Neurology and Stroke Flashcards
An 84-year-old man has been brought into hospital because of self-neglect. He lives alone in a ground floor flat and has daily carer who have found him to be increasingly suspicious, accusing them of stealing and moving his property and becoming physically aggressive. In the past month he had been refusing to let them in. He also seemed to be experiencing auditory hallucinations and
had lost weight. Examination was normal except for BMI 19 and MMSE 18/30. Bloods, CXR, urine, cultures normal. CT is shown.
Which one of the following is most likely?
a. Alcoholic hallucinosis
b. Alzheimer’s disease
c. Delirium
d. Paranoid schizophrenia
e. Pick’s disease
b. Alzheimer’s disease
Alzheimer’s dementia can present as self-neglect
and weight loss, especially when the patient is liv-
ing alone. Paranoid ideation is also quite common
and may be used by the patient as an explanation
for symptoms of memory loss (e.g. misplacing
items), as is physical aggression whereas auditory
and visual hallucinations are less common. Alzheimer’s
disease is the commonest cause of dementia, and most cases are sporadic; 5% of cases are inherited
as an autosomal dominant trait mutations in
the amyloid precursor protein (chromosome 21),
presenilin 1 (chromosome 14), and presenilin 2
(chromosome 1) genes are thought to cause the
inherited form. Risk of Alzheimer’s disease is
increased in those with the apolipoprotein E allele
E4 (present in 20% of population) is 15 times
higher than those with two E3 alleles. Mild AD
is characterized by minor behavioral changes, loss of memory of recent events (e.g. conversations,
events), misplace items, struggle to find the right
word in conversation, confused or lose track of
day/date, difficulty planning and making decisions,
visuospatial impairment, and lose interest in people
or activities. Moderate AD will need reminders
about self-care, increasingly forgetful, not recognize
people, place themselves/others at risk (e.g.
miss medication, leave gas stove on), easily
upset/angry/aggressive, night-day reversal, agitation,
socially inappropriate, delusions/hallucinations.
Severe AD is characterized by increasing
dependence on others for nursing care, bed/
wheelchair bound, weakness, unable to recognize
familiar objects/people, incontinence, difficulty
eating/swallowing and gradual loss of speech.
Death is usually 8-10 years after symptom onset.
Pathological changes include widespread cerebral
atrophy, particularly involving the cortex and hippocampus.
In AD, FDG-PET can show hypometabolism
in the temporoparietal regions and/or the
posterior cingulum. On microscopy there are cortical
plaques due to deposition of type A-Betaamyloid
protein and intraneuronal neurofibrillary
tangles caused by abnormal aggregation of the tau
protein (excessive phosphorylation). There is also
reduced acetylcholine due to damage to ascending
forebrain projection, hence acetylcholinesterase
inhibitors (donepezil, galantamine, and rivastigmine)
as options for managing mild to moderate
Alzheimer’s disease. Memantine (a NMDA receptor
antagonist) is reserved for patients with moderate—severe
Alzheimer’s disease.
Alzheimer’s dementia can present as self-neglect and weight loss, especially when the patient is liv- ing alone. Paranoid ideation is also quite common and may be used by the patient as an explanation for symptoms of memory loss (e.g. misplacing items), as is physical aggression whereas auditory and visual hallucinations are less common. Alzhei- mer’s disease is the commonest cause of dementia, and most cases are sporadic; 5% of cases are inher- ited as an autosomal dominant trait mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14), and presenilin 2 (chromosome 1) genes are thought to cause the inherited form. Risk of Alzheimer’s disease is increased in those with the apolipoprotein E allele E4 (present in 20% of population) is 15 times higher than those with two E3 alleles. Mild AD is characterized by minor behavioral changes, loss of memory of recent events (e.g. conversations, events), misplace items, struggle to find the right word in conversation, confused or lose track of day/date, difficulty planning and making decisions, visuospatial impairment, and lose interest in peo- ple or activities. Moderate AD will need reminders about self-care, increasingly forgetful, not recog- nize people, place themselves/others at risk (e.g. miss medication, leave gas stove on), easily upset/angry/aggressive, night-day reversal, agita- tion, socially inappropriate, delusions/hallucina- tions. Severe AD is characterized by increasing dependence on others for nursing care, bed/ wheelchair bound, weakness, unable to recognize familiar objects/people, incontinence, difficulty eating/swallowing and gradual loss of speech. Death is usually 8-10 years after symptom onset. Pathological changes include widespread cerebral atrophy, particularly involving the cortex and hip- pocampus. In AD, FDG-PET can show hypome- tabolism in the temporoparietal regions and/or the posterior cingulum. On microscopy there are cor- tical plaques due to deposition of type A-Beta- amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein (excessive phosphorylation). There is also reduced acetylcholine due to damage to ascending forebrain projection, hence acetylcholinesterase inhibitors (donepezil, galantamine, and rivastig- mine) as options for managing mild to moderate Alzheimer’s disease. Memantine (a NMDA recep- tor antagonist) is reserved for patients with moder- ate—severe Alzheimer’s disease.
A 70-year-old gentleman attends outpatient clinic with his wife. She reports that her husband’s behavior has changed and that he has
become increasingly forgetful over the past year. He has gained 10 kg of weight over the past 6 months. His wife reports that he
has an uncontrollable appetite occasionally eating to the point of vomiting. She also states that he has a lack of interest when
the grandchildren visit. Over the last 4 weeks she has noticed that her husband has become more unsteady on his feet having had a number of falls. On examining him in clinic he has impaired word comprehension, reduced safety awareness on mobilizing and a positive palmomental reflex. There is no tremor, rigidity or shuffling gait. MMSE is 22/30. CT head is shown. Which one of the following is most likely?
a. Depression
b. Hypomania
c. Pick’s disease
d. Lewy body dementia
e. CJD
c. Pick’s disease
Frontotemporal lobar degeneration (FTLD) is
the third most common type of cortical dementia
after Alzheimer’s and Lewy body dementia.
Common features of frontotemporal lobar
dementias include: Onset <65 years, insidious
onset, relatively preserved memory and visuospatial
skills, personality change and social conduct
problems. CT shows cortical loss in the frontal
and temporal lobes, and FDG-PET/CT shows
hypometabolism. There are three recognized
types of FTLD:
1. Frontotemporal dementia (Pick’s disease).
Most common type and is characterized
by personality change and impaired social
conduct. Other common features include
hyperorality, disinhibition, increased appetite,
and perseveration behaviors. Focal
gyral atrophy (“knife-blade” atrophy) is
characteristic of Pick’s disease and is localized to frontal and temporal lobes only.
Microscopic findings include Pick bodies,
gliosis, neurofibrillary tangles, and senile
plaques.
2. Progressive non-fluent aphasia (chronic
progressive aphasia). Patients have nonfluent
speech, they make short utterances
that are agrammatic but comprehension is
relatively preserved.
3. Semantic dementia: Here the patient has a
progressive fluent aphasia but speech lacks
content and conveys little meaning. Unlike
in Alzheimer’s memory is better for recent
rather than remote events.
Frontotemporal lobar degeneration (FTLD) is the third most common type of cortical dementia after Alzheimer’s and Lewy body dementia. Common features of frontotemporal lobar dementias include: Onset <65 years, insidious onset, relatively preserved memory and visuospa- tial skills, personality change and social conduct problems. CT shows cortical loss in the frontal and temporal lobes, and FDG-PET/CT shows hypometabolism. There are three recognized types of FTLD:
1. Frontotemporal dementia (Pick’s disease). Most common type and is characterized by personality change and impaired social conduct. Other common features include hyperorality, disinhibition, increased appe- tite, and perseveration behaviors. Focal gyral atrophy (“knife-blade” atrophy) is characteristic of Pick’s disease and is
localized to frontal and temporal lobes only. Microscopic findings include Pick bodies, gliosis, neurofibrillary tangles, and senile plaques.
2. Progressive non-fluent aphasia (chronic progressive aphasia). Patients have non- fluent speech, they make short utterances that are agrammatic but comprehension is relatively preserved.
3. Semantic dementia: Here the patient has a progressive fluent aphasia but speech lacks content and conveys little meaning. Unlike in Alzheimer’s memory is better for recent rather than remote events.
A 64-year-old man presents with a 6 month history of abnormal behaviors which have been noticed by his wife. He has described
seeing vivid visual hallucinations of clowns in his living room which sometimes talk to him and appear very real. He believes that
he is the head of a circus and is about to go on a world tour although this is not true. At times he is lucid and is fully independent
but at other times he is disorientated in time and place and is unable to perform simple tasks such as preparing food and going to
the shops. His wife thinks that his mood is also lower since the onset of symptoms. He presented in A +E today because of having a
second fall in 2 weeks. There is no history of infective symptoms. He went to see his GP two days ago who thought that he may
have a UTI and prescribed trimethoprim. He has a history of stroke 10 years ago and hypertension and takes warfarin, amlodipine,
and enalapril. Physical examination is unremarkable except for slightly increased tone on the left side compared to the right. Which
one of the following is most likely?
a. Alzheimer’s disease
b. Semantic dementia
c. Hypothyroidism
d. Lewy body dementia
e. Schizophrenia
d. Lewy body dementia
Lewy body dementia is an increasingly recognized
cause of dementia, accounting for up to
20% of cases. The characteristic pathological feature
is alpha-synuclein cytoplasmic inclusions
(Lewy bodies) in the substantia nigra, paralimbic,
and neocortical areas. The relationship between
Parkinson’s disease and Lewy body dementia is
complicated, particularly as dementia is often
seen in Parkinson’s disease. Also, up to 40% of
patients with Alzheimer’s have Lewy bodies.
Neuroleptics should be avoided in Lewy body
dementia as patients are extremely sensitive and
may develop irreversible Parkinsonism. Features
include progressive cognitive impairment, Parkinsonism,
and visual hallucinations (other features
such as delusions and non-visual
hallucinations may also be seen). Two out of
three are needed for diagnosis. The visual hallu-
cinations are often very vivid. He also has a few
supportive features of Lewy body dementia hallucinations
in other modalities, delusions, depression
and repeated falls. Diagnosis is usually
clinical, but SPECT is increasingly used. It is currently
commercially known as a DaT scan. Dopaminergic
iodine-123-I FP-CIT is used as the
radioisotope. The sensitivity of SPECT in diagnosing
Lewy body dementia is around 90% with
a specificity of 100%. Currently, evidence best
supports cholinesterase inhibitors in the treating
of Lewy body dementia. It must be remembered
that these patients have high sensitivity to neuroleptics
so Olanzapine should not be used here.
Lewy body dementia is an increasingly recog- nized cause of dementia, accounting for up to 20% of cases. The characteristic pathological fea- ture is alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic, and neocortical areas. The relationship between Parkinson’s disease and Lewy body dementia is complicated, particularly as dementia is often seen in Parkinson’s disease. Also, up to 40% of patients with Alzheimer’s have Lewy bodies. Neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible Parkinsonism. Features include progressive cognitive impairment, Par- kinsonism, and visual hallucinations (other fea- tures such as delusions and non-visual hallucinations may also be seen). Two out of three are needed for diagnosis. The visual hallu- cinations are often very vivid. He also has a few supportive features of Lewy body dementia hallu- cinations in other modalities, delusions, depres- sion and repeated falls. Diagnosis is usually clinical, but SPECT is increasingly used. It is cur- rently commercially known as a DaT scan. Dopa- minergic iodine-123-I FP-CIT is used as the radioisotope. The sensitivity of SPECT in diag- nosing Lewy body dementia is around 90% with a specificity of 100%. Currently, evidence best supports cholinesterase inhibitors in the treating of Lewy body dementia. It must be remembered that these patients have high sensitivity to neuro- leptics so Olanzapine should not be used here.
A 55-year-old man presents with cognitive decline over a 6-month period. He continues to progress and develops myoclonus and a left
hemiparesis. On examination, he is alert and orientated to time and place but appears easily startled every time you start a sentence. There is bilateral finger-nose and heel-shin dysmetria, mild postural tremor and mild speech slurring. Blood tests are normal including thyroid and liver function. Lumbar puncture: WCC<1, RBC 16, Protein 0.5 g/l, Glucose 3.4 mmol/l, gram stain negative, and no organisms cultured. An EEG demonstrated brief periodic spikes. A MRI head (FLAIR sequence) is shown. Which one of the following is most likely?
a. Alzheimer’s disease
b. Creutzfeldt-Jakob disease
c. Carbon monoxide poisoning
d. Huntington’s disease
e. Pick’s disease
b. Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease is a rapidly progressive
spongiform encephalopathy due to accumulation of prion proteins resistant to proteases. Sporadic
CJD accounts for 85% of cases whereas 10-15%
of cases are familial. The mean age of onset is
65 years, except for new variant CJD which
affects younger patients (mean age 25 years). Features
include dementia, myoclonic jerks (often
stimulus-sensitive), startle response, and less
commonly extrapyramidal signs. New variant
CJD usually has psychological symptoms such
as anxiety, withdrawal and dysphonia. MRI shows
high signal on the cortical sulci surfaces (ribboning)
and increased signal in putamen and caudate
head. EEG shows periodic spikes with sharp
waves in sporadic CJD. CSF profile is usually
normal but positive for 14-3-3 protein.
Creutzfeldt-Jakob disease is a rapidly progressive spongiform encephalopathy due to accumulation
of prion proteins resistant to proteases. Sporadic CJD accounts for 85% of cases whereas 10-15% of cases are familial. The mean age of onset is 65 years, except for new variant CJD which affects younger patients (mean age 25 years). Fea- tures include dementia, myoclonic jerks (often stimulus-sensitive), startle response, and less commonly extrapyramidal signs. New variant CJD usually has psychological symptoms such as anxiety, withdrawal and dysphonia. MRI shows high signal on the cortical sulci surfaces (ribbon- ing) and increased signal in putamen and caudate head. EEG shows periodic spikes with sharp waves in sporadic CJD. CSF profile is usually normal but positive for 14-3-3 protein.
