Myopathy, NMJ, peripheral nerve, anterior horn

Question 1

Brachial neuritis
a) Presentation vs cervical radiculopathy
b) Investigations
c) Management

Answer 1

a) - Severe acute pain in the shoulder/upper arm initially, not affected by movement (cervical radiculopathy is affected by movement), may keep them awake at night.
- The pain lasts 2-3 days
- ~1 week later - weakness/wasting in affected arm, affecting approx 2 nerves of brachial plexus (cervical radiculopathy tends to occur at same time as the pain)
- May be triggered by vaccination, infection, surgery, trauma

b) - MRI spine to r/o other cause
- 3 weeks post-onset, perform NCS (earlier than this may show false negative)

c) - Pain management
- Once pain improved, physiotherapy
- Improves without treatment after a few months

Question 2

Myotomes
a) Upper limbs C4-T1
b) Lower limbs L2-S1

Answer 2

C4 - shoulder shrug
C5 - shoulder abduction, elbow flexion
C6 - wrist extension
C7 - elbow extension
C8 - finger flexion, thumb abduction
T1 - finger abduction

L2 - hip flexion
L3 - knee extension
L4 - foot dorsiflexion
L5 - hallux dorsiflexion
S1 - foot plantarflexion

Question 3

Dermatomes
a) Upper limb
b) Trunk
c) Lower limb

Answer 3

Upper limb:
C4: over the acromioclavicular joint
C5: “regimental badge”
C6: the palmar side of the thumb
C7: the palmar side of the middle finger
C8: the palmar side of the little finger
T1: medial aspect ACF

Trunk:
- T4: nipple
- T6: xiphoid process
- T10: umbilicus

Lower limb:
L1: the inguinal region and the very top of the medial thigh.
L2: the middle and lateral aspect of the anterior thigh.
L3: the medial epicondyle of the femur.
L4: the medial malleolus.
L5: the dorsum of the foot at the third metatarsophalangeal joint.
S1: the lateral aspect of the calcaneus.
S2: at the midpoint of the popliteal fossa.
S3: at the horizontal gluteal crease (the horizontal crease formed by the inferior aspect of the buttocks and the posterior upper thigh).
S4/5: the perianal area.

Question 4

Innervation of lower limb
a) Describe the nerve roots and movements for each of the main nerves in the lower limb
b) Explain the presentation of each palsy
c) Peroneal nerve palsy vs. L5 radiculopathy
d) Which disc protrusion causes (i) L5 radiculopathy, (ii) C7 radiculopathy
e) Assessment of footdrop
f) What is meralgia paraesthetica? How is it differentiated from other pathology?

Answer 4

Common peroneal nerve:
- Peroneal Eversion Dorsiflexion (PED)
- Compression at fibular head/trauma, mononeuritis, MND
- Damage causes weakness in eversion and dorsiflexion (preserved inversion and plantarflexion)
- Also have reduced sensation in lateral aspect of leg

Tibial nerve:
- Tibial Inversion Plantarflexion (TIP)
(not a cause of footdrop)
- May be caused by tarsal tunnel syndrome (pain, numbness affecting first 3 1/2 toes), e.g. by fallen arches

Sciatic nerve:
- L5-S2
- LED + TIP (all movements at foot)
- Plus… knee flexion

L5 radiculopathy: (LIED)
- L5 Inversion Eversion Dorsiflexion
- Plus… hip abduction
- Lateral hip pain common, pain on SLR/dorsiflexion
- Lumbar disc disease, sciatica

Obturator nerve:
- Hip adduction
- Medial sensation of thigh

Femoral nerve:
- L2-L4
- Damage causes weakness of hip flexion (iliopsoas, L2 root) and knee extension (quads, L3 root), with sensory loss in anterior thigh and medial leg
- Will also cause loss of antero-medial sensation to the leg and hallux (saphenous nerve)
- May be caused by retroperitoneal haematoma (beware patients on anticoagulation)

d) - Cervical spinal nerves (C1-8) arise ABOVE the corresponding cervical vertebral bones (C8 arises above T1). Therefore, C7 radiculopathy will be caused by a C6/7 disc protrusion (as C7 arises above C7 vertebra - i.e. between C6 and C7)
- Thoracic and lumbar spinal nerves arise BELOW corresponding vertebral bones. Therefore, L5 radiculopathy will be caused by an L5/S1 disc protrusion (as L5 root arises below L5 vertebra - i.e. between L5 and S1)

