Neuromuscular disorders

Question 1

Genetic predispositions to MS

Answer 1

HLA-DRB1*15- increases risk

3-4% increased risk among first-degree relatives

Question 2

Environmental predispositions to MS

Answer 2

Low vitamin D
Smoking
Infection: EBV, HHV
Early life obesity

Question 3

Schilder disease

Answer 3

Affects children/ young adults

Large areas of demyelination

Question 4

Pathological process in MS

Answer 4

Autoimmune, inflammatory destruction of myelin with partial preservation of axons
- T cells mediated
- Causes atrophy of oligodendrocytes and gliosis

B cell dysfunction
- synthesis of IgG bands
- Anti-CD20 agents effective in exacerbation

Question 5

Marcus Gunn pupil

Answer 5

Unilateral relative afferent pupillary defect
- afferent pupil dilating when light swung between both eyes

Question 6

Intranuclear opthalmoplegia is caused by a lesion to the __________

Answer 6

Medial longitudinal fasciculus

Question 7

Intranuclear opthalmoplegia features

Answer 7

• Medial rectus palsy on same side
• Intact convergence reflex
• Lateral nystagmus in contralateral eye

Question 8

Mechanism of Intranuclear opthalmoplegia

Answer 8

CN6 nucleus in pons (lateral rectus)
- Communicates to medial longitudinal fasciculus —> CN 3 nucleus in midbrain

CN3 innervates medial rectus

Activation of lateral gaze (CN6) alllows conjugate eye movememnt

Lesion in MLS causes palsy on medial rectus on same side
- CN6 still functioning on contralateral side- causing nystagmus

Question 9

Pronator drift test showing pronation and downward arm drift is typical of what lesion?

Answer 9

Upper motor neuron lesion

Question 10

Pronator drift test showing pronation and upward arm drift is typical of what lesion?

Answer 10

Cerebellar lesion

Question 11

Pathophysiology of neuromyelitis optica

Answer 11

Anti-aquaporon-4 antibody
- Destroys membrane of astrocytes involved in humoral immune response

Causes demyelination and axonal damage of optic nerve and spinal cord

Question 12

Neuromyelitis optica acute treatment

Answer 12

Loading steroids with tapering over 2-8 weeks

Severe= plasmaphersis

Question 13

Acute disseminated encephalomyelitis is associated with…

Answer 13

Infection (i.e. measles)
Vaccination

Question 14

Diagnostic features of Acute disseminated encephalomyelitis

Answer 14

Clinical- rapid progression
- motor, sensory, CN, brainstem involvement
- optic neuritis
- reduced GCS

LP
- high lymphocyte
- raised protein

MRI spine/ brain
- B/L lesions

Question 15

Acute disseminated encephalomyelitis management

Answer 15

High-dose IV steroids
Acyclovir empirically

2nd line
- IV immune globulin

Question 16

First line treatment for MS

Answer 16

High dose IV steroids

2nd line- plasmapheresis, ACTH gel

Question 17

Lifestyle modifications for MS

Answer 17

Exercise
Smoking cessation
Manage sleep disorders

Question 18

Most commonly used disease-modifying MS medication

Answer 18

Interferon- beta
Glatiramer acetate

Question 19

Ocrelizumab is used in what MS phenotype

Answer 19

Primary, progressive MS

Question 20

Adverse effects of interferon-beta

Answer 20

Injection site reaction
Flu-like symptoms
Liver dysfunction
Leukopenia
Depression

Question 21

Glatiramer acetate (copolymer-1)

Answer 21

Decoy for T cells instead of myelin
- reduced Th1 inflammation and increases anti-inflammatory Th2

Question 22

What disease-modifying MS medication is teratogenic?

Answer 22

Teriflunomide

Question 23

What medication used in MS can aid mobility by blocking K channels, allowing increased AP in demyelinated axons?

Answer 23

Dalfampridine

Question 24

Poor prognostic factors for disease progression in MS

Answer 24

Male
Onset >40
Multiple early motor and cerebellar involvement
Incomplete recovering after exacerbation

High relapse within first 2 years of MS onset

Question 25

Effect of pregnancy on MS

Answer 25

Decreased exacerbation during pregnancy Increased exacerbation risk post-partum

Question 26

Effect of MS on pregnancy

Answer 26

Low fetal birth weight Increased rate of C-section/ assisted deliver

Question 27

Medication cautions for MS during pregnancy

Answer 27

Stop most-disease modifying medications at least 4 months before conception - glatiramere acetate is the safest Avoid steroids in 1st trimester Avoid breastfeeding for DM medications

Question 28

What are the two approved drugs for ALS?

Answer 28

Riluzole Edaravone

Question 29

Life-expectancy prognosis for ALS

Answer 29

Most (70%)- 3-5 years from onset

Question 30

Common infection causes associated with GBS

Answer 30

Typically 2-4 weeks before: C. jejuni CMV EBV

Question 31

Clinical presentation of GBS

Answer 31

Bilateral ascending flaccid paralysis over days Glove-stocking paraesthesia Hypo/areflexia CN weakness- most commonly facial nerve Respiratory distress Autonomic dysfunction

Question 32

GBS prognosis

Answer 32

Most (80%) have spontaneous remission with near complete recovery in 6 months. 3-7% die from complications

Question 33

Indications for IV immunoglobulins/ plasmapheresis in GBS

Answer 33

Severe flaccid paralysis (unable to walk unsupported for >10m Bulbar palsy Progressive respiratory failure/ autonomic dysfunction Mechanical ventilation

Question 34

Diagnostic features of GBS

Answer 34

Labs- exclude infection or electolyte disturbance CSF- increased protein, normal WCC (<10/ mcL) Nerve conduction studies - Sural nerve typically intact EMG - Shows neuropathy instead of myopathy - Pathological spontaneous activity= unfavourable prognosis

Question 35

Monitoring in GBS

Answer 35

1. Monitor for respiration function with PFTs 2. Autonomic function: cardiac monitoring, bladder/ bowel function 3. Motor/sensory function, including swallowing

Question 36

What tool can be used to predict the need for mechanical ventilation in GBS?

Answer 36

Erasmus GBS respiratory insufficiency score

Question 37

Poor prognostic factor for long-term disability in GBS

Answer 37

Rapid progression of symptoms Severe symptoms at peak of disease Older age Axonal damage

Question 38

Friedreich ataxia - aetiology

Answer 38

GAA trinucleotide repeat exapnsion - FXN gene, chromsome - autosomal recessive Oxidative damage of CNS and PNS (intramitochondrial iron accumulation)

Question 39

Friedreich ataxia - clinical features

Answer 39

neuro: - Progressive ataxia - Upper limb action + intentional tremors - Impaired dorsal column sensation - Loss of deep tendon reflexes - Spastic paralysis - Nystagmus Skeletal- scoliosis, foot inversion, hammertoes Cardiac - Hypertrophic CMP - palpitations, arrhythmias