Neurology

Question 1

What is the significance of CSF oligoclonal bands?

Answer 1

> serum = high immunoglobulins in CSF
Classically seen in MS
Also seen in other demyelinating diseases of childhood like ADEM and ATM

Question 2

A 4 year old boy presents with 2 days of fever, headache, and altered gait.

His Mother has brought him to ED because he has stopped moving the left side of his body.

CSF studies show pleocytosis but are negative on both culture and PCR.

MRI brain is shown below. What is the diagnosis and what treatment would you offer?

Answer 2

MRI - multiple periventricular white matter lesions are seen on T2 (CSF = white)
History with these Ix findings highly suggestive of ADEM.
Initial management would be with 5 days of 15 mg/m2 methylprednisolone

Question 3

Which spinal levels are involved in the abdominal reflexes?

Answer 3

T7-12

Question 4

What is the significance of MOG antibodies in paediatrics?

Answer 4

Myelin oligodendrocyte glycoprotein
May be associated with MS, optic neuritis or transverse myelitis

Question 5

What is the clinical significance of NMO antibodies in paediatrics?

Answer 5

Neuromyelitis optica antibodies are antibodies against aquaporin 4, found on astrocyte feet
NMO has only recently been recognised as a syndrome distinct from MS - initially characterised as being optic neuritis + transverse myelitis without brain white matter lesions, it has since been recognised as having some characteristic brain lesions:
Area postrema syndrome - intractable hiccups or vomiting
Acute brain steam syndrome - cranial nerve palsies, dysarthria
Diencephalic syndrome - narcolesy, SIADH, galactorrhoea
Cerebral lesions may be found in some patients

Question 6

10 year old boy complains of sudden onset back back, he has bilateral leg weakness with hyperreflexia and urinary retention.

MRI shown below.

What is the most likely diagnosis?

Answer 6

MRI shows a T2 hyperintense cord signal at the level of T10
This, with the history is suggestive of transverse myelitis

Question 7

Which of the following is NOT a typical finding of optic neuritis?

a. Reduced visual acuity
b. colour desaturation on ishihara
c. central scotoma
d. RAPD
e. pain on eye movement
f. conjunctival injection

Answer 7

f. conjunctival injection

Question 8

Spot diagnosis

Answer 8

Single parasagittal FLAIR image demonstrating multiple periventricular demyelinating plaques extending radially away from the body of the lateral ventricle. These are characteristic of Dawson’s fingers in a patient with known multiple sclerosis.

Question 9

Name the typical location of lesions in MS?

a. juxtacortical
b. periventricular
c. deep white matter
d. infratentorial

Answer 9

a. juxtacortical
b. periventricular
c. deep white matter
d. infratentorial

Question 10

A patient commences IFN-beta1b (Avonex) for multiple sclerosis
What adverse events will you warn them about?

Answer 10

This is SC injection so injection site reactions
Can also cause flu like symptoms, LFT derangement and leukopenia

Question 11

What is the mechanism of fingolimod for use in MS?

Answer 11

Fingolimod (FTY720) is a first-in-class orally bioavailable compound that has shown efficacy in advanced clinical trials for the treatment of multiple sclerosis (MS). In vivo, fingolimod is phosphorylated to form fingolimod-phosphate, which resembles naturally occurring sphingosine 1-phosphate (S1P), an extracellular lipid mediator whose major effects are mediated by cognate G protein-coupled receptors. There are at least five S1P receptor subtypes, known as S1P1–5, four of which bind fingolimod-phosphate. These receptors are expressed on a wide range of cells that are involved in many biological processes relevant to MS. S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. Fingolimod-phosphate initially activates lymphocyte S1P1 via high-affinity receptor binding, yet subsequently induces S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system (CNS).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859693/#:~:text=Fingolimod%2Dphosphate%20initially%20activates%20lymphocyte,central%20nervous%20system%20(CNS).

