CASPR2 (Anti-contactin-associated protein-like 2) antibody is a neural specific antibody associated with varied autoimmune neurological disorders including autoimmune encephalitis and autoimmune epilepsy.
CASPR2 is a cell adhesion molecule expressed in both central and peripheral nervous system. The CASPR2 autoantibodies function by blocking interaction with its binding partner contactin-2. These interactions are essential to prevent repetitive firing, and maintain resting potential of nerves, their disruption can lead to hyper-excitability.
Since its discovery in 2011 it has been utilized by neuroimmunology laboratories throughout the world. It has helped in diagnosis and appropriate treatment of many patients, some of whom would’ve not been diagnosed or misdiagnosed in the absence of this biomarker.
People of all ages can be affected by this antibody; however, rates are higher among older adult patients compared to children. It affects men more frequently than women (more than 70% patients are men).
The varied symptoms associated with CASPR2 autoimmunity including diffuse pain, muscle twitching, irregular heart rate or blood pressure, memory problems, seizures, walking difficulty and movement disorders.
Most patients require an MRI of the brain and an electroencephalogram (EEG) to evaluate for signs of central nervous system inflammation. Cerebral spinal fluid (CSF) analysis should be considered for all patients with CASPR2 autoimmunity. However, a considerable proportion of CASPR2 patients can have benign CSF without any evidence of inflammation in the CSF. Furthermore, CASPR2 autoantibodies seem to have higher sensitivity in the serum compared to CSF, but detection of these autoantibodies in CSF has high specificity for an autoimmune etiology. Low titers of CASPR2 antibodies have been detected in serum among patients with non-specific presentation as well.
Thymoma has been detected among minority of patients with CASPR2 autoantibodies. The frequency of underlying thymoma seems be higher among patients with who are positive for both CASPR2 and LGI1 (leucine-rich glioma-inactivated1) antibodies.
CT or MRI chest should be performed in all patients to evaluate for underlying thymoma, as management of underlying tumor is essential for favorable outcomes. Initial or first line immunotherapy for patients with CASPR2 autoimmunity include corticosteroids, intravenous immunoglobulin, or plasma exchange.
Some patients that don’t respond to first line immunotherapies require early initiation of second-line immunotherapy such as rituximab or mycophenolate. These second line agents are also utilized for long-term immunosuppression, as a subset of patients may have a relapsing course.
Additionally, patients with peripheral hyper-excitability syndromes or seizures require symptomatic therapies in the form of anti-seizure medications. If neuropsychiatric dysfunction is also a part of patients’ presentation mood stabilizers or anti-psychotics are required. Patients with diffuse pain require neuropathic pain medications such as pregabalin, gabapentin or duloxetine.
The majority of patients have a favorable response to early immunotherapy and, if needed, tumor removal. There is a risk that the disease relapse in approximately 20-30% of patients but most these relapses are responsive to immunotherapy as well.
Divyanshu Dubey, M.B.B.S., Department of Neurology, Mayo Clinic, Rochester.
Bob Given was diagnosed with CASPR2 encephalitis at the age of 71. Up until that point he was running his CPA firm and was heavily involved in the community. Then suddenly his world was taken from him. Nevertheless, Bob feels he is lucky. Lucky to have been diagnosed quickly, lucky to have received proper treatment. But most of all lucky to be here with his wife and family and be able to give back. He is determined to raise AE Awareness as this will ultimately result in patients getting an early diagnosis with appropriately aggressive treatment, thereby improving outcomes.