Anti-CASPR2 Encephalitis

Anti-CASPR2 (contactin-associated protein-like 2) encephalitis is an autoimmune neurologic disorder caused by IgG autoantibodies targeting CASPR2, a transmembrane protein in the voltage-gated potassium channel complex. CASPR2 is expressed at juxtaparanodal regions of myelinated nerves and limbic system, explaining the heterogeneous central and peripheral nervous system manifestations.

Three clinical phenotypes are recognized: limbic encephalitis (memory impairment, seizures, psychiatric symptoms), Morvan syndrome (peripheral nerve hyperexcitability, dysautonomia, encephalopathy, insomnia), and isolated neuromyotonia (Isaacs syndrome with continuous muscle fiber activity). Patients may present with cerebellar ataxia, neuropathic pain, hyperhidrosis, and weight loss. Approximately 20-50% have associated thymoma, particularly with Morvan syndrome.

Diagnosis requires CASPR2 IgG detection in serum and CSF (cell-based assay preferred), brain MRI showing limbic abnormalities, EMG showing neuromyotonic discharges, and tumor screening with CT chest and dedicated thymus imaging. Management includes thymoma resection when present, first-line immunotherapy with high-dose corticosteroids, IVIG, and plasma exchange, and second-line therapy with rituximab, cyclophosphamide, or azathioprine for relapsing or refractory cases. Symptomatic treatment with carbamazepine or phenytoin for neuromyotonia. Long-term outcomes are favorable with early treatment, but psychiatric and cognitive symptoms may persist.