Question 12

Describe the potential adverse effects of fingolimod

Answer 12

QT prolongation, bradycardia
Macular edema (biggest risk in first 6 months, goes away if ceased)
Infections – cryptococcal meningitis, disseminated herpes and varicella, progressive multifocal encephalopathy from JC virus
Deranged LFTs – monitor
Lymphopenia

Question 13

What is the most common cause of paediatric arterial ischaemic stroke?

Answer 13

A = 50% is arteriopathy
Can be focal cerebral arteriopathy, post varicella arteriopathy, Moya Moya, congenital cerebral artery hypoplasia (PHACE)

25% are cardiogenic (congenital cyanotic heart disease)
Other causes - thrombophilia - prothrombin gene mutation, sickle cell, factor V leiden, protein C & S deficiency

Question 14

Define the following terms

Rigidity
Akinesia
Hypokinesia
Bradykinesia

Answer 14

Rigidity = inability of the muscles to relax normally
Akinesia = inability to initiate movement
Hypokinesia = reduction in the amount of spontaneous movement
Bradykinesia = slowness of movement

Question 15

Define chorea and name some common causes

Answer 15

Chorea: non-rhythmic, non-suppressible jerky movements primarily of the distal muscles or the muscles of the face

Causes: Sydenham chorea, Wilsons, autoimmune (SLE, NMDA encephalitis), CNS infections (toxoplasmosis, neurosyphilis, viral encephalitis), basal ganglia lesions (stroke, bleed), medications (AED, antipsychotics)’

https://www.youtube.com/watch?v=wTCnbga3sqg

Question 16

Name the 3 diagnostic criteria for Tourette’s syndrome

Answer 16

Multiple motor and vocal tics
Present for >12 months
No more than 3 months tic free

Question 17

Child who develops ataxia around the age of 3 with bronchiectasis and abnormal skin markings: spot diagnosis

Answer 17

Answer = ataxia telangectasia
Mutation the ATM gene which is involved in DNA repair an the regulation of the cell cycle
Features
Ataxia age 2-3 (first)
Immune deficiency - recurrent sinopulmonary
Eye movement abnormalities
Cutaneous telangectasia

Other features
Café au lait macules
Pulmonary disease
Recurrent sinuopulmonary infections and bronchiectasis
Interstitial lung disease/ pulmonary fibrosis
Neuromuscular disease
Malignancy
High risk of Lymphoreticular tumours + brain tumours
Radiation sensitivity
Growth retardation
Diabetes mellitus

Question 18

Spot diagnosis:

12 year old patient. 2 years of worsening ataxia, legs worse than arms.
On neurological exam you note dysarthric speech and loss of crude touch, proprioception and vibration with pain and temperature intact

What will you find on genetic testing?

Answer 18

This is Friedrich’s ataxia
Genetic tests would should >35 repeats of GAA on mitochondrial protein frataxin
Oxidative injury leads to deposits of iron in the mitochondria
Cerebellum and dorsal columns particularly affected
Other manifestations:
Diabetes mellitus
Hypertrophic cardiomyopathy

Question 19

What are the clinical features of syringomyelia?
Name some causes

Answer 19

Numbness in a ‘cape like’ distribution
Wasting of the small muscles in the hand
This is due to a predominant ‘central cord’ syndrome
May have bladder urgency and scoliosis
Causes include
Congenital - tethered cord, Chiari malformation (particularly type 1), NTD
Acquired - trauma, tumour, infectious ect

Question 20

You review a 10 month old child in clinic who has rapidly progressive macrocephaly and gross motor delay.

You perform and MRI which shows cystic dilatation of the 4th ventricle, small cerebellar vermis and enlarged posterior fossa.

What is the diagnosis?

Answer 20

The answer is Dandy Walker malformation
Mnemonic for CSF system attached

Alternative is:

Monroe (sounds like mono) - IV foramin (1st one)
Aqueduct of sylvius (or cerebral) - H20, water flows in aqueduct, is the 2nd one
Foramen of lushke and magende - Lushke is the L lateral apeture

Question 21

You see an adolescent patient with disabling migraines and decide to institute prophylaxis. They are obese and have troublesome asthma.

