appetites.
New-onset hirsutism with virilization, particularly in an older woman, and
accompanied by a serum total testosterone level >200 ng/dL (6.9 nmol/L) is almost
always due to a tumor.
Prostate and Hypogonadism
Men with hypogonadism often have a low prostate-specific antigen level that
doubles with therapy and then stabilizes by 6 months after therapy initiation; a
greater increase should indicate discontinuation of therapy and evaluation for
prostate cancer.
Kallmann syndrome
hypogonadotrophic hypogonadism
absent sense of smell.
Absent olfactory bulbs are present on 75% of MRI scans in these patients.
The syndrome results in absence of GNRH.
This patient should be managed with androgen replacement therapy
fertility can be restored in the majority of patients with either pulsed GNRH or
gonadotrophin therapy.
Once fertility treatment stops " who do not desire fertility " it is necessary to give
testosterone for men and oestrogen and progestins for women
The main health risk, for both men and women, of untreated Kallmann
Syndrome is osteoporosis. Therefore, regular bone-density scans (every two years )
are advisable
Acquired hypogonadotrophic hypogonadism

Low testosterone and gonadotropin levels

Sleep apnea has been associated with hypogonadism and can be reversed by
application of continuous positive-airway pressure testosterone replacement
therapy can worsen sleep apnea, so do sleep study first.
Common causes
o pituitary tumors,,,prolactinoma,,,, Hyperprolactinaemia may be associated with a
HH and signs such as galactorrhoea may be present. pituitary MRI would be the best
imaging technique
o trauma
o infiltrative diseases (such as hemochromatosis).
o chronic illnesses,
o malnutrition,
o obesity, and aging.
o drugs include alcohol, Anabolic corticosteroids, opioid-induced hypogonadism
cocaine, and ketoconazole.
Hypogonadism and Testosterone level
patient, who is normal weight, with normal total testosterone level, it is very
likely that his free testosterone level will also be normal
A discrepancy in the levels can occur in obese men in whom the sex
hormonebinding globulin (SHBG) level is decreased, which causes a decrease in
the total testosterone level.
SHBG may increase with age, so that measurement of free testosterone levels
may be helpful when assessing gonadal function in older patients.
The best screening test for male hypogonadism is an early morning
measurement of the total testosterone level.
A random serum testosterone level greater than 350 ng/dL (12.15 nmol/L)
excludes hypogonadism. Values consistently less than 200 ng/dL (6.94 nmol/L)
almost always confirm hypogonadism, but values in the 200 to 350 ng/dL (6.94-12.15
nmol/L) range are equivocal.
If the level is equivocal, a second measurement, which includes free and
bioavailable testosterone levels and/or the SHBG level,
PRL, LH, and FSH levels also are measured to determine the type of
hypogonadal state and to guide further evaluation and treatment.
Hypergonadotrophic hypogonadism
Low testosterone
o Klinifelter,,,, need Karyotype study "primary infertility" NO children
o Testicular tumour, infiltration or idiopathic failure secondary infertility patient may
have children ultrasonic evaluation of the testes is the most appropriate investigation
Type 1 polyglandular syndrome
mucocutaneous candidiasis,
hypoparathyroidism and
Addisons, whereas
Type 2 polyglandular syndrome
hypothyroidism and
Type 1 diabetes,
coeliac and
myasthenia gravis may also be seen.

Adrenal Incidentaloma
Clinically inapparent adrenal masses are discovered in 0.4% to 6.9% of imaging
studies performed during evaluation of nonadrenal disorders.
Most adrenal nodules are hormonally silent and have no malignant potential. As
many as 30%, however, secrete cortisol, aldosterone, androgens, or catecholamines.
In patients with normal BP who have an incidentally discovered adrenal nodule,
o Subclinical Cushing syndrome should first be excluded with an overnight 1-mg
dexamethasone suppression test.
o A screening test for pheochromocytoma (by measurement of the plasma
metanephrine level) is also recommended by most experts, even if the patient is
normotensive. The rationale for screening is that patients with pheochromocytoma
may only be intermittently hypertensive.
In patients with hypertension who have an incidentally discovered adrenal
o screening for hypercortisolism and
o pheochromocytoma is essential, as is
o measurement of serum aldosterone and plasma renin activity.
Adrenal androgens, such as dehydroepiandrosterone sulfate, should only be
assessed in masculinized female patients, just as the estrogen level should be
measured in feminized male patients.
Progressive osteoporosis in a patient on bisphosphonate therapy who has
adequate calcium and vitamin D intake is an indication to change the bisphosphonate
to teriparatide. (recombinant human parathyroid hormone) is given via daily
subcutaneous injection for a recommended duration of 1 to 2 years. Teriparatide can
significantly decrease the incidence of both vertebral and nonvertebral fractures.
Because animal studies have shown an increased risk of osteosarcoma, this agent
should be avoided in patients with
o Paget disease of bone,
o previous radiation therapy involving the skeleton, or
o a history of skeletal cancer.
polyuria and polydipsia
o diabetes mellitus (prevalence 4%),
o hypercalcaemia (prevalence 14%) and
o hypokalaemia.
o Diabetes insipidus is rare (prevalence: 1 in 25,000).
Initial laboratory screening for polyuria and polydipsia
o U+E,
o calcium, and
o glucose.
o If these tests are normal, investigations should be directed towards rarer causes.
Hypervolaemic hyponatraemia,
elevated JVP,
ascites, and
peripheral oedema,
caused by renal, cardiac, or liver failure.
Hypovolaemic hyponatraemia
caused by salt loss, usually from the kidneys or gut.
tachycardia, hypotension, dry mucous membranes
low JVP.
Laboratory features include elevated serum urea and sometimes creatinine.

