Basic Science and Pathophysiology

The NMJ consists of a motor nerve terminal and muscle membrane.

Its function is to amplify a relatively weak nerve impulse and thereby produce a strong electrical impulse in the muscle capable of initiating muscle contraction.

There are three components of the NMJ:

• Presynaptic membrane
• Synaptic cleft
• Postsynaptic membrane

Abnormalities of the NMJ

Abnormalities of the NMJ in MG are postsynaptic in location (in contrast to the presynaptic abnormality in Lambert-Eaton syndrome).

Anti-acetylcholine receptor (anti-AChR) antibodies are found in 80-90% of patients with generalised MG and 50-60% of Ocular MG.

Approximately 10-20% of patients with acquired MG do not have anti-AChR antibodies (seronegative MG). The presence of antibodies against muscle specific protein kinase (MuSK) appears to define a subgroup of patients with MG.

Although MG is predominantly caused by antibodies produced by B-cells, T-cells have also been shown to be important in the pathogenesis.

Thymic abnormalities are found in nearly 75% of patients with MG. Pathological changes are lymphoid follicular hyperplasia (70%) and thymoma (10%). The remaining 20% have other abnormalities.

Learning bite

Statistically, 80% of patients have acetylcholine receptor (AChR) antibodies. Most of those patients who don’t have AChR antibodies have MuSK antibodies instead. Approximately 75% of patients have thymus abnormalities and 10% of these patients have thymoma.