A 81-year-old male experiences progressive cognitive decline over the past 10 years. His wife reports that every 6 months or so
she will notice another significant decrease in his functioning. It is now at the point where he is aggressive and has little short-term memory. Past medical history includes hypertension and percutaneous coronary intervention after a myocardial infarction. Examination findings include poor attention and memory,
mild left hemiparesis (face, arm, and leg), and brisk reflexes throughout with extensor plantar reflex bilaterally and a shuffling
gait. Which one of the following is most appropriate?
a. Referral for subthalamic nucleus deep brain stimulation
**
c. Carotid endarterectomy
d. Commence carbidopa/levodopa
e. Commence memantine
b. Treat cardiovascular risk factors
Vascular dementia is one of the most common
causes of dementia after Alzheimer’s disease, causing
around 15% of cases. The history and findings
are most suggestive of a vascular dementia caused
by multiple strokes, hence management of stroke
risk factors is the primary option as there is no
licensed treatment for it. Targeted treatment is
made more difficult as there are multiple subtypes
of vascular dementia depending on profile of
ischemia: multi-infarct (cortical) dementia, small
vessel (subcortical white matter) dementia, hypoperfusion
dementia (watershed infarcts), hemorrhagic
dementia, CADASIL, and mixed vascularAlzheimer’s
disease type.
Vascular dementia is one of the most common causes of dementia after Alzheimer’s disease, caus- ing around 15% of cases. The history and findings are most suggestive of a vascular dementia caused by multiple strokes, hence management of stroke risk factors is the primary option as there is no licensed treatment for it. Targeted treatment is made more difficult as there are multiple subtypes of vascular dementia depending on profile of ischemia: multi-infarct (cortical) dementia, small vessel (subcortical white matter) dementia, hypo- perfusion dementia (watershed infarcts), hemor- rhagic dementia, CADASIL, and mixed vascular- Alzheimer’s disease type.
A 55-year-old man presents with a 2-month history of weakness in his right arm. He has also noticed that his voice has become softer. He is finding it hard to use door handles and open jars. On two occasions his wife has noticed him stumbling whilst walking. On examination he has fasciculations over his right deltoid muscle and wasting of the interossei muscles of the right hand. Power is 4/5 in right shoulder abduction with absent reflexes in the right arm but present elsewhere. Coordination and sensation are normal with a negative Romberg’s test. Which one of the following is the most likely diagnosis?
a. Cervical myelopathy
b. Diabetic neuropathy
c. Amyotrophic lateral sclerosis
d. Multiple sclerosis
e. Hereditary sensory motor neuropathy
c. Amyotrophic lateral sclerosis
Motor neuron diseases (MND) result in progressive
degeneration of upper motor neurons (Betz
cells) and/or lower motor neurons (anterior horn
cells). Genetic studies have implicated Cu/Zn
superoxide dismutase-1 (SOD1) gene in sporadic
cases. They rarely presents before 40 years of
age. Various patterns/subtypes are recognized
including: amyotrophic lateral sclerosis (Lou Gehrig
disease), progressive bulbar palsy (bulbar onset
ALS), primary lateral sclerosis, spinal muscular
atrophy, X-linked spinobulbar muscular atrophy
(Kennedy disease) and hereditary spastic parapar-
esis. ALS is the most common form and may
present with limb symptoms (tripping, foot drop,
wasting of the small hand muscles, wrist drop) in
75% or bulbar symptoms (slurred speech, hoarseness,
decreased volume of speech, aspirating/choking
on meals) in 25% of cases. Progression of
disease results in muscle atrophy, fasciculations,
spasticity, muscle cramps, voice changes, dysphagia,
dysarthria, and drooling. Other clues which point towards a diagnosis of motor neuron disease
include absence of sensory signs/symptoms, both
UMN and LMN symptoms, no cerebellar signs,
no ocular signs and abdominal reflexes are usually
preserved and sphincter dysfunction is a late feature.
MRI is usually performed to exclude the differential
diagnosis of cervical cord compression or
cranial lesion, and shows T2 hyperintensity (better
seen on FLAIR) along the length of the corticospinal
tract. The diagnosis of motor neuron disease is
clinical, but EMG and nerve conduction studies
will show normal sensory conduction with abnormal
spontaneous (fasciculation) and evoked muscle
potentials. Riluzole is the only drug that has been
proven to demonstrate a disease modifying effect
in motor neurone disease, increasing survival from
diagnosis from 12 to 15 months and should be
started; therapies to reduce oxidative stress such
as addition of vitamin E and N-acetylcysteine
(NAC) are not recommended. Non-invasive ventilation
is the only other therapy that seems to prolong
life expectancy but only if the patient can
tolerate greater than 4 h of NIV per day and does
not have severe bulbar dysfunction. NIV is recommended
when the patient has developed signs of
respiratory distress, type 2 respiratory failure,
FVC< 50% or the patient has reported orthopnea/nocturnal
hypoventilation. However, patients
with severe bulbar palsy or cognitive impairment
are excluded. Tracheostomy and long term invasive
mechanical ventilation have been used in
selected cases with respiratory deterioration
despite being largely neurologically intact. Prognosis
poor: 50% of patients die within 3 years
Motor neuron diseases (MND) result in progres- sive degeneration of upper motor neurons (Betz cells) and/or lower motor neurons (anterior horn cells). Genetic studies have implicated Cu/Zn superoxide dismutase-1 (SOD1) gene in sporadic cases. They rarely presents before 40 years of age. Various patterns/subtypes are recognized including: amyotrophic lateral sclerosis (Lou Geh- rig disease), progressive bulbar palsy (bulbar onset ALS), primary lateral sclerosis, spinal muscular atrophy, X-linked spinobulbar muscular atrophy (Kennedy disease) and hereditary spastic parapar- esis. ALS is the most common form and may present with limb symptoms (tripping, foot drop, wasting of the small hand muscles, wrist drop) in 75% or bulbar symptoms (slurred speech, hoarse- ness, decreased volume of speech, aspirating/chok- ing on meals) in 25% of cases. Progression of disease results in muscle atrophy, fasciculations, spasticity, muscle cramps, voice changes, dyspha- gia, dysarthria, and drooling. Other clues which
point towards a diagnosis of motor neuron disease include absence of sensory signs/symptoms, both UMN and LMN symptoms, no cerebellar signs, no ocular signs and abdominal reflexes are usually preserved and sphincter dysfunction is a late fea- ture. MRI is usually performed to exclude the dif- ferential diagnosis of cervical cord compression or cranial lesion, and shows T2 hyperintensity (better seen on FLAIR) along the length of the corticosp- inal tract. The diagnosis of motor neuron disease is clinical, but EMG and nerve conduction studies will show normal sensory conduction with abnor- mal spontaneous (fasciculation) and evoked muscle potentials. Riluzole is the only drug that has been proven to demonstrate a disease modifying effect in motor neurone disease, increasing survival from diagnosis from 12 to 15 months and should be started; therapies to reduce oxidative stress such as addition of vitamin E and N-acetylcysteine (NAC) are not recommended. Non-invasive ven- tilation is the only other therapy that seems to pro- long life expectancy but only if the patient can tolerate greater than 4 h of NIV per day and does not have severe bulbar dysfunction. NIV is recom- mended when the patient has developed signs of respiratory distress, type 2 respiratory failure, FVC<50% or the patient has reported orthop- nea/nocturnal hypoventilation. However, patients with severe bulbar palsy or cognitive impairment are excluded. Tracheostomy and long term inva- sive mechanical ventilation have been used in selected cases with respiratory deterioration despite being largely neurologically intact. Prog- nosis poor: 50% of patients die within 3 years
An 18-month-old girl presents with leg weakness. Tremors, primarily of the hands, had
been noted since 4 months of age. She was
crawling by 9 months of age and cruising
about the furniture by 12 months. Her language development was normal. Her 4-yearold sister was developing normally. Cranial
nerve examination was normal, and specifically, fasciculations of the tongue were not
noted. She was able to sit, crawl, and pull to a
stand. She could walk holding onto furniture
but could not walk independently. Deep tendon reflexeswere absent throughout, and there
were no Babinski signs. Sensory examination
was normal. Which one of the following is
the next appropriate test?
a. Serum ceruloplasmin
b. Electromyography
c. Nerve conduction studies
d. Survival motor neuron gene testing
e. MRI head
d. Survival motor neuron gene testing
Spinal muscular atrophy is a congenital lower
motor neuron disorder manifesting as progressive,
symmetric proximal muscular weakness occurring
in 1 in 6000 to 1 in 10,000 births (second most
common autosomal recessive disease in humans
after cystic fibrosis). It is the leading inherited
cause of infant death. Spinal muscular atrophy is
classified clinically by the age at symptom onset
and disease severity into type I (WerdnigHoffman
disease, acute), type II (intermediate
form, usually 7-18 months old and can sit unsupported
but can’t walk independently), type III
(Kugelberg-Welander disease, mildest form, presents
>18 months and able to achieve independent
walking), and type IV SMA (adult-onset). Spinal
muscular atrophy is inherited in autosomal recessive
fashion or is sporadic. Mutations or deletions
in the telomeric SMN (survival of motor neuron)
gene occur in most patients. The loss of functional
SMN protein results in premature neuronal cell
death. The SMN protein has a role in cardiac
development. If the history and physical examination suggest spinal muscular atrophy, a
positive DNA test for deletion of the survival
motor neuron gene eliminates the need for electrophysiological
testing and muscle biopsy. However,
the SMN gene is deleted only in 96% of
patients, serum creatine kinase activity may be 1
to 2 times normal. Electromyography reveals large
motor units; nerve conduction velocities and sensory
conduction times are normal, ruling out
motor neuropathies. Muscle biopsy reveals group
atrophy of type 1 and type 2 muscle fibers as
opposed to the normal checkerboard pattern. In
the most severe cases (Type I), children never gain
the ability to sit unsupported and severe respiratory
problems mean children rarely survive
beyond two years of age. Type II SMA may
shorten life expectancy, but improvements in care
standards mean the majority of people can live
long, fulfilling, and productive lives. Survival into
adulthood is now expected. Life expectancy is usually
unaffected in Types III and IV.
Spinal muscular atrophy is a congenital lower motor neuron disorder manifesting as progressive, symmetric proximal muscular weakness occurring in 1 in 6000 to 1 in 10,000 births (second most common autosomal recessive disease in humans after cystic fibrosis). It is the leading inherited cause of infant death. Spinal muscular atrophy is classified clinically by the age at symptom onset and disease severity into type I (Werdnig- Hoffman disease, acute), type II (intermediate form, usually 7-18 months old and can sit unsup- ported but can’t walk independently), type III (Kugelberg-Welander disease, mildest form, pre- sents >18 months and able to achieve independent walking), and type IV SMA (adult-onset). Spinal muscular atrophy is inherited in autosomal reces- sive fashion or is sporadic. Mutations or deletions in the telomeric SMN (survival of motor neuron) gene occur in most patients. The loss of functional SMN protein results in premature neuronal cell death. The SMN protein has a role in cardiac development. If the history and physical examination suggest spinal muscular atrophy, a positive DNA test for deletion of the survival motor neuron gene eliminates the need for elec- trophysiological testing and muscle biopsy. How- ever, the SMN gene is deleted only in 96% of patients, serum creatine kinase activity may be 1 to 2 times normal. Electromyography reveals large motor units; nerve conduction velocities and sen- sory conduction times are normal, ruling out motor neuropathies. Muscle biopsy reveals group atrophy of type 1 and type 2 muscle fibers as opposed to the normal checkerboard pattern. In the most severe cases (Type I), children never gain the ability to sit unsupported and severe respira- tory problems mean children rarely survive beyond two years of age. Type II SMA may shorten life expectancy, but improvements in care standards mean the majority of people can live long, fulfilling, and productive lives. Survival into adulthood is now expected. Life expectancy is usu- ally unaffected in Types III and IV.
A 41-year-old man presents with confusion
and headaches for the last few weeks. He
was diagnosed with HIV 15 years ago and
has been stable on highly active antiretroviral
treatment. Other past medical history
includes an episode of Pneumocystis jirovecii
pneumonia 1 year ago. His latest CD4 count
is 29 cells/μl. An MRI (T1 C+) is shown. The
enhancing lesions on MRI show increased
uptake on Thallium-201 Chloride SPECT
scan. Which one of the following is likely to
be required?
a. Sulfadiazine + pyrimethamine
b. Dexamethasone
c. Methotrexate
d. Amphotericin B
e. Image guided aspiration and intravenous
antibiotics.
c. Methotrexate
Common focal cerebral lesions in HIV patients are
toxoplasmosis (50%), primary CNS lymphoma
(30%), and less commonly cerebral tuberculosis.
Typically, PCNSL in immunocompetent individuals
(whether HIV positive or not) will appear as a
single homogenously enhancing lesion, or spread
across the corpus callosum (butterfly pattern)
and has a dramatic response to dexamethasone
treatment hence is easier to differentiate from
infection. In immunocompromised patients, however,
imaging appearances of PCNSL are more
variable—with smaller lesions and faster growth
outstripping blood supply leading to necrosis
(ring-enhancing lesions) and making them challenging
to differentiate from other ring-enhancing
lesions seen in immunocompromised individuals
such as toxoplasma (multiple lesions) and tuberculosis
(usually only single abscess). Several limitations
of diagnostic testing also complicate
matters and are worthy of note. Firstly, even when
primary CNS lymphoma presents with its classical,
homogeneously enhancing imaging appearance a
cytological diagnosis is still required before treatment
with methotrexate can start. In this scenario,
if there is little intracranial mass effect lumbar
puncture can be performed and CSF cytology,
flow cytometry, PCR for immunoglobin clonal
gene rearrangements (to establish monoclonality)
and EBV PCR (80% positive in AIDS-related
PCNSL). Despite this, CSF is often nondiagnostic
and serial samples may be required or
alternatively brain biopsy which is the gold standard.
Additionally, many patients receive dexamethasone due to raised ICP or focal deficits
which (i) further reduces the chance of diagnostic
LP and (ii) may cause the lesion to “disappear” and
prevent accurate brain biopsy. In those AIDS
patients in whom diagnostic uncertainty between
cerebral toxoplasma and PCNSL remains after
non-diagnostic CSF, brain biopsy should be
considered in the context of negative serological
screening for toxoplasma and thallium-enhanced
SPECT scan results (negative in toxoplasma, positive
in PCNSL). Treatment for toxoplasma
includes sulfadiazine and pyrimethamine, whereas
it is methotrexate chemotherapy for PCNSL (or
radiotherapy as second-line therapy).