The source of salt loss (gut or kidney) can be identified with a urinary sodium;
o a value greater than 20 mmol/l indicates renal loss.
Euvolaemic hyponatraemia
cause primarily by SIADH and hypothyroidism.
Serum urea is normal or low.
Anorexia nervosa
normocytic normochromic anaemia due to bone marrow suppression,
hypokalaemia from laxative abuse,
metabolic alkalosis resulting from vomiting and the gastrointestinal loss of HCl,
hypocalcaemia from dietary deficiency and the associated protein deficiency,
increased serum amylase level from frequent vomiting.
Gitelmans syndrome
hypokalaemic alkalosis
NO hypovolaemia
NO hypertension.
presenting at older age
caused by mutation in the thiazide-sensitive Na-Cl transporter
resultant salt wasting leads to activation of the renin-angiotensin system also
leading to raised aldosterone levels
Gitelmans is associated with hypocalciuria and
Treatment is with potassium and magnesium replacement.
Where patients fail to respond to supplementation, potassium sparing diuretics
may be required to restore serum potassium levels.
Thiazide abuse
normal BP,
hypokalaemia and
high bicarbonate
Bartter's syndrome
usually presents in childhood with polyuria,
nocturnal enuresis and
growth retardation
An anti-obesity drug should only be considered for those with a body mass index
(BMI) of 30 kg/m2 or greater in whom at least three months of managed care
involving supervised diet, exercise and behaviour modification fails.
If risk factors (for example, diabetes mellitus, coronary heart disease,
hypertension and obstructive sleep apnoea) are present, it may be appropriate to
prescribe a drug to individuals with a BMI of 28 kg/m2 or greater.
Anti-obesity drug treatment should also be discontinued if weight loss is less
than five percent after the first 12 weeks.
Combination drug therapy is contraindicated at present and drugs should never
be used as the sole element of treatment.
Diet and exercise have been shown to be ineffective over the long term.
Mixed metabolic and respiratory alkalosis
pH 7.66 (7.36-7.44)
pO2 7.4 kPa (11.3-12.6)
pCO2 4.6 kPa (4.7-6.0)
HCO3 34 mmol/L (20-28)
Features of laxative abuse include:

Metabolic alkalosis
Diarrhoea whilst nil by mouth
Loss of haustral pattern on barium enema but relatively normal macroscopic
Pigmentation of colonic mucosa (anthracenes, e.g. senna) and sometimes skin
Pseudostrictures from spasm lasting hours
Raised stool magnesium (osmotic laxatives)
Uric acid kidney stones
Protein-losing enteropathy
Somatostatinomas are exceedingly rare, and are characterized by the triad of
steatorrhoea and

GIT and Hepatology

It can present at any age with
o intermittent dysphagia to both solids and liquids,
o regurgitation,
o severe retrosternal chest pain and
o aspiration pneumonia.
A chest X-ray may show an air-fluid level behind the heart.
Barium swallow usually shows dilatation of the oesophagus with a tapering lower
end, and the loss of normal peristalsis.
Upper gastrointestinal endoscopy should always be performed in suspected
achalasia to exclude a tumour, which can present similarly
However, all these investigations may be normal and
The definitive diagnostic test is oesophageal manometry
Treatment options include
o endoscopic pneumatic dilation of the LOS (successful in 80% of cases),
o intra-sphincteric botulinum toxin injection or
o surgical division of the LOS (Hellers cardiomyotomy).
A 7% increase in squamous cell carcinoma over 25 years
Oesophageal diseases and manometry
Scleroderma cause low resting lower oesophageal sphincter (LOS) pressure
Gastro-oesophageal reflux disease
o cause low LOS pressure
Nutcracker oesophagus,
Non-specific oesophageal dysmotility,,,
o failure of LOS relaxation (high residual pressure)
Oesophageal spasm
o failure of LOS relaxation (high residual pressure)
o absent distal peristalsis which may be accompanied by a high resting LOS pressure.
Candida causes
o odynophagia (painful swallowing) rather than dysphagia, and is not associated with
any specific manometric findings.
Globus is a psychological condition and should only be diagnosed in the absence
of abnormal findings
Extrinsic compression form hilar tumours can be missed on endoscopy but do

not result in recognised patterns at manometry.

Nutcracker esophagus
is a disorder of the movement of the esophagus
dysphagia, to both solid and liquid foods,
chest pain
may also be asymptomatic.
Age : 6th and 7th decades of life.
Diagnosis is made by an esophageal motility study
o "increased pressures during peristalsis" with a diagnosis made when pressures
exceed 180 mmHg;
o LOS relaxes normally in nutcracker esophagus, but has an elevated pressure of
greater than 40 mm Hg at baseline
Medical therapy
o calcium-channel blockers
o isosorbide dinitrate
o sildenafil
o botulinum toxin
Oesophageal carcinoma
The diagnostic test of choice remains histology.
Once diagnosis is confirmed, a CT scan is necessary to stage disease for disease
extent and to consider surgical resectability.
The incidence of adenocarcinoma in the UK is rising, while that of squamous-cell
carcinoma is falling.
If the patient has metastases as demonstrated by the presence of enlarged
supraclavicular nodes, and therefore would not be a suitable candidate for
Squamous cell carcinoma of the oesophagus is more responsive to radiotherapy
than adenocarcinoma
5-year survival after radiation therapy is put at between 6% and 20%.
Oesophageal stents are used in the treatment of tracheo-oesophageal fistulas and
palliation in advanced disease.
Presently, there are no genetic screening tests for oesophageal carcinoma.
Oesophageal perforation
History of Severe gastroenteritis is associated with vomiting and diarrhoea.
Sudden-onset chest pain
pleural effusion
A gastrograffin swallow, will demonstrate the site of the perforation.
Barretts esophagus Recommendation
Low grade
o 8-12 weeks of continuous high dose PPI and then
o re-endoscopy ,,,,If some improvement is seen then
o 6 monthly review is suggested until stable / improved disease has been identified
on at least 2 successive endoscopies. Once this milestone has occurred then
o surveillance can be reduced to 2 yearly.
High grade
o associated with a focus of invasive adenocarcinoma in 3040% of patients.
o if the changes persist after intensive acid suppression high dose PPI and are
confirmed by two expert pathologists, then
o oesophagectomy is currently recommended But
o In those unfit for surgery, endoscopic ablation or mucosal resection should be
NICE Guideline for high grade

