11. A 20-year-old woman presents with progressive speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline and psychosis. Which gene mutation might explain this clinical presentation?
Clinical
12. 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 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 clinical features would suggest a poorer prognosis and prompt early 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
13. A 37-year-old woman presents with a 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 papilloedema. She has a full range of eyes movements. Computed tomography of her head is normal. What is the most likely diagnosis?
A. Cerebral venous thrombosis
B. Herpes simplex encephalitis
C. Cerebral abscess
D. Glioblastoma multiforme
E. Third nerve palsy
14. A 28-year-old woman is seen in neurology outpatients several weeks following a witnessed unprovoked grand mal convulsion. She had another episode 6 months previously that was not witnessed but involved an unexplained loss of consciousness, urinary incontinence and tongue injury. Magnetic resonance imaging (MRI), electroencephalography (EEG) and electrocardiography (ECG) are all normal. She wants to know more about epilepsy and the likelihood of further episodes. You should tell her that:
A. With treatment, the risk of a further seizure is greater than 50% within 2 years
B. Without treatment, the risk of a further seizure is less than 25% within 2 years
C. Appropriate drug treatment can maintain more than 70% of patients with epilepsy seizure free
D. Epilepsy is associated with a standardised mortality rate of 1.1
E. Epilepsy affects 1 in 500 people in developed countries
15. A 37-year-old man has had several 30-min episodes of a severe unilateral headache over the last day following alcohol intake. He has had three previous similar episodes. His eye waters, is red and the most intense pain is felt behind the eye and the temple. Which one of the following diagnosis is most likely?
A. Classical migraine
B. Trigeminal neuralgia
C. Acute closed angle glaucoma
D. Cluster headache
E. Temporal arteritis
16. 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
17. A 64-year-old woman presents with a rapid onset of symmetrical weakness in her legs. Magnetic resonance imaging (MRI) of her brain and spinal cord is normal and a diagnosis of Guillain–Barré syndrome is suspected. Which one of the following is correct?
A. In the first week following onset albuminocytological dissociation [high level of protein in the cerebrospinal fluid (CSF) with normal cell count] is present in over 95% of patients
B. The presence of knee-jerk reflexes cannot exclude the diagnosis
C. Over 95% of patients 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
18. In a patient with features of parkinsonism and dementia, which one of the following clinical manifestations is most likely to be present in Lewy body dementia?
A. Tremor
B. Rigidity
C. Visual hallucinations
D. Improvement with neuroleptics
E. Myoclonic jerks
19. A 25-year-old man presents with an acute right-sided weakness and slurred speech. He has had one tonic–clonic seizure prior to this presentation. He does not smoke and has no history of hypertension, diabetes mellitus or hyperlipidaemia. On examination he has hypotonia and greater weakness in the proximal muscles than the distal muscles of the arms and legs. Laboratory investigation shows a high lactate-to-pyruvate ratio. Which is the most likely diagnosis?
A. Dermatomyositis
B. Inclusion body myositis
C. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)
D. Motor neurone disease
E. Polymyositis
20. A 62-year-old woman presents following multiple falls, which have been increasing in frequency over the past 6 months. She says that she feels unsteady almost all the time and is frequently light-headed. On examination, she has bradykinesia, cogwheeling of both upper extremities, gait ataxia and a systolic blood pressure fall of 35 mmHg on standing with no change in pulse. Which one of the following is the most likely diagnosis for this patient?
A. Huntington disease
B. Multiple system atrophy
C. Parkinson disease
D. Progressive supranuclear palsy
E. Primary adrenal insufficiency
21. A 65-year-old woman who is known to have myasthenia gravis for the past 4 years had been started on oral antibiotics for an upper respiratory tract infection. Two days later she is brought to the hospital with confusion and arterial blood gases reveal an elevated partial arterial carbon dioxide (PaCO2) of 55 mmHg (37–45 mmHg). What is the most appropriate treatment for her presentation?
A. Combination of high-dose prednisolone and azathioprine
B. Plasmapheresis
C. Intravenous pyridostigmine
D. Urgent thymectomy
E. Intravenous antibiotics
22. A 58-year-old man presents with a 2-month history of progressively worsening weakness of both legs. On examination, he has bilateral proximal and distal leg weakness with diminished tendon reflexes. What is the next most appropriate investigation?
A. Magnetic resonance imaging of the cervical spine
B. Computed tomography of the brain
C. Nerve biopsy
D. Muscle biopsy
E. Nerve conduction study
23. A 35-year-old woman complains of an uncontrollable urge to move her legs at night accompanied by an aching discomfort. Which of the following features would be consistent with a diagnosis of restless legs syndrome?
