Autoimmune neurological diseases

Abstract 

Myasthenia gravis (MG) is one of the best understood autoantibody-mediated disorders. The pathogenic antibodies against the acetylcholine receptor (AChR) have been well characterized and are known to impair neuromuscular transmission by direct blockade, complement mediated damage and accelerate receptor-mediated endocytosis. The clinical presentation is characterized by fatiguable weakness with a predilection for the extra-ocular, facial, bulbar, respiratory and proximal limb muscles. Diagnosis is confirmed by the presence of antibodies against the AChR or muscle-specific kinase in the serum. Electrophysiology demonstrates a decrement on repetitive nerve stimulation and increased jitter on single-fibre studies. Symptomatic relief is attained with an acetylcholinesterase inhibitor, pyridostigmine, but definitive treatment requires immunosuppressive drugs. Thymectomy is indicated for 10–15% of patients who have thymomas and may be indicated in young patients with AChR antibodies to try to improve their MG. Lambert–Eaton myasthenic syndrome is associated with small cell lung cancer in 50% of patients, particularly smokers. Immunosuppressive treatment regimes are similar to those used in MG, but 3,4-diaminopyridine is used for symptomatic relief. Limbic encephalitis associated with antibodies to voltage-gated potassium channel antibodies (VGKC) is a newly described disorder characterized by the subacute onset of short-term memory loss, seizures and confusion. Investigations reveal low serum sodium, high signal in the hippocampi on magnetic resonance imaging, a high titre of VGKC antibodies, and anterograde and retrograde memory loss on neuropsychological assessment. Patients respond very well to prolonged treatment with high-dose steroids.

Keywords: autoantibody, immunosuppression, limbic encephalitis, myasthenia gravis, neuromuscular junction