Neuromyotonia

Neuromyotonia, also known as Isaacs' syndrome, is a rare autoimmune peripheral nerve hyperexcitability disorder. It is characterized by continuous spontaneous activity in motor nerves at rest, producing symptoms such as myokymia (visible twitching of muscle), cramps, stiffness, fasciculations, and delayed relaxation after contraction. Symptoms may be exacerbated by rest, heat, or exercise, and can be accompanied by fatigue and weakness in some cases.

Most cases are autoimmune in origin. Circulating autoantibodies commonly target the voltage-gated potassium channel (VGKC) complex, particularly CASPR2, and less often LGI1. The syndrome can be associated with other autoimmune conditions and, in some instances, with thymoma or other malignancies. A related condition, Morvan syndrome, may include autonomic dysfunction and encephalopathy along with neuromyotonia.

Pathophysiology involves autoantibody-mediated disruption of potassium channel function on motor nerve terminals, leading to increased motor nerve membrane excitability and continuous, spontaneous motor unit firing. This results in the characteristic myokymia and cramps.

Diagnosis relies on clinical features supported by electrophysiology and serology. Electromyography (EMG) typically shows continuous spontaneous activity with myokymic discharges; nerve conduction studies are often normal or show mild abnormalities. Detection of VGKC-complex antibodies, especially CASPR2 and sometimes LGI1, supports the diagnosis. Imaging may be undertaken to identify associated tumors, such as thymoma, if indicated.

Treatment is tailored to the underlying mechanism and symptoms. First-line management includes anticonvulsants that stabilize nerve membranes, such as carbamazepine, oxcarbazepine, lamotrigine, or mexiletine; gabapentinoids may also help. Immunotherapy (corticosteroids, IVIG, plasmapheresis) and, in some cases, rituximab are used for autoimmune-related disease or when symptoms are severe or persistent. Treating any associated tumor is important. The prognosis varies, with many patients experiencing improvement with treatment, though relapses can occur and some may have chronic symptoms.