Common focal cerebral lesions in HIV patients are toxoplasmosis (50%), primary CNS lymphoma (30%), and less commonly cerebral tuberculosis. Typically, PCNSL in immunocompetent individ- uals (whether HIV positive or not) will appear as a single homogenously enhancing lesion, or spread across the corpus callosum (butterfly pattern) and has a dramatic response to dexamethasone treatment hence is easier to differentiate from infection. In immunocompromised patients, how- ever, imaging appearances of PCNSL are more variable—with smaller lesions and faster growth outstripping blood supply leading to necrosis (ring-enhancing lesions) and making them chal- lenging to differentiate from other ring-enhancing lesions seen in immunocompromised individuals such as toxoplasma (multiple lesions) and tubercu- losis (usually only single abscess). Several limita- tions of diagnostic testing also complicate matters and are worthy of note. Firstly, even when primary CNS lymphoma presents with its classical, homogeneously enhancing imaging appearance a cytological diagnosis is still required before treat- ment with methotrexate can start. In this scenario, if there is little intracranial mass effect lumbar puncture can be performed and CSF cytology, flow cytometry, PCR for immunoglobin clonal gene rearrangements (to establish monoclonality) and EBV PCR (80% positive in AIDS-related PCNSL). Despite this, CSF is often non- diagnostic and serial samples may be required or alternatively brain biopsy which is the gold stan- dard. Additionally, many patients receive dexamethasone due to raised ICP or focal deficits which (i) further reduces the chance of diagnostic LP and (ii) may cause the lesion to “disappear” and prevent accurate brain biopsy. In those AIDS patients in whom diagnostic uncertainty between cerebral toxoplasma and PCNSL remains after non-diagnostic CSF, brain biopsy should be considered in the context of negative serological screening for toxoplasma and thallium-enhanced SPECT scan results (negative in toxoplasma, pos- itive in PCNSL). Treatment for toxoplasma includes sulfadiazine and pyrimethamine, whereas it is methotrexate chemotherapy for PCNSL (or radiotherapy as second-line therapy).
A 31-year-old man was diagnosed with HIV
5 years ago and had been taking highly active
antiretroviral therapy until 8 months ago when
he decided to stop. He had been doing well on
highly active antiretroviral therapy, but stopped
taking hismedications 8months ago because he
thought that he would be better off. Two
months ago, he was successfully treated for
Pneumocystis carinii pneumonia. He now presents with confusion and speech deficit. His
CD4 count is 155/ul. MRI appearances are
shown below. CSF PCR is positive for JC virus.
Which one of the following is most likely?
a. Adrenoleukodystrophy
b. Multiple sclerosis
c. Subacute sclerosing panencephalitis
d. Progressive multifocal leukoencephalopathy
e. AIDS dementia complex
d. Progressive multifocal leukoencephalopathy
Adrenoleukodystrophy, MS, SSPE, are all demyelinating
diseases, but PML is the only one linked
to JC virus in the context of immunocompromised
patients (e.g. AIDS, post-transplantation). Generalized
CNS disorders in patients with HIV include
viral encephalitis, Cryptococcus meningitis, PML
and AIDS dementia complex. Progressive multifocal
leukoencephalopathy (PML) results in widespread
demyelination due to infection of oligodendrocytes
by JC virus (a polyoma DNA virus; papovavirus)
resulting in subacute onset of behavioral changes,
speech,motor,andvisualimpairment.OnCTthis
may appear as single or multiple lesions, no mass
effect, no enhancement but MRI clearly shows widespread
high T2 and FLAIR signal. Encephalitis may
be due to CMV or HIV itself rather than HSV.
Cryptococcus is the most common fungal infection
of CNS and presents with meningism, seizures, and
focal neurological deficit with raised CSF pressure
on LP and positive India Ink staining. AIDS dementia
complex is caused by HIV itself (i.e. HIV encephalopathy/encephalitis)
and correlates with high viral
loads and the duration of the infection. With the use
of HAART, a milder form of cognitive dysfunction,
minor cognitive motor disorder (MCMD) has
become common. MCMD accounts for approximately
30% of patients with HIV infection, while
HIV-associated dementia accounts for less than
10%. Imaging findings include widespread cortical
atrophy, ventricular enlargement and white matter
damage.
Adrenoleukodystrophy, MS, SSPE, are all demye- linating diseases, but PML is the only one linked to JC virus in the context of immunocompromised patients (e.g. AIDS, post-transplantation). General- ized CNS disorders in patients with HIV include viral encephalitis, Cryptococcus meningitis, PML and AIDS dementia complex. Progressive multifocal leukoencephalopathy (PML) results in widespread demyelination due to infection of oligodendrocytes by JC virus (a polyoma DNA virus; papovavirus) resulting in subacute onset of behavioral changes, speech, motor, and visual impairment. On CT this may appear as single or multiple lesions, no mass effect, no enhancement but MRI clearly shows wide- spread high T2 and FLAIR signal. Encephalitis may be due to CMV or HIV itself rather than HSV. Cryptococcus is the most common fungal infection of CNS and presents with meningism, seizures, and focal neurological deficit with raised CSF pressure on LP and positive India Ink staining. AIDS demen- tia complex is caused by HIV itself (i.e. HIV enceph- alopathy/encephalitis) and correlates with high viral loads and the duration of the infection. With the use of HAART, a milder form of cognitive dysfunction, minor cognitive motor disorder (MCMD) has become common. MCMD accounts for approxi- mately 30% of patients with HIV infection, while HIV-associated dementia accounts for less than 10%. Imaging findings include widespread cortical atrophy, ventricular enlargement and white matter damage.
A 43-year-old man has been having nightly,
unilateral, throbbing headaches with the pain
focused at the back of his left eye. They have
been occurring daily for the past week. The
patient recalls having had a similar headache
5 years ago that lasted for several weeks. The
patient has noticed that the headache is associated with lacrimation and nasal congestion.
Which one of the following would be appropriate next in acute management?
a. Dihydroergotamine
b. Glyceryl trinitrate
c. Indometacin
d. Inhaled 100% oxygen
e. Propanolol
d. Inhaled 100% oxygen
This patient describes features of cluster headache,
which is most likely to be terminated with
inhalation of pure oxygen within minutes. Cluster
headaches usually occur at night when the patient
is asleep, and so practical access to the oxygen
tank is possible. Propranolol is a β-adrenergicblocking
agent that is useful in the prophylaxis
of some vascular headaches, but it is of no value
in aborting a cluster headache. Dihydroergotamine
suppositories may abort some vascular
headaches, but they do not have as obvious an
effect in cluster as in classic or common migraine
syndromes.
This patient describes features of cluster head- ache, which is most likely to be terminated with inhalation of pure oxygen within minutes. Cluster headaches usually occur at night when the patient is asleep, and so practical access to the oxygen tank is possible. Propranolol is a β-adrenergic- blocking agent that is useful in the prophylaxis of some vascular headaches, but it is of no value in aborting a cluster headache. Dihydroergota- mine suppositories may abort some vascular headaches, but they do not have as obvious an effect in cluster as in classic or common migraine syndromes.
A 18-year-old female presents with a severe
right-sided throbbing headache associated
with nausea, vomiting, and photophobiawhich
failed to respond to ibuprofen. There are no
other neurological features in the history.
She has been having similar headaches 3-4
times per month for the past year. Her mother
had a similar problem. Her examination is
normal. Which one of the following would
be appropriate next in acute management?
a. Amitriptyline
b. Propanolol
c. Sumatriptan
d. Topiramate
e. Verapamil
c. Sumatriptan
This patient has common migraine (migraine
without aura). Of the agents listed, only sumatriptan
is generally considered of use to abort a
headache. The triptans are a group of medications
that act as agonists at serotonergic receptors
(specifically, the 5HT-1 receptors), and
they have been found to be very effective at stopping
migraine headaches. Additional agents that
might be of benefit in abortive therapy include
ibuprofen,
aspirin,
acetaminophen,
isometheptene, or ergotamine. Several medications
are effective as prophylactic agents in the
treatment of migraine. These include amitriptyline
hydrochloride, propranolol, verapamil, and
valproate. Verapamil and amitriptyline may be
used as prophylactic (preventative) therapy.
Most experts recommend initiating prophylactic
therapy only when headaches occur at least one
to two times per month. Metoclopramide hydrochloride,
sumatriptan, and ergotamine tartrate
are appropriately used to treat an acute attack
of migraine and should not be prescribed on a
daily basis. Daily use of these medications can
establish a rebound syndrome that results in a
chronic daily headache.
This patient has common migraine (migraine without aura). Of the agents listed, only suma- triptan is generally considered of use to abort a headache. The triptans are a group of medica- tions that act as agonists at serotonergic recep- tors (specifically, the 5HT-1 receptors), and they have been found to be very effective at stop- ping migraine headaches. Additional agents that might be of benefit in abortive therapy include ibuprofen, aspirin, acetaminophen, isometheptene, or ergotamine. Several medica- tions are effective as prophylactic agents in the treatment of migraine. These include amitripty- line hydrochloride, propranolol, verapamil, and valproate. Verapamil and amitriptyline may be used as prophylactic (preventative) therapy. Most experts recommend initiating prophylactic therapy only when headaches occur at least one to two times per month. Metoclopramide hydro- chloride, sumatriptan, and ergotamine tartrate are appropriately used to treat an acute attack of migraine and should not be prescribed on a daily basis. Daily use of these medications can establish a rebound syndrome that results in a chronic daily headache.
A 45-year-old man is referred urgently to
hospital with a severe headache. The pain
had started gradually three days before and
was now severe. The patient reported the
headache was exacerbated by an upright posture with relief obtained by lying flat. Since
the headache started the patient had been
unable to stand for more than a few minutes
at a time but was reasonably comfortable
when lying down. The patient denied any
focal neurological symptoms and was constitutionally well. Clinical examination did not
demonstrate any focal neurological signs or
features of meningism. CT brain: no evidence of intra-axial or extra-axial bleeding;
no space occupying lesion; no hydrocephalus.
MRI brain with gadolinium: diffuse pachymeningeal enhancement without leptomeningeal
enhancement; subtle downward displacement
of brain on sagittal views. Which one of the
following would be appropriate next in acute
management?
a. Epidural blood patch
b. Flat bed rest
c. Laminectomy dural repair and sealant
d. Lumbar puncture
e. MRI whole spine with STIR
a. Epidural blood patch
The clinical presentation is consistent with
spontaneous intracranial hypotension, in particular
given the strong relationship of pain to
upright posture. The patient has known connective
tissue disease and so is at increased risk
for this diagnosis. The MRI brain with gadolin-
ium images are characteristic for spontaneous
intracranial hypotension and so confirm the
diagnosis. Lumbar puncture is often difficult
in spontaneous intracerebral hypotension and
would not change initial management unless
CSF infection needed excluding. Post lumbar puncture headache (PLPH), a common complication
of a lumbar puncture (30%) and is
thought to be caused by excess leakage of cerebrovascular
fluid causing a relatively low intracranial
pressure. Risk factors include: factors
which may contribute to headache; increased
needle size; direction of bevel; not replacing
the stylet; increased number of LP attempts;
factors that do not contribute to headache;
increased volume of CSF removed; bed rest following
procedure; increased fluid intake post
procedure; opening pressure of CSF; and position
of patient. Management is conservative,
including administering analgesia and sufficient
fluids and caffeine. If this fails to resolve the
headache after 72 h an epidural blood patch.
The clinical presentation is consistent with spontaneous intracranial hypotension, in partic- ular given the strong relationship of pain to upright posture. The patient has known con- nective tissue disease and so is at increased risk for this diagnosis. The MRI brain with gadolin- ium images are characteristic for spontaneous intracranial hypotension and so confirm the diagnosis. Lumbar puncture is often difficult in spontaneous intracerebral hypotension and would not change initial management unless CSF infection needed excluding. Post lumbar
puncture headache (PLPH), a common compli- cation of a lumbar puncture (30%) and is thought to be caused by excess leakage of cere- brovascular fluid causing a relatively low intra- cranial pressure. Risk factors include: factors which may contribute to headache; increased needle size; direction of bevel; not replacing the stylet; increased number of LP attempts; factors that do not contribute to headache; increased volume of CSF removed; bed rest fol- lowing procedure; increased fluid intake post procedure; opening pressure of CSF; and posi- tion of patient. Management is conservative, including administering analgesia and sufficient fluids and caffeine. If this fails to resolve the headache after 72 h an epidural blood patch.
A 26-year-old female presents with difficulty
walking and complains of problems with her
vision in her right eye. She had an episode of
diarrhea a week ago, but has no other relevant
past medical history apart from problems with
her left eye 3 months earlier which had
resolved. On examination there is a right relative afferent papillary defect. Visual acuity and
color vision are 6/6 (20/20) with 17/17 Ishihara
plates on the left, and 6/60 (20/200) with 0/17
Ishihara plates on the right. She reports no diplopia with a full range of eye movements, no
facial weakness and normal facial sensation.
Fundoscopy was unremarkable. Examination
revealed 2/5 power on the left arm and leg in
all movements; and 4/5 in all movements in
right arm and leg, brisk reflexes bilaterally with
extensor plantar responses. There is patchy
loss of sensation to cotton wool on right
lateralwrist and anterior aspectleftlateral shin.
Anal tone and saddle sensation are intact. MRI
brain is normal and MRI spine (Sagittal T2
+T1 with gad) shown below. CSF shows
WCC 12/mm3
, RBC <1/mm3
, Glucose
4.5 mmol/dl, Protein 0.9 g/l, and negative for
oligoclonal bands.Which one of the following
tests is likely to be positive?
a. Anti-acetylcholine receptor antibody
b. Anti-aquaporin 4 antibody
c. Anti-muscle specific kinase antibody
d. Anti-voltage gated calcium channel antibody
e. Anti-voltage gated potassium channel
antibody
b. Anti-aquaporin 4 antibody
Neuromyelitis optica (NMO; Devic’s disease) is
monophasic or relapsing-remitting demyelinating
CNS disorder Although previously thought to be a
variant of multiple sclerosis, it is now recognized to
be a distinct disease, particularly prevalent in Asian
populations. Features of optic neuritis include unilateral
decrease in visual acuity over, poor discrimination
of colors, “red desaturation,” pain worse
on eye movement, relative afferent pupillary
defect and a central scotoma. Diagnosis of
NMO requires bilateral optic neuritis, transverse
myelitis and 2 of the following:
1. Spinal cord lesion involving three or more
spinal levels (longitudinally extensive transverse
myelitis)
2. Initially normal MRI brain
3. Aquaporin 4 positive serum antibody (positive
in 80%)
Adults are especially likely to develop a
pattern more typical of relapsing-remitting MS
after an initial episode of neuromyelitis optica.
