Neuromuscular Junction Diseases (MG, LEMS, Botulism)

Question 1

Prominent feature of diseases affecting NMJ?

Answer 1

Fatigueability.

Question 2

What is myasthenia graves?

Answer 2

Progressive autoimmune disorder due to anti-AChR antibodies resulting in early saturation at the NMJ and inadequate muscle activation with increasing nerve stimulation

Question 3

What condition is myasthenia gravis associated with?

Answer 3

Thymoma

• 15% have thymic neoplasia
• 85% have thymic hyerplasia

Question 4

Epidemiology of myasthenia gravis?

Answer 4

Bimodal onset:

• 20s (mostly women)
• 60s (mostly men)

Question 5

What are the signs and symptoms of myasthenia graves?

Answer 5

• Fatigueable, symmetric or asymmetric weakness w/o reflex changes, sensory changes or coordination abnormalities
• Ocular (diplopia/ptosis), bulbar (dysarthria/dysphagia), proximal limb weakness

Question 6

What may exacerbate MG symptoms?

Answer 6

Infection, pregnancy, menses, various drugs

Question 7

Ix in MG work up?

Answer 7

• Tensilon test (assess for improvement over 2min following edrophonium injection)
• EMG: repetitive stimulation, decremental response
• RFTs (FVC to monitor adequacy of resp effort over time)
• Anti-AChR Ab
• MUSK Ab if Anti-AChR -ve
• CT/MRI (thymic changes)

Question 8

Treatment of MG?

Answer 8

• Thymectomy (85% show improvement or remission)
• Symptomatic relief: acetylcholinesterase inhibitor (e.g. pyridostigmine)
• Immunosuppression (steroids, or steroid sparing therapy)
• IVIg and plasmapharesis for crises

Question 9

Prognosis MG?

Answer 9

• 30% spontaneous remission

- W/ Rx: life expectancy equal to normal, QoL may vary

Question 10

What is Lambert Eaton Myasthenic Syndrome?

Answer 10

Autoimmune disorder due to antibodies against presynaptic voltage-gated calcium channels causing decreased ACh release at NMJ

Question 11

What is Lambert Eaton Myesthenic syndrome associated with?

Answer 11

Small cell carcinoma of the lung

Question 12

Signs and symptoms of LEMS?

Answer 12

• Weakness of sk muscle w/o sensory or coordination abnormalities
• Reflexes diminished or absent BUT increase after muscle contraction
• Bulbar/occular muscles affected in 25% (v 90% in MG)
• Prominent anticholinergic Sx

Question 13

Anticholinergic Sx? (e.g. in LEMS)

Answer 13

• Dry mouth
• Impotence
• Constipation
• Blurred vision

Question 14

Ix in ?LEMS?

Answer 14

• Edrophonium: no response
• EMG
• Screen for malignancy (esp SmC lung Ca)

Question 15

EMG findings in LEMS?

Answer 15

• Rapid (>10Hz) repetitive stimulation: incremental response

- Post exercise facilitation: incremental response with exercise

Question 16

Rx LEMS?

Answer 16

• Tumour removal
• ACh modulation (increased release = diaminopyridine, decreased destruction = pyridostigmine)
• Immunomodulation (steroids, plasmapharesis, IVIg)

Question 17

What causes botulism?

Answer 17

Toxin produced by spores of Clostridium botulinum bacteria found in soil and water; enter body through wounds or improperly prepared food.

Question 18

Signs and symptoms of botulism?

Answer 18

• Diff w/ convergence, ptosis, paralysis of extraocular muscles
• Dilated, poorly reactive pupils
• Other autonomic dysfunction: jaw weakness, dysarthria, dysphagia
• Spread to trunk/limbs: ado pain / N/ V; symmetric weakness w/ paralysis and decreased deep tendon reflexes
• Anticholinergic Sx

Question 19

Ix botulism?

Answer 19

• Blood test for toxin

- Stool culture

Question 20

Rx botulism?

Answer 20

• Botulinum anti-toxin

- Supportive therapy as required

Question 21

What is MuSK myasthenia?

Answer 21

Abx binding to MuSK cause the subunits of ACh receptor to deaggregate and lose function