Refractory epilepsy is not uncommon in pediatric patients; consideration of whether seizures are acutely symptomatic of a primary disease process is critical. In this case, a healthy 7-year-old child presented with intractable focal seizures in the setting of a mild viral prodrome and headache. This case highlights a comprehensive work up of new-onset, refractory epilepsy in a patient with features of encephalitis, and it describes a diagnostic quandary that ultimately led to a rare unifying diagnosis. 

Immune-mediated processes are increasingly described as a significant cause of encephalitis in children. Associated antibodies, disease states, and clinical syndromes including paraneoplastic etiologies are continuously being elucidated. Anti-N-methyl-D-aspartate receptor encephalitis and its association with teratoma, and opsoclonus-myoclonus syndrome (OMS) with neuroblastoma are now well-characterized, but a growing number of antibodies are being implicated in pediatric paraneoplastic syndromes. Glutamic acid decarboxylase (GAD) 65-ab–associated neurological syndromes include stiff-person syndrome, epilepsy, cerebellar ataxia, encephalomyelitis, limbic encephalitis, and OMS. Though not classically considered high risk for association with an underlying malignancy, GAD65-abs have increasingly been implicated paraneoplastic neurological syndromes related to neuroendocrine, lung, and thymic neoplasms primarily. There have been rare reports of GAD65-abs disease related to hematologic malignancy, but a specific association between Burkitt lymphoma and GAD65 encephalitis has not yet been reported.

In this case of explosive-onset, refractory epilepsy, broad work up revealed evidence of CNS inflammation and autoimmunity which ultimately led to the diagnosis of GAD65-ab–associated paraneoplastic encephalitis related to an underlying Burkitt lymphoma in a previously healthy 7-year-old patient. This case emphasizes the importance of considering paraneoplastic etiologies in pediatric patients with acute or subacute, progressive neurologic symptoms with evidence of inflammation based on CSF or neuroimaging.