o Consider offering endoscopic therapy as an alternative to oesophagectomy to

people with high-grade dysplasia and intramucosal cancer , taking into account
individual patient preferences and general health.
o Endoscopic therapy is particularly suitable for patients who are considered
unsuitable for surgery or who do not wish to undergo oesophagectomy
o Do not use in combination with each other argon plasma coagulation, laser ablation
or multipolar electrocoagulation alone, or in combination with each other, unless as
part of a clinical trial
o If using endoscopic mucosal resection, consider following with an additional
ablative therapy (radiofrequency ablation, argon plasma coagulation or
photodynamic therapy) to completely remove residual flat dysplasia
After Helicobacter eradication
is associated with a reduction in the risk of gastric maltoma and gastric
carcinoma "so the patient can be reassured that she no longer has a significantly
increased risk of GI cancer"
there is no specific need for re-dosing of eradication therapy,
oesophageal carcinoma is not related to Helicobacter
Dyspepsia, in the absence of alarm symptoms
should be treated with
o lifestyle advice and
o PPI if needed 4 months
If after one month symptoms are not controlled then testing for Helicobacter
pylori (breath test or serology) could be carried out.
There needs to be a two-week wash-out period off the PPI for hydrogen breath
test to be reliable.
Malabsorption + Low B12
Terminal ileal disease
o Crohns disease," bimodal presentation with peaks between 15-30 years and
between 60-80 years"
o terminal ileal resection,
o ileal tuberculosis,,, high ESR abnormal CXR
o pernicious anaemia,,, but Symptoms of malabsorption are absent
Excess B12 utilisation in the gut by bacteria,,, Vitamin B12 is selectively
metabolised by the bacteria and the folate is left so there is high folate + low B12
o Small intestinal diverticulae, age 60-70 years
o fistulae,
o radiation enteritis " fibrotic strictures and adhesions" may occur after 5 years
o systemic sclerosis
A normal serum gastrin excludes pernicious anaemia
Celiac disease
faecal occult blood may be positive
secondary hyperparathyroidism may occur due to vitamin D deficiency
The best initial screening tests are serological either tissue transglutaminase or
anti-endomysial antibodies, but
These tests may be invalid in the presence of selective IgA deficiency
Small bowel follow-through may show total or subtotal villous atrophy
Short bowel syndrome
removal of more than one-half of the small intestine, malabsorption syndrome
may result.
It may occur in patients with
o Crohns disease or those with
o ischaemic bowel who have undergone significant bowel resection.
Presentation with

o diarrhoea and steatorrhoea,

o weight loss,
o anaemia,
o osteoporosis/osteomalacia,
o electrolyte disturbances and hypovolaemia
o Renal and gall bladder stone "ileal resection"
o In patients with more than 100 cm of jejunum,
oral intake
lactose exclusion
a course of metronidazole to eradicate bacterial overgrowth.
o In patients with less than 100 cm of jejunum, total parenteral nutrition is
Colonic diverticulae and anemia
o cramping abdominal pains with
o intermittent diarrhoea alternating with constipation
o weight is steady
Lower GI blood loss may occur as frank haemorrhage or occult losses
Occult blood in the stool is present in approximately 25% of patients with
Iron deficiency is therefore a commoner overall cause of anaemia related to this
condition than is Vitamin B12 deficiency.
Vitamin B12 deficiency related to bacterial overgrowth and malabsorption is
relatively uncommon in this condition
Radiation enteritis
occurs 9 to 14 months following radiation exposure
o intermittent rectal bleeding,
o loose stool
o weight loss
o obstructed defecation,
o rectal pain or urgency.
results in a chronically ischaemic intestinal segment that may lead to stricture
Diagnosis can be
o Barium enema shows luminal narrowing with some irregularity of the bowel wall
o confirmed with colonoscopy
o Biopsy is not diagnostic but is helpful to exclude other causes
o rectal sucralfate, metronidazole combined with topical anti-inflammatory
treatment, and heater probe appear promising
Inflammatory bowel disease
Indeterminate colitis
o In around 10% of patients, it is impossible to distinguish ulcerative from
Crohns colitis
o ulcerative colitis is strongly associated with pANCA
o the presence of anti-Saccharomyces cerevisiae antibodies favour Crohns
The criteria to determine ulcerative colitis severity include:
1. Stool frequency >6
2. ESR greater than 30 mm/hr

3. pulse rate (greater than 90 bpm);

4. temperature (greater than 37.8oC in 2 out of 4 days);
5. anaemia (Hb <75% predicted). < 10.5g
In severe ulcerative colitis, patients should be treated with
o intravenous Hydrocortisone "not oral prednisolone"
o Rectal hydrocortisone also can be given
o fluids,
o potassium supplementation
o subcutaneous heparin and
o elemental diet.
o No Antibiotics
o The patient should also have daily examination and monitoring including
review by surgeons,
blood tests,
stool chart,
heart rate,
temperature and
abdominal X-rays.
Woman with well-controlled crohn disease on azatioprine want to be pregnant
Stop azathioprine although there is no increase in fetal anomalies
if her disease flares up again then azathioprine could be re-instituted
Give folic acid supplements
Give Low dose corticosteroids <20 mg instead of azathioprine
o Give Stress doses of steroids should be used during labour and delivery if the
mother received steroids (even low-dose) for more than 2-3 weeks
o use of oral calcium and vitamin D supplements is recommended.
o neonate should be monitored for evidence of adrenal insufficiency and infection
Pregnant with exacerbated crohn disease presents with bloody diarrhea with tender
Flexible sigmoidoscopy is the most appropriate investigations
presence of bloody diarrhoea fits best with predominantly distal disease.
The bowel preparation is much more severe with colonoscopy than that for
flexible sigmoidoscopy, and the procedure itself causes significantly more
If distal disease is identified then rectal corticosteroids would be the treatment of

Cancer Screening in patient with ulcerative colitis

Patients with extensive UC should be screened 8 to10 years from the onset of
symptoms by Colonoscopy
Second decade Colonoscopy should be performed 3-yearly
Third decade Colonoscopy should be performed 2-yearly
Fourth decade Colonoscopy should be performed yearly
Patients with concomitant UC and PSC Colonoscopy should be performed yearly
Patients post-liver transplant for PSC still should have yearly screening.
Toxic megacolon
a severe colitis (almost always pancolitis)
dilatation of the colon >5.5 cm radiologically.

o most often occurs in the context of ulcerative colitis,

o but can also occur in Crohns,
o pseudomembranous colitis,
o ischaemic colitis and other
o colitides.
It is an absolute contraindication to barium enema examination because of the
risk of bowel perforation.
Mortality is high (around 20%),
o High-dose steroids and iv fluids
o intravenous antibiotics
o avoiding antidiarrhoeal drugs and opioid analgesics
o knee-elbow position to aid evacuation of gas per rectum, and inserting a nasogastric
tube to aspirate bowel gas and fluids
o If no improvement is seen in 24 h, early surgery (usually colectomy) is indicated.

