UNC5A IgG in a Previously Reported CASPR2/LGI1-Negative VGKC-Associated Peripheral Nerve Hyperexcitability Syndrome: Long-Term Clinical and Electrophysiological Follow-Up.

Abstract

Autoimmune peripheral nerve hyperexcitability (PNH) syndromes are most commonly associated with antibodies against CASPR2 or LGI1. However, a subset of patients with clinically and electrophysiologically confirmed PNH remains negative for these established neuronal surface antibodies despite persistent VGKC antibody positivity. This report presents the long-term follow-up of a patient previously diagnosed with a Morvan-like autoimmune PNH syndrome following enteroviral infection. Serial neurophysiological studies demonstrated persistent motor axonal hyperexcitability, while treatment with intravenous immunoglobulin (IVIg) resulted in sustained clinical stabilization and substantial functional improvement. Additional research-based immunological analyses identified UNC5A IgG reactivity in serum using a live cell-based assay. UNC5A antibodies have previously been identified predominantly in the context of thymoma-associated neuromyotonia, including patients with Morvan syndrome and myasthenia gravis, often in association with CASPR2 antibodies. The identification of UNC5A IgG in a patient with electrophysiologically confirmed CASPR2/LGI1-negative PNH and persistent VGKC antibodies represents a hypothesis-generating association rather than evidence of a causal or pathogenic role. UNC5A IgG may represent an associated biomarker or a secondary immune phenomenon within a broader autoimmune response. This observation extends the clinical context in which UNC5A reactivity has been identified and supports further investigation of UNC5A and other candidate neuronal surface antigens in CASPR2/LGI1-negative PNH.