Contactin-associated protein-like 2 antibodies (CASPR2) encephalopathy in 3-year-old dizygotic twins

CASPR2 is a transmembrane protein, which mediates cell-cell interactions in the nervous system. Antibodies have been identified in patients with symptoms of the central and/or peripheral nervous system and been linked to neoplasia. Different antibodies were found in children with encephalitis/encephalopathy, but no CASPR2 antibodies could be demonstrated. We report a case of 3-year-old dizygotic twins suffering from CASPR2 positive encephalitis with different clinical findings.

The girl was presented with a 2-week history of hypersomnia and psychotic symptoms. Despite brisk tendon reflexes and increased signal intensity in the reticular formation in cranial MRI studies, clinical examination and extensive work-up were normal. We treated her with a high intravenous immunoglobulin regimen with minor results. After a methylprednisolone pulse, her condition improved. She was given a second pulse due to severe insomnia and put on oral tapering. Her symptoms completely resolved 8 weeks after the first presentation, and CASPR2 antibodies were negative on follow-up.

Her brother was presented with a 3-week history of stereotypic eye-squinting and irritability. He suffered from his first atonic seizures 3 weeks later. Clinical examination was normal except for brisk tendon reflexes. EEG showed polymorphic epileptic discharges. MRI scans were identical to his sister. CASPR2 antibodies were detected. He responded well to corticosteroids and was put on oral tapering. After reducing prednisolone below 10 mg/day, his seizures relapsed. After increasing the prednisolone, seizures stopped again. The following reductions were tolerated well and the patient's clinical examination is now normal.

To our knowledge, no children have been reported with CASPR2 antibodies associated encephalopathy.

Encephalitis associated with CASPR2 antibodies can occur in children who present with seizures or neuropsychiatric symptoms. The response to immunomodulation is usually well. Because of the association with neoplasia, a long-time follow-up is necessary.