Maintaining remission in Crohns disease

Thiopurines (azathiaprine and 6-mercaptopurine) are the most effective agents
If not tolerated, methotrexate could be used as an alternative.
5-ASA compounds such as balsalazide and sulphasalazine have a role in
maintaining remission and are generally well tolerated but are not as effective as
There is no role for steroids in maintaining remission only in the treatment
of acute flares as is the case with dietary modification.
Ciclosporin is only of value in acute severe ulcerative colitis.
Infliximab is of value in long-term remission in fistulating Crohns (and
possibly in non-fistulating disease) but is generally use ed alongside a thiopurine).
Differentiation between ulcerative colitis and whippl disease
Both have
Sacroiliatis, Large joint arthritis
Weight loss
But whippl has malabsorption "which is absent in ulcrative colitis as
High MCV "B12 and folate deficiency"
Intermittent melaena "Between episodes of melaena he is asymptomatic"
upper endoscopy and colonoscopy Then
In the stable outpatient setting, a Meckels scan may be more useful in excluding
a Meckel diverticulum.
In centres where it is offered, capsule endoscopy may be a reasonable alternative
to Meckel's scan.
A mesenteric angiogram is most effective during active blood loss not when the
patient is asymptomatic
A barium swallow and barium enema will not find any part of the bowel not
already seen by OGD and colonoscopy.
Colovesical fistula
Recurrent urinary tract infections,
altered bowel habit,
brown discoloration of urine and
intermittent air bubbles on passing urine.
Causes of gastrointestinal fistulae include

o crohns disease,
o diverticulitis and
o colorectal tumours
Mesenteric ischaemia
Plain X-ray is often normal, although mucosal oedema and thumb printing
Mesenteric angiography is the best diagnostic test.
CT scan show evidence of bowel wall thickening and thumb-printing.
More than two thirds of patients with ischaemic colitis respond favourably and
rapidly to simple conservative measures with spontaneous recovery within 24 to 48
The remaining one-third requires exploratory laparotomy
Conservative management includes
o close monitoring,
o appropriate intravenous rehydration and
o broad-spectrum antibiotics that cover enteric flora and
o aggressive measures to correct processes that may have precipitated the ischaemic
For those who do not settle or develop peritonism, surgery is required.
Causes of bacterial bloody GE in the UK
campylobacter infection is the commonest cause
followed, by salmonella and shigella.
Campylobacter GE
Infection usually arises from eating undercooked frozen food eg barbeques
colicky abdominal pain,
blood mixed with diarrhoea.
pyrexial and clinically dehydrated
The symptoms are usually self-limiting, lasting up to 5 days
Chronic pancreatitis
Diarrhea with bulky pale stools
Serum folate low
B12 low
Faecal elastase low
o Alcohol (60-90%)
o cystic fibrosis
o Hypertriglyceridaemia,
o autoimmune pancreatitis (e.g. associated with primary sclerosing cholangitis)
o surgery
o Hereditary pancreatitis (autosomal dominant)
o pancreas divisum (congenital pancreatic abnormality of fusion),
o hyperparathyroidism,
o uraemia are rare causes.
o Gallstones (more commonly associated with recurrent acute pancreatitis) may be a
contributing cause in ~20-25% of cases.
Faecal elastase is a sensitive marker of pancreatic insufficiency
Imaging of the pancreatic duct and biliary tree by ERCP/MRCP Magnetic
Resonance would however be required to exclude a mass lesion particularly in light of
the significant weight loss.
In early disease there may be
o no X-ray calcification of the pancreas
o ERCP can be normal

o CT Abdomen can also be normal

Secretin test
chronic pancreatitis
o normal volume (> 2 ml/kg) and
o low in HCO3 (< 80 mEq/l)
pancreatic duct obstruction
o low volume (< 2 ml/kg),
o normal HCO3 (> 80 mEq/l)
o normal enzyme levels suggest perhaps secondary to a tumour and should prompt
Pancreatic pseudocysts
They cannot be diagnosed until more than 6 weeks after the acute attack,
o abdominal pain
o mass,
o fever
o persistently raised amylase and liver function tests.
o Small pseudocysts usually resolve on their own but
o those that are greater than 6 cm in diameter seldom disappear spontaneously and
may lead to complications such as haemorrhage and infection,,,managed by
endoscopic or percutanous drainage or
surgical intervention
Acute mesenteric ischaemia
Risk factors of atherosclerosis
o IHD recent history of myocardial infarction
o diabetic,
o smoker
o acute abdominal pain 15-30 min post-meal, Increased intestinal motility after a
meal exacerbates ischaemia, causing pain
o relative hypotension
o acidosis
o modest elevations in amylase.
o An arterial blood gas will no doubt show a metabolic acidosis
o CT scan will help exclude
necrosis of the pancreas,
o mesenteric angiography
o laparotomy
Meckel's diverticulum
o haemorrhage,
o volvulus and
o intussusception, mostly in children younger than 10 years of age.
o Tc-99m pertechnetate scintigraphy In virtually all patients who present with

bleeding, ectopic gastric mucosa can be demonstrated

o Tc-99m has an overall specificity and sensitivity of 90% for establishing the
Once bleeding occurs, surgery is recommended.

