Myasthenia Gravis

Rare autoimmune disorder characterised by skeletal muscle weakness and fatigability

Clinical features

• Variable ocular motility disorder

• 70% of cases present with ocular signs

  • 90% will suffer ocular features at some point

• Ocular MG becomes generalised in 50% at 2 years

• Diplopia/ophthalmoplegia with normal pupils (may mimic cranial nerve palsies)

• Ptosis: fatigable, asymmetrical

• Accommodative fatigue

• Symptoms worsening towards the end of the day

• Sustained eccentric gaze of >1 minute reveals fatiguability, with upgaze showing levator fatigue

• Cogan’s twitch: overshoot of the lid when looking up after looking down

• Spontaneous twitching

• Nystagmoid movements in extremes of gaze

• Fatigable weakness of limbs, speech, jaw, swallow, breathing, choking

• Thymoma: poor prognostic indicator

Osserman’s grading system

1. Ocular only
2. Generalised
3. Aggressive with crises
4. Late progressive
5. Muscle atrophy

Tests

• Serology

  • Serum acetylcholine receptor antibodies: present in >90% of generalised patients but only 50% of ocular patients

  • Muscle specific tyrosine (MuSK) antibodies: present in 5%

    • However anti-MuSK is positive in 50% of those who are seronegative for AChR (these patients are likely a distinct subgroup with more bulbar symptoms and poorer response to ACh-esterase inhibitors

  • Low density lipoprotein-related receptor protein 4 (LRP4) antibodies may be present in double seronegative cases

  • Thyroid function should be checked

  • Anti-skeletal muscle antibodies (SM) present in 85% of patient with thymoma (especially in younger patients)

  • ANA should be checked to exclude SLE and RA

• Thymus scan: CT or MRI

• Ice-pack test:

  • Measure ptosis
  • Apply ice to closed eyelid
  • Positive if ptosis improves by at least 2mm

• Tensilon (edrophonium) test has been discontinued

• Electrophysiology

  • Single fibre electromyography: can test frontalis in ocular MG or extensor digiti communis in systemic MG

    • Highly sensitive for MG
    • Results are unaffected by use of pyridostigmine

  • Repetitive nerve stimulation

    • Much less sensitive than SFEMG
    • Results are masked by pyridostigmine use
    • Commonest rate of stimulation is 3Hz

Management

• Anticholinesterases: pyridostigmine

  • Start at 30-60mg daily then twice daily with gradual increase to maximum 450mg daily
  • Propantheline for GI disturbance

• Immunosuppression with corticosteroids, DMARDS (azathioprine), IVIg, plasmapheresis

  • Can precipitate myasthenic crisis

• Thymectomy: even used in non-thymomatous MG but must be done if there is a thymoma

• Management of diplopia (prisms etc)

Drugs to avoid

• Aminoglycosides eg gentamicin
• Neuromuscular blockers (eg. various anaesthetics)
• Chlorpromazine
• Opiates and other respiratory depressants
• Penicillamine

Lambert-Eaton syndrome

• Disorder of presynaptic calcium channels causing impaired ACh release
• Associated with small cell lung cancer (paraneoplastic syndrome)
• Ocular manifestation: reduced lacrimation (autonomic dysfunction) and dry eyes, ocular motility disorders (less common than in MG), tonic pupils
• Not fatigable unlike MG therefore ophthalmoplegia improves with testing