e) Footdrop:
- Causes: peroneal neuropathy (habitual leg crossing, fibular neck compression, “slimmer’s palsy”, MND, mononeuritis, diabetes, alcohol, B12), L5 radiculopathy (back pain), sciatic neuropathy (hip surgery), lumbar plexopathy, compartment syndrome (painful!)
- Assess normal gait (slap/drag) and heel walking
- Assess foot movements (dorsi/plantar/inversion/eversion) and knee/hip (hip abduction weak - L5; knee flexion weak - sciatic)
- Assess sensation - midfoot (L5 dermatome), lateral leg (common peroneal)
- Assess for back pain. Assess for fibular compression. Assess for Baker’s cysts
- Tinels sign - tap at fibular head - if causes symptoms likely fibular compression cause
- Assess for other neurology ?fasiculations/ atrophy/ reflexes/ plantars - ?ALS etc.

f) - Compression of lateral femoral cutaneous nerve (L2-L3) around the inguinal ligament/ASIS
- Risk factors - bending down, cycling, pregnancy, obesity, pressure or trauma in that area (e.g. tight low-waisted trousers)
- Presents with purely sensory symptoms - pain, paraesthesia and numbness in the anterolateral thigh, often worse with walking/bending down
- vs L2-L3 nerve/root compression - does NOT cause weakness (normal hip flexion) and no back pain; pain/symptoms reproduced by pressing medial to ASIS or extension of hip (but have NORMAL straight leg raise)
- Should also exclude retroperitoneal mass (e.g. tumour, haemorrhage) and diabetic amyotrophy (tends to be symmetrical)
- NCS may be useful
- Management - weight loss, avoid compression, NSAIDs, neuropathic agents, steroid injections, surgery

Question 5

Internuclear ophthalmoplegia and one-and-a-half syndrome

Answer 5

INO:
- Caused by damage to the MLF* (causes include MS - often bilateral, stroke - usually unilateral)
- Ipsilateral weakness in ADduction
- Contralateral horizontal nystagmus on ABduction
- No issue with ABduction on ipsilateral side or ADduction on contralateral side
- Lesion in the medial longitudinal fasciculus (connection between CN 3 and 6)

*MLF in the medial medulla - abnormalities could be part of a medial medullary syndrome

OAHS*:
- Caused by pontine lesions affecting the paramedian pontine reticular formation and MLF (causes include pontine stroke, tumour, MS)
- Ipsilateral horizontal gaze palsy
- Contralateral weakness in ADduction, often with nystagmus on ABduction
(could also be caused by CN VI palsy on ipsilateral side and MLF damage on contralateral side)

*One eye cannot move at all, the other can move halfway (i.e. one and a half syndrome)

Question 6

Demyelinating polyneuropathies
- AIDP (GBS) - typical presentation, results and management
- vs Miller-Fisher - triad, antibodies, etc.
- vs BBE
- vs CIDP
- vs MMN
- features on NCS

Answer 6

GBS:
- Causes include 75% preceding GI/resp infection, lymphoma, vaccines
- Clinical fx: ascending symmetrical weakness, areflexia, sensory loss, may involve bulbar/respiratory muscles, autonomic dysreflexia. Note that back pain is a common feature so don’t assume this means CES
- Peak symptoms at 4 weeks
- Monitor FVC, ECG
- CSF - albuminocytological dissociation (elevated protein with normal WCC)
- Anti-GM1 antibodies may be present (esp. recent c.jejuni infection)
- NCS: segmental demyelination with conduction block and temporal dispertion (in severe cases may cause axonal degeneration, with action potential amplitude reduction)
- Rx: supportive, IVIG, plasma exchange

Miller-Fisher:
- Similar to GBS, acute progression over days, often 1-4 weeks following infection, e.g. gastroenteritis
- Classic triad: ataxia, ophthalmoplegia, areflexia
- Affects cranial/facial nerves (e.g. opthlalmoplegia, ptosis, facial palsy, dysphagia, dysarthria) but not limb weakness
- CSF elevated protein, antibodies to ganglioside GQ1b (90%)
- May progress to involve limbs/respiratory (evolving into GBS)

