NMJ Diseases

Question 1

What is the NMJ?

Answer 1

The point at which neuromuscular transmission is effected

Composed of the presynaptic nerve terminal

Synaptic cleft

Postsynaptic muscle motor end-plate

Question 2

What is the neurophysiology of the NMJ?

Answer 2

Depolarizing action potential

Open voltage gated Ca2+ channels in nerve terminal

Ca2+ influx mobilizes synaptic vesicles

Acetylcholine is released into the synaptic cleft

ACh binds to Nicotinic ACh receptors in the motor end-plate

Na+ influx into muscle causes post synaptic muscular depolarizing action potential

Excitation-contraction coupling by Ca2+ influx

ACh broken down by acetylcholinesterase in motor end-plate

Question 3

How are NMJ disorders classified?

Answer 3

PRE SYNAPTIC

Lambert Eaton syndrome
Snake venom (beta bungaratoxin)
Botulism

POST SYNAPTIC

Myasthenia gravis
Snake venom (Alpha bungaratoxin)
Organophosphate poisoning

Question 4

What is myasthenia gravis?

Answer 4

Most common NMJ disorder

Acquired organ-specific autoimmune disease

Unknown cause

Common in young women (generalized)
Older men (oculobulbar)

Antibodies against nicotinic ACh receptors in motor end-plate

Leading to fatigability of ocular, proximal limb, bulbar and respiratory muscles

> 50% present with ptosis and ophtalmoplegia

Autonomic, sensory and nerve conduction normal

Often associated with thymus disease
70% thymic hyperplasia
10% thymoma

And autoimmune thyroid disease

Question 5

What are the types of MG?

Answer 5

OCULAR
ptosis
Diplopia

BULBAR
Dysarthria 
Dysphonia
Dysphagia 
Weak face and jaw

LIMBS
Proximal muscle fatigability

RESPIRATORY
shortness of breath

Question 6

What are the investigations for MG?

Answer 6

Edrophonium (tensilon) test

Neurophysiology-fatigability

Serum Anti-AChR antibodies 85%

EMG (decreasing amplitude, increasing jitter)

CT thorax for thymus

Spirometry for vital capacity

Question 7

How is MG managed?

Answer 7

Oral anticholinesterases
Pyridostigmine > neostigmine
*give atropine for side effects

Immunosuppressive
Prednisolone

Immunomodulation
IV Ig
Plasmapharesis
Thymectomy

Question 8

What is Lambert Eaton myasthenic syndrome?

Answer 8

Auto antibodies against presynaptic VGCC

Anti-VGCC

60% of cases have small cell lung carcinoma

Proximal muscle weakness in lower limbs

Ocular and bulbar sparing

Increased amplitude of compound muscle action potential

Question 9

What are the DDx for MG?

Answer 9

Generalized MG
*chronic fatigue syndrome

Ocular MG
*mitochondrial myopathy
Oculopharyngeal dystrophy

Oculo bulbar MG
*multiple sclerosis

Question 10

How is myasthenic crisis managed?

Answer 10

Identify and treat precipitating cause

45 degrees semi recumbent position

Secure airway and ventilation

IV Neostigmine 10 mg/24 hours 
SC atropine 0.5 mg tds 
Prednisolone 100 mg daily
Consider plasmapharesis or IVIg
Change to oral anticholinesterase when able to swallow

Cholinergic crisis

Withdraw all anticholinesterases
Monitor vital capacity
Wean from ventilation
Re introduce oral anticholinesterases titration