Management of acute episodes is with prednisolone
or plasma exchange, and recovery from acute
optic neuritis usually takes 4-6 weeks. Long
term treatment is with immunosuppression
(e.g. azothiaprine, rituximab). Disease modifying
drugs used in MS are not used in the treatment
of NMO.
Neuromyelitis optica (NMO; Devic’s disease) is monophasic or relapsing-remitting demyelinating CNS disorder Although previously thought to be a variant of multiple sclerosis, it is now recognized to be a distinct disease, particularly prevalent in Asian populations. Features of optic neuritis include uni- lateral decrease in visual acuity over, poor discrim- ination of colors, “red desaturation,” pain worse on eye movement, relative afferent pupillary defect and a central scotoma. Diagnosis of NMO requires bilateral optic neuritis, transverse myelitis and 2 of the following:
1. Spinal cord lesion involving three or more spinal levels (longitudinally extensive trans- verse myelitis)
2. Initially normal MRI brain
3. Aquaporin 4 positive serum antibody (pos-
itive in 80%)
Adults are especially likely to develop a pattern more typical of relapsing-remitting MS after an initial episode of neuromyelitis optica. Management of acute episodes is with predniso- lone or plasma exchange, and recovery from acute optic neuritis usually takes 4-6 weeks. Long term treatment is with immunosuppression (e.g. azothiaprine, rituximab). Disease modifying drugs used in MS are not used in the treatment of NMO.
A 10-year-old girl presents with subacute
mental status change and left arm weakness.
She had a viral illness 1 week ago. On examination she appears drowsy. She has a left
sided hemiparesis with bilateral nystagmus.
Fundoscopy reveals papilledema. There are
no skin rashes. MRI head FLAIR sequence
is shown. MRI spine showed a longitudinally
extensive transverse myelitis. Which one of
the following is most likely?
a. Multiple sclerosis
b. Acute disseminating encephalomyelitis
c. Neurosarcoidosis
d. Neuromyelitis optica
e. Systemic lupus erythematosis
f. Lyme disease
b. Acute disseminating encephalomyelitis
Acute disseminated encephalomyelitis (ADEM,
postinfectious encephalomyelitis) is a demyelinating
disease of the brain, brainstem, and spinal
cord that is indistinguishable from MS on MRI.
It is, however, monophasic, meaning that it
occurs acutely on a single occasion and not in a
recurrent fashion like MS. It usually develops
within days or weeks of a viral illness (e.g. scarlet
fever, measles, chickenpox) or immunization. It is
characterized by an acute onset of multifocal neurological
symptoms with rapid deterioration,
which can be fatal if untreated. Non-specific signs
such as headache, fever, nausea, and vomiting
may also accompany the onset of illness. Motor
and sensory deficits are frequent and there may
also be brainstem involvement including occulomotor
defects. The diagnosis is suggested by the
MRI or CT picture of rapidly evolving white
matter damage associated with a high ESR and
a CSF under increased pressure with elevated
red cell and white cell counts and elevated protein
content. The CSF glucose content is usually
normal. Management involves intravenous glucocorticoids
and the consideration of IV immunoglobulins
where this fails.
Acute disseminated encephalomyelitis (ADEM, postinfectious encephalomyelitis) is a demyelin- ating disease of the brain, brainstem, and spinal cord that is indistinguishable from MS on MRI. It is, however, monophasic, meaning that it occurs acutely on a single occasion and not in a recurrent fashion like MS. It usually develops within days or weeks of a viral illness (e.g. scarlet fever, measles, chickenpox) or immunization. It is characterized by an acute onset of multifocal neu- rological symptoms with rapid deterioration, which can be fatal if untreated. Non-specific signs such as headache, fever, nausea, and vomiting may also accompany the onset of illness. Motor and sensory deficits are frequent and there may also be brainstem involvement including occulo- motor defects. The diagnosis is suggested by the MRI or CT picture of rapidly evolving white matter damage associated with a high ESR and a CSF under increased pressure with elevated red cell and white cell counts and elevated protein content. The CSF glucose content is usually normal. Management involves intravenous glu- cocorticoids and the consideration of IV immu- noglobulins where this fails.
A 35-year-old female presents with three days of increasing weakness in the right arm and reduced visual acuity in the left eye. She has had a similar episode 2 years ago which she recovered from completely. On examination
she has weakness in wrist extension and finger abduction in the left hand and visual acuity in the left eye was measured at 6/24 with an associated reduction in color saturation. Blood
tests were unremarkable. Her MRI scan is shown (Axial T1 with contrast and FLAIR). Which one of the following options should be used in acute management?
a. Commence high dose oral prednisone
and wean over a month
b. IV methylprednisolone
c. Natalizumab infusion
d. Interferon beta
e. Biopsy
b. IV methylprednisolone
Multiple sclerosis is a chronic, predominantly
autoimmune demyelinating disease of the central
nervous system (CNS) characterized by subacute
neurologic deficit (relapses last at least 24 h) correlating
with CNS lesions separated in time and
space, excluding other possible disease. Peak presentation
at 20-40 years. Subtypes include:
Relapsing-remitting MS (80%): relapses followed
by complete or near-complete recovery, most of
which later transition to secondary progressive
MS during which there progression of disability
with few or no relapses. Primary progressive
MS (20%) shows progression of disability from
the onset, rarely with relapses. Presentation is
with optic neuritis, neurological symptoms
related to transverse myelitis (e.g. bladder dysfunction,
myelopathy) or intracranial plaques of
demyelination. Lhermitte’s sign is an electrical
sensation radiating down the spine when the neck
is passively flexed and is believed to signify spinal
cord demyelination. Uhthoff’s phenomenon
describes the worsening of MS symptoms with
higher body temperature (e.g. hot weather, exercise,
fever). Eye signs include nystagmus, RAPD (Marcus Gunn pupil), and internuclear opthalmoplegia.
Atypical presentations include trigeminal
neuralgia, seizures and acute psychiatric
disturbance. Diagnosis of MS requires demonstration
of lesions disseminated in time and space
(McDonald criteria), hence after a single episode
it is termed “clinically indeterminate syndrome”
(unless there is past medical history and old and
newer lesions on MRI). If there are >3 whitematter
lesions on MRI the 5-year risk of developing
multiple sclerosis is c. 50%. MRI features of
demyelinating plaques include T1 hypointense
(black holes), T2 and FLAIR hyperintense, and
if new/active inflammation they enhance on T1
+ GAD sequences. T2/FLAIR imaging may also
show linear regions of perivenous demyelination
perpendicular to the corpus callosum known as
Dawson’s fingers. Other investigations include
lumbar puncture which may show a raised protein
and in 80% positive for oligoclonal bands (in CSF
but not in serum) signifying increased intrathecal
synthesis of IgG. Visual evoked potentials may be
delayed, but well preserved waveform. Treatment
in multiple sclerosis is focused at reducing duration
of relapses (acute) and reducing the frequency
of relapses (disease modifying drugs) as
there is no cure. For acute relapses high dose steroids
(e.g. oral or IV methylprednisolone) may be
given for 3-5 days to shorten the length of an
acute relapse, although they do not alter the
degree of recovery (i.e. whether a patient returns
to baseline function).
Multiple sclerosis is a chronic, predominantly autoimmune demyelinating disease of the central nervous system (CNS) characterized by subacute neurologic deficit (relapses last at least 24 h) cor- relating with CNS lesions separated in time and space, excluding other possible disease. Peak pre- sentation at 20-40 years. Subtypes include: Relapsing-remitting MS (80%): relapses followed by complete or near-complete recovery, most of which later transition to secondary progressive MS during which there progression of disability with few or no relapses. Primary progressive MS (20%) shows progression of disability from the onset, rarely with relapses. Presentation is with optic neuritis, neurological symptoms related to transverse myelitis (e.g. bladder dys- function, myelopathy) or intracranial plaques of demyelination. Lhermitte’s sign is an electrical sensation radiating down the spine when the neck is passively flexed and is believed to signify spinal cord demyelination. Uhthoff’s phenomenon describes the worsening of MS symptoms with higher body temperature (e.g. hot weather, exer- cise, fever). Eye signs include nystagmus, RAPD
(Marcus Gunn pupil), and internuclear opthal- moplegia. Atypical presentations include trigem- inal neuralgia, seizures and acute psychiatric disturbance. Diagnosis of MS requires demon- stration of lesions disseminated in time and space (McDonald criteria), hence after a single episode it is termed “clinically indeterminate syndrome” (unless there is past medical history and old and newer lesions on MRI). If there are >3 white- matter lesions on MRI the 5-year risk of develop- ing multiple sclerosis is c. 50%. MRI features of demyelinating plaques include T1 hypointense (black holes), T2 and FLAIR hyperintense, and if new/active inflammation they enhance on T1 + GAD sequences. T2/FLAIR imaging may also show linear regions of perivenous demyelination perpendicular to the corpus callosum known as Dawson’s fingers. Other investigations include lumbar puncture which may show a raised protein and in 80% positive for oligoclonal bands (in CSF but not in serum) signifying increased intrathecal synthesis of IgG. Visual evoked potentials may be delayed, but well preserved waveform. Treatment in multiple sclerosis is focused at reducing dura- tion of relapses (acute) and reducing the fre- quency of relapses (disease modifying drugs) as there is no cure. For acute relapses high dose ste- roids (e.g. oral or IV methylprednisolone) may be given for 3-5 days to shorten the length of an acute relapse, although they do not alter the degree of recovery (i.e. whether a patient returns to baseline function).
A 43-year-old female presents with a second
episode of loss of sensation in her left anterior
thigh and right foot. This is her second episode
within the past 4 months. She had recently
reported an episode of left anterior shin numbness 1 year ago, when anMRI with gadolinium
8 NEUROLOGY AND STROKE 131
demonstrated “spots in her spinal cord” and
she was diagnosed with transverse myelitis.
Her past medical history also includes ulcerative colitis, diagnosed aged 27years old and primary sclerosing cholangitis. Routine bloods
are normal except for mild derangement of
liver function tests.Which one of the following
is most appropriate?
a. Interferon beta
b. Glatiramer acetate
c. Fingolimod
d. Natalizumab
e. Mitoxanthrone
b. Glatiramer acetate
Clinical and imaging features (focal lesion that
does not exceed two vertebral segments in length
and does not affect more than half the crosssectional
area of the cord) suggest relapsingremitting
MS with plaques in the cervical spinal
cord. In general, current evidence suggests starting
disease-modifying therapy at the point of diagnosis
of relapsing-remitting forms of MS since
damage continues to occur (based on MRI studies)
even between relapses. As such, disease modifying
therapy is used in those with “active” relapsing MS
defined either as 2 or more relapses in the last
2 years or one recent relapse and/or signs of new
lesions on MRI. Interferon beta 1a or 1b can be
used in relapsing remitting MS, secondary progressive
MS if there are still significant relapses
and clinically isolated syndrome, but is contraindicated
with deranged liver function. Glatiramer
acetate may act as a myelin decoy for the immune system and is not contraindicated in liver dysfunction.
Fingolimod is the only oral drug and is a
sphingosine 1 phosphate receptor modulator
affecting lymphocyte migration that has been
proven to reduce number of relapses and slow
the rate of number of new MRI lesions. However,
it was also associated with increased incidence of
varicella zoster, tumor formation, and progressive
multifocal leucoencephalopathy (PML) hence
reserved for patients who fail 1st line therapies.
Similarly, while natalizumab is effective in modifying
multiple sclerosis progression, it is also associated
with PML and not considered a 1st line
treatment. Mitoxanthrone is a chemotherapy
agent that inhibits DNA synthesis and repair,
associated with significant cardiotoxicity, reserved
as last resort. Other problems may also need symptomatic
treatment:
* Fatigue—exclude common causes (e.g. anemia,
hypothyroid or depression), amantadine,
mindfulness training and CBT.
* Spasticity—physiotherapy, baclofen, and
gabapentin are first-line. Other options
include diazepam, dantrolene, and tizanidine.
Botox.
* Bladder dysfunction—ultrasound first to
assess bladder emptying. If significant residual
volume !
intermittent self-catheterization,
whereas if no significant residual volume anticholinergics
may improve urinary frequency.
* Oscillopsia may respond to gabapentin.
Clinical and imaging features (focal lesion that does not exceed two vertebral segments in length and does not affect more than half the cross- sectional area of the cord) suggest relapsing- remitting MS with plaques in the cervical spinal cord. In general, current evidence suggests start- ing disease-modifying therapy at the point of diag- nosis of relapsing-remitting forms of MS since damage continues to occur (based on MRI studies) even between relapses. As such, disease modifying therapy is used in those with “active” relapsing MS defined either as 2 or more relapses in the last 2 years or one recent relapse and/or signs of new lesions on MRI. Interferon beta 1a or 1b can be used in relapsing remitting MS, secondary pro- gressive MS if there are still significant relapses and clinically isolated syndrome, but is contraindi- cated with deranged liver function. Glatiramer acetate may act as a myelin decoy for the immune
system and is not contraindicated in liver dysfunc- tion. Fingolimod is the only oral drug and is a sphingosine 1 phosphate receptor modulator affecting lymphocyte migration that has been proven to reduce number of relapses and slow the rate of number of new MRI lesions. However, it was also associated with increased incidence of varicella zoster, tumor formation, and progressive multifocal leucoencephalopathy (PML) hence reserved for patients who fail 1st line therapies. Similarly, while natalizumab is effective in modi- fying multiple sclerosis progression, it is also asso- ciated with PML and not considered a 1st line treatment. Mitoxanthrone is a chemotherapy agent that inhibits DNA synthesis and repair, associated with significant cardiotoxicity, reserved as last resort. Other problems may also need symp- tomatic treatment:
* Fatigue—exclude common causes (e.g. ane- mia, hypothyroid or depression), amantadine, mindfulness training and CBT.
* Spasticity—physiotherapy, baclofen, and gabapentin are first-line. Other options include diazepam, dantrolene, and tizanidine. Botox.
* Bladder dysfunction—ultrasound first to assess bladder emptying. If significant residual volume ! intermittent self-catheterization, whereas if no significant residual volume anti- cholinergics may improve urinary frequency.
* Oscillopsia may respond to gabapentin.