BBE:
- Brachial-cervical-pharyngeal weakness with ophthalmoplegia, ataxia and encephalopathy (Miller fisher with confusion or coma)
- May have hyperreflexia and upgoing plantars
- also associated with GQ1b antibody

CIDP:
- Symptoms lasting >8 weeks, slowly progressing
- Typical - symmetrical distal and proximal weakness, areflexia
- Atypical - multifocal (asymmetric)

MMN:
- Pure motor neuropathy (LMN pattern of weakness)
- Asymmetrical, predominantly affecting upper limbs, does not affect bulbar muscles, often following a particular peripheral nerve
- Weakness may be worse in the cold
- Conduction blocks on NCS
- Anti-GM1 antibodies
- Rx: IVIG

Question 7

Nerve conduction studies
- Axonal vs demyelinating neuropathy
- Examples of each
- Which does isoniazid cause? How can this risk be reduced?

Answer 7

Axonal
- action potential amplitude reduced, conduction speed preserved
- Amplitude of compound muscle action potential (CMAP) correlates with the number of motor nerve axons, and amplitude of sensory nerve action potential (SNAP) reflects the number of sensory nerve axons.
- There may also be evidence of active denervation in EMG - neurogenic pattern (few motor units but some with very high activity - positive sharp waves and fibrillations)
- Alcoholic neuropathy is pure axonal; paraneoplastic is usually axonal; diabetic is mixed axonal and demyelinating.
- MND causes retrograde axonal neuropathy, and should not have features of demyelination or conduction block
- Isoniazid causes axonal neuropathy, often painful, which can be reduced by use of pyridoxine (vitamin B6)

Demyelinating
- conduction speed reduced, action potentials normal.
Note that in severe demyelinating disease, axonal loss may follow.
- GBS/CIDP demyelinating; compressive neuropathy demyelinating
- Note that severe cases of demyelinating neuropathy may progress to involve the axons

Question 8

Patterns of neuropathy:
a) Symmetric, length-dependent distal weakness with sensory loss (Most Common type)
b) Symmetric proximal and distal weakness with sensory loss and areflexia
c) Multiple mononeuropathies
d) Asymmetric weakness with intact sensory exam
e) Asymmetric weakness with pain in a dermatomal distribution
f) Sensory ataxia with or without weakness
g) Significant autonomic involvement

Answer 8

a) Metabolic neuropathies (e.g. diabetes), toxic neuropathies, Charcot-Marie-Tooth disease

b) Inflammatory demyelinating polyneuropathies (CIDP and GBS)

c) Vasculitic neuropathy (mononeuritis multiplex), hereditary neuropathy with liability to pressure palsies (HNPP)

d) Motor neuron disease, multifocal motor neuropathy, atypical CIDP

e) Radiculopathy

f) Sensory neuronopathies from paraneoplastic syndrome, Sjogren’s syndrome, DM, etc.

g) Amyloidosis, diabetic neuropathy, Sjogren’s, Parkinson’s-Plus syndromes

Question 9

Trendelenburg sign
- what is it
- cause

Answer 9

• When standing on affected leg, pelvis will drop to contralateral side
• Damage to superior gluteal nerve (e.g. IM injection)

Question 10

Demyelination
a) Wallerian vs. segmental demyelination
b) Findings on NCS

Answer 10

Wallerian demyelination involves demyelination distal to a focal lesion/trauma (e.g. nerve compression)

Segmental demyelination occurs from an inflammatory process (e.g. GBS)

b) Reduced conduction velocity
Prolonged F wave latency
Normal action potential amplitude (SNAP and CMAP)

Question 11

Genetic cause of adrenal insufficiency + demyelination
a) Name
b) Inheritance and gene
c) Presentation
d) Tests
e) Treatment

Answer 11

a) X-linked adrenoleukodystrophy

b) X-linked
- ABCD1 gene

c) 3 types:
- Childhood form - age 4-8, seizures, mobility issues, learning disability
- Early adulthood form - age 20s, MS-like presentation (myelopathy) + Addisonian syndrome
- Addisonian-only form

d) Very long chain fatty acids (VLCFA)

e) Lorenzo oil can reduce serum levels of VLCFA
Only curative treatment is bone marrow transplant

