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. 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 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 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). 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
b. Treat cardiovascular risk factors
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, 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 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 reflexes were 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 (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 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 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 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 demye- linating 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, and visual impairment. On CT this 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 demen- tia 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.
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 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.
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 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 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 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 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 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) 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 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 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 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 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 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 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, 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 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 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.