A 43-year-old female presents with a 2 week
history of mild left arm weakness and headache. MRI was done at presentation (shown).
She was discharged on dexamethasone 2 mg
twice daily due to her focal neurology with a
plan for awake craniotomy and resection. An
image guidance scan is repeated one week later
but there is no longer any ring-enhancement.
Which one of the following is most likely?
a. Cerebral abscess
b. High grade tumor
c. Metastasis
d. Primary CNS lymphoma
e. Demyelination
e. Demyelination
Tumefactive demyelination is inflammatory
demyelinating disease which presents as a solitary
large (>2 cm) focus of demyelination
within a cerebral hemisphere with associated
edema that may simulate neoplasm or abscess.
Presentation is acute (
3 weeks) with headache,
seizures, and focal neurologic deficits. Often it
may be a monophasic episode of disease without
recurrence, but some may evolve into relapsingremitting
MS. Imaging features in 50% have
contrast enhancement in the form of an incomplete
ring, without enhancement at junctions
with gray matter (or basal ganglia depending on
orientation), and there is usually minimal mass
effect. Advanced MR imaging techniques may
be useful, and the rCBV values are significantly
lower than for high-grade glial neoplasms. Management
is with high-dose corticosteroid therapy.
Radiation or surgical excision of lesions misdiagnosed
as tumor will cause additional irreversible neurologic deficits. Equally, ring-enhancing
lesions in the setting of MS should not be considered
to be TDL—neoplasia and abscess should be
excluded first.
Tumefactive demyelination is inflammatory demyelinating disease which presents as a soli-
tary large (>2 cm) focus of demyelination within a cerebral hemisphere with associated edema that may simulate neoplasm or abscess. Presentation is acute ( 3 weeks) with headache, seizures, and focal neurologic deficits. Often it may be a monophasic episode of disease without recurrence, but some may evolve into relapsing- remitting MS. Imaging features in 50% have contrast enhancement in the form of an incom- plete ring, without enhancement at junctions with gray matter (or basal ganglia depending on orientation), and there is usually minimal mass effect. Advanced MR imaging techniques may be useful, and the rCBV values are significantly lower than for high-grade glial neoplasms. Man- agement is with high-dose corticosteroid therapy. Radiation or surgical excision of lesions misdiag- nosed as tumor will cause additional irreversible
neurologic deficits. Equally, ring-enhancing lesions in the setting of MS should not be consid- ered to be TDL—neoplasia and abscess should be excluded first.
A 31-year-old female suffered multiple cuts
and burns to both arms. On examination
there is marked wasting of brachioradialis
and the small muscles in both hands, with
reduced biceps and brachioradialis reflex.
She is weak in both arms, distally more than
proximally. Her lower limb and cranial nerve
examination is unremarkable. On testing
upper limb sensation, vibration and proprioception are intact but there appears to be
reduced pain and temperature sensation over
the C3/C4/C5 dermatomes. Which one of
the following is most likely?
a. Chiari malformation
b. Chronic inflammatory demyelinating
polyneuropathy
c. Guillain-Barré syndrome
d. Miller Fisher syndrome
e. Multiple sclerosis
a. Chiari malformation
The presence of loss of pain and temperature sensation
in a “cape-like” distribution is highly suggestive
of syringomyelia, which is commonly
associated with Chiari I malformation. It may
be slowly progressive, cause wasting and weak-
ness of the arms, spinothalamic tract deficit (pain
and temperature), loss of reflexes and upgoing
plantars, and Horner’s syndrome.
The presence of loss of pain and temperature sen- sation in a “cape-like” distribution is highly sug- gestive of syringomyelia, which is commonly associated with Chiari I malformation. It may be slowly progressive, cause wasting and weak- ness of the arms, spinothalamic tract deficit (pain and temperature), loss of reflexes and upgoing plantars, and Horner’s syndrome.
A 64-year-old man presents with sudden
onset severe headache while watching television, followed by confusion and a tonicclonic seizure. Past medical history included
a 20 pack year smoking history, hypertension, hypercholesterolemia and myocardial
infarction two years ago requiring stenting.
On examination, GCS M5V4E3 but was protecting his own airway. Pupils were equal and
reactive. The patient was spontaneously
moving all his limbs and had downgoing
plantar reflexes. Cardiovascular, respiratory
and abdominal examination was unremarkable. Initial observations were blood pressure
220/115 mmHg, heart rate 89 beat/min, O2
sats (15 l O2) 100%, Respiratory rate 19/
min, temperature 37.1°C. CT brain is normal and lumbar puncture shows WCC 3/
mm3
, RBC 3, protein 0.6 g/l, glucose
5.4 mmol/l, and no xanthochromia. MRI is
shown (FLAIR). Which one of the following
is most likely?
a. Acute disseminated encephalomyelitis
b. Herpes simplex virus encephalitis
c. Multiple sclerosis
d. Posterior circulation stroke
e. Posterior reversible encephalopathy syndrome
e. Posterior reversible encephalopathy syndrome
Posterior reversible leucoencephalopathy syndrome
may present with thunderclap headache,
usually followed rapidly by confusion, seizures
and visual symptoms. The most common causes
of PRES are hypertensive encephalopathy and
eclampsia. Hypertension is commonly observed.
CT brain and lumbar puncture results are usually
normal or near normal. The elevation of
CSF protein with hypertensive encephalopathy
is variable because intracranial hemorrhage
may occur with the hypertensive crisis, but most
patients will have moderate increases in CSF
protein.
Diagnosis is made by evidence of vasogenic
brain edema on MRI brain. PRES is often associated
with reversible cerebrovascular vasoconstriction
syndrome with vasospasm on cerebral
angiography. Management in this case will
require blood pressure control in the critical care
setting. Other causes of thunderclap headache
include aneurysmal subarachnoid hemorrhage,
cerebral venous sinus thrombosis, internal carotid
artery dissection, pituitary apoplexy reversible
cerebral vasoconstriction syndrome, and benign
coital headache.
Posterior reversible leucoencephalopathy syn- drome may present with thunderclap headache, usually followed rapidly by confusion, seizures and visual symptoms. The most common causes of PRES are hypertensive encephalopathy and eclampsia. Hypertension is commonly observed. CT brain and lumbar puncture results are usu- ally normal or near normal. The elevation of CSF protein with hypertensive encephalopathy is variable because intracranial hemorrhage may occur with the hypertensive crisis, but most patients will have moderate increases in CSF protein.
Diagnosis is made by evidence of vasogenic brain edema on MRI brain. PRES is often associ- ated with reversible cerebrovascular vasoconstric- tion syndrome with vasospasm on cerebral angiography. Management in this case will require blood pressure control in the critical care setting. Other causes of thunderclap headache include aneurysmal subarachnoid hemorrhage, cerebral venous sinus thrombosis, internal carotid artery dissection, pituitary apoplexy reversible cerebral vasoconstriction syndrome, and benign coital headache.
A 12-year-old boy with Lyme disease and
bilateral facial weakness is being treated with
a cephalosporin. The child’s facial strength
improves, but he notices twitching of the left
corner of his mouth whenever he blinks his
eye. This involuntary movement disorder is
probably an indication of which one of the
following?
a. Horner’s syndrome
b. Marcus Gunn phenomenon
c. Mononeuritis multiplex
d. Parinaud syndrome
e. Recurrent meningitis
b. Marcus Gunn phenomenon
Aberrant regeneration of a cranial nerve is not all
that uncommon, but it is more often seen after
injury to the third nerve than to the seventh.
For unknown reasons, the regenerating motor
fibers miss their original targets and innervate new destinations. With cranial ALS, facial twitching
occurs, but it is not preceded by unilateral
weakness, and it is seen as the weakness evolves,
not as it remits. Sarcoidosis may produce facial
weakness with aberrant regeneration, but this
patient’s history does not suggest this idiopathic
granulomatous disease. There is nothing to suggest
that his Lyme disease is recurring, although
recurrent meningitis may develop with inadequate
treatment.
Aberrant regeneration of a cranial nerve is not all that uncommon, but it is more often seen after injury to the third nerve than to the seventh. For unknown reasons, the regenerating motor fibers miss their original targets and innervate new destinations. With cranial ALS, facial twitch- ing occurs, but it is not preceded by unilateral weakness, and it is seen as the weakness evolves, not as it remits. Sarcoidosis may produce facial weakness with aberrant regeneration, but this patient’s history does not suggest this idiopathic granulomatous disease. There is nothing to sug- gest that his Lyme disease is recurring, although recurrent meningitis may develop with inade- quate treatment.
A 25-year-old woman has progressive gait
disorder. The initial physical examination
reveals hepatosplenomegaly and left sided
ataxia and abnormal finger-nose test. Urinalysis reveals proteinuria and microscopic
hematuria. Which one of the following findings is most likely?
a. Neurofibromas
b. Ash leaf spots
c. Retinal telangiectasia
d. Kayser-Fleisher rings
e. Facial angiofibromas
c. Retinal telangiectasia
The association of erythrocytosis with cerebellar
signs, microscopic hematuria, and hepatosplenomegaly
suggests von Hippel-Lindau syndrome.
This hereditary disorder is characterized by
polycystic liver disease, polycystic kidney disease,
retinal angiomas (telangiectasia), and cerebellar
tumors. This is an autosomal dominant inherited
disorder with variable penetrance. Men are more
commonly affected than women. Although neoplastic
cysts may develop in the cerebellum in
persons with von Hippel-Lindau syndrome,
these usually do not become sufficiently large to
cause an obstructive hydrocephalus. Other abnormalities
that occur with this syndrome include
adenomas in many organs. Hemangiomas may
be evident in the bones, adrenals, and ovaries.
Hemangioblastomas may develop in the spinal
cord or brainstem, as well as in the cerebellum.
The association of erythrocytosis with cerebellar signs, microscopic hematuria, and hepatospleno- megaly suggests von Hippel-Lindau syndrome. This hereditary disorder is characterized by polycystic liver disease, polycystic kidney disease, retinal angiomas (telangiectasia), and cerebellar tumors. This is an autosomal dominant inherited disorder with variable penetrance. Men are more commonly affected than women. Although neo- plastic cysts may develop in the cerebellum in persons with von Hippel-Lindau syndrome, these usually do not become sufficiently large to cause an obstructive hydrocephalus. Other abnor- malities that occur with this syndrome include adenomas in many organs. Hemangiomas may be evident in the bones, adrenals, and ovaries. Hemangioblastomas may develop in the spinal cord or brainstem, as well as in the cerebellum.
A 62-year-old female has discomfort in her
limbs and trouble getting off the toilet. She
is unable to climb stairs and has noticed a rash
on her face. On examination, she is found to
have weakness about the hip and shoulder
girdle. She has purplish-red discoloration of
the skin around her eyes, erythematous discoloration over the finger joints and purplish
nodules over the elbows and knees. Which
one of the following is the most likely
diagnosis?
a. Becker muscular dystrophy
b. Dermatomyositis
c. Inclusion body myositis
d. Myotonic dystrophy
e. Polymyositis
b. Dermatomyositis
Dermatomyositis is an inflammatory disorder
causing a symmetrical, proximal muscle weakness
and skin lesions. Polymyositis is a variant where
skin lesions are not prominent. It may be idiopathic,
associated with connective tissue disorders
or a paraneoplastic syndrome in about 20% of
cases overall. Lung, ovarian, gastrointestinal
tract, breasts, and other malignancies can cause
it hence a thorough search for a primary is indicated.
Skin manifestations include a lilac (heliotrope)
rash around the eyes, photosensitive skin,
macular rash over back and shoulder, Gottron’s
papules, nail fold capillary dilatation and
flat-topped purplish nodules over the elbows
and knees. Other features are proximal muscle
weakness with tenderness, Raynaud’s syndrome,
respiratory muscle weakness, interstitial lung dis-
ease and dysphagia/dysphonia.
Dermatomyositis is an inflammatory disorder causing a symmetrical, proximal muscle weakness and skin lesions. Polymyositis is a variant where skin lesions are not prominent. It may be idio- pathic, associated with connective tissue disorders or a paraneoplastic syndrome in about 20% of cases overall. Lung, ovarian, gastrointestinal tract, breasts, and other malignancies can cause it hence a thorough search for a primary is indi- cated. Skin manifestations include a lilac (helio- trope) rash around the eyes, photosensitive skin, macular rash over back and shoulder, Gottron’s papules, nail fold capillary dilatation and flat-topped purplish nodules over the elbows and knees. Other features are proximal muscle weakness with tenderness, Raynaud’s syndrome, respiratory muscle weakness, interstitial lung dis- ease and dysphagia/dysphonia.
A 67-year-old male is investigated for chest
pain and painful swallowing progressing over
the last few months with no response to proton pump inhibitors. There is no history of
weight loss or anorexia or smoking. On
examination you note a left-sided partial ptosis, and he reports diplopia on testing extrocular muscle movements. Sustained upward
gaze exacerbates his ptosis. There is no limb
muscle weakness or sensory disturbance.
CXR is shown. Which one of the following
tests is likely to be helpful?
a. Anti-acteylcholine receptor antibodies
b. Anti-GM1 antibody
c. Anti-GQ1b antibody
d. Anti-muscle specific kinase antibody
e. Anti-voltage gated calcium channel
antibody
a. Anti-acteylcholine receptor antibodies
Myasthenia gravis is an autoimmune damage
that occurs at the neuromuscular junction, specifically
at postsynaptic membrane acetylcholine receptors. A functional acetylcholine deficiency
develops at the synapse because receptors are
blocked or inefficient. Myasthenia is more common
in women (2:1). Approximately 1/3 of patient
have a thymoma (commonest tumor of anterior
mediastinum) which can cause death by airway
compression or cardiac tamponade. The chest
X-ray shows a partially delineated mediastinal
mass (anterior mediastinum) with regular borders,
bulging the left upper mediastinal contour suggestive
of a thymoma. Other associations include
thymic hyperplasia and autoimmune disorders
(pernicious anemia, autoimmune thyroid disorders,
rheumatoid, SLE). Presentation is with ocular
weakness (90%) including ptosis, opthalmoparesis
generally worse with sustained upward gaze. More
severe disease includes limb weakness, difficulty
with swallowing, and respiratory difficulties. The
key feature is muscle fatigability—muscles become
progressively weaker during periods of activity
and slowly improve after periods of rest. Patients
usually report fatigue that increases as the day
progresses. Investigations include single fiber
electromyography (high sensitivity 92-100%),
CT thorax to exclude thymoma, CK is normal,
around 85-90% of patients have antibodies to
acetylcholine receptors. In the remaining patients,
about 40% are positive for anti-muscle-specific
tyrosine kinase antibodies. Tensilon test (intravenous
edrophonium) reduces muscle weakness
temporarily—not commonly used anymore due
to the risk of cardiac arrhythmia. Management
includes initiating long-acting anticholinesterases
(e.g. pyridostigmine), immunosuppression and
thymectomy. Myasthenic crises (severe enough to
require intubation) may be triggered by other medications,
infection or other physiological stressors
and necessitate plasma exchange or intravenous
immunoglobulin.