Question 12

MG vs LEMS

Answer 12

• Both commonly cause proximal muscle weakness and can affect the respiratory, bulbar and ocular muscles
• MG affects CNs more often, especially extra-ocular muscles (90% MG have ptosis or diplopia vs 20-25% in LEMS)
• Both may be paraneoplastic: MG may be associated with thymoma, while 60% LEMS is from SCLC (smoking history)
• Both cause fatigable weakness, but LEMS may be better in the evening while MG is always worse in the evening
• LEMS almost always (90%) have autonomic symptoms (e.g. dry mouth, postural hypotension, urinary/bowel/sexual dysfunction); autonomic symptoms less common in MG
• LEMS - hyporeflexic (reflexes may improve after exertion); MG reflexes normal
• Antibodies to post-synaptic ACh receptor or MuSK in MG; antibodies to pre-synaptic voltage gated calcium channels in LEMS
• MG is more steroid responsive; LEMS often only improves if underlying malignancy is treated (though you can trial 3,4-Diaminopyridine i.e. amifampridine)

Question 13

Spinal shock vs neurogenic shock

Answer 13

Spinal shock
- Flaccid paralysis and areflexia that occurs in the acute phase of a traumatic or ischaemic spinal cord injury (last hours to days, before progressing to typical UMN spinal cord pattern of weakness)

Neurogenic shock
- Hypotension + bradycardia (or lack of appropriate tachycardia)
- Caused by spinal cord lesions above T6, affecting sympathetic tone

Question 14

Anterior vs. medial vs. posterior cavernous sinus syndrome

Answer 14

Anterior - affects V1
Medial - affects V1 + V2
Posterior - affects V1 + V2 + V3

Question 15

Orbital apex syndrome vs. cavernous sinus syndrome vs. superior orbital fissure syndrome

Answer 15

Orbital apex syndrome:
- involves the optic canal and superior orbital fissure
- involves the optic nerve, plus CN III, IV and VI
- commonly causes proptosis and chemosis, may also cause Horner’s
- is generally indolent in presentation (weeks - months)
- may be caused by tumour extension into orbital apex (e.g. NP tumour, Burkitt’s, schwannoma, metastates)
- may also be caused by inflammatory (sarcoid, vasculitis) or infective (invasive sinusitis or orbital cellulitis)

Cavernous sinus syndrome
- Does not affect optic nerve, but commonly affects CN III, IV, V1, V2, VI
- Main cause is CST, which can be septic (usually staph aureus) or aseptic. Other causes include tumour infiltration, trauma and infective infiltration
- Septic CST usually results from peri-orbital or sinus infection, but may be from sepsis or distant site (septic emboli)
- Aseptic CST occurs in a pro-thrombotic state - genetic (e.g. antithrombin 3 def/protein C or S def/factor V leiden) or acquired (pregnancy, COCP, APLS, nephrotic syndrome, leukaemia, PRV)
- Presents with retro-orbital headache, proptosis, chemosis, ophthalmoplegia, fever (if septic CST), Horner’s, stroke-like syndrome, features of raised ICP
- Does NOT involve optic nerve, unless progressing into the orbital apex
- CN VI (lateral gaze) palsy often first due to position within sinus (surrounded by blood)
- Diagnose via cerebral MR venography
- Rx: fluids, LMWH

Superior orbital fissure syndrome:
- Main cause is trauma
- Features include the above (ophthalmoplegia, chemosis, proptosis), but…
- Does NOT affect optic nerve (vs. orbital apex syndrome)
- Does NOT cause Horner’s, unlikely to be painful, and unlikely to have features of raised ICP/sepsis (vs. CST)

Question 16

Amyloidosis
- types
- typical neurological involvement (20% cases)
- other clinical features
- histology
- management

Answer 16

Types:
- Primary (AL) - associated with MGUS, average age 65
- Secondary (AA) - associated with IBD, RA, AS and malignancy

Sensory neuropathy with autonomic features (postural hypotension)
Carpal tunnel syndrome common

Other features:
- Renal involvement (90%) - nephrotic syndrome, progresses to ESRD
- Restrictive cardiomyopathy
- Spontaneous periorbital purpura - racoon eye sign
- Thyroid nodule/goitre

Histology of involved site: Congo red-positive amyloid deposits, with typical apple-green birefringence under polarised light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence

Management:
- Chemotherapy/stem cell transplant
- Renal supportive therapy
- Heart failure therapy - diuretics, PPM, etc.

