Localising weakness to the neuromuscular junction

What it is

The neuromuscular junction is where the nerve impulse from the spinal cord meets muscle: the axon releases acetylcholine at the synapse onto nicotinic acetylcholine receptors, with voltage-gated Ca2+ channels on the nerve side. Weakness that arises at that point has a pattern of its own, and three things mark it: 1) no reflexes involvement; 2) fluctuation in weakness with use; 3) possible additional involvement of EOM and facial muscles. The first of them is reported of disorders of the NMJ in one source, while another has reduced or absent reflexes in Lambert-Eaton myasthenic syndrome and deep tendon reflexes not affected in myasthenia gravis.

Myasthenia gravis is the most common NMJ disorder, an autoimmune disease of the neuromuscular junction characterized by weakness and fatigability. Lambert-Eaton myasthenic syndrome is uncommon.

How it presents

In myasthenia gravis eye muscle weakness is the most common initial symptom: ptosis, diplopia and blurred vision, worse at the end of the day. Bulbar muscle weakness or slurred speech follows, with difficulty chewing and/or swallowing, then proximal limb weakness on rising from a chair, climbing stairs or brushing hair, and respiratory muscle weakness causing dyspnea. Muscle fatigue worsens throughout the day and with increased activity, and that fatigability is the most important feature. Deep tendon reflexes are not affected, which is the line against GBS.

Lambert-Eaton myasthenic syndrome runs the other way. There is proximal muscle weakness with reduced or absent reflexes, and autonomic symptoms: dry mouth, constipation, erectile and ejaculatory dysfunction, and orthostatic dysregulation. It improves with muscle use. Active muscle contraction or repeated muscle tapping increases reflex activity, and the Lambert sign is muscle strength improving with repetitive or ongoing use.