What would be the most appropriate prophylactic medication?

a. topomax
b. propanolol
c. flunarizine
d. cyproheptadine

Answer 21

Topomax - associated with weight loss

Flunarizine and propanolol are associated with weight gain

Question 22

Identify the seizure type

Answer 22

This EEG shows 3 Hz (3 per second) spike and wave which is characteristic of absence epilepsy
May be triggered by hyperventilation
In atypical absence the spike and wave tends to be 1.5 - 2

Question 23

You review a 14 year old patient in ED. They have had a 3 minute GTC at home whilst getting ready for school and have been brought in by ambulance.

BGL, screening electrolytes and FBE are normal.

The patient is well with a normal neurological examination.

On further history the patient reports that they often notice jerking movements of their body in the morning and that they had a few of these before the seizure.

The parents have noticed the child dropping things.

What EEG pattern would you expect?

Answer 23

Answer: this stem is highly suggestive of juvenile myoclonic epilepsy.

The EEG will show 3-6 Hz polyspike and wave discharges - see attached

Age of onset is adolescence

Seizure types include myoclonic, and in <50% absence
May be triggered by photic stimulation, tiredness

Treated with valproate (most effective, but not recommended in adolescent females), lamotrigine and keppra

Question 24

What is the diagnosis based on this eeg?

Answer 24

Infantile spasms or west syndrome

Question 25

What EEG findings would you expect in Lennox-Gastaut syndrome?

Answer 25

<2.5 Hz generalised spike and slow wave discharges Other features might include generalised slowing, paroxysmal fast activity often multifocal spikes and sharp waves

Question 26

What EEG findings would you expect in progressive myoclonic epilepsy?

Answer 26

Generalised + multi focal spikes + sharp waves May also see progressive background slowing with disease progression, photic activation of IEDs may be seen

Question 27

A 5 year old male patient is brought for review because of a ?seziure episode They were woken from sleep with an abnormal sensation in their throat then were found to be drooling with contractions on the left side of their face They appeared to be aware of their parents speaking to them and clung to them for comfort but did not respond verbally to questions The episode lasted 4 minutes What EEG findings would you expect?

Answer 27

The stem is highly suggestive of benign rolanidc epilepsy Occasionally the seizure may also progress to a focal seizure with impaired awareness or focal to bilateral tonic clonic seizure You would expect wide based centro-temporal spikes, worse in sleep or during drowsiness

Question 28

Which of the following symptoms is most common in ADEM? a. pyramidal signs b. seizures c. ataxia d. optic neuritis

Answer 28

Answer = A pyramidal signs

Question 29

Which of the following is NOT true regarding the differences between ADEM and MS? a. MRI involvement of the spinal cord in ADEM is rare b. in ADEM there is relative sparing of the periventricular white matter and corpus callosum, whilst these areas are classically effected in MS c. encephalopathy is frequent in ADEM but rare in MS d. seizures may occur in ADEM but are rare in MS

Answer 29

a. MRI involvement of the spinal cord in ADEM is rare - FALSE, THERE MAY BE SPINAL CORD INVOLVEMENT W/O CLINICAL SIGNS AND AS SUCH CORD SHOULD BE INCLUDED IN NEUROINFLAMMATION PROTOCOLS b. in ADEM there is relative sparing of the periventricular white matter and corpus callosum, whilst these areas are classically effected in MS - TRUE c. encephalopathy is frequent in ADEM but rare in MS - TRUE d. seizures may occur in ADEM but are rare in MS - TRUE

Question 30

What is the risk of relapse in NMO antibody (ie: antibodies to aquaporin 4) positive neuroinflammation?

