27th June 2023

Common disorders of the NMJ

Myasthenia Gravis

This is an autoimmune condition affecting the NMJ. Antibodies are directed against the acetylcholine receptor on the postsynaptic membrane of the NMJ, resulting in fluctuating muscle weakness and fatiguability. The muscles involved can include bulbar, ocular (except pupils), proximal limbs and respiratory. Electrophysiology demonstrates diminished amplitude of the evoked EMG response. Associated conditions include thymomas and thymic hyperplasia, so a CT mediastinum is an important investigation. Treatment is with a long-acting anticholinesterase inhibitor such as pyridostigmine, immunosuppressants such as steroids and thymectomy if required. It is also important to avoid drugs that may exacerbate symptoms, such as beta-blockers, certain antibiotics (fluoroquinolone, aminoglycosides), magnesium, phenytoin, and prednisolone.

Lambert-Eaton Myasthenia Syndrome (LEMS)

This is also an autoimmune disorder associated with autoantibodies targeting the presynaptic voltage-gated calcium channels leading to a decrease in acetylcholine release. Unlike myasthenia gravis, muscles become less weak on repetitive movement, and EMG shows improvement with repetitive stimulation. Additionally, ocular and bulbar muscles are rarely affected, instead autonomic symptoms such as dry mouth are noted. Since LEMS is commonly a paraneoplastic syndrome, particularly associated with small-cell lung cancer, it is important that LEMS is diagnosed early and malignancy is investigated if not already known. Treatment is directed at the cause. Immunosuppression, 3-4 -diaminopyridine (3,4-DAP such as amifampridine), IV immunoglobulins or plasma exchange can also be used.