Multiple hamartomatous polyps in GIT tract

familial juvenile polyposis,
Cowdens syndrome,
Peutz-Jeghers syndrome,
neurofibromatosis type one, and
Multiple endocrine neoplasia syndrome type 2, all
These syndromes are distinct from the more common adenomatous syndromes
such as HNPCC and FAP
Cowdens syndrome
is an inherited
defect in the PTEN tumour suppressor gene.
oral mucosal papillomas,
palmoplantar keratoses and
trichilemmomas (benign tumours of hair follicles).
The syndrome is important to diagnose early because of the high risk of
malignancy, particularly of the breast and thyroid.
Thyroid dysfunction is common even in the absence of cancer.
Hereditary non-polyposis colorectal cancer syndrome
It is an autosomal dominant syndrome
early-onset colorectal cancer.
It may account for 1-2% of all cases of colorectal cancer
In 55-60% of cases, cancers are right sided also at increased risk of cancer of the
endometrium, stomach, small bowel and genitourinary tract.
Mutations responsible : DNA mismatch repair gene
HNPCC-related cancers in three or more relatives, one of whom is a first-degree
relative of the other two
Individual at risk should be offered colonoscopic screening at 2-year intervals
from the age 20-25 years which should be continued up to the age of 40 years
PeutzJeghers syndrome
an autosomal dominant
multiple hamartomatous polyps throughout the gastrointestinal tract " upper
and lower GIT"
and mucocutaneous melanocytic macules.
The condition has equal sex
Germline mutation of the serine threonine kinase STK 11 gene on chromosome
There is significant risk of eventual malignant transformation
Almost 50% of all PeutzJegher patients develop and die from cancer by the
age of 57 years.
The mean age at first diagnosis of cancer is 43 years.
The cumulative risks of cancer development are highest for the stomach, colon,
pancreas and breast.
Regular surveillance examinations, endoscopies and ultrasound imaging (yearly)
are recommended.

ZollingerEllison syndrome
The best initial screen is a fasting gastrin level on three separate days, as the
secretion of gastrin is pulsatile.
o Three samples in the normal range make a gastrinoma unlikely.
This is usually followed by basal acid output estimation and a secretin
stimulation test.
After this, patients usually move on to imaging studies
o Surgical resection If there is no hepatic metastases
o Intravenous and then oral proton pump inhibitors are useful in the acute situation
to reduce acid secretion.
o Octreotide, interferon and chemotherapy may be useful in non-surgically resectable
Portal hypertension
Normal hepatic venous pressure gradient = Hepatic wedge pressure - Inferior
vena cava pressure (normal HVPG = 1-5 mmHg)
If HVPG >5 mmHg it is PH
If HVPG >10 mmHg it is Clinical PH
Type of PH
o If HVPG >5 mmHg it is either sinusoidal "intrahepatic" OR post-sinusoidal 'hepatic
o If HVPG <5 mmHg it is presinusoidal "portal vein" eg
Longstanding portal vein thrombosis

Hepatorenal syndrome
Treatment,,,, drug which given intravenously to improve renal function is
agonists of vasopressin V1 receptors such as terlipressin. This causes splanchnic
vascoconstriction, which may reverse the early splanchnic vasodilatation seen in
hepatorenal syndrome.
Alcoholic hepatitis
Hepatic decompensation with coagulopathy,
encephalopathy and
The AST/ALT ratio is usually greater than 2
Ferritin is a non-specific acute phase reactant and is normally elevated in
alcoholic liver disease
Alcoholic fatty liver
The histological changes seen in the liver can return to normal within 24
develops more quickly in the female sex " business woman"
Liver function tests are deranged with an
o increase in the aminotransferase levels
o Gamma glutamyl transpeptidase (GGT) may be elevated in relation to alcohol use,
it is neither specific nor sensitive.
Abstinence and an adequate diet are the mainstays of treatment

Excess alcohol use is a cause of a secondary hyperlipidaemia

Non-alcoholic steatohepatitis
Whilst only approximately 2% of patients with fatty infiltration progress to
cirrhosis and liver failure, where
Non-alcoholic steatohepatitis exists progression to cirrhosis is as high as 10%.
There is no proven treatment for NASH, but patients should be advised to lose
Chronic hepatitis B in pregnancy
Infants born to mothers known to carry hepatitis B can be treated with
antibodies to the hepatitis B virus (HBIg). When given with the vaccine within twelve
hours of birth, the risk of acquiring hepatitis B is reduced 90%.This treatment allows
a mother to safely breastfeed her child
Chronic hepatitis B
Chronic hepatitis B is defined as the persistence HBsAg in the circulation for
more than six months after clinical infection.
HBeAg is a marker of infectivity
but patients with Hepatitis B virus (HBV) pre-core mutant
o do not synthesise HbeAg ,,,
o Typically patients have lower concentration of HBV DNA,,,,
o Response to interferon is not good and relapse rates tend to be high.
Treatment of chronic hepatitis is aimed at patient with active disease and viral
replication, preferably at a stage before cirrhosis has developed
The indication for hepatitis B treatment is based on
1. abnormal alanine aminotransferase on at least one occasion,
2. liver biopsy showing fibrosis
3. hepatitis B viraemia > 105 copies/ml and/or detectable HbeAg
Pegylated interferon should be started first whether the patient is e antigen
positive or e antigen negative, and
o if there is lack of response, consider adefovir or lamivudine
Adefovir is preferred over lamivudine due to its low resistance rate
Treatment of Chronic hepatitis B + cirrhosis + Ascitis
HBeAg negative
o If there is active hepatitis B (ie any detectable DNA in blood) requires treatment by
viral suppression.
o Lamivudine safe and effective drug for the suppression of hepatitis B virus,,
Resistance occurs in 15% of patients at 1 year and 60% at 4 years. Adefovir is licensed
for second line treatment of Lamivudine resistant HBV.
HBeAg positive
o Antiviral + Interferon , but Interferon is contraindicated in patients with
decompensated liver disease,,, The appearance of ascites in a patient with cirrhosis
indicates decompensation of their liver disease
Liver transplantation is effective in end stage liver disease caused by hepatitis B
but adequate viral suppression is the initial treatment of choice pending assessment
of suitability for transplantation.
Hepatitis C
degree of activity is determined by the
o hepatitis C RNA level determined by PCR.
o This is usually positive within one to two weeks of exposure.
Treatment for acute hepatitis is usually only supportive.
The treatment for chronic hepatitis C depends on
the genotype; Those with genotype 2 or 3 can achieve a sustained response after 24
weeks. In genotype 1 and 4, antiviral is continued for 48 weeks due to lower response