Question 17

Subacute combined degeneration of the cord
- Spinal tract involvement
- Clinical features
- vs. tabes dorsalis

Answer 17

• Involves dorsal columns initially (sensory loss, paraesthesia, sensory ataxia), then corticospinal tracts (UMN pattern of weakness), then spinocerebellar tracts (gait ataxia)
  Spinothalamic tracts generally last to be affected
• Spastic weakness
• Ankle jerks often absent, while reflexes elsewhere tend to be brisk including flexor plantar responses
• Symmetrical involvement

Tabes dorsalis (due to tertiary syphilis) often causes Argyll-Robertson pupil also

Question 18

Spinal bulbar muscular atrophy
a) Other name
b) Cause
c) Presentation

Answer 18

a) Kennedy’s disease

b) X-linked recessive condition causing defective androgen receptor (AR) gene, resulting in CAG repeats. These lead to degeneration of lower motor neurones affecting the spinal and cranial nerves

c) Onset in males age 20-50:
- LMN pattern of weakness, affecting mainly proximal and bulbar muscles (spares the extra-ocular muscles)
- Muscle cramping
- Perioral and tongue fasciculations
- Muscle wasting, hyporeflexia
- Androgen insensitivity - infertility, gynaecomastia
- May have sensory loss

Question 19

Duchenne’s vs. Becker muscular dystrophy

Answer 19

DMD:
- X-linked condition causing COMPLETE loss of dystrophin (required for skeletal muscle cell membrane integrity), more common than Becker’s
- Age of onset generally before 6
- Proximal muscle weakness (Gower sign, calf hypertrophy), progressing to involve respiratory muscles, also causes dilated CM, may affect bulbar muscles
- Wheelchair bound by around age 12
- Death occurs around mid 20s (resp failure or cardiac failure/arrhythmia)

Becker’s:
- X-linked condition resulting in partial loss of dystrophin
- Age of onset usually around 12
- Wheelchair bound usually by mid 20s
- Death usually in 40s (cardiomyopathy, respiratory failure)

Question 20

HNPP
- Inheritance
- Presentation
- Feature on NCS

Answer 20

• Autosomal dominant
• Mononeuropathies, commonly median, ulnar and common peroneal nerve palsies
• Conduction slowing at multiple entrapment sites

Question 21

Female carriers of DMD
- risk

Answer 21

20% risk of cardiomyopathy

Question 22

Ulnar nerve
a) entrapment vs medial epicondylitis
b) Ulnar claw vs hand of benediction

Answer 22

a) Both can have pain in medial elbow
Medial epicondylitis will not cause paraesthesia/weakness

b) Ulnar claw:
Ulnar lesions distal to the elbow cause inability to extend 4th/5th digits due to weakness of these interossei. If lesion proximal to wrist, will have sensory loss on dorsal/volar aspects of hand. If lesion at wrist, will only have sensory loss on volar aspect

Hand of benediction:
High median nerve palsy - when asked to make fist, they cannot flex 2nd/3rd digits

Question 23

Combination palsies
a) CN V and VI
b) CN IX, X and XII
c) CN V, VII and VIII
d) CN III, IV, V and VI

Answer 23

a) Gradenigo syndrome - inflammation or infection of Petrous temporal bone

b) Jugular foramen syndrome

c) CPA

d) Cavernous sinus

Question 24

Pure motor syndromes

Answer 24

• NMJ disease
• MND
• MMN
• Pure motor variant of AIDP/CIDP
• Botulism
• Myopathy

Question 25

NMO
a) Area postrema syndrome - % presentation, symptoms, lesion site on MRI
b) % seropositive
c) What is the most common other antibody causing optic neuritis/transverse myelitis (not categorised as NMO)
d) Associated conditions
e) Disease course
f) Management