A. Improvement in symptoms with the dopaminergic agonist ropinirole
B. Improvement in symptoms with the dopaminergic antagonist chlorpromazine
C. Evidence of iron overload with elevated ferritin
D. Improvement during pregnancy
E. Glove and stocking peripheral sensory neuropathy
24. A 28-year-old woman presents with visual loss in her right eye and pain behind the eye with eye movement. Fundoscopy reveals optic neuritis in that eye. Magnetic resonance imaging (MRI) of the head and cerebrospinal fluid (CSF) examination are normal. Which one of the following statements is true for this patient?
A. Optic neuritis is a distinct clinical entity unrelated to multiple sclerosis
B. It is possible that this patient will progress to multiple sclerosis in spite of normal MRI head and CSF examination
C. This patient has a greater than 90% chance of progress to definite multiple sclerosis within 12 months
D. Without treatment, this patient has a high likelihood of permanent unilateral visual loss
E. Treatment with high-dose methylprednisolone will preserve her vision at 12 months
25. A 26-year-old Thai man presents with profound weakness after a meal with friends. He reports that for several years he has had similar episodes after exercise and large meals. Which one of the following diagnostic tests should be performed immediately for this patient?
A. Assessment of serum potassium level
B. Blood glucose
C. Synacthen test
D. Electromyography
E. Testing for acetylcholine receptor antibodies
26. An 83-year-old woman with a past history of controlled hypertension presents 3½ h following a sudden onset of left-sided weakness due to an ischaemic stroke. Which one of the following statements is true regarding thrombolysis with tissue plasminogen activator (tPA)?
A. Patients over the age of 80 years do not benefit from thrombolysis
B. Patients do not benefit from thrombolysis later than 3 h from stroke onset
C. Thrombolysis is associated with an increased risk of death and intracerebral haemorrhage in the first week following treatment
D. Aspirin should be administered in conjunction with thrombolysis
E. Intracerebral haemorrhage occurs in less than 1% of patients treated with thrombolysis
27. A 36-year-old woman presents with a sudden onset of headache and right-sided hemiparesis. She has no history of cardiovascular or neurological disease and was well and doing yoga daily before the onset of her symptoms. She does not take alcohol or illicit drugs. Her examination reveals a blood pressure of 130/70 mmHg and pulse of 80 beats/min in sinus rhythm. Her cardiac and respiratory examinations are normal, and her neurological examination confirms a hemiparesis. Laboratory studies reveal an erythrocyte sedimentation rate of 28 mm/h, a normal haematological and biochemical profile, and a negative urinary drug screen. Anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies and anti-neutrophil cytoplasmic antibodies (ANCAs) are negative. Computed tomography (CT) of her head reveals hypodensity of her left temporal–parietal region consistent with an ischaemic region. What is the next best step for this patient?
A. Administration of high-dose intravenous corticosteroids
B. Biopsy of the temporal artery
C. Magnetic resonance angiography
D. Cerebral spinal fluid examination for oligoclonal bands
E. Visual evoked potentials
28. The first presentation of a patient with new variant Creutzfeldt–Jakob disease (nvCJD) is likely to be with:
A. Myoclonic jerks
B. Psychiatric symptoms
C. Akinesia
D. Dementia
E. Visual loss
Theme: Neuromuscular disorders (for Questions 29–32)
A. Limb girdle dystrophy
B. Guillain–Barré syndrome
C. Myotonic dystrophy
D. Dermatomyositis
E. Facioscapulohumeral dystrophy
F. Myasthenia gravis
G. Oculopharyngeal dystrophy
H. Motor neurone disease (also known as amyotrophic lateral sclerosis)
For each of the following patients, select the most likely diagnosis.
29. A 38-year-old man presents with muscle weakness and wasting. On examination, cataracts, frontal baldness and testicular atrophy were also present.
30. A 57-year-old man presents with progressive weakness and swallowing difficulties. Examination shows muscle wasting, fasciculation in the muscles of both legs, hyperactive reflexes generally and upgoing plantar responses.
31. A 53-year-old man presents with difficulty swallowing and progressive bilateral ptosis. On examination, there is also proximal weakness and ophthalmoplegia but no evidence of fatigability. His father had the same problem in his late 50s.
32. A 48-year-old Aboriginal woman has noticed difficulty rising from a chair and climbing stairs for 2 months prior to presentation. On examination, periungual telangiectasia is observed and erythematous psoriasiform dermatitis is present on the scalp.
