Contactin-associated protein 2 (Caspr2) antibodies associated with refractory temporal seizures, rapid cognitive decline, and emotional lability

Abstract

Background: Caspr2 is a transmembrane protein facilitating intercellular communication. It is found primarily in the central nervous system, specifically cerebellum and hippocampus. Anti-Caspr2 antibodies, more commonly seen in men (M/F: 4), also bind voltage-gated potassium channels. The antibodies are associated with limbic encephalitis, seizures, Morvan’s syndrome, peripheral nerve hyperexcitability, and cerebellar ataxia. Malignancy exists in 20% of cases. Methods: Case report and review of literature. Results: A 71-year-old man presented with subacute onset refractory seizures failing several anti-convulsants, emotional lability, and rapid decline in memory and executive function. EEG showed an electrographic seizure over the left hemisphere. MRI brain demonstrated mild diffuse cerebral atrophy, chronic ischemic changes, and mild diffusion restriction in the medial frontal lobes. Cerebrospinal fluid was normal. Serum Antithyroid peroxidase and antithyroglobulin antibodies were negative. TSH was slightly elevated and eltroxin didn’t help. Anti-Caspr2 antibodies were highly positive. EMG ruled out neuromyotonia. Body CT and PET scans indicated no malignancy. Treatment with IVIG stopped the seizures and cognition dramatically improved. Conclusions: Recognizing anti-Caspr2 antibody-associated encephalitis in elderly males with new onset refractory epilepsy and rapid cognitive decline is important for timely initiation of immunomodulation to avoid permanent deficits. Rapid executive dysfunction was unique in this case.