Abstracts

Rationale: Intractable epilepsy remains a significant medical challenge, resulting in recurrent and prolonged ICU admissions. Autoimmune encephalitis is emerging as a treatable cause of intractable epilepsy. It is characterized by antibodies against cerebral antigens, such as potassium channels (LGI1, CASPR2), calcium channels, or neurotransmitter receptors (AMPA, GABA, NMDA). Diagnosis requires a syndrome consistent with an antibody identified in serum or CSF (CSF is not always more specific) using methods that minimize risk of false-positives. There is no accepted treatment for these disorders, but typical approaches involve chronic high-dose steroids (often for months or years), methotrexate or mycophenolate. Rituximab is an monoclonal antibody that depletes B-cells, which are precursors to plasma cells that secrete pathogenic antibodies. It is effective for antibody-associated disorders such as lupus, myasthenia gravis and neuromyelitis optica. Methods: 3 patients were admitted to INOVA Fairfax ICU with recalcitrant status epilepticus, and demonstrated serum antibodies against NMDAR, LGI1 or VGCC using a cell based assay (Mayo Clinic Labs). Results: All patients demonstrated complete epilepsy control and improvement in symptoms with rituximiab. None of the patients have tumors identified so far. There were no rituximab-associated safety events. Case 1: 32-year-old woman with psychosis, MRI with subtle temporal lobe edema and gliosis, and EEG with frequent focal seizures, who was diagnosed with anti-NMDAR encephalitis. She remains asymptomatic and seizure-free on rituximab for two years. Case 2: 72-year-old woman with rapidly progressive dementia and brachiofacial spasms, MRI with right mesiotemporal FLAIR signal change, normal CSF, and EEG with intermittent rhythmic generalized slowing, who was diagnosed with anti-LGI1 encephalitis. She initially responded to high-dose prednisone (1 mg/kg), but, upon tapering steroids, developed recurrent epilepsy and dementia. She remains seizure-free on rituximab for 1 year with improvement in cognition to premorbid levels. Case 3: 19-year-old man with fevers and complex partial seizures with negative infectious evaluation. CSF and initial MRI were normal. EEG showed left fronto-temporal sharp waves with intermittent slowing that did not respond to IVIG or IV methylprednisolone, but rapidly responded to a single dose of rituximab. He demonstrated full recovery and remains asymptomatic on rituximab for 6 months. Anti-VGCC antibodies were identified. This is the first case of VGCC-associated epilepsy, although encephalopathy has been reported with this antibody. He did not have Lambert-Eaton syndrome, which can also be associated with VGCC. Conclusions: These results suggest that empiric treatment with rituximab can be considered as add-on therapy for the treatment of recalcitrant status epilepticus. Also, tumors may not be immediately apparent in paraneoplastic syndromes. Further studies are needed to establish safety and efficacy. Funding: Funding: intramural INOVA funds.