liver histology generally only indicated in those with genotype 1 and 4, as treatment
is longer
RNA level
clinical presentation.
o The goal is to identify as early as possible the patients who may respond to the
o This is in the form of oral ribavirin and subcutaneous interferon alpha.
The transaminase levels bears no correlation with disease severity and often goes
up and down over time
Hepatitis C and pregnancy
About 5% infants born to HCV infected women become infected.
This occurs at the time of birth and there is no way of preventing this
Elective Caesarean section does Not reduce the risk of transmission
Factors associated with increase infant infection
o high viral load at delivery increases the risk of transmission
o co-infection with HIV increase the risk of transmission.
o There is no evidence that breast-feeding increases the risk of transmission, but
mothers with cracked or bleeding nipples are advised to formula-feed until they are
Ribavirin is teratogenic
There is no vaccine for hepatitis C children under 1 year
as there is transmission of the antibodies from the mother they may test positive
in the first year "anti hepatitis c" even they have NO active disease
Intrahepatic cholestasis of pregnancy
o Itching of palms and soles, is the commonest symptom
o Mild jaundice is seen in 50% of patients,
o epigastric pain,
o anorexia, malaise
o NO nausea NO vomiting
o bleeding tendency.
o NO constitutional symptoms
Liver function tests
o cholestatic picture,
o high alkaline phosphatase (>4 normal)
o modest elevations in aspartate transaminase (<300 IU/l)
o bilirubin (<100 mol/l).
o prolonged prothrombin time.
o serum bile acid increased
o Normal albumin "so exclude acute fatty liver of pregnancy"
o Normal platelete "so exclude HELLP syndrome"
There is an increased
risk of fetal distress,
preterm labour and
perinatal death,
o therefore careful fetal monitoring is essential.
Management includes
o ursodeoxycholic acid
o cholestyramine for itch,
o sometimes vitamin K if there is deranged clotting.
Prognosis is excellent for the mother, with symptoms resolving within 24
weeks of delivery.
It will recur in 40% cases.
Fatty liver of pregnancy

o nausea and vomiting
o pain in the epigastrium or right upper quadrant
o Encephalopathy
o Ascites
o gestational age 2842 week range.
o Ultrasound is the best imaging modality and allows other conditions such as
cholecystitis to be excluded
o Abnormal investigations include
raised ammonia levels,
elevated aminotransferase levels,
elevated white cell count,
low albumin and
disseminated intravascular coagulation in up to 75%.
o Delivery of the fetus Spontaneous resolution of the condition usually follows
o iv fluids and glucose,
o correction of coagulopathy with fresh-frozen plasma,
o reduction of exogenous ammonia intake through protein restriction or dietary
laxatives to speed evacuation of nitrogenous wastes
o severe headache, BP is 140/90 mmHg
o peripheral oedema,
o indigestion
o proteinuria
o Eclampsia is above + seizures
o Microangiopathic haemolytic anaemia,
Hb 9.0 g/dl
WCC 7.1 x109/l
PLT 68 x109/l
Creatinine 185 mol/l
AST 205 U/l
ALT 150 U/l
ALP 301 U/l
Bilirubin 80 mol/l
Urine protein ++
o control of blood pressure
o rapid assessment of the pregnancy by the obstetric team.
o delivery of the child
Child Pugh score
based on
prothrombin time,

Grade A predicts a life expectancy about 1520 years with a 10% abdominal
peri-operative mortality.
Grade C predicts life expectancy about 13 years and an 80% per-op mortality.
Grade B indicates transplantation consideration with a 30% per-operative
A serum sodium less than 110 mmol/l also carries a poor prognosis.
Cirrhosis may result in falsely elevated levels of CA-125.
Budd Chiari syndrome
Presentation "It can present either acutely or chronically"
o Acute
abdominal pain,
sometimes fulminant hepatic failure
o Chronic
signs of cirrhosis and
portal hypertension
o primary polycythaemia,
o leukaemia
o oral contraceptive pill
o thombophilias as
"antiphospholipid syndrome"
o Renal failure
o The prolonged APTT
o normal PT is suggestive of lupus anticoagulant.
o Other causes include malignancy (especially hepatocellular, renal and adrenal),
o Ascitic fluid analysis will show a high protein content
o Colour flow Doppler ultrasound of the hepatic vasculature show obliteration of the
hepatic veins
o Liver biopsy usually shows centrilobular congestion with fibrosis
Treatment is with
o Control of the ascites and
o Treatment with streptokinase and subsequent anticoagulation may be attempted if
the thrombus is known to be of recent onset
o Liver transplantation is the only option in the acute presentation, which has a very
poor prognosis, with two-thirds of patients dead within 1 year
Liver cirrhosis with varices
Propranalol is potentially most effective in reducing progression of cirrhosis.
Management of acute hemorrhage
o Fresh-frozen plasma should be used for the coagulopathy, which could be made
worse by repeated blood transfusions. Vitamin K should also be given, but will not
work immediately.
Procedures for controlling bleeding
o Combination of banding + terlipressin appears to be most effective in
controlling acute variceal bleed,
rebleeding rate and

early complications.
o Combination of Sclerotherapy + terlipressin as a second choice if banding is not
possible for technical reasons
o Sclerotherapy is superior to
balloon tamponade alone,
terlipressin alone and
a combination of terlipressin and balloon tamponade
o terlipressin , Somatostatin, octreotide is effective in acute management of variceal
bleed, but combined therapy has been shown to be more effective.
o Terlipressin is more effective than octreotide, but it is contraindicated in ischaemic
heart disease
o Sengstaken tube is an effective, until endoscopy can be performed
o After endoscopic therapy, 50% of patients will re-bleed within 10 days and up to
80% re-bleed over a 2-year period.
o Mortality of variceal bleed is 50% with each episode.
o Transjugular intrahepatic portosystemic shunt (TIPPS) can be used in cases where
haemorrhage cannot be stopped with two sessions of endoscopic therapy over 5 days.
o Surgery is occasionally performed
o According to the British Society of Gastroenterology guidelines, patients with grade
2 or 3 varices on elective endoscopy require propranolol prophylaxis
Spontaneous bacterial peritonitis
o History of chronic liver disease
o worsening of jaundice with a rising bilirubin and increasing ascites and increasingly
drowsy,,, features like encephalopathy
o Pain and pyrexia may frequently be absent
occurs in around 8% of cirrhotic
A raised neutrophil count alone in ascitic fluid is enough to commence
Mortality is high at up to 25% and recurs in 70% of patients within one year.
Primary biliary cirrhosis
Lethargy and pruritus are the usual first symptoms before jaundice
Once jaundice develops survival is less than 2 years
Associated with other autoimmune conditions
o Sjgrens syndrome,
o scleroderma,
o SLE.
o membranous glomerulonephritis and
o renal tubular acidosis
Common serum abnormalities at presentation include
o raised alkaline phosphatase, and GGT
o mildly elevated transaminases
o elevated serum lipids.
o antimitochondrial antibodies (in 9095% of cases)
o The presence of anti-mitochondrial antibody of a titre > 1:40 is highly suggestive of
Imaging important to exclude biliary obstruction
o Abdominal US "first choice"
o Abdominal CT scan
o in early disease, high dose ursodeoxycholic acid is well tolerated, improves liver

biochemistry and may slow disease progression.

