S59. Response to immunotherapy in antibody-negative autoimmune epilepsy

Abstract

Introduction Autoimmune epilepsy has been linked to a number of neural specific antibodies and the diagnosis is generally established by identifying one of these antibodies. Recognizing an autoimmune etiology is important because the mainstay of treatment is immunotherapy rather than anti-seizure drugs. However, antibodies may not always be detected and a clinical response to immunotherapy can support the diagnosis. We present a patient who showed significant improvement after immunotherapy even though no antibodies were detected. Methods Case report. Results 79 year old woman with history of breast cancer developed tremors, cognitive issues and generalized tonic-clonic seizures. MRI brain was unremarkable. EEG revealed frontal- temporal sharp waves and diffuse slowing. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis and raised protein. She gave a history of tick exposure and family members had Lyme disease. Lyme screening assay was positive for IgG, but IgM was negative. Testing for Epstein Barr virus, cytomegalovirus, herpes simplex virus, toxoplasma, Neurosyphilis, Gram stain and fungus culture was negative. Paraneoplastic panel (serum and CSF) and autoimmune panel including NMDA, GAD, and AMPA receptors were also negative. Heavy metal screening for arsenic, mercury, lead and copper was negative. Neuron specific enolase and 14-3-3 studies were unremarkable. Her seizures responded to fosphenytoin, and she was later switched to levetiracetam. She was treated with a course of ceftriaxone for presumed Neuroborreliosis. She improved clinically and was discharged. One month later, the patient returned with worsening tremors, cognitive dysfunction and seizures. She underwent extensive testing for etiology including MRI and CSF studies, which were unremarkable. Paraneoplastic/autoimmune panel was again negative. EEG showed temporal sharp waves and slowing. CT chest/abdomen/pelvis revealed a lung mass concerning for a malignancy. The patient was presumed to have a paraneoplastic syndrome due to history of cancer and new left upper lung mass, and was treated with IVIG. She had significant clinical improvement with resolution of seizures, and improvement in tremors and cognitive dysfunction. She is currently status post 7 treatments of IVIG without any relapse for >6 months. EEG was repeated and revealed resolution of slowing and sharp wave activity. Conclusion Although extensive testing for paraneoplastic and autoimmune antibodies was negative in our patient, the significant clinical and EEG response to immunotherapy with IVIG confirmed the diagnosis of autoimmune epilepsy. Since not all antibodies have been described and not all the described antibodies have commercially available testing, negative results do not exclude the possibility of autoimmune epilepsy. A trial of immunotherapy is warranted in such cases, if there is strong clinical suspicion.