Answers
Basic Science
1. Answer A
The fundamental defect in myasthenia gravis is a decrease in the number of available acetylcholine receptors (AChR) at the postsynaptic muscle membrane in the neuromuscular junctions due to an autoimmune antibody mediated mechanism (Chaudhuri and Behan, 2009).
Myasthenia gravis is a neuromuscular disorder characterised by weakness and fatigability of skeletal muscles. In the neuromuscular junction, acetylcholine is released by motor nerve endings in response to the arrival of an action potential. The acetylcholine then combines with AChRs that are densely packed on the postsynaptic muscle membrane. In myasthenia gravis, an autoimmune attack by anti-AChR antibodies both reduces the number of AChRs by endocytosis and blocks the active site of the receptors (the site that normally binds acetylcholine).
The thymus is hyperplastic in 65% of patients with myasthenia gravis while 10% have thymic tumours. Muscle-like cells on the thymus (myoid cells) bear AChRs on their surface and are postulated to serve as the source of autoantigen.
Lambert–Eaton myasthenic syndrome (LEMS), which resembles myasthenia gravis, is associated with antibodies against P/Q-type calcium channels. These antibodies interfere with the normal calcium flux needed for the release of acetylcholine. Clinically, the differentiating features of LEMS are depressed or absent reflexes and incremental responses on repetitive nerve stimulation. Patients with myasthenia gravis have normal reflexes and characteristically show rapid decrease in the amplitude of evoked responses on repetitive nerve stimulation.
The fundamental defect in myasthenia gravis is a decrease in the number of available acetylcholine receptors (AChR) at the postsynaptic muscle membrane in the neuromuscular junctions due to an autoimmune antibody mediated mechanism (Chaudhuri and Behan, 2009).
Myasthenia gravis is a neuromuscular disorder characterised by weakness and fatigability of skeletal muscles. In the neuromuscular junction, acetylcholine is released by motor nerve endings in response to the arrival of an action potential. The acetylcholine then combines with AChRs that are densely packed on the postsynaptic muscle membrane. In myasthenia gravis, an autoimmune attack by anti-AChR antibodies both reduces the number of AChRs by endocytosis and blocks the active site of the receptors (the site that normally binds acetylcholine).
The thymus is hyperplastic in 65% of patients with myasthenia gravis while 10% have thymic tumours. Muscle-like cells on the thymus (myoid cells) bear AChRs on their surface and are postulated to serve as the source of autoantigen.
Lambert–Eaton myasthenic syndrome (LEMS), which resembles myasthenia gravis, is associated with antibodies against P/Q-type calcium channels. These antibodies interfere with the normal calcium flux needed for the release of acetylcholine. Clinically, the differentiating features of LEMS are depressed or absent reflexes and incremental responses on repetitive nerve stimulation. Patients with myasthenia gravis have normal reflexes and characteristically show rapid decrease in the amplitude of evoked responses on repetitive nerve stimulation.
Chaudhuri, A. and Behan, P.O. (2009). Myasthenic crisis. QJM 102, 97–107.
2. Answer D
Hemiballismus is a rare movement disorder characterised by a large movement of an entire limb or limbs on one side of the body (Hawley and Weiner, 2012). The acute development of hemiballismus is often caused by focal lesions in the contralateral basal ganglia and subthalamic nucleus. Many aetiologies exist for this rare disorder, with vascular causes and non-ketotic hyperglycaemia being the most common. Prognosis is favourable for most patients with complete resolution. It is first important to treat underlying causes such as hyperglycaemia, infections or neoplastic lesions. When pharmacological treatment is necessary, anti-dopaminergic drugs, such as haloperidol and chlorpromazine, can be helpful. Other treatments include topiramate, intrathecal baclofen and botulinum injections.
Hemiballismus is a rare movement disorder characterised by a large movement of an entire limb or limbs on one side of the body (Hawley and Weiner, 2012). The acute development of hemiballismus is often caused by focal lesions in the contralateral basal ganglia and subthalamic nucleus. Many aetiologies exist for this rare disorder, with vascular causes and non-ketotic hyperglycaemia being the most common. Prognosis is favourable for most patients with complete resolution. It is first important to treat underlying causes such as hyperglycaemia, infections or neoplastic lesions. When pharmacological treatment is necessary, anti-dopaminergic drugs, such as haloperidol and chlorpromazine, can be helpful. Other treatments include topiramate, intrathecal baclofen and botulinum injections.
Hawley, J.S. and Weiner, W.J. (2012). Hemiballismus: current concepts and review. Parkinsonism Relat Disord 18, 125–129.