Myasthenia gravis is an autoimmune damage that occurs at the neuromuscular junction, speci- fically at postsynaptic membrane acetylcholine
receptors. A functional acetylcholine deficiency develops at the synapse because receptors are blocked or inefficient. Myasthenia is more com- mon in women (2:1). Approximately 1/3 of patient have a thymoma (commonest tumor of anterior mediastinum) which can cause death by airway compression or cardiac tamponade. The chest X-ray shows a partially delineated mediastinal mass (anterior mediastinum) with regular borders, bulging the left upper mediastinal contour sugges- tive of a thymoma. Other associations include thymic hyperplasia and autoimmune disorders (pernicious anemia, autoimmune thyroid disor- ders, rheumatoid, SLE). Presentation is with ocular weakness (90%) including ptosis, opthalmoparesis generally worse with sustained upward gaze. More severe disease includes limb weakness, difficulty with swallowing, and respiratory difficulties. The key feature is muscle fatigability—muscles become progressively weaker during periods of activity and slowly improve after periods of rest. Patients usually report fatigue that increases as the day progresses. Investigations include single fiber electromyography (high sensitivity 92-100%), CT thorax to exclude thymoma, CK is normal, around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about 40% are positive for anti-muscle-specific tyrosine kinase antibodies. Tensilon test (intrave- nous edrophonium) reduces muscle weakness temporarily—not commonly used anymore due to the risk of cardiac arrhythmia. Management includes initiating long-acting anticholinesterases (e.g. pyridostigmine), immunosuppression and thymectomy. Myasthenic crises (severe enough to require intubation) may be triggered by other med- ications, infection or other physiological stressors and necessitate plasma exchange or intravenous immunoglobulin.
A 65-year-old presents with a 3 month history of progressive weakness. She had initially noticed difficulty opening jars, but
now also has difficulty walking up stairs.
She denied any pain or sensory symptoms.
Past medical history included osteoporosis,
type 2 diabetes mellitus and hypertension.
8 NEUROLOGY AND STROKE 133
On neurological examination there were no
fasciculations, tone was normal and sensation
was intact. Power was reduced in finger flexion (3/5), wrist flexion (4/5), knee extension
(3/5), and hip flexion (4/5) bilaterally. Upper
limb reflexes were present but diminished,
but the knee jerk was absent and there were
flexor plantar responses bilaterally. There
was no tenderness over any muscle groups.
Cranial nerve examination was unremarkable. Blood results were normal except for
CRP 10 mg/l, ESR 41 mm/h, CK 290 u/l.
Which one of the following is most likely?
a. Diabetic amyotrophy
b. Inclusion body myositis
c. Polymyalgia rheumatica
d. Polymyositis
e. Chronic inflammatory demyelinating
polyneuropathy
b. Inclusion body myositis
Inclusion body myositis is the most common primary
myopathy in the elderly manifesting as a
slowly progressive weakness, usually affecting finger
and wrist flexion initially (but does affect
both proximal and distal muscles). Lower limb
weakness may also occur with quadriceps. In
upper and lower limbs flexors affected more than
extensors. Reflexes are usually diminished as in
other myopathies. Creatine kinase levels are usually
normal or only mildly raised, in contrast to
polymyositis (where creatine kinase levels are
usually markedly elevated). Associated with cyto-
plasmic inclusions on muscle biopsy. Muscles are often tender in polymyositis, the distal muscles
are usually not affected until the disease is
advanced and CK is significantly raised. Diabetic
amyotrophy is characterized by painful wasting of
the proximal lower limb muscles.
Inclusion body myositis is the most common pri- mary myopathy in the elderly manifesting as a slowly progressive weakness, usually affecting fin- ger and wrist flexion initially (but does affect both proximal and distal muscles). Lower limb weakness may also occur with quadriceps. In upper and lower limbs flexors affected more than extensors. Reflexes are usually diminished as in other myopathies. Creatine kinase levels are usu- ally normal or only mildly raised, in contrast to polymyositis (where creatine kinase levels are usually markedly elevated). Associated with cyto- plasmic inclusions on muscle biopsy. Muscles are
often tender in polymyositis, the distal muscles are usually not affected until the disease is advanced and CK is significantly raised. Diabetic amyotrophy is characterized by painful wasting of the proximal lower limb muscles.
A 77-year-old male presents with a 2-day history of right temporal throbbing headache.
He has had migraines previously but never
this severe and usually occipital. There was
no other past medical history of note. On
examination, his right scalp is tender and a
prominent right temporal artery is noted.
He is apyrexic with no skin rashes. His blood
tests are as follows:Hb 13.1 g/dl, Plt 45010-
9/l, WCC 11.5, ESR 85, Na 142, K 4.0., Urea
10, Cr 118 umol/l, CRP 23 mg/l. Which one
of the following would you do next?
a. CT angiogram
b. Biopsy
c. Start prednisolone
d. Start azothiaprine
e. Carotid duplex ultrasound
c. Start prednisolone
Temporal (giant cell) arteritis. is large vessel vasculitis
which overlaps with polymyalgia rheumatica
(PMR) typically in a patient >60 years
old, usually rapid onset with evidence of headache
and jaw claudication in many, and visual disturbances
secondary to anterior ischemic optic
neuropathy in the presence of a tender, palpable
superficial temporal artery. In contrast, PMR
usually presents with myalgia, morning stiffness
in proximal limb muscles (not weakness), lethargy,
depression, low-grade fever, anorexia, night
sweats with a raised ESR but normal CK. Investigations
for temporal arteritis include raised
inflammatory markers: ESR >50 mm/hr and
CRP may also be elevated, normal CK. Treatment
with high dose prednisolone is started on
clinical suspicion (due to the risk to vision) while
awaiting temporal artery biopsy, and also because
histology shows changes which characteristically
“skips” certain sections of affected artery whilst
damaging others hence a negative temporal artery
biopsy does not rule out temporal arteritis.
Patients with visual symptoms should be seen
the same-day by an ophthalmologist as visual
damage is often irreversible. If there is no
response to prednisolone the diagnosis should
be reconsidered.
Temporal (giant cell) arteritis. is large vessel vas- culitis which overlaps with polymyalgia rheuma- tica (PMR) typically in a patient >60 years old, usually rapid onset with evidence of head- ache and jaw claudication in many, and visual dis- turbances secondary to anterior ischemic optic neuropathy in the presence of a tender, palpable superficial temporal artery. In contrast, PMR usually presents with myalgia, morning stiffness in proximal limb muscles (not weakness), leth- argy, depression, low-grade fever, anorexia, night sweats with a raised ESR but normal CK. Inves- tigations for temporal arteritis include raised inflammatory markers: ESR >50 mm/hr and CRP may also be elevated, normal CK. Treat- ment with high dose prednisolone is started on clinical suspicion (due to the risk to vision) while awaiting temporal artery biopsy, and also because histology shows changes which characteristically “skips” certain sections of affected artery whilst damaging others hence a negative temporal artery biopsy does not rule out temporal arteritis. Patients with visual symptoms should be seen the same-day by an ophthalmologist as visual damage is often irreversible. If there is no response to prednisolone the diagnosis should be reconsidered.
A 65-year-old male has been diagnosed with small cell lung cancer and is currently undergoing chemotherapy. Over the last few months he
has noticed his vision deteriorating and complains of diplopia. He also feels weaker in his upper limbs although his symptoms do fluctuate. On examination he has mild ptosis of the eyelids bilaterally and a complex ophthalmoparesis affecting both eyes. He also has reduced power proximally in the upper limbs. Which one of the following may be associated
with this clinical picture?
a. Anti-Ro antibody
b. Anti-voltage gated potassium channel
antibody
c. Anti-voltage gated calcium channel
antibody
d. Anti-Hu antibody
e. Anti-GQ1b antibody
c. Anti-voltage gated calcium channel antibody
Lambert-Eaton myesthenic syndrome (LEMS)
is a paraneoplastic myesthenic syndrome associated
with small-cell lung cancer where antibodies
to voltage-gated calcium channels (VGCCs)
have been reported in 75-100%. It presents
similarly to myasthenia gravis, with proximal
muscle weakness, hyporeflexia and autonomic
features but does not show fatiguability of muscle
strength—strength actually improves with
greater effort.
Lambert-Eaton myesthenic syndrome (LEMS) is a paraneoplastic myesthenic syndrome associ- ated with small-cell lung cancer where antibodies to voltage-gated calcium channels (VGCCs) have been reported in 75-100%. It presents similarly to myasthenia gravis, with proximal muscle weakness, hyporeflexia and autonomic features but does not show fatiguability of muscle strength—strength actually improves with greater effort.
A 17-year-old girl presents with a second episode on waking earlier in the morning where
she could not move at all for 2 h. She reports
no loss of consciousness and was aware
throughout the episode. There is no other significant past medical history or epilepsy. Routine systemic and neurological examination is
normal. A 12 lead ECG demonstrated a jerky
baseline with flat T waves.What one of the following is most likely?
a. Andersen-Tawil syndrome
b. Cataplexy
c. Hyperkalemia periodic paralysis
d. Hypokalemic period paralysis
e. Night terror
c. Hyperkalemia periodic paralysis
Periodic paralysis can be classified into hypokalemic
and hyperkalemic periodic paralysis and
Andersen-Tawil (long-QT) syndrome, due to
mutations in skeletal muscle ion channels.
Onset is most commonly in childhood and adolescents,
with attacks of paralysis lasting hours
and neurological examination is normally unremarkable in between attacks. Diagnosis
of hypokalemic periodic paralysis is often made
clinically by episodes of paralysis, typically
occur at night and may be triggered by carbohydrate
meals, in association with low serum
potassium but genetic testing can help if known
mutations are present. Management is with
lifelong potassium supplementation.
Periodic paralysis can be classified into hypoka- lemic and hyperkalemic periodic paralysis and Andersen-Tawil (long-QT) syndrome, due to mutations in skeletal muscle ion channels. Onset is most commonly in childhood and ado- lescents, with attacks of paralysis lasting hours and neurological examination is normally
unremarkable in between attacks. Diagnosis of hypokalemic periodic paralysis is often made clinically by episodes of paralysis, typically occur at night and may be triggered by carbo- hydrate meals, in association with low serum potassium but genetic testing can help if known mutations are present. Management is with lifelong potassium supplementation.
A 10-year-old presents to your neurology
clinic reporting 9 months of subtle and gradual
onset, progressive lower limb weakness. For
the past 18 months, he has noticed a difficulty
in keeping up with his peers in PE lessons,
which he initially put down to “not being very
sporty.” However, he feels weak whenever he
walks and has particular difficulty getting up
from a chair. His appearance is shown below.
Formal examination of power is 4/5 bilaterally
in shoulder abduction, adduction and normal
5/5 distally. 4/5 is also noted in hip flexion
and extension, 4+/5 in knee flexion and extension, 5/5 in ankle plantar and dorsiflexion. The
weaknesses demonstrated are not fatiguable
and are persistent. Reflexes are present in all
areas, plantars are downgoing. He has no other
past medical history. What is the likely
diagnosis?
a. Becker muscular dystrophy
b. Duchenne muscular dystrophy
c. Emery-Dreifuss syndrome
d. Facial-scapulo humeral syndrome
e. Limb-girdle dystrophy
b. Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) and
Becker muscular dystrophy (BMD) are X-linked
recessive disorders caused by mutations in the
dystrophin gene on Xp21 (DMD occurs in 1 in
3000-6000 live births; BMD is much less com-
mon). Dystrophin is part of a large membrane
associated protein in muscle which connects the
muscle membrane to actin, part of the muscle cytoskeleton.
In DMD there is a frameshift mutation
resulting in one or both of the binding sites are lost
leading to a severe form while in BMD there is a
non-frameshift insertion in the dystrophin gene
resulting in both binding sites being preserved
leading to a milder form. DMD usually presents
with skeletal muscle weakness before the age of
5 years, calf pseudohypertrophy, Gower’s sign
(child uses arms to stand up from a squatted position)
and intellectual impairment (in 30%) which
progresses if untreated such that boys become
wheelchair-bound by their early teens. Historically,
death occurs by age 25 years, primarily from
respiratory dysfunction and less often from heart
failure. A multidisciplinary treatment approach
including steroids, scoliosis surgery, ventilatory
support, and cardiac therapy has improved survival.
