Disorders of the Neuromuscular Junctions

The neuromuscular junction (NMJ) is a specialized synapse between a neuron and the muscle it innervates. It allows efferent signals from the nervous system to contract muscle fibers. This contraction is often regulated by acetylcholine, a neurotransmitter, via calcium-dependent mechanisms.

Disorders of the NMJ result from the dysregulation of the pathway of neuromuscular transmission, usually because of an alteration of one or more key proteins. The most common pathology is antibody-mediated damage or downregulation of ion channels or receptors, which can lead to diseases such as acquired neuromyotonia (Isaacs syndrome), Lambert-Eaton myasthenic syndrome (LEMS), and—probably most well-known—myasthenia gravis (MG). These three conditions have many commonalities.

Other important groups of disorders include exogenous toxins (organophosphates, botulinum toxin) and the subset of congenital myasthenic syndromes, a result of NMJ protein mutations.

It is important to recognize the classic clinical findings in these disorders so as not to miss them in clinical practice. It is important also to understand the clinical associations with these syndromes (e.g., MG with thymoma or LEMS with small-cell lung cancers). Finally, there are various diagnostic modalities used to test for these disorders (e.g., antibody testing and repetitive stimulation testing), and management often involves pharmacologically counteracting the pathologic dysfunction at the motor end plate.