o Liver transplantation is an option for end stage disease, where the
development of portal hypertension,
jaundice and hepatocellular failure
bilirubin greater than 100 mol/l.
Intractable pruritus
o The 5-year survival post transplant is about 7080%.
Hereditary haemochromatosis
HFE gene on chromosome 6
Genetic screening for homozygous C282Y or H63D mutations
Cardiac and liver damage may improve with treatment but joint pain and
diabetes often remain.
Wilson disease
Ataxia and tremor are common
In Fulminant W.D. there is massive hepatic necrosis releasing the abnormally
sequestered copper from the hepatocytes into the circulation leading to haemolysis
and increased serum copper
Kayser Fleischer rings on the cornea are the most specific sign although they may
be absent in up to 50% of cases.
Serum caeruloplasmin is low, but is sometimes normal and can also be reduced
by advanced liver failure from any cause, so it is a non-specific test.
Urinary copper excretion is increased
The diagnosis can also be made by liver biopsy
Genetic testing is unhelpful in most cases unless there is a strong family history,
as there are 200 mutations in the gene known
Autoimmune hepatitis.
o an initial period of high-dose prednisolone,
o azathioprine is often added as a steroid-sparing agent
Confirming diagnosis
o Liver biopsy is the investigation most likely to confirm the diagnosis
o Generally in these cases imaging is unhelpful
Hydatid liver disease
Calcification is often seen on plain abdominal X-ray.
Ultrasound is demonstrate cysts
CT is occasionally used when the character of the cysts is unclear.
Serology is neither specific nor sensitive.
o high dose albendazole of 10 mg/kg is given for 1-3 months followed by
percutaneous aspiration and sterilisation with alcohol.
o Percutaneous aspiration on its own is contraindicated as toxins can be released
causing cardiovascular collapse.
o Surgery
Amoebic liver abscess
o without bowel changes in up to 50% of cases.
o high swinging fever
o right upper quadrant pain
o raised right hemidiaphragm and dullness on examination.
o Ultrasound or CT abdomen first choice
o Stool examination although this test has limitations in terms of sensitivity

o Stool antigen detection may be helpful and facilitates early diagnosis before an
antibody response occurs (<7 d) and differentiates pathogenic from nonpathogenic
Entamoeba infection
o Serology " Indirect haemagglutination test" is positive in greater than 95% but this
could be past or present infection.
o Metronidazole is the first line treatment for the amoebic dysentery, and diloxanide
is used to destroy the cysts.
o Abscess drainage is only needed if
concerned about a mass rupture as it can spread into the lung or
if there is no response to oral treatments.
Hepatic adenoma caused by oral contraceptive pill
Stop the oral contraceptive pill
Patients who experience some regression after stopping the pill, there is still a
risk of malignant transformation, and then arrange
later surgical resection
if Patients are unwilling/unable to undergo elective tumour resection, such
patients should be monitored with alpha-fetoprotein measurement
Hepatocellular carcinoma
o Ultrasound and CT scan
o A rising alpha-fetoprotein indicative of a hepatoma and
o biopsy is not always necessary to avoid seeding of tumour
Surgical Treatment is the only proven potentially curative therapy
o Hepatic resection should be considered as a primary therapy in any patient with
non-cirrhotic liver.
o liver transplantation in any cirrhotic patient with
cirrhosis and a single small HCC (<5 cm) or
cirrhosis and up to three lesions (<3 cm).
Non-surgical therapy is only used when
surgical therapy is not possible and
with extrahepatic dissemination.
o Percutaneous ethanol injection has been shown to produce necrosis of small HCC
and is best suited for peripheral lesions.
o Chemoembolisation can produce tumour necrosis and has been shown to affect
survival in highly selected patients with good liver reserve.
o Systemic chemotherapy has a poor response rate and
o hormonal therapy like tamoxifen has shown no survival benefit in controlled trials.
o Interferon has been used for treatment of HCC rather than the underlying viral
infection, but remains controversial.
Acute graft-versus host-disease after liver transplantation
It develops from 15 days after transplantation
Presentation is with
o jaundice,
o hepatomegaly and
o abnormal liver function tests, the earliest and most common finding being a rise in
the serum levels of
conjugated bilirubin and
alkaline phosphatase.
This reflects damage to the bile canaliculi, leading to cholestasis.
Other disorders need to be excluded, such as
o hepatic veno-occlusive disease,
o hepatic infections (primarily viral hepatitis) and

o drug toxicity.
A biopsy gives definite histological diagnosis
o A transjugular hepatic biopsy may be preferred if an adequate amount of tissue can
be obtained.
o The primary histologic finding is
extensive bile duct damage
o the first and most effective treatment option is the use of corticosteroids
o If higher doses of steroids are not successful in controlling GVHD by 3 to 5 days,
second-line treatments are less successful. These include
antithymocyte globulin, and
mycophenolate mofetil.
Kings criteria for liver transplant include:
1) > 1 week between onset of jaundice and encephalopathy
2) Bilirubin > 300 mol/l
3) PT > 50
4) Drug induced liver failure
5) Age <10 or >40
Patient has to meet 3/5 of the above OR
PT > 100
Long-term prophylaxis with hepatitis B immunoglobulin is associated with a
significant lower risk of re-infection post transplant. Alternatives include use of
nucleoside analogues such as famciclovir and lamivudine.
Primary sclerosing cholangitis
Jaundice tends to fluctuate in primary sclerosing cholangitis, unlike primary
biliary cirrhosis, which is progressive
If associated with ulcerative colitis,, Colectomy has no effect on the natural
history of PSC development at all.
Ultrasound is normal in 50% of patients at an early stage of disease.
MRCP has an accuracy of diagnosis for PSC of 90%, compared to 97% for ERCP
but with a much better safety profile. In addition, MRCP gives the possibility of
visualising bile ducts proximal to any obstruction.
Liver transplantation is best choice
Survival post liver transplant however is around 90%, although the chance of
rejection is higher in PSC patients.
10-15% of PSC patients eventually develop cholangiocarcinoma.
cholangiocarcinoma to be a contraindication to liver transplantation
When cholangiocarcinoma with local invasion occur, the treatment of choice is
stenting via ERCP. The procedure is successful at relieving symptoms of jaundice
Sphincter of Oddi dysmotility (SOD)
can cause backup of bile and pancreatic juices which can result in biliary colic.
recurrent admissions for intermittent upper abdominal pain especially after fatty
More prolonged obstruction may result in bile leaking back into the bloodstream,
which can cause transient abnormal liver biochemistry.
SOD most commonly occurs in young females especially those who have
previously undergone cholecystectomy.
At ERCP, delayed drainage of contrast is seen and
SOD manometry can confirm the diagnosis,,,There is usually a high resting
pressure with marked phasic contractions and often some retrograde peristalsis.
Endoscopic sphincterotomy or balloon sphincteroplasty often relieves this

