Carbamazepine-Responsive Double-Negative VGKC-Complex Antibody Isaacs Syndrome—A Case Report and Literature Review

Abstract

Isaacs syndrome (IS), commonly referred to as acquired neuromyotonia, is a rare condition characterized mainly by voltage-gated potassium channel (VGKC) antibody-mediated syndrome of peripheral nerve hyperexcitability (PNH). Few case reports have documented IS patients in the absence of both leucine-rich glioma inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies (double negative). We report a rare case of a 34-year-old healthy female, presenting with a 15-year history of paroxysmal leg cramping and stiffness, preceded by generalized hyperhidrosis and palpitations. Physical examination documented hyperhidrosis, myokymia, and hypertrophic calf muscles. Electromyogram revealed myokymic discharges and neuromyotonic discharges—findings classically seen in Isaacs syndrome. To document the presence of autoantibodies against VGKC, serum LGI1 and CASPR2 antibodies were done; however, both turned out to be absent (double negative). Diagnostic tests to search for an autoimmune or a paraneoplastic etiology were done, which also showed unremarkable results. Despite the unrevealing serologic and imaging tests, a diagnosis of Isaacs syndrome was still made due to the presenting clinical features. Full resolution of symptoms was achieved upon initiation of carbamazepine. Absence of an autoimmune and a paraneoplastic syndrome is possible in IS, especially in cases with double-negative autoantibody status. This is the fifth reported case in published literature of such autoantibody status and highlights the vital role of a physician’s clinical acumen when dealing with rare diseases such as Isaacs syndrome. Knowing the cardinal features of a disease as well as the possible phenotypic varieties allows prompt diagnosis and treatment.