Neurology Flashcards
The pathogenesis of myasthenia gravis is best explained by:
A. Antibody-mediated decrease in the number of available acetylcholine receptors (AChR) at the post synaptic neuromuscular junctions
B. Antibodies against P/Q type calcium channels in motor nerve terminals
C. Defect in acetylcholine release by the nerve terminals at the NMJ
D. Genetic or acquired deficiency of choline acetyltransferase leading to a deficiency of ACh
E. Auto-antibodies that bind to choline acetyltransferase at the NMJ
Answer: A - Antibody-mediated decrease in the number of available acetylcholine receptors (AChR) at the post synaptic neuromuscular junctions
The fundamental defect in MG is a decrease in the number of ACh receptors at the postsynaptic membrane in the NMJ due to an antibody mediated mechanism.
MG is a neuromuscular disorder characterised by weakness and fatigability of skeletal muscles. In the NMJ, ACh is released by motor nerve endings in response to the arrival of an action potential. The ACh then combines with the AChRs that are densely packed on the postsynaptic muscle membrane. In MG, an autoimmune attack by anti-AChR antibodies reduces the number of AChRs by endocytosis and blocks the active site of receptors.
65% of patients have a hyperplastic thymus while 10% have thymic tumours.
Lambert-Eaton myasthenic syndrome (LEMS) which resembles MG is associated with antibodies against P/Q type calcium channels. These interfere with normal calcium influx needed for release of ACh. Clinically the differentiating features of LEMS are 1. Depressed/absent reflexes and 2. Incremental responses on nerve repetitive nerve stimulation. Standard MG should demonstrate normal reflexes and characteristically rapidly decrementing amplitude on a repetitive nerve stimulation test.
A 75 year old woman develops sudden movements of her arm; she throws her arm outwards and uncontrollably injures herself. Which one of the following areas is most likely to have sustained an insult?
A. Corpus callosum B. Globus pallidus C. Hippocampus D. Subthalamic nucleus E. Thalamis
Answer: D - Subthalamic nucleus
Hemiballismus is often causes by CONTRALATERAL focal lesions in the basal ganglia and subthalamic nucleus. The most common causes are vascular/stroke and non-ketotic hyperglycaemia.
Partial epilepsy is most associated with:
A. Mesial temporal sclerosis B. Abnormality in thalamocortical circuits C. Abnormality in the frontal cortex D. Stroke E. Head trauma
Answer: A Mesial temporal sclerosis
The most common adult seizure disorder and temporal lobe epilepsy is associated with mesial temporal sclerosis.
Which one of the following can explain the sudden onset of a right third nerve palsy and left hemiplegia involving the face, arm and leg?
A. Left internal capsule infarct B. Left medullary infarct C. Right medullary infarct D. Right midbrain infarct E. Right occipital infarct
Answer: D - Right midbrain infarct
The involvement of the right 3rd cranial nerve and the right pyramidal tract would suggest the lesion is at the level of the 3rd cranial nerve nucleus in the midbrain.
A midbrain infarct is most commonly a consequence of hypertensive cerebral vascular disease, though can be cardio or athero-embolic.
The 3rd nerve involvement excludes a lesion of the internal capsule, medulla, cervical cord or occipital lobe.
Rarely, hemiparesis with contralateral 3rd nerve palsy can result from a hemispheric space occupying lesion which compresses the contralateral 3rd nerve and cerebral peduncle against the clinoid process.
Which one of the following is associated with a right-sided Horner syndrome?
A. Dilated right pupil
B. Increased sweating of the right side of the face
C. Constricted right pupil
D. Weakness of lateral movement of the right eye
E. Weakness of the left orbicular oculi muscle
Answer: C - Constricted right pupil
Horner syndrome results from interruption of the sympathetic supply to the head and is characterised by: On affected side - 1. Miosis (constricted pupil) 2. Ptosis 3. Warm dry skin (anhydrosis)
Which one of the following is correct concerning these demyelinating diseases?
A. Acute disseminated encephalomyelitis (ADEM) involves the grey matter of the brain and spinal cord
B. Adrenoleukodystrophy is an autosomal recessive disorder
C. GBS does not involve the autonomic system
D. MS is frequently hereditary
E. Progressive multifocal leukoencephalopathy is caused by a polyoma virus
Answer: E - Progressive multifocal leukoencephalopathy is caused by a polyoma virus
PML is a severe inflammatory demyelinating disease of the CNS caused by reactivation of the JC polyomavirus
Adrenoleukodystrophy (ALD) is an X-linked disorder that results in the accumulation of very long chain fatty acids (VLCFA) in all tissues. There is a wide range of phenotypes including childhood cerebral dysfunction, adrenomyeloneuropathy and Addison’s disease. ALD is characterised by inflammatory demyelination with symmetrical loss of myelin in the cerebral and cerebellar white matter. The parieto-occipital regions are usually affected first, with asymmetric progression of the lesions toward the frontal or temporal lobes.
