Myasthenia Gravis (Greek and Latin words meaning grave muscle weakness.

) Definition: autoimmune mediated neuromuscular junction disorder that preferentially involving ocular, facial & bulbar muscles Aetiology : 1. Congenital 2. Acquired a. Autoimmune secondary to thymoma b. Drug induced c. Seronegative d. Ocular e. Neonatal Pathogenesis: d/t IgG or IgG autoantibodies to nicotinic receptors at the myoneuronal junction Mechanism
Modulation of AchRs causing endocytosis and degradation AChRs.

Blocking antibodies which bind to AChR Complement binding causing damage to post synaptic membrane.

Modified Osserman Classification for MG Group 1 : ocular Group 2 : mild generalized Group 3 : moderate to severe generalized Group 4 : acute, severe, developing over weeks to months Group 5 : late severe with marked bulbar involvement Clinical Feature fluctuating weakness increased with exertion Ocular involvement - Diplopia, ptosis, pupillary abnormality Fascial muscle myasthenic snarl Bulbar involvement swallowing & masticatory difficulty, speech bcum nasal quality Generalized neck & limb muscle fatigability (U>L) Respiratory muscle involvement type II respi. failure Tendon reflex preserved & may remain brisk Sensation preserved No muscle wasting

Myasthenic crisis - an exacerbation of weakness sufficient to endanger life. Most common cause of crisis intercurrent infection. Surgery (e.g. thymectomy) may also precipitate crisis. The usual serious threats to life are:
i. Respiratory failure - caused by respiratory muscle weakness ii. Aspiration - secondary to pharyngeal weakness (bulbar muscle weakness) Anticholinergic drug should be withdrawn Lambert Eaton Myasthenic Syndrome (d/t small cell ca) Weakness : Proximal > Distal Legs and arms, complain of dysphagia Rarely extra ocular eye involvement - ptosis and transient diplopia Improves on brief sustained exercise May worsen with sustained exercise, heat or fever Depressed tendon reflexes at rest; reappear after brief exercise Serum antibodies - IgG against voltage gated Calcium Channels -presynaptic disorder Diagnosis - Incremental response after rapid (50Hz) RNS Treatment - 3,4 aminopyridine +/- pyridostigmine, immunosuppression, IVIG and treatment of neoplasm Differential Diagnosis 1. Ocular involvement a. Exclude thyroid opthalmopathy b. Chronic progressive external opthalmoplegia c. Miller Fisher variant -however reflexes absent/ reduced d. LEMS -very rarely e. Intracranial lesion - MRI Brain is essential 2. Bulbar Involvement a. Ocular pharyngeal dystrophy b. Guillain Barre Syndrome- reflexes absent c. LEMS 3. Generalised - Other myopathies, LEMS, polymyositis, drugs(botulism) Management Investigation 1. Serology anti AChR antibodies 2. TRO other diff TFT,RF,ESR,ANA 3. CXR & CT TRO thymoma 4. Tensilon test - - an AChE inhibitor - 2 mg given intravenously - rapid onset ( 30 to 45 secs) - false + in LEMS, ALS 5. Electrophysiology testing Treatment 1. Anti Cholinesterase - Pyridostigmine - 60mg tid to 120mg qid - Neostigmine 1-2.5mg IM/SC 2. Steroid prednisolone 2mg/kg OD 3. Immunosuppressants Azathioprine / cyclosporine 4. Plasmapharesis manage crisis, remove antibodies 5. Intravenous human immune globulin 6. Thymectomy

*ALS amyotrophic lateral sclerosis, LEMS lambert-eaton myasthenic syndrome