Answer 30

80% Aggressive disease High probability of blindness or wheelchair dependence Treat aggressively/early with immunomodulation (see below) teroids: high dose IV methylprednisolone (30 mg/kg/day) for 3-5/7 ○ Up to 80% respond within 1-5 days ○ Followed by long taper (3-6 months) • IVIG/plasma exchange ○ Early initiation of escalation therapy is recommended in steroid unresponsive relapse with better outcomes for PLEX within 30 days cf 30-90 days • Immunomodulatory therapy recommended after first attack if confirmed AQP4 antibody positive • Mycophenolate (with 3-6 months steroid cover because MMF can take ~4 months to be active)) ○ Reduced relapse rate by 87% (JAMA Neurology 2014) • Rituximab ○ Reduced relapse rate by 88% (JAMA Neurology 2014) ○ Either redosing as B cells repopulate (>10 x 10^6/L) § Risk of 're-population' relapse § Or 500 mg Q3 month dose

Question 31

Spot diagnosis: a neonate with encephalopathy, low platelets, deranged LFTs and calcifications on brain imaging Infective screen including CMV is negative Later develops chillblaines

Answer 31

Aicardia-Goutieres syndrome Interferonopathy

Question 32

True or false Patients with charcot marie tooth disease tend to have champagne bottle legs, wasting of the small muscle of the hand and pes planus

Answer 32

False They will have champagne bottle legs, wasting of the small muscle of the hand and pes CAVUS

Question 33

What is the most common form of CMT?

Answer 33

CMT1a - this is a demyelinating neuropathy CMT 2... are axonal

Question 34

What is the genetics/inheritance pattern on CMT1a

Answer 34

Autosomal dominant Duplication - more severe the duplication the more severe the phenotype The specific mutation is in the protein PMP22 Locus is chromosome 17p11

Question 35

Does this report suggest an axonal or demyelinating neuropathy?

Answer 35

Demyelinating - reduced conduction velocity In axonal would be decreased amplitude due to fibre loss

Question 36

Describe the pharmacology of carbamazepine

Answer 36

Na channel blocker Enzyme inducer May reduce levels of lamotrigine, valproate and TOP, PMP, zonisamid

Question 37

What are the indications for and adverse effects of carbamazepine

Answer 37

1st line FS GTCS Nuisance: tics, transient leukopenia, hyponatraemia, weight gain, nausea, dizziness Serious, SJS (HLA1502) agranulocytosis, aplastic anaemia, liver toxicity

Question 38

What is the mechanism of action of ethosuximide?

Answer 38

Blockade of T type calcium channels in the thalamocortical neurons

Question 39

What is the mechanism of action of lacosamide and how does this relate to its adverse effects?

Answer 39

sodium channel inhibitor Nuisance: diplopia, headache, dizziness, nausea Serious: cardiac arrhythmia (if predisposed) Note usually used for focal seizures

Question 40

What are the indications for the use of lamotrigine?

Answer 40

LGS, focal and tonic clonic, >2yrs Broad spectrum

Question 41

Name the MOA and adverse effects for lamotrigine

Answer 41

Nuisance: headache, ataxia, dizziness, tremor but usually less than other AEDS Serious: SJS, rarely liver toxicity Na channel blocker

Question 42

What is the mechanism of action of levetiracetam

Answer 42

Binds to synaptic vesicle protein SV2A, reduced glutamate vesicle release

Question 43

What are the adverse effects of oxcarbazepine

Answer 43

Somnolence, headache, dizziness, nausea, apathy, rash, hypertrichosis, gingival hypertrophy, hyponatraemia

Question 44

Describe the pharmacology of phenytoin

Answer 44

Na channel blocker Enzyme inducer Nuisance: gingival hyperplasia, coarsening of the facies, hirsutism, nystagmus and ataxia Serious: SJS, liver toxicity

Question 44

Describe the pharmacology of phenytoin

Answer 44

Na channel blocker Enzyme inducer Nuisance: gingival hyperplasia, coarsening of the facies, hirsutism, nystagmus and ataxia Serious: SJS, liver toxicity

Question 45

What is the mechanism of action of topiramate?