- Adrenomyeloneuropathy usually presents in men 20-40yrs with spastic paraparesis (stiffness, weakness)
- Female carriers often develop symptoms in adulthood, usually peripheral neuropathy and later myelopathy/gait disorder
ADEM usually affects the white matter and tends to follow viral infection (e.g. measles) or vaccination.
A 64 year old man presents with loss of feeling in the left little toe. On examination he has difficulty standing on tiptoe on the left side and left ankle jerk is absent. This is most likely due to:
A. Common peroneal nerve compression B. S1 radiculopathy C. L5 radiculopathy D. Sciatic nerve compression E. Posterior tibial nerve compression
Answer: B - S1 radiculopathy
S1 innervates the little toe and S1 radiculopathy is associated with loss of ankle jerk. Other findings can be decreased plantar and toe flexion.
L5 radiculopathy is associated with decreased foot dorsiflexion and toe extension with normal ankle jerk.
Common peroneal nerve compression leads to foot drop with weakness of foot dorsiflexion and eversion. It can be seen with prolonged immobilisation (i.e. following general anaesthesia or with plaster cast). Reflexes are preserved.
Sciatic nerve compression may be associated with hip fracture/dislocation or other trauma. There is sensory loss over the posterior aspect of the thigh, gluteal regions and entire lower leg (medial calf and arch may be spared). Key is the preservation of the knee jerk while the ankle jerk is lost.
Posterior tibial nerve compression leads to sensory symptoms, such as aching or burning over the sole of the foot with positive Tinel’s sign over the nerve posterior to the medial malleolus and sensory loss over the sole of the foot.
FOOT DROP TIPS:
- Differentials: Peroneal neuropathy, L5 radiculopathy, less commonly sciatic neuropathy, lumbar plexopathy, mononeuritis multiplex, myopathy
- Most common cause of foot drop (dorsiflexion weakness) = common peroneal neuropathy (most compression at neck of fibula)
- Check the following:
- Foot dorsiflexion and eversion (peroneal)
- Plantarflexion and inversion (tibial nerve)
- Hip abduction (superior gluteal nerve, L5 root) –> Differentiate L5 radiculopathy rom peroneal
EMQ Pathophysiology of neurological disorders
A. Wallerian degeneration
B. Presynaptic block of release of Acetylcholine
C. Segmental demyelination
D. Reduced ACh in presynaptic vesicles
E. Axonal destruction
F. Antibodies against postsynaptic receptors
G. Loss of anterior horn cells
H. Antibodies against presynaptic calcium channels
- What is the major features of idiopathic acute inflammatory demyelinating polyneuropathy (AIDP/GBS)?
- Which is the correct description of the pathophysiological feature of Lambert-Eaton myasthenic syndrome?
- Answer: C - Segmental demyelination
- Answer: H - Antibodies against presynaptic calcium channels
LEMS is an autoimmune disease with antibodies directed against presynaptic voltage-gated calcium channels. It can occur sporadically or as a paraneoplastic syndrome (often small cell lung cancer). The syndrome typically presents with proximal weakness legs > arms and similarly to MG, exacerbated by activity. Autonomic dysfunction occurs in 75% (dry mouth, blurred vision, constipation, orthostatic hypotension). Calcium entry into pre-synaptic terminals is initially blocked, resulting in reduced release of ACh and reduced muscle contraction. On exercise, continuous influx of calcium results in accumulation of calcium in the presynaptic nerve terminal (mitochondrial removal cannot keep up pace). This results in normal or near-normal amounts of ACh with short term muscle contraction and grip may become more powerful over a few seconds. LEMS can be mistaken for MG but it usually spares ocular/bulbar muscles and MG usually relatively spares the legs. NCS are useful and show compound action potentials reduced in MG and are not increased on repetitive stimulation.
EMQ Genetic basis for neurological disorders
A. Hexosaminidase A B. KALIG-1 C. APO E4 D. Retinoblastoma (Rb_ protein E. Amyloid precursor protein F. Neurofibromin G. Beta-amyloid protein H. Merlin (also known as schwannomin)
- A large brain tumour is seen on CT in a 30 year old man. Examination shows multiple skin nodules across back. Which genetic mutation could account for the presentation?
- A 20 year old woman presents with progressive speech and swallowing difficulty, unsteadiness of gait, spasticity, cognitive decline and psychosis. Which gene mutation might explain this condition?
- Answer: F - Neurofibromin
Patient has NF1 - Answer: A - Hexosaminidase A
Patient has Tay-Sachs disease (also known as GM2 gangliosidosis or hexominidase A defiency), an autosomal recessive lysosomal storage disorder with progressive mental and physical deterioration from 6 months usually resulting in death by age of 4yrs. Late onset Tay-Sachs disease can present as late as 30-40s.
A 49 year old man presents with sudden onset of left facial weakness. He experienced a respiratory infection 2 weeks ago and has had a dull ache behind the left ear for 2 days. This morning while shaving, he noticed a drooping of the left side of his face. Examination reveals a complete paralysis of the left upper face and forehead. Hearing, taste and sensation are normal and the other cranial nerves are functioning normally. No rash or vesicles are noted. Which one of the following features would suggest a poorer prognosis and prompt treatment with prednisolone?