Answer 25

a) 10%, hiccups/vomiting, dorsal medulla

b) 80% have AQP-4 IgG (90% of these are female)

c) Myelin oligodendrocyte glycoprotein (MOG-IgG)

d) Up to half of patients with NMOSD and AQP4-IgG have other detectable serum autoantibodies (e.g., thyroperoxidase, antinuclear, and Ro/SS-A antibodies), and one third have an autoimmune disease, most commonly thyroiditis, systemic lupus erythematosus, or Sjögren’s syndrome. Always test for AQP-4 antibodies in these disorders as NMO will be a more common cause of CNS demyelination than the AI condition itself (e.g. lupus myelitis)

e) - Usually transverse myelitis and optic neuritis present
- MRI spine usually shows longitudinal segment extending across 3 or more spinal segments
- 90% relapse in 1 year without treatment. Generally relapsing-remitting course.

f) - Acute - steroids (only 20% effective)
- Chronic - relapse prevention e.g. rituximab

Question 26

Reflex (spastic) vs flaccid bladder/bowels

Answer 26

Reflex (spastic):
- Lesion T12 or above (above cauda equina)
- UMN signs
- Anal wink/bulbocavernosus present

Flaccid:
- Lesion below T12 (cauda equina)
- LMN signs
- Absent anal wink/bulbocavernosus reflex
- Note spinal shock may initially be flaccid (LMN) but after days will then become spastic (UMN)

Question 27

How does riluzole work

Answer 27

Glutamate antagonist, reducing glutamate induced nerve damage

Question 28

Bells palsy
a) vs UMN lesions
b) Demographics and disease course
c) Important differentials
d) Treatment
- usual
- if Ramsay Hunt syndrome

Answer 28

a) - Mouth weakness occurs in both (flattened naso-labial fold, drooping)
- Weakness of eye closure (including widened palpebral fissure) and forehead wrinkling occurs only in peripheral (LMN) lesions

b) - Median age 30-50
- Time to peak severity is over hours-days (if time to peak <5 mins, worry about unilateral pontine infarct)
- Generally lasts months but most recover

c) - Unilateral pontine stroke (usually there will be associated features)
- Lyme disease (systemic features, risk groups, bullseye)
- Facial nerve Schwannoma (more insidious onset)
- Trauma
- ENT infection e.g. parotitis - (clinical exam/symptoms)
- Other - MS (UMN), GBS (bilateral), ALS, diabetes, sarcoid, etc.

d) If presenting within 72h,
- 10 days of oral prednisolone (50mg/day) + artificial tears
- In Ramsay Hunt, add oral aciclovir also

Question 29

Friedreich’s ataxia
a) Cause
b) Presentation
c) Investigations

Answer 29

a) - GAA trinucleotide repeat expansion in the FXN gene on Chromosome 9 (encodes mitochondrial protein called Frataxin which is involved in mitochondrial ATP production)
- Leads to inadequate frataxin causing iron accumulation/O2 free radical formation —> oxidative damage
- Death of cells highly dependent on mitochondrial function (neurons/cardiomyocytes and pancreatic beta cells)
- Autosomal recessive (equally common in males and females)

b) - Progressive limb and gait ataxia < 25 years (usually age 10-15 onset)
- Loss of proprioception/ vibration sense
- Dysarthria
- Cardiomyopathy
- Diabetes
- Scoliosis
- Muscle weakness
- Vision/hearing loss

c) - MRI spine - shrinkage of cervical cord
- ECHO - LVH, cardiomyopathy

Question 30

Causes of muscle cramps on exercise

Answer 30

• Fabry disease - lancinating pain in legs with exercise/hot weather/fever. An X-linked recessive disease causing deficiency in enzyme alpha galactosidase A which causes accumulation of ceremide trihexodase. Also associated with hypertension, kidney failure, infarctions and haemorrhages. Improves with enzyme replacement
• McArdle disease (glycogen storage myopathy)

