disorders of neuromuscular junction

Question 1

what are the 2 main diseases of neuromuscular transmission??

Answer 1

myasthenia gravis

lambert eaton myasthenic syndrome [LEMS]

Question 2

define myasthenia gravis

Answer 2

• Autoimmune disease mediated by Abs to nicotinic Ach receptors.

Interferes w/ NM transmission via depletion of working post-synaptic receptor sites

Question 3

myasthenia gravis epidemiology

Answer 3

• rare
• any age

W>M

Question 4

aetiology of myasthenia gravis

Answer 4

antibody-mediated autoimmune disease

Question 5

myasthenia gravis associations

Answer 5

• < 50yrs: MG commoner in women and assoc. w/ other AI disease (DM, RA, Graves) and thymic hyperplasia

>50yrs: MG commoner in men and assoc. w/ thymicatrophy or thymic tumour – thymomas

Question 6

ddx of muscle fatiguability

Answer 6

• Polymyositis
• SLE

Botulism

Question 7

s/s of myasthenia gravis

Answer 7

• ↑ing muscular fatigue
• Extra-ocular: bilateral ptosis, diplopia (early)
• Bulbar: voice deteriorates on counting to 50, swallowing and chewing
• Face: myasthenic snarl on attempting to smile
• Neck: head droop
• Limb: asymmetric, prox. weakness
• Normal tendon reflexes

Weakness worsened by: pregnancy, K↓, infection, emotion, change pf climate, exercise, drugs (β-B, gent, opiates, tetracyclines, quinine)

Question 8

ix of myasthnia gravis

Answer 8

• single fibre electromyography: high sensitivity (92-100%)
• CT thorax to exclude thymoma
• CK normal
• autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies
• TFTs
• resp function: decreased FVC
• Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used anymore due to the risk of cardiac arrhythmia

Question 9

mx of myasthenia gravis

Answer 9

• Symptom Control
• Anticholinesterase: e.g. pyridostigmine.
  
  • Cholinergic SEs = ↑salivation, lacrimation, sweats, vomiting, miosis
• Immunosuppression
• Rx relapses w/pred – 5mg à↑5mg/wkà reduce on remission
• Steroids may be combined w/ azathioprine ormethotrexate
• Thymectomy
• Consider if young onset (<50) and disease not control byanticholinesterases

Remission in 25%, benefit in further 50%

Question 10

complications

Answer 10

• Myasthenic Crisis
• Weakness of respiratory muscles during relapse maybe lethal.
• Monitor FVC: vent support if <20ml/kg
• Plasmapheresis or IVIg

Rx trigger for relapse (drugs, infection…)

Question 11

myasthenia gravis- exacerbating factors

Answer 11

The most common exacerbating factor is exertion resulting in fatigability, which is the hallmark feature of myasthenia gravis

. Symptoms become more marked during the day

The following drugs may exacerbate myasthenia:

• penicillamine
• quinidine, procainamide
• beta-blockers
• lithium
• phenytoin
• antibiotics: gentamicin, macrolides, quinolones, tetracyclines

Question 12

myasthenia gravis- prognosis

Answer 12

Relapsing or slow progression

Question 13

LEMS defintion

Answer 13

rare autoimmune disorder that is characterized by muscle weakness of the limbs

Question 14

LEMS epidemiology

Answer 14

• rare
• M>W
• median age: >60

Question 15

LEMS: pathophys

Answer 15

Abs to VGCC ↓ influx of Ca2+ during presynaptic excitation → ↓ presynaptic ACh-vesicle fusion

Question 16

LEMS: aetiology

Answer 16

• Paraneoplastic: e.g SCLC
• Autoimmune

Question 17

LEMS: s/s

Answer 17

• As for MG except: LEMS
• Leg weakness early (before eyes)
• Extra: Autonomic (dry mouth, constipation, impotence) and areflexia
• Movement (excersise) improves symptoms
• Small response to edrophonium

Question 18

LEMS ix

Answer 18

EMG

incremental response to repetitive electrical stimulation

Radiological follow-up

Six-monthly radiological follow-up will be needed for patients at special risk of developing small-cell lung cancer, i.e. smokers with a history of Lambert-Eaton syndrome for less than 5 years.

Question 19

LEMS- mx

Answer 19

• treatment of underlying cancer
• immunosuppression, for example with prednisolone and/or azathioprine
• 3,4-diaminopyridine is currently being trialled**
• intravenous immunoglobulin therapy and plasma exchange may be beneficial

Question 20

botulinism- definition, s/s, rx

Answer 20

pathophys:

• Botulism is an extremely severe form of food poisoning due to ingestion of a preformed neurotoxin - botulin - from the spore-bearing anaerobe Clostridium botulinum (gram-positive bacilli). Types A, B and E most commonly produce disease in man. Types F and G are rare causes of botulism in humans.
• The organism may be found in any food except for acid fruits which inhibit germination. Canned foods which have been incompletely sterilised are commonly implicated. Traditionally, home-bottled vegetables are a prime cause in the U.K.
• The toxin prevents the presynaptic release of acetylcholine causing paralysis through its action at neuromuscular junctions; other clinical manifestations largely result from its actions at parasympathetic terminals

.

• Clinical features:
• Descending flaccid paralysis w/ no sensory signs
• Anti-cholinergic effects: mydriasis, cycloplegia, n/v, dry mouth, constipation

Rx: benpen + antiserum