Autoimmune Peripheral Nervous System Hyperexcitability

A 25-year-old man was seen for assessment of progressive pain. He had a distant history of Guillain-Barré syndrome at age 8 years, at which time he had symmetrical proximal and distal weakness of the upper and lower extremities with loss of ambulation. No facial weakness, dysarthria, dysphagia, ptosis, diplopia, or respiratory weakness occurred. At his initial evaluation there was touch hypersensitivity of the muscles and skin. He had no weakness or cognitive involvement, although the pain made it difficult for him to concentrate. His creatine kinase value improved with hydration, but pain and muscle twitching persisted. On examination, he had diffuse extremity and truncal fasciculations and myokymia and reported pain in not only the areas of twitching but also other areas of his extremities and trunk. On neurophysiologic testing, fibular and tibial motor compound muscle action potentials were decreased in amplitude, with normal ulnar and median motor responses. Needle electromyography of muscles proximally and distally showed diffuse spontaneous firing of muscles ranging in frequency with waxing and waning characteristics. These findings were thought to be consistent with a primary hyperexcitable disorder of muscles with a superimposed old polyradiculoneuropathy and possibly a myopathy. Expanded autoimmune neuroimmunologic testing of serum identified immunoglobulin G-directed cerebellar molecular staining consistent with voltage-gated potassium channel autoantibodies. Radioimmunoprecipitation assay identified voltage-gated potassium channel-immunoglobulin Gs and led to reflex testing for contactin-associated protein 2-immunoglobulin G; autoantibodies were positive. Computed tomography of the chest with contrast was performed, and lymphadenopathy was identified. The patient was clinically diagnosed with contactin-associated protein 2 - immunoglobulin G–positive Isaacs syndrome. A trial of high-dose gabapentin was attempted, with only mild benefits. Next, intravenous immunoglobulin was initiated. Diabetes developed, and he was hospitalized requiring initiation of insulin. His condition is now managed variably with intravenous immunoglobulin and scheduled daily gabapentin. The immune system has long been recognized to help regulate pain via non- immunoglobulin G–mediated mechanisms. Specifically, cytokines decrease the nociceptive nerve fiber thresholds and are released after diverse tissue insults. This allows for speeded healing by increased blood flow and protection of the region by pain guarding mechanisms. It is now recognized that, in rare cases, immunoglobulin G-mediated autoimmunity can lead to otherwise idiopathic pain disorders.