Question 31

CIDP
a) Typical presentation
b) Subtypes
c) Management

Answer 31

a) - Course over 8 weeks
- Non length dependent neuropathy with proximal and distal weakness
- Absent or reduced tendon reflexes

b) Typical
Asymmetric focal
Pure Sensory
Pure motor

c) Steroids, then IVIG. PLEX if resistant

Question 32

Myasthenia Gravis
a) Essential investigations
b) Classifying MG
c) Deciding on outpatient vs inpatient management
d) Management of ocular MG
e) Management of generalised MG
f) Indications for IVIG or PLEX
g) Indications for thymectomy

https://pn.bmj.com/content/15/3/199

Answer 32

a) - Antibodies - ACh-R antibodies + MuSK if ACh-R negative
- Thyroid function tests
- Neurophysiology - Repetitive nerve stimulation is the initial test; if negative, consider single-fibre electromyography. Focus the testing on symptomatic muscle
- MR Brain +/- spine to r/o structural cause
- CT Thorax to assess for thymoma
- If diagnostic doubt, refer to MG specialist for possible edrophonium/tensilon test

b) - ACh-R/MuSK seropositive/seronegative
- Thymoma/no thymoma
- Ocular/generalised
- Congenital: (may mimic seronegative autoimmune myasthenia)

c) - Choose inpatient care: For significant bulbar symptoms early on, low vital capacity, respiratory symptoms or progressive deterioration.
- Choose outpatient care: For ocular symptoms, mild-to-moderate limb weakness and mild bulbar symptoms

d) - Consider thymectomy at presentation if thymoma, ACh-R antibody positive or under 45 years old
- Pyridostigmine* 30mg QDS and dose titrated up
- Anticholinergics for side effects (e.g. mebeverine, propantheline)
- If symptomatic despite pyridostigmine, start alternate day prednisolone 5mg/day and titrate up
- Azathioprine 1st line steroid sparer
- IVIG or PLEX (if IVIG contraindicated) if symptoms persist
- Monitoring of FVC/SBC and swallow function
- Avoidance of drugs which exacerbate myasthenia

*ACh-esterase inhibitor - They prolong the action of acetylcholine by inhibiting the action of acetylcholinesterase

e) - As for ocular, but prednisolone starting dose 10mg/day (start 100mg/day in ventilated patients)
- Avoid pyridostigmine in ICU patients due to exacerbating secretion burden

f) - Severe bulbar or respiratory symptoms
- IVIG is first line, PLEX if IVIG contraindicated

g) - Thymoma
- If ACh-R antibody positive or under 45 years, even if no thymoma
- Outcomes better with earlier thymectomy
- Reduces risk of generalisation in ocular MG, reduces corticosteroid requirements

Question 33

MS: McDonald criteria
a) Can only be applied in what circumstances
b) How is DIS demonstrated
c) How is DIT demonstrated
d) 4 areas of typical MRI lesions
e) How is PPMS diagnosed
f) How can diagnosis be made without MRI/CSF findings

Answer 33

a) - In the context of a ‘typical MS syndrome’ with symptoms lasting at least 24h and not attributed to another cause.
- Typical syndromes include optic neuritis, transverse myelitis, brainstem syndrome, Lhermitte’s sign

b) - 2 or more clinical lesions in different areas
- MRI evidence of CNS lesions in different areas

c) - 2 or more clinical relapses over time (separated by at least 30 days)
- MRI evidence of demonstrating older CNS lesions (either separate to presenting neurology, or through longitudinal MRI scans showing new lesions developing over time)
- Presence of CSF-restricted oligoclonal bands*

*OCBs are 2 or more immunoglobulins that ‘band’ together during electrophoresis, demonstrating CNS inflammation. Present in 90% MS patients, but can also be present in GBS, post-stroke, HIV, SLE.

d) periventricular, cortical/juxtacortical, infratentorial and spinal cord

e) Continued progression for one year plus any two of:
- One or more MRI lesions in the brain typical of MS
- Two or more MRI lesions in the spinal cord
- Oligoclonal bands in the spinal fluid

f) Clinical diagnosis can be made (without MRI or CSF findings) if there are 2 or more relapses AND EITHER:
- Objective clinical evidence of two or more lesions, OR
- Objective clinical evidence of one lesion together with reasonable historical evidence of a previous relapse*

*Reasonable historical evidence for one past attack, in the absence of documented objective neurological findings, can include historical events with symptoms and evolution characteristic for a previous inflammatory demyelinating attack

Question 34

MS management
a) Acute relapse
b) When is DMD indicated
c) Choice of DMD
d) DMDs and pregnancy
e) Symptom management