Ascending cholangitis
In the acute setting
o the most important first steps in management are to
exclude bowel perforation erect chest X ray
evaluate the degree of metabolic compromise due to sepsis/shock (arterial blood
gas, ABG) to
Subsequent acute management would include an
o abdominal ultrasound for any biliary dilatation, which may be a precursor to
o urgent ERCP
o Blood cultures should also be taken prior to commencing antibiotics, but should not
delay their administration.
o Ultrasonography is excellent for
gallstones and cholecystitis.
assessing bile duct dilatation.
However, it often misses stones in the distal bile duct
o ERCP is both diagnostic and therapeutic and is considered the criterion standard
for imaging the biliary system.
ERCP should be reserved for patients who may require therapeutic intervention.
Patients with a high clinical suspicion for cholangitis should proceed directly to
ERCP has a high success rate (98%) and is considered safer than surgical and
percutaneous intervention.
Diagnostic use of ERCP carries a complication rate of approximately 1.38% The
major complication nclude pancreatitis, bleeding, and perforation.
o For diagnostic purposes, ERCP has now generally been replaced by MRCP
o MRCP is a noninvasive imaging modality that is increasingly being used in the
diagnosis of biliary stones and other biliary pathology.
MRCP is accurate for detecting choledocholithiasis, neoplasms, strictures, and
dilations within the biliary system.
Limitations of MRCP include the inability for invasive diagnostic tests such as bile
sampling, cytologic testing, stone removal, or stenting.
It has limited sensitivity for small stones (<6 mm in diameter).
Absolute contraindications are the same as for a traditional MRI, which include
presence of a cardiac pacemaker,
cerebral aneurysm clips,
ocular or cochlear implants, and
ocular foreign bodies.
Relative contraindications include the
presence of cardiac prosthetic valves,
metal prostheses, and
penile implants.

Carcinoid syndrome
Diagnosis Carcinoid Tumor
o chest and abdominal computed tomography (CT)
o pentreotide imaging has been shown to have a sensitivity of 80%+ for detection of
Diagnosis Carcinoid syndrome

o 24-h urine collection for 5-HIAA

o Liver ultrasonography to visualise the liver metastases.
Management of the carcinoid syndrome is largely palliative and involves
o Reducing the tumour mass by a combination of surgical resection, hepatic artery
embolisation and,
o Rarely, cytotoxic chemotherapy.
o The effects of the tumour products can be inhibited
octreotide or
Investigations for iron deficiency anaemia in elderly
Any level of anaemia with evidence of iron deficiency (i.e. microcytosis,
hypochromasia or low serum ferritin) should be investigated.
upper and lower gastrointestinal (GI) tract to exclude malignancy.
There is no evidence of the benefit of colonoscopy over good contrast studies for
the detection of GI cancer and therefore either is acceptable.
Coeliac disease is estimated to account for up to 6% of total cases of IDA, and
this can sometimes occur in the presence of normal B12 and folate levels.
o anti-endomysial antibody or
o tissue transglutaminase antibody) with
o duodenal biopsy used to confirm positive results or to make a diagnosis in
serologogy-negative patients in whom coeliac disease is strongly suspected e.g. those
selective immunoglobulin A (IgA) deficiency or
with a strong family history)
Urinary testing for blood is recommended as an estimated 1% of patients with
IDA will have renal tract malignancy caused by haematuria and haemosiderin
deposition in the tumour.
Faecal occult blood testing is of no benefit in the investigation of established IDA
as it is insensitive and non-specific, although it may have a role in population
screening for GI cancer.
Iron deficiency anaemia In women aged less than 50 years who menstruate regularly
Menstrual blood loss is a common cause of IDA
For this reason it is recommended that in the absence of warning features in the
personal medical history or family history, or on examination, that a trial of ferrous
sulphate and 3-month review , and
Only those patients who remain anaemic after an appropriate interval (or who
are transfusion dependent) are investigated further.
Pre-menopausal women who have IDA and a strong family history of colorectal
cancer should be investigated immediately
British Society of Gastroenterology guidelines state that a strong family history
consists of one first-degree relative affected aged <45 years, or two affected firstdegree relatives
dermatitis, depression and dementia.
tremor, ataxia, insomnia, fits and neuropathy.
It most commonly presents in
o China and Africa and
o side-effect of tuberculosis (TB) treatment
o carcinoid syndrome.
Drugs causing chronic diarrhoea include
broad-spectrum antibiotics,
antihypertensives such as diuretics,

cholesterol lowering drugs,
sodium valproate,
colchicines and
oral hypoglycaemic drugs.
Diagnostic paracentesis
serum to ascites albumin gradient
o ascites related to portal hypertension (gradient > 11g/L) increased
alcoholic hepatitis,
fulminant hepatic failure,
Budd Chiari syndrome,
acute or chronic portal vein obstruction,
cardiac diseases
spontaneous bacterial peritonitis secondary to cirrhosis.
o ascites not related to portal hypertension (gradient < 11g/L).decreased
nephrotic syndrome,
protein losing enteropathy,
peritoneal carcinomatosis,
tuberculous peritonitis,
pancreatic duct leak and biliary ascites.