BMD is associated with a more variable presentation
of skeletal muscle weakness from the age
of 10 onwards and absence of intellectual impair-
ment, and carries a better prognosis, with most
patients surviving to the age of 40-50 years. Cardiac
involvement is seen in both disorders, and
the severity is not correlated with the severity of
skeletal muscle involvement. CK is elevated to
5-10 times normal in both. Facioscapulohumeral
muscular dystrophy is autosomal dominant and
the third most common after the DMD and myotonic
dystrophy. Muscle weakness tends to follow a
slowly progressive but variable course. The patient
initially presents with facial and/or shoulder girdle
muscle weakness, which progresses to involve the
pelvic musculature. The limb-girdle muscular dystrophies
are a group of disorders with a limbshoulder
and pelvic girdle distribution of weakness,
but with otherwise heterogeneous inheritance and
genetic cause. The onset of muscle weakness is variable
but usually occurs before age 30 with com-
plaints of difficulty with walking or running
secondary to pelvic girdle involvement. As the disease progresses, involvement of the shoulder
muscles and then more distal muscles occurs, with
sparing of facial involvement. Emery-Dreifuss
muscular dystrophy is a rare X-linked disorder in
which skeletal muscle symptoms are often mild
but with cardiac involvement that is both common
and serious. It is characterized by a triad of early
contractures of the elbow, Achilles tendon, and
posterior cervical muscles; slowly progressing
muscle weakness and atrophy, primarily in humeroperoneal
muscles; and cardiac involvement.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene on Xp21 (DMD occurs in 1 in 3000-6000 live births; BMD is much less com- mon). Dystrophin is part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cyto- skeleton. In DMD there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form while in BMD there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form. DMD usually presents with skeletal muscle weakness before the age of 5 years, calf pseudohypertrophy, Gower’s sign (child uses arms to stand up from a squatted posi- tion) and intellectual impairment (in 30%) which progresses if untreated such that boys become wheelchair-bound by their early teens. Histori- cally, death occurs by age 25 years, primarily from respiratory dysfunction and less often from heart failure. A multidisciplinary treatment approach including steroids, scoliosis surgery, ventilatory support, and cardiac therapy has improved sur- vival. BMD is associated with a more variable pre- sentation of skeletal muscle weakness from the age of 10 onwards and absence of intellectual impair- ment, and carries a better prognosis, with most patients surviving to the age of 40-50 years. Car- diac involvement is seen in both disorders, and the severity is not correlated with the severity of skeletal muscle involvement. CK is elevated to 5-10 times normal in both. Facioscapulohumeral muscular dystrophy is autosomal dominant and the third most common after the DMD and myo- tonic dystrophy. Muscle weakness tends to follow a slowly progressive but variable course. The patient initially presents with facial and/or shoulder girdle muscle weakness, which progresses to involve the pelvic musculature. The limb-girdle muscular dys- trophies are a group of disorders with a limb- shoulder and pelvic girdle distribution of weakness, but with otherwise heterogeneous inheritance and genetic cause. The onset of muscle weakness is var- iable but usually occurs before age 30 with com- plaints of difficulty with walking or running secondary to pelvic girdle involvement. As the disease progresses, involvement of the shoulder muscles and then more distal muscles occurs, with sparing of facial involvement. Emery-Dreifuss muscular dystrophy is a rare X-linked disorder in which skeletal muscle symptoms are often mild but with cardiac involvement that is both common and serious. It is characterized by a triad of early contractures of the elbow, Achilles tendon, and posterior cervical muscles; slowly progressing muscle weakness and atrophy, primarily in humer- operoneal muscles; and cardiac involvement.
A 55-year-old male known alcoholic is found confused on a street by a policeman not orientated in time or place. He is able to follow your commands in lifting his upper and lower limbs during his neurolog- ical exams. All reflexes were present. He fails to follow your finger with his eyes on cranial nerve examination and you note horizontal nystagmus. His gait is grossly ataxic.
Alcohol-related neurological disorders:
a. Alcoholic cerebellar degeneration
b. Alcoholic hallucinosis
c. Alcoholic neuropathy
d. Alcohol withdrawal seizures
e. Beriberi
f. Delerium tremens
g. Marchiafava-Bignami disease
h. Tobacco-alcohol amblyopia
i. Wernicke’s encephalopathy
j. Wernicke-Korsakoff syndrome
i. Wernicke’s encephalopathy
i, Wernicke encephalopathy. Thiamine deficiency can result in this classic triad of nys- tagmus, opthalmoplegia and ataxia requiring urgent replacement
A 45-year-old heavy drinker (30 units per day) presents 72 h after his last drink with agitation, and pointing around the room as if having hallucinations. He has a coarse tremor, sinus tachycardia at 120 bpm and sweating.
Alcohol-related neurological disorders:
a. Alcoholic cerebellar degeneration
b. Alcoholic hallucinosis
c. Alcoholic neuropathy
d. Alcohol withdrawal seizures
e. Beriberi
f. Delerium tremens
g. Marchiafava-Bignami disease
h. Tobacco-alcohol amblyopia
i. Wernicke’s encephalopathy
j. Wernicke-Korsakoff syndrome
f. Delerium tremens
A 60-year-old female is brought in by police as she was wandering and confused. She was disorientated in place and time, did not remember her birthday, was unable to recall three objects after 5 min and identified the hospital cleaner as her father and seemed to recognize people she had never met. On examination pupils were reactive, there was an ophthalmoparesis, nystagmus on attempted horizontal gaze and ataxic gait. Motor and sensory systems were normal.
Alcohol-related neurological disorders:
a. Alcoholic cerebellar degeneration
b. Alcoholic hallucinosis
c. Alcoholic neuropathy
d. Alcohol withdrawal seizures
e. Beriberi
f. Delerium tremens
g. Marchiafava-Bignami disease
h. Tobacco-alcohol amblyopia
i. Wernicke’s encephalopathy
j. Wernicke-Korsakoff syndrome
j. Wernicke-Korsakoff syndrome
j, Wernicke-Korsakoff syndrome. Repre- sents the addition of anterograde amnesia, ret- rograde amnesia and confabulation to Wernicke’s encephalopathy.
A 34-year-old male working in a feltprocessing plant develops tremors, memory
disturbances and personality change over
the course of months. On examination, he
has prominent gait ataxia, limb and facial
tremors, and decreased pain and temperature sense in his feet.
Poisoning:
a. Aluminum
b. Arsenic
c. Carbon monoxide
d. Cyanide
e. Ergot
f. Lead
g. Manganese
h. Mercury
i. Organophosphates
j. Thallium
h. Mercury
A 23-year-old volunteers abroad painting houses during a 3-month exchange. Towards the end of the trip he develops weakness in both wrists. On examination, there is bilateral wrist drop without any sen- sory deficit. An EMG reveals evidence of a peripheral motor neuropathy.
Poisoning:
a. Aluminum
b. Arsenic
c. Carbon monoxide
d. Cyanide
e. Ergot
f. Lead
g. Manganese
h. Mercury
i. Organophosphates
j. Thallium
f. Lead
A 45-year-old worker in an insecticide factory complains of severe stomach pain. She also has had problems with her memory, excessive drowsiness, and a senso- rimotor neuropathy with absent tendon reflexes.
Poisoning:
a. Aluminum
b. Arsenic
c. Carbon monoxide
d. Cyanide
e. Ergot
f. Lead
g. Manganese
h. Mercury
i. Organophosphates
j. Thallium
b. Arsenic
A 22-year-old farm worker has seizure. Neurological examination reveals fascicula- tions and occasional myoclonus. He is ataxic and has absent deep tendon reflexes. A sensory neuropathy is evident in his legs. Ulcers are evident on his fingers and toes. He says his diet was poor and mostly made food from his rye crop
Poisoning:
a. Aluminum
b. Arsenic
c. Carbon monoxide
d. Cyanide
e. Ergot
f. Lead
g. Manganese
h. Mercury
i. Organophosphates
j. Thallium
e. Ergot
A 38-year-old miner develops a shuffling gait, tremor, and drooling. His speech is difficult to understand and becomes quieter as he talks. On examination, cogwheel rigidity is evident in his arms and legs. His tremor is most evident when his limbs are at rest.
Poisoning:
a. Aluminum
b. Arsenic
c. Carbon monoxide
d. Cyanide
e. Ergot
f. Lead
g. Manganese
h. Mercury
i. Organophosphates
j. Thallium
g. Manganese
A 15-year-old boy has moderate mental retardation, attention deficit disorder, a long face, enlarged ears, and macroorchid- ism. Development has been steady but always at a delayed pace.
Genetic syndromes with learning disability:
a. Angelman’s syndrome
b. Cri du Chat syndrome
c. Down’s syndrome
d. Fragile X syndrome
e. Neurofibromatosis
f. Prader-Willi syndrome
g. Rett syndrome
h. Tuberous sclerosis
i. Velocardiofacial syndrome
j. Williams syndrome
d. Fragile X syndrome
An 11-year-old girl presents with obesity, excessive and indiscriminate gorging, small hands, feet, hypogonadism and mental retardation.
Genetic syndromes with learning disability:
a. Angelman’s syndrome
b. Cri du Chat syndrome
c. Down’s syndrome
d. Fragile X syndrome
e. Neurofibromatosis
**
g. Rett syndrome
h. Tuberous sclerosis
i. Velocardiofacial syndrome
j. Williams syndrome
f. Prader-Willi syndrome
A 7-year-old boy is noted to have character- istic elfin facies, short stature and cardiovas- cular defects.
Genetic syndromes with learning disability:
a. Angelman’s syndrome
b. Cri du Chat syndrome
c. Down’s syndrome
d. Fragile X syndrome
e. Neurofibromatosis
f. Prader-Willi syndrome
g. Rett syndrome
h. Tuberous sclerosis
i. Velocardiofacial syndrome
j. Williams syndrome
j. Williams syndrome
A 13-year-old boy has a history of thymus abnormalities, ear deformities, cleft palate, cardiac defects and short stature. He has annual blood tests to assess serum calcium.
Genetic syndromes with learning disability:
a. Angelman’s syndrome
b. Cri du Chat syndrome
c. Down’s syndrome
d. Fragile X syndrome
e. Neurofibromatosis
f. Prader-Willi syndrome
g. Rett syndrome
h. Tuberous sclerosis
**
j. Williams syndrome
i. Velocardiofacial syndrome
A 5-year-old girl with progressive deterio- ration in cognitive function and loss of lan- guage displays stereotypic hand movements.
Genetic syndromes with learning disability:
a. Angelman’s syndrome
b. Cri du Chat syndrome
c. Down’s syndrome
d. Fragile X syndrome
e. Neurofibromatosis
f. Prader-Willi syndrome
g. Rett syndrome
h. Tuberous sclerosis
i. Velocardiofacial syndrome j. Williams syndrome
g. Rett syndrome
A 3-year-old boy presents with gait ataxia, choreoathetoid movements in his right hand and recurrent ear infections or epi- sodes of unexplained fever. On examination he had dilated venules on his ear, mild dys- arthria and a wide based ataxic gait. Deep tendon reflexes were absent.
Hereditary ataxia:
a. Abetalipoproteinemia
b. Ataxia telangiectasia
c. Ataxia with isolated vitamin E deficiency
d. Episodic ataxia type 1
e. Episodic ataxia type 2
f. Fragile X tremor ataxia syndrome
g. Friedreich’s ataxia
h. Machado-Joseph disease (SCA3)
i. Mitochondrial disorders
j. Spinocerebellar ataxias (SCA1
b. Ataxia telangiectasia
A 24-year-old presents with progressive unsteadiness on walking over the past 6 months. Over the past 3 months, he has noticed a lack of articulation with his speech. On examination, his cardio- vascular, respiratory and abdominal sys- tems are normal. His finger-nose test is impaired bilaterally and he is unable to tandem walk. He denies any neck stiff- ness or headache. He has a full range of eye movements. He has absent reflexes in his lower limbs and upgoing plantars bilaterally.
Hereditary ataxia:
a. Abetalipoproteinemia
b. Ataxia telangiectasia
c. Ataxia with isolated vitamin E deficiency
d. Episodic ataxia type 1
e. Episodic ataxia type 2
f. Fragile X tremor ataxia syndrome
g. Friedreich’s ataxia
h. Machado-Joseph disease (SCA3)
i. Mitochondrial disorders
j. Spinocerebellar ataxias (SCA1
g. Friedreich’s ataxia
A 36-year-old male presents with a 5-year history of increasing, progressive “clumsi- ness.” He cannot write legibly or even hold a key still using either hand to open a door. On examination, his cranial nerves were unremarkable except for mild multi- directional nystagmus at primary gaze. Fundoscopy was normal. Limb examina- tion revealed significant impairment of finger-nose and heel-shin testing. His gait, tone, power, sensation and reflexes were normal with downgoing plantars. A brief mini-mental state examination scored 30/30. Serum ANA was negative.
Hereditary ataxia:
a. Abetalipoproteinemia
b. Ataxia telangiectasia
c. Ataxia with isolated vitamin E deficiency
d. Episodic ataxia type 1
e. Episodic ataxia type 2
f. Fragile X tremor ataxia syndrome
g. Friedreich’s ataxia
h. Machado-Joseph disease (SCA3)
i. Mitochondrial disorders
j. Spinocerebellar ataxias (SCA1)
j. Spinocerebellar ataxias (SCA1)
At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb ataxia develops, followed by a peripheral neuropathy. Dur- ing adolescence, retinitis pigmentosa develops. Peripheral blood smear shows acanthocytosis.
Hereditary ataxia:
a. Abetalipoproteinemia
b. Ataxia telangiectasia
c. Ataxia with isolated vitamin E deficiency
d. Episodic ataxia type 1
e. Episodic ataxia type 2
f. Fragile X tremor ataxia syndrome
g. Friedreich’s ataxia
h. Machado-Joseph disease (SCA3)
i. Mitochondrial disorders
j. Spinocerebellar ataxias (SCA1)
a. Abetalipoproteinemia
A 36-year-old man with tuberculosis is started on therapy with isoniazid, rifampin, and ethambutol. After 2 months his liver en- zymes are slightly deranged and he reports pins-and-needles sensations in his feet. Neurological examination reveals preserved power, but hypoactive deep tendon reflexes in the legs and impaired position sense.
Nutritional deficiency:
a. Folate
b. Niacin
c. Pyridoxine (vitamin B6) deficiency
d. Riboflavin
e. Thiamine (vitamin B1) deficiency
f. Vitamin A deficiency
g. Vitamin B12 deficiency
h. Vitamin C deficiency
i. Vitamin E deficiency
j. Vitamin D deficiency
k. Vitamin K
c. Pyridoxine (vitamin B6) deficiency
Patientsonantitu- berculous therapy with isoniazid may develop
isolated pyridoxine deficiency and subsequent peripheral neuropathy
A 47-year-old known alcoholic female is found wandering and brought to the emer- gency room. She is disoriented to time, place, and person, but has no external evi- dence of head trauma. Examination reveals ataxic gait, paresis of conjugate gaze, and horizontal nystagmus. She does not have any ethanol in her bloodstream on testing.
Nutritional deficiency:
a. Folate
b. Niacin
c. Pyridoxine (vitamin B6) deficiency
d. Riboflavin
e. Thiamine (vitamin B1) deficiency
f. Vitamin A deficiency
g. Vitamin B12 deficiency
h. Vitamin C deficiency
i. Vitamin E deficiency
j. Vitamin D deficiency
k. Vitamin K
e. Thiamine (vitamin B1) deficiency
Symptoms suggest Wernicke’s encephalopathy
A 59-year-old man developed progressive cramping of his legs, gait unsteadiness and paresthesia affecting his hands and feet over 1 year. He has also had some episodes of urinary incontinence. On examination, he has a spastic paraparesis with severe distur- bance of position and vibration sense in his legs, absent knee and ankle reflexes. Blood results show a megaloblastic anemia.
Nutritional deficiency:
a. Folate
b. Niacin
c. Pyridoxine (vitamin B6) deficiency
d. Riboflavin
e. Thiamine (vitamin B1) deficiency
f. Vitamin A deficiency
g. Vitamin B12 deficiency
h. Vitamin C deficiency
i. Vitamin E deficiency
j. Vitamin D deficiency
k. Vitamin K
g. Vitamin B12 deficiency
Symptoms suggest subacute combined degeneration of the cord.
A 5-year-old boy develops progressive gait ataxia and limb weakness over the course of 3 months. Examination reveals diffusely absent deep tendon reflexes, proximal mus- cle weakness, ophthalmoparesis, and poor pain perception in the feet. Blood tests reveal elevated creatine kinase levels and evidence of liver disease without features of liver failure.
Nutritional deficiency:
a. Folate
b. Niacin
c. Pyridoxine (vitamin B6) deficiency
d. Riboflavin
e. Thiamine (vitamin B1) deficiency
f. Vitamin A deficiency
g. Vitamin B12 deficiency
h. Vitamin C deficiency
i. Vitamin E deficiency
j. Vitamin D deficiency
k. Vitamin K
i. Vitamin E deficiency
A 12-month-old develops progressive blindness and delayed cognitive milestones. Fundal examination shows a cherry red spot. There is a deficiency of hexaminosidase A.
Sphingolipidosis:
a. Batten’s disease
b. Cerebrotendinous xanthomatosis c. Fabry disease
d. Gaucher’s disease
e. GM1 gangliosidosis
f. Krabbe disease
g. Metachromatic leukodystrophy
h. Neimann-Pick disease
i. Sandhoff’s disease
j. Tay-Sachs disease
k. Wolman disease
j. Tay-Sachs disease
This is a ganglioside
storage disease that occurs more commonly
in Ashkenazi Jews than in the general population.
The early-onset form will produce
macrocephaly and a cherry red spot in the
fundus (retinal ganglion cells become distended
with glycolipid making retinal pale
compared to fovea lacking ganglion cells).
Children exhibit mental retardation, seizures,
blindness and die prematurely.
Thisisaganglioside storage disease that occurs more commonly in Ashkenazi Jews than in the general popu- lation. The early-onset form will produce macrocephaly and a cherry red spot in the fundus (retinal ganglion cells become dis- tended with glycolipid making retinal pale compared to fovea lacking ganglion cells). Children exhibit mental retardation, sei- zures, blindness and die prematurely
An 8-month-old boy develops spasticity, head retraction, and difficulty swallowing. There is abnormal accumulation of gluco- cerebroside and the child will deteriorate and die within 3 years.
Sphingolipidosis:
a. Batten’s disease
b. Cerebrotendinous xanthomatosis
c. Fabry disease
d. Gaucher’s disease
e. GM1 gangliosidosis
f. Krabbe disease
g. Metachromatic leukodystrophy
h. Neimann-Pick disease
i. Sandhoff’s disease
j. Tay-Sachs disease
k. Wolman disease
d. Gaucher’s disease
Non-paraneoplastic limbic encephalitis
Antibodies:
a. Anti-muscle specific kinase
b. Anti-NMDA receptor antibody
c. Anti-voltage gated calcium channel antibody
d. Anti-Aquaporin 4 antibody
e. Anti-Hu (ANNA-1)
f. Anti-Yo (PCA-1)
g. Anti-Ri (ANNA-2)
h. Anti-Tr
i. Anti-GAD
j. Anti-voltage gated potassium channel antibody
k. Anti-TA Ma2
l. Anti-GQ1b
m. Anti-myelin associated glycoprotein/sulfated glucoronul paragloboside
n. Anti-GD1b
j. Anti-voltage gated potassium channel antibody
Neuromyelitis optica (Devic’s disease)
Antibodies:
a. Anti-muscle specific kinase
b. Anti-NMDA receptor antibody
c. Anti-voltage gated calcium channel
antibody
d. Anti-Aquaporin 4 antibody
e. Anti-Hu (ANNA-1)
f. Anti-Yo (PCA-1)
g. Anti-Ri (ANNA-2)
h. Anti-Tr
i. Anti-GAD
j. Anti-voltage gated potassium channel
antibody
k. Anti-TA Ma2
l. Anti-GQ1b
m. Anti-myelin associated glycoprotein/sul-
fated glucoronul paragloboside
n. Anti-GD1b
d. Anti-Aquaporin 4 antibody
Guillain-Barré syndrome
Antibodies:
a. Anti-muscle specific kinase
b. Anti-NMDA receptor antibody
c. Anti-voltage gated calcium channel
antibody
d. Anti-Aquaporin 4 antibody
e. Anti-Hu (ANNA-1)
f. Anti-Yo (PCA-1)
g. Anti-Ri (ANNA-2)
h. Anti-Tr
i. Anti-GAD
j. Anti-voltage gated potassium channel
antibody
k. Anti-TA Ma2
l. Anti-GQ1b
m. Anti-myelin associated glycoprotein/sul-
fated glucoronul paragloboside
n. Anti-GD1b
l. Anti-GQ1b
Myasthenia gravis
Antibodies:
a. Anti-muscle specific kinase
b. Anti-NMDA receptor antibody
c. Anti-voltage gated calcium channel
antibody
d. Anti-Aquaporin 4 antibody
e. Anti-Hu (ANNA-1)
f. Anti-Yo (PCA-1)
g. Anti-Ri (ANNA-2)
h. Anti-Tr
i. Anti-GAD
j. Anti-voltage gated potassium channel
antibody
k. Anti-TA Ma2
l. Anti-GQ1b
m. Anti-myelin associated glycoprotein/sul-
fated glucoronul paragloboside
n. Anti-GD1b
a. Anti-muscle specific kinase
Lambert-Eaton myasthenic syndrome
Antibodies:
a. Anti-muscle specific kinase
b. Anti-NMDA receptor antibody
c. Anti-voltage gated calcium channel
antibody
d. Anti-Aquaporin 4 antibody
e. Anti-Hu (ANNA-1)
f. Anti-Yo (PCA-1)
g. Anti-Ri (ANNA-2)
h. Anti-Tr
i. Anti-GAD
j. Anti-voltage gated potassium channel
antibody
k. Anti-TA Ma2
l. Anti-GQ1b
m. Anti-myelin associated glycoprotein/sul-
fated glucoronul paragloboside
n. Anti-GD1b
c. Anti-voltage gated calcium channel
antibody
A 4-year-old is found to have dwarfism, mental retardation, and clouding of his cor- neas. Tests show an α-L-iduronidase deficiency.
Mucopolysaccharidoses:
a. Hunter syndrome
b. Hurler syndrome
c. Sanfilippo syndrome A
d. Sanfilippo syndrome B
e. Sanfilippo syndrome C
f. Sanfilippo syndrome D
g. Maroteaux-Lamy syndrome h. Morquio syndrome A
i. Morquio syndrome B
j. Natowicz syndrome
k. Sly syndrome
b. Hurler syndrome
A 6-year-old child is diagnosed with X- linked recessive mild learning difficulty due to iduronate sulfatase deficiency.
Mucopolysaccharidoses:
a. Hunter syndrome
b. Hurler syndrome
c. Sanfilippo syndrome A
d. Sanfilippo syndrome B
e. Sanfilippo syndrome C
f. Sanfilippo syndrome D
g. Maroteaux-Lamy syndrome h. Morquio syndrome A
i. Morquio syndrome B
j. Natowicz syndrome
k. Sly syndrome
a. Hunter syndrome
A 7-year-old child presents with severe skele- tal dysplasia, short stature. Test shows abnor- mal accumulation of keratan sulfate secondary to deficiency of galactose-6-sulfate sulfatase.
Mucopolysaccharidoses:
a. Hunter syndrome
b. Hurler syndrome
c. Sanfilippo syndrome A
d. Sanfilippo syndrome B
e. Sanfilippo syndrome C
f. Sanfilippo syndrome D
g. Maroteaux-Lamy syndrome
h. Morquio syndrome A
i. Morquio syndrome B
j. Natowicz syndrome
k. Sly syndrome
h. Morquio syndrome A
Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunction- ing of lysosomal enzymes needed to break down glycosaminoglycans forming bone, cartilage,
tendons, corneas, skin, and connective tissue. Buildup of glycosaminoglycans collect in the cells, blood and connective tissues cause progres- sive cellular damage which affects appearance, tis- sue function and mental development. All are autosomal recessive except for Hunter syndrome. Treatment is with enzyme replacement.
A 19-year-old male presents with diplopia, ataxia, and heart block.
Mitochondrial disorders:
a. Alpers-Huttenlocher syndrome
b. Ataxia neuropathy syndromes
c. Chronic progressive external ophthalmo-
plegia
d. Kearns-Sayre syndrome
e. Leber’s hereditary optic neuropathy
f. Leigh syndrome
g. MELAS
h. MEMSA
i. MERRF
j. NARP
d. Kearns-Sayre syndrome
A 24-year-old male presents with reduced vision in both eyes over several weeks, and has developed “spasms” of his left hand and complains of palpitations. ECG is sug- gestive of ventricular pre-excitation.
Mitochondrial disorders:
a. Alpers-Huttenlocher syndrome
b. Ataxia neuropathy syndromes
c. Chronic progressive external ophthalmo-
plegia
d. Kearns-Sayre syndrome
e. Leber’s hereditary optic neuropathy
f. Leigh syndrome
g. MELAS
h. MEMSA
i. MERRF
j. NARP
e. Leber’s hereditary optic neuropathy
A 34-year-old female with a history of migraines present’s with stroke-like epi- sodes affecting her left arm and leg, lactic acidosis, and cognitive impairment.
Mitochondrial disorders:
a. Alpers-Huttenlocher syndrome
b. Ataxia neuropathy syndromes
c. Chronic progressive external ophthalmo-
plegia
d. Kearns-Sayre syndrome
e. Leber’s hereditary optic neuropathy
f. Leigh syndrome
g. MELAS
h. MEMSA
i. MERRF
j. NARP
g. MELAS
Mitochondrial DNA is inherited maternally, and some of these disorders are thus transmitted from mother to children of both sexes. The mito- chondrial disorders, also termed mitochondrial
myopathies, encephalomyopathies, or respiratory chain disorders, are a heterogeneous group of dis- eases resulting from abnormalities in mitochon- drial DNA and respiratory chain function, hence manifest in tissue with a high respiratory workload such as brain, retina and skeletal mus- cle, especially extraocular and cardiac muscle
A 36-year-old female complianed of a syn- copal episode. She described dizziness and fatigue on her way to her bedroom, shortly after she passed out. She regained con- sciousness after a few minutes, feeling tired and soaked in her sweat. Her PE was normal. Her resting ECG was within
normal. Routine laboratory work up was
normal. Echocardiography was normal.
Syncope:
a. Autonomic failure
b. Cardiac arrhythmia
c. Carotid sinus syncope
d. Cerebrovascular steal
e. Dehydration
f. Drug-induced orthostatic syncope g. Epileptic seizure
h. Hypoglycemia
i. Neurally mediated (vasovagal) syncope
j. Non-epileptic attack disorder
k. Situational syncope
l. Structural cardiac disease
i. Neurally mediated (vasovagal) syncope
A 51-year-old female presents to the ER complaining of a sudden syncopal episode while climbing up the stairs. Her PE showed that she is in respiratory distress, BMI of 40, hemodynamically stable, cardiac examination showed normal. Routine laboratory work up was normal. Echocardi- ography was normal apart from mild MR
and mild TR.
Syncope:
a. Autonomic failure
b. Cardiac arrhythmia
c. Carotid sinus syncope
d. Cerebrovascular steal
e. Dehydration
f. Drug-induced orthostatic syncope g. Epileptic seizure
h. Hypoglycemia
i. Neurally mediated (vasovagal) syncope
j. Non-epileptic attack disorder
k. Situational syncope
l. Structural cardiac disease
b. Cardiac arrhythmia
A 72-year-old with a 10-year history of
Parkinson’s disease presents with recurrent syncopal episodes on standing up from a sitting position.
Syncope:
a. Autonomic failure
b. Cardiac arrhythmia
c. Carotid sinus syncope
d. Cerebrovascular steal
e. Dehydration
f. Drug-induced orthostatic syncope g. Epileptic seizure
h. Hypoglycemia
i. Neurally mediated (vasovagal) syncope
j. Non-epileptic attack disorder
k. Situational syncope
l. Structural cardiac disease
a. Autonomic failure
A 45-year-old woman with chronic atrial fibrillation discontinues warfarin treatment and abruptly develops problems with lan- guage comprehension. She is able to pro- duce some intelligible phrases and produces sound quite fluently; however, she is unable to follow simple instructions or to repeat simple phrases. On attempting to write, she becomes very frustrated and agitated. Emergency MRI reveals a lesion of the left temporal lobe that extends into the superior temporal gyrus.
Disorders of language:
a. Akinetic mutism
b. Anomic aphasia
c. Broca’s aphasia
d. Cerebellar mutism
e. Conduction aphasia
f. Global aphasia
g. Mixed transcortical aphasia
h. Transcortical motor aphasia
i. Transcortical sensory aphasia (fluent)
j. Wernicke’s aphasia
j. Wernicke’s aphasia
A 62-year-old man has had a left hemi- sphere stroke. He has impaired naming and repetition. His speech is nonfluent. Comprehension is preserved.
Disorders of language:
a. Akinetic mutism
b. Anomic aphasia
c. Broca’s aphasia
d. Cerebellar mutism
e. Conduction aphasia
f. Global aphasia
g. Mixed transcortical aphasia
h. Transcortical motor aphasia
i. Transcortical sensory aphasia (fluent)
j. Wernicke’s aphasia
c. Broca’s aphasia
A 28-year-old woman is hit in the left neck while playing lacrosse. Approximately 2 h later she begins having language difficulties. Her speech is fluent and nonsensical. She cannot understand commands, but repeats well.
Disorders of language:
a. Akinetic mutism
b. Anomic aphasia
c. Broca’s aphasia
d. Cerebellar mutism
e. Conduction aphasia
f. Global aphasia
g. Mixed transcortical aphasia
h. Transcortical motor aphasia
i. Transcortical sensory aphasia (fluent)
j. Wernicke’s aphasia
i. Transcortical sensory aphasia (fluent)
