Abstracts

Rationale: Antibody-associated inflammatory brain diseases (AB-associated IBrainD) are being recognized as an important cause of encephalopathy and refractory epilepsy. Although anti NMDAR antibody is the most common cause of autoimmune encephalitis (AE), new neurotropic antibodies are being identified. Anti-glutamic acid decarboxylase 65 (GAD 65) antibody, a known cause for other disorders, is seldom associated with AE. Herein, we report a pediatric case of an anti-GAD65 positive AE. Methods: Case: A 9 year-old boy presented with a febrile prodrome (4 days), generalized epilepsy, and encephalopathy. He subsequently developed refractory seizures, unresponsive to high dose IV corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis, pentobarbital coma, and multiple anti-epileptic drugs. GAD-65 Ab was positive in both the serum and the CSF. His condition stabilized only after a Rituximab dose (500 mg/m2). The patient was transferred to an inpatient rehabilitation facility on Prednisone, Felbamate, Phenobarbital, Lacosamide, Levetiracetam, Topiramate and Clobazam. He was finally discharged following gradual motor and cognitive improvement. AEDs were gradually weaned. However, 3 months after Rituximab, profound hypogammaglobulinemia (IgG 280, IgM/IgA undetectable) was found that required monthly IVIG treatment. Another course of Rituximab was given after 8 months due to a rise in serum anti-GAD65. The patient has revealed marked neurological recovery and currently remains seizure free at 10 months (on Topiramate and weaning Phenobarbital). However, IgA/IgM levels remain undetectable. Such profound effects on humoral immunity by Rituximab are usually seen only in immunocompromised patients, typically those with antibody deficiency syndrome. Results: Discussion: There are multiple diagnostic terms that could be applied to this case including FIRES (Febrile infection related Epilepsy syndrome), AB-associated IBrainD, AE and autoimmune encephalopathy with refractory epilepsy. Perhaps, all these entities share a common pathophysiologic association which could be autoimmune/inflammatory in nature. With the detection and association of newer autoantibodies against different CNS structures (cell surfaces, synaptic proteins and channels), an argument can be made in favor of routine autoantibody testing for such patients. Also, larger studies will be needed to further characterize these associations and develop appropriate guidelines. Conclusions: Anti GAD65 is difficult to treat and may require early Rituximab treatment. Other anti GAD 65 AE case reports had similar success with Rituximab. Therefore, Rituximab treatment should be considered at an earlier stage for better outcomes. The unusual side effects of Rituximab in this case indicate pre-existing unrecognized immune abnormalities and host factors illustrating the need to monitor immune parameters