3. Answer A
While partial epilepsy, which is the most common seizure disorder in adults, can be associated with head trauma, stroke and tumour, the strongest association is with mesial temporal sclerosis (Chang and Lowenstein, 2003). This is characterised by hippocampal neuronal loss and chronic fibrillary gliosis centred on the pyramidal cell layer. It can be imaged with Magnetic resonance imaging (MRI) and features can include reduced hippocampal volume, increased signal intensity on T2-weighted imaging and disturbed internal architecture.
Epilepsy syndromes fall into two general groups – generalized and partial syndromes. In generalised epilepsy, the seizures begin with simultaneous involvement of both cerebral hemispheres. In partial epilepsy, in contrast, seizures originate in one or more local foci, although they can spread to involve the whole brain.
Most of the partial epilepsies arise from abnormality in the mesial temporal lobe. Recordings from intracranial electrodes demonstrate an ictal onset in mesial temporal structures, such as the hippocampus, amygdala and adjacent parahippocampal cortex; surgical resection of these areas in suitable patients can abolish the seizures.
While partial epilepsy, which is the most common seizure disorder in adults, can be associated with head trauma, stroke and tumour, the strongest association is with mesial temporal sclerosis (Chang and Lowenstein, 2003). This is characterised by hippocampal neuronal loss and chronic fibrillary gliosis centred on the pyramidal cell layer. It can be imaged with Magnetic resonance imaging (MRI) and features can include reduced hippocampal volume, increased signal intensity on T2-weighted imaging and disturbed internal architecture.
Epilepsy syndromes fall into two general groups – generalized and partial syndromes. In generalised epilepsy, the seizures begin with simultaneous involvement of both cerebral hemispheres. In partial epilepsy, in contrast, seizures originate in one or more local foci, although they can spread to involve the whole brain.
Most of the partial epilepsies arise from abnormality in the mesial temporal lobe. Recordings from intracranial electrodes demonstrate an ictal onset in mesial temporal structures, such as the hippocampus, amygdala and adjacent parahippocampal cortex; surgical resection of these areas in suitable patients can abolish the seizures.
Chang, B.S. and Lowenstein, D.H. (2003). Epilepsy. N Engl J Med 349, 1257–1266.
4. Answer D
The involvement of the right third cranial nerve and the right pyramidal tract would suggest the lesion is at the level of the third cranial nerve nucleus in the midbrain. A midbrain infarct is most commonly a consequence of hypertensive cerebral vascular disease and may arise from an embolus with a cardiac origin or proximal atherosclerotic lesion. It is also sometimes known as Weber syndrome and due to occlusion of paramedian branches of the posterior cerebral artery or of basilar bifurcation perforating arteries. The involvement of the third nerve excludes a lesion in the internal capsule, medulla, cervical cord and occipital lobe. Sometimes contralateral parkinsonism may develop due to involvement of the basal ganglia projections. On rare occasions, hemiparesis with contralateral third cranial nerve palsy can result from a hemispheric space-occupying lesion, which compresses the contralateral third cranial nerve and the cerebral peduncle against the clinoid process.
The involvement of the right third cranial nerve and the right pyramidal tract would suggest the lesion is at the level of the third cranial nerve nucleus in the midbrain. A midbrain infarct is most commonly a consequence of hypertensive cerebral vascular disease and may arise from an embolus with a cardiac origin or proximal atherosclerotic lesion. It is also sometimes known as Weber syndrome and due to occlusion of paramedian branches of the posterior cerebral artery or of basilar bifurcation perforating arteries. The involvement of the third nerve excludes a lesion in the internal capsule, medulla, cervical cord and occipital lobe. Sometimes contralateral parkinsonism may develop due to involvement of the basal ganglia projections. On rare occasions, hemiparesis with contralateral third cranial nerve palsy can result from a hemispheric space-occupying lesion, which compresses the contralateral third cranial nerve and the cerebral peduncle against the clinoid process.
5. Answer C
Horner syndrome results from interruption of the sympathetic supply to the head and is characterised by enophthalmos, miosis, ptosis and a warm dry skin (anhydrosis) on the affected side of the face. The loss of sympathetic tone causes vasodilatation of the cutaneous vessels of the cheek and nasal mucosa with absence of sweating and a feeling of nasal obstruction. There is also narrowing of the palpebral fissure where the ptosis is due to weakness of the superior tarsal muscle or Muller’s muscle. There is also a contraction of the pupil due to the unopposed action of the autonomic parasympathetic inflow via the oculomotor nerve. The movement of the eyeball is unaffected.