Answer 45

Main: downregulates NMDA receptor activity Na channel blocker Enhances GABA receptor activity

Question 46

What are the indications for topiramate use?

Answer 46

Broad LGS, focal and tonic clonic seizures

Question 47

What are the adverse effects of topomax?

Answer 47

Nuisance: cognitive dysfunction, weight loss, hyperhidrosis, fever Serious: precipitation of glaucoma, renal calculi (weak carbonic anhydrase inhibitor in the brain)

Question 48

Describe the pharmacology of valproate

Answer 48

Enzyme inhibitor, increases levels of lamotrigine, phenobarbitol and felbamate Displaces phenytoin from protein binding sites Inhibits GABA transaminases, induces GABA synthesis

Question 49

What are the adverse effects of valproate?

Answer 49

Nuisance: weight gain, hyperammonaemia tremor, alopecia, menstrual irregularities Serious: hepatic and pancreatic toxicity

Question 50

Describe the adverse effects of triptans

Answer 50

Adverse effects of triptans Caused by central serotonergic effects Include: § Tightness in the chest, jaw and fingers due to vascular constriction § Subsequent feeling of grogginess and fatigue

Question 51

Name the medications thought to be associated with idiopathic intracranial hypertension

Answer 51

Prolonged steroid therapy or steroid withdrawal, ?growth hormone treatment, OCP Nalidixic acid, doxycycline, minocycline, tetracycline, nitrofurantoin, isoretinoin (for acne), valproate

Question 52

Which cranial nerve is most commonly impaired in IIH?

Answer 52

6th cranial nerve (abducens)

Question 53

What is the most common ophthalmological defect in idiopathic intracranial hypertension?

Answer 53

Visual field loss Usually inferonasal and enlarged physiological blind spot

Question 54

What is Miller-Fisher syndrome

Answer 54

Rare GBS variant The clinical hallmark of MFS is a triad presentation of acute ophthalmoplegia, areflexia, and ataxia in the setting of a preceding bacterial or viral illness. Distal paresthesia with or without weakness is also present. Symptoms on an average peak in four weeks or less, with supporting ancillary criteria as described by Brighton for GBS by Fokke C et al. in 2014. Other associated symptoms include diplopia or blurred vision, dysarthria, dizziness, and extremity tingling. https://www.ncbi.nlm.nih.gov/books/NBK507717/

Question 55

What is the mechanism of the symptoms of tic paralysis?

Answer 55

Acts on pre-synaptic motor terminals to inhibit the release of acetylcholine

Question 56

what is the most common cause of epilepsy worldwide?

Answer 56

Neurocysticercosis (NCC), the most common cause of epilepsy worldwide, is caused by brain cysts from the Taenia solium tapeworm.

Question 57

what are the clinical features of Emery-Dreifuss muscular dystrophy (EDMD)

Answer 57

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of: joint contractures that begin in early childhood; slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles; and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure along with variable cardiac rhythm disturbances. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade and respiratory function may be impaired in some individuals

Question 58

what is the underlying cause of krabbe disease

Answer 58

Krabbe disease (globoid cell leukodystrophy) is a rare autosomal recessive disorder caused by the deficiency of the enzyme galactocerebrosidase (GALC; also known as galactosylceramidase) Is a lysosomal storage disease Presents with irritability and reflux, then spasticity, finally areflexia and profound weakness In children with infantile-onset Krabbe disease, the most frequent MRI abnormalities involve the deep cerebral white matter, dentate nucleus, and cerebellar white matter

Question 59

an 17 months old child develops gait disturbance and frequent falls Hypotonia and areflexia develops Child becomes apathetic, dull and has slurred speech Brain MRI reveals symmetric white matter lesions with a periventricular and/or frontal predominance what condition are you suspicious for?

Answer 59

Metachromatic leukodystrophy