Abstracts

Rationale: Contactin-associated protein 2 (Caspr2) was reported to have an important role in concentrating voltage-gated potassium channels (VGKC) in juxtaparanodes of myelinated exons in the peripheral nervous system and the central nervous system. Caspr2 encephalitis is a relatively rare disease associated with limbic encephalitis, peripheral nerve hyperexcitability, or Morvan syndrome. In this study, we described a series of patients in whom Caspr2 antibodies have been identified. Methods: From June 2012 to May 2014, 1820 patients suspected to have autoimmune encephalitis were screened for the presence of autoantibodies against neuronal surface proteins and intracellular neuronal antigens. Cell-based indirect immunofluorescence tests were employed to identify the autoantibodies (against NMDA, LGI1, Caspr2, AMPA1, AMPA2, GABA_B) and paraneoplastic antibodies (Anti-Hu, -Yo, -Ri, Ma2, CV2, CRMP5). Clinical information and result of the tests were obtained by the authors or provided by the referring physicians. This study was approved by the Institutional review board of the Seoul National University Hospital. The written informed consent was obtained from all patients or their representatives. Results: Six patients were found to be positive for anti-Caspr2 antibody. Another autoantibodies or paraneoplastic antibodies were not detected in any patients. The median age of the patients was 43.5 years (range, 8-65 years) and a male to female ratio was 1:1. Four patients presented with generalized tonic clonic seizures, and 3 patients showed altered mental status or confusion. In 1 patient, the sole clinical manifestation was migraine which was aggravated since 2 years ago. Electroencephalogram (EEG) was performed in 5 patients, all of which showed abnormalities. Epileptiform discharges were found in 3 patients (60%), focal slowing in 3 (60%) and diffuse background slowing in 2 (40%). Of the 5 patients who underwent cerebrospinal fluid (CSF) examination, 3 (60%) showed normal CSF profiles while 1 had pleocytosis and increased protein concentration (46/mm³, 69 mg/dL, respectively) and only mild pleocytosis (5/mm³) was observed in the other patient. Magnetic resonance imaging (MRI) scans revealed abnormal findings in 3 patients (50%), each of which was diffuse meningeal enhancement, T2 high signal intensity in bilateral hippocampus, and diffusion restriction in bilateral caudate nucleus. Only 2 patients received immunotherapy with a combination of immunoglobulins and high-dose steroids. All of them showed improvement in seizure frequency. Conclusions: We investigated clinical features and laboratory findings in Caspr2 antibodies positive patients. Seizures were the most common initial presentation and immunotherapy showed some response in seizure management. Further study is required to evaluate the benefit of immunotherapy and long term outcome in Caspr2 encephalitis.