Answer 34

a) - Defined as new or worsening symptoms lasting >24h where infection/other causes ruled out
- Must be treated within 14 days of symptom onset
- Oral methylprednisolone 0.5mg/day for 5 days
- If fails, IV methylprednisolone 1mg/day for 3-5 days

b) - ‘Active’ MS - 2 or more relapses in last 2 years. Or based on MRI findings.
- ‘Very active’ MS - 1 or more relapses despite DMD treatment or based on MRI findings.
- CIS - may decide to start treatment to prevent onset of MS if there appears to be high risk for development or on patient request

c) - For ‘Active’ MS - generally start a ‘Category 1’ drug - dimethyl fumarate or fingolimod preferred (moderately effective - reduce relapse by ~ 50%). Other options include Beta-interferon, glatiramer, teriflunomide (less effective - reduce relapse by ~30%)
- For ‘Very active’ MS - generally start a ‘Category 2’ drug (highly effective - reduce relapse by ~ 70%) like natalizumab or alemtuzumab. These have higher SE profile.
- For CIS, only beta-interferon and glatiramer are licensed

d) - Advise to stop all DMDs when trying to conceive and throughout pregnancy (unless very active disease and advice by neurologist to continue)
- Advise to restart as soon after delivery as possible due to increased risk of post-partum relapse

e) - Amantadine or modafinil for fatigue
- Gabapentin for oscillopsia
- Baclofen +/- gabapentin (+/- CBD oil) for spasticity
- Amitriptyline for emotional lability

Question 35

Anterior spinal cord syndrome
a) Usual cause
b) Clinical features

Answer 35

a) Anterior spinal artery infarct/bleed
- Affects anterior 2/3 of spinal cord

b) - Loss of motor function (CST) below level of lesion
- Loss of pain and temperature sensation (STT) below level of lesion
- Relative preservation of vibration/light touch/proprioception (dorsal column)

Question 36

Critical illness myopathy
a) Risk factors
b) Presentation
c) EMG findings
d) Prognosis

Answer 36

a) Increased risk with duration on ICU, ventilator use, sedation/muscle relaxant use, steroids, inotropes

b) Muscle weakness, may also have sensory loss and diminished reflexes (neuro-myopathy)

c) Myopathic motor unit potentials, fibrillations

d) Most recover after several weeks

Question 37

Neuromuscular ventilatory failure
a) Most common causes
b) Clinical presentation
c) Investigations

Answer 37

a) MG, LEMS, GBS, MND, polymyositis, DMD, etc.

b) - Orthopnoea
- Early morning headaches

c) - FVC or single breath counts
- Overnight oximetry
- ABGs

Question 38

Peripheral neuropathy
a) Classifying
b) Associated features to differentiate
c) Investigations
d) Common and rarer causes

Answer 38

a) - Length dependent, non- length dependent
- Pure sensory vs pure motor vs sensorimotor
- Polyneuropathy vs mononeuropathy vs mononeuritis multiplex
- Axonal vs demyelinating vs mixed

b) - Malignancy/AI disease - fever, weight loss
- Vasculitis symptoms - rashes, bleeding, pulmonary-renal involvement
- RA/SLE - joint involvement
- Sjogren’s - dry mouth/dry eyes

c) - Nerve conduction studies
- Glucose, HbA1c
- FBC, U&E, LFT, bone profile, Mg, ESR
- B12/folate, vitamin D, TFTs
- Immunoglobulins

d) Common causes:
- Diabetes, alcohol, drugs/toxins, metabolic, vitamin deficiency, hypothyroid

Rarer causes:
- Immune mediated, AIDP/CIDP, paraneoplastic, myeloma/MGUS, connective tissue disease, inherited (e.g. CMT, HNPP), infections, CANVAS

Question 39

Myotonic dystrophy
a) inheritance
b) onset and features

Answer 39

a) Autosomal dominant. DPMK gene trinucleotide repeats

b) - onset age 10-30
- frontal balding
- face/neck/distal muscle wasting
- bilateral cataracts and ptôsis
- recurrent jaw dislocation
- myotonia on hand shaking
- progressive dementia
- arrhythmia
- eventually affects bulbar and respiratory muscles