Myasthenia Gravis

Question 1

Facts

Answer 1

Acetyl choline receptor IgG positive in 75%

Anti- muscle specific kinase (MuSK) is positive in 50% of those negative for AChR and is predominantly seen in facial, bulbar and respiratory weakness.

Can affect ocular, bulbar, respiratory or limb weakness. 15% pure ocular.

Often coexists with other autoimmune disorders

15% have thymoma

Question 2

Clinical signs

Answer 2

Check for cushingoid feature secondary to steroid use, thymectomy scar or viral capacity meter (always offer to check FVC)

Ptosis (bilateral and assynetrical) and Diplopia (complex ophthalmoplegia) which are fatiguable and worse towards end of day.

Normal pupillary reflexes (unlike GBS or botulism)

Weakness of face, jaw, speech (could be bulbar) and swallow

Respiratory muscle weakness

Proximal limb weakness

Reflexes may be initially normal but diminish with repeated percussion

Diplopia May show fatiguability if worsens with prolonged gaze

Hold upgaze for several seconds to see if Ptosis develops or worsens

Question 3

Diagnostic testing

Answer 3

AChR antibodies
Striated muscle antibodies (seen in 90% with thymoma)
MuSK ab
Electrophysiological studies - repetitive stimulation and single-fibre EMG (most-sensitive test)

Tensillon (edrophonium) year is now out of favour. Lots of false positive and negative and can precipitate heart block

Question 4

Management

Answer 4

Check FVC - if <1.5 L needs HDU, I’d <1.2 L ITU

SALT assessment

Avoid exacerbating drugs ie aminoglycosides, quinine, beta-blockers, phenytoin

• anticholinesterases ie pyridostigmine. Effective early and as adjunct to immunotherapy. Can precipitate crisis in early stages
• corticosteroids may establish remission but can cause a paradoxical worsening of sx in first 2 weeks so should be started in hospital
• immunomodulation eg azathiaprine, methotrexate, mycophenalate, ciclosporin
• IV Ig or plasma exchange in acute setting (doesn’t cause paradoxical worsening)

Question 5

Differential diagnosis for MG

Answer 5

Ophthalmoplegia

CN disorder
Thyroid eye disease
GBS
Oculopharyngeal muscular dystrophy
Botulism

Bulbar and respiratory weakness

MND
Botulism
GBS

Proximal weakness

Lambert Eaton
Myopathies
Inflammatory myositis
Congenital myasthenia

Question 6

Lambert-Eaton syndrome

Answer 6

50% malignancy, 50% autoimmune associated

VGCC ab >90%

Proximal muscles most affected
Autonomic features
Ocular, bulbar and respiratory muscle less affected

Question 7

Neurophysiological findings in MG and LES

Answer 7

Normal Nerve conduction velocities

Sequential reduction in amplitude of the muscle response

Sequential increment in amplitude with fast repetitive stimulation in LES

Single-fibre EMG is time-consuming test measuring difference in firing times that are part of the same motor unit. Increased variability of the interval or ‘jitter’ suggests the NMJ is abnormal. However this is also seen in MND, myositis and LEMS

Question 8

Thymectomy

Answer 8

All patients with MG should have CT or MR mediastinum as 15% have thymoma. 50% of those with a thymoma will get MG

10% of thymoma’s will
Be malignant so all should be resected

For those without thymoma there is still thought to be increased chance of remission or improvement with thymectomy. It is indicated in seropositive patients with generalised disease and under 60. Role in ocular MG less certain

Thymectomy not effective for patients wtb MuSK positive