Muscle-specific kinase antibodies: a novel cause of peripheral nerve hyperexcitability?

Antibodies that target the postsynaptic neuromuscular junction (NMJ) protein, muscle-specific kinase (MuSK), have been associated with myasthenia gravis (MG), often with cramps and fasciculations, after administration of acetylcholinesterase inhibitors (AChE-I).

In this report, 2 patients are described with elevated MuSK antibodies and evidence of peripheral nerve hyperexcitability (PNH) unrelated to AChE-I medication.

Patient 1 presented with facial neuromyotonia and fasciculations, without overt weakness. EMG studies demonstrated myokymic discharges in facial muscles, with bursts of discharges after voluntary activation, and widespread fasciculation potentials in limb muscles. Patient 2 presented with bulbar weakness and fasciculations in the tongue and limbs, initially diagnosed as bulbar-onset amyotrophic lateral sclerosis. Subsequent investigation identified the presence of MuSK antibodies.

We hypothesize that MuSK antibodies may induce these phenotypes through disruptive actions at the NMJ, in particular the binding of acetylcholinesterase (AChE) to MuSK via its collagen Q (ColQ) tail, producing a reduction in synaptic AChE activity.