Autoimmune Epilepsy Secondary to CASPR2 Antibody Encephalitis: A Case Report Highlighting Diagnostic Challenges and Management

CASPR2 (contactin-associated protein-like 2) is a cell adhesion molecule expressed in both the central and peripheral nervous systems. CASPR2 autoantibodies are associated with autoimmune encephalitis and epilepsy; however, the initial presentation and subsequent treatment can be challenging. We report a rare case of CASPR2-related new-onset seizures, culminating in a motor vehicle accident, as well as dysautonomia in a 50-year-old man with a prior history of vasovagal syncope. The patient experienced three types of seizures: (i) focal preserved consciousness seizures, (ii) focal preserved consciousness seizures/dysautonomia, and (iii) focal impaired consciousness seizures. Post-ictal confusion included stripping clothes off due to feeling hot. Video electroencephalogram (EEG) monitoring confirmed bilateral temporal lobe seizures. Further evaluation revealed anti-CASPR2 antibody positivity in both serum and cerebrospinal fluid (CSF), consistent with autoimmune epilepsy. Despite treatment with intravenous (IV) methylprednisolone (1 g/day for five days) and multiple antiseizure medications (levetiracetam, lacosamide, and oxcarbazepine), the patient experienced persistent recurrent seizures, cognitive deficits, and medication-related side effects. This prompted adding IV immunoglobulin therapy, which helped with seizure control. This case underscores the diagnostic challenges of CASPR2 autoimmune epilepsy and highlights the importance of early recognition and treatment.