The sympathetic pathway may be interrupted in the cervical spinal cord, from the sympathetic trunk, the brachial plexus, over the lung apex in the superior cervical ganglion, within the adventitia of the internal carotid artery or through the cavernous sinus. Conditions that can produce a Horner syndrome include anything that might destroy the cervical sympathetic chain, such as invading malignancy at the lung apex. Brainstem stroke can also cause Horner syndrome and other neurological symptoms may then co-exist such as diplopia, vertigo and ataxia, whilst the presence of neck pain should point towards the possibility of a carotid dissection.
Horner syndrome results from interruption of the sympathetic supply to the head and is characterised by enophthalmos, miosis, ptosis and a warm dry skin (anhydrosis) on the affected side of the face. The loss of sympathetic tone causes vasodilatation of the cutaneous vessels of the cheek and nasal mucosa with absence of sweating and a feeling of nasal obstruction. There is also narrowing of the palpebral fissure where the ptosis is due to weakness of the superior tarsal muscle or Muller’s muscle. There is also a contraction of the pupil due to the unopposed action of the autonomic parasympathetic inflow via the oculomotor nerve. The movement of the eyeball is unaffected.
The sympathetic pathway may be interrupted in the cervical spinal cord, from the sympathetic trunk, the brachial plexus, over the lung apex in the superior cervical ganglion, within the adventitia of the internal carotid artery or through the cavernous sinus. Conditions that can produce a Horner syndrome include anything that might destroy the cervical sympathetic chain, such as invading malignancy at the lung apex. Brainstem stroke can also cause Horner syndrome and other neurological symptoms may then co-exist such as diplopia, vertigo and ataxia, whilst the presence of neck pain should point towards the possibility of a carotid dissection.
6. Answer E
Adrenoleucodystrophy (ALD) is a hereditary demyelinating disease (X-linked disorder). ALD is the most common peroxisomal disorder of beta-oxidation that results in accumulation of very long chain fatty acids (VLCFA) in all tissues. ALD consists of a spectrum of phenotypes, including childhood cerebral forms, adrenomyeloneuropathy and Addison disease. These disorders vary in the age at and severity of clinical presentation. ALD is caused by mutations in the ATP-binding cassette, Subfamily D, Member 1 gene (ABCD1 gene), located at Xq28, which encodes an ATP-binding cassette (ABC) transporter, similar to the cystic fibrosis transmembrane conductance regulator (CFTR). ALD is characterised by inflammatory demyelination, resulting in symmetric 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.
Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the central nervous system (CNS) characterised by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord (Tenembaum et al., 2007). The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurological signs and deficits. Children are preferentially affected. In the absence of specific biological markers, the diagnosis of ADEM is still based on the clinical and radiological features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS).
Progressive multifocal leucoencephalopathy (PML) is a severe inflammatory demyelinating disease of the central nervous system that is caused by reactivation of the polyomavirus JC.
Guillain–Barré syndrome is an acute polyneuropathy. Some subtypes cause change in sensation or pain as well as dysfunction of the autonomic nervous system.
MS is an acquired inflammatory demyelinating disease which rarely shows familial aggregation, though there has been an increasing interest in associations of the disease with HLA DR and other genetic loci.
Adrenoleucodystrophy (ALD) is a hereditary demyelinating disease (X-linked disorder). ALD is the most common peroxisomal disorder of beta-oxidation that results in accumulation of very long chain fatty acids (VLCFA) in all tissues. ALD consists of a spectrum of phenotypes, including childhood cerebral forms, adrenomyeloneuropathy and Addison disease. These disorders vary in the age at and severity of clinical presentation. ALD is caused by mutations in the ATP-binding cassette, Subfamily D, Member 1 gene (ABCD1 gene), located at Xq28, which encodes an ATP-binding cassette (ABC) transporter, similar to the cystic fibrosis transmembrane conductance regulator (CFTR). ALD is characterised by inflammatory demyelination, resulting in symmetric 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.
Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the central nervous system (CNS) characterised by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord (Tenembaum et al., 2007). The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurological signs and deficits. Children are preferentially affected. In the absence of specific biological markers, the diagnosis of ADEM is still based on the clinical and radiological features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS).
Progressive multifocal leucoencephalopathy (PML) is a severe inflammatory demyelinating disease of the central nervous system that is caused by reactivation of the polyomavirus JC.
Guillain–Barré syndrome is an acute polyneuropathy. Some subtypes cause change in sensation or pain as well as dysfunction of the autonomic nervous system.
MS is an acquired inflammatory demyelinating disease which rarely shows familial aggregation, though there has been an increasing interest in associations of the disease with HLA DR and other genetic loci.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