A. Abrupt onset of symptoms B. Age younger than 60 years C. Complete paralysis D. Previous similar episode E. Recent respiratory infection
Answer: C - Complete paralysis
Bell’s palsy. The abrupt onset of unilateral facial weakness with lower motor neurone (forehead) involvement preceded by pain behind the ear is classical. Early treatment with prednisolone significantly improves chance of complete recovery at 3 and 9 months and is appropriate for those with features suggesting poorer prognosis.
Such features include severe/complete paralysis, older age, hyperacusis altered taste and evidence of axonal degeneration on EMG.
A 37 year old woman presents with severe headache and new onset ptosis of the left eye. her pupil sizes are normal. She does not have fatigability of her eye movements but fundoscopy shows mild bilateral papilledema. She has a full range of eye movements. CT head is normal. What is the most likely diagnosis?
A. Cerebral venous thrombosis B. HSV encephalitis C. Cerebral abscess D. Glioblastoma multiforme E. 3rd nerve palsy
Answer: A - Central venous thrombosis
A 28 year old woman is seen in neurology outpatients several weeks following a witnessed unprovoked grand mal convulsion. She had a another episode 6 months previously that was not witnessed but involved an unexplained loss of consciousness, urinary incontinence and tongue injury. MRI, EEG and ECG are normal. She wants to know about epilepsy and the likelihood of further episodes. You should tell her:
A. With treatment, the risk of further seizures is greater than 50% within 2yrs
B. Without treatment, the risk of further seizures is less than 25% within 2yrs
C. Appropriate drug treatment can maintain more than 70% of patients with epilepsy seizure free
D. Epilepsy has a standardised mortality rate or 1.1
E. Epilepsy affects 1 in 500 people in developed countries
Answer: C - Appropriate drug treatment can maintain more than 70% of patients with epilepsy seizure free
The risk of a second seizure within 2 years is approximately 50%. 75% can achieve remission at 5 years.
Treatment is usually reserved for those who have had at least 2 seizures and the risk of a 3rd seizure is over 60%.
Mortality rates are typically 2-3x general population (e.g. SUDEP, accidents including drowning)
A 37 year old man has had several 30 minute episodes of severe unilateral headache over the last day following alcohol intake. He has had 3 previous similar episodes. His eye waters, is red and the most intense pain is felt behind the eye and temple. Which one of the following diagnoses is most likely?
A. Classical migraine B. Trigeminal neuralgia C. Acute closed angle glaucoma D. Cluster headache E. Temporal arteritis
Answer: D - cluster headache
Cluster headache attacks are extremely painful and distressing. They are unilateral, generally lasting 15mins to 3 hours with associated characteristic ipsilateral cranial autonomic features (lacrimation, nasal congestion, rhinorrhoa, ptosis, eyelid oedema, miosis and sweating) and agitation. Attacks occur from once every other day to 8x daily in bouts lasting several weeks but usually complete remission between bouts. Acute attacks should be treated with high flow oxygen and or parenteral triptans. Verapamil can be helpful prophylxais.
There is a marked male predominance, an association with smoking, precipitation by alcohol and occurences more at night.
Which one of the following features of Parkinson disease is most likely to respond to deep brain stimulation?
A. Autonomic dysfunction B. Cognitive decline C. Loss of balance D. On-off fluctuations E. Sleep disorders
Answer: D - On-off fluctuations
DBS is a surgical technique in which electrodes attaches to leads are implanted in specific regions of the brain. The electrodes are connected to a device called an impulse generator which delivers electrical stimuli to the brain, modulating neural signalling.
2 sites in the brain have been targeted for DBS - the subthalamic nucleus and the internal segment of the globus pallidus.
Typically levodopa responsive symptoms (including tremor, on-off fluctuations and dyskinesia) are most likely to improve with DBS. Other symptoms (gait, balance and speech) are less likely to improve and can worsen.
A 64 year old woman presents with rapid onset of symmetrical weakness in her legs. MRI brain and spinal cord is normal. A diagnosis of Guillain-Barre is suspected, which of the following is correct?
A. In the first week following onset, albumincytological dissociation (high protein in CSF with normal cell count) is present in >95%
B. The presence of normal knee jerks cannot exclude the diagnosis
C. Over 95% will completely recover
D. Sensory symptoms with distal paraesthesia excludes the diagnosis
E. Autonomic dysfunction occurs in 50% of patients and is associated with arrhythmias
Answer: B - The presence of normal knee jerks cannot exclude the diagnosis
Albuminocytologic dissociation is seen in about 50% in the 1st week and 75% in the 3rd week.
Up to 10% have normal reflexes.
The presence of distal paraesthesia is common (though overt objective sensory loss is not typical)
Autonomic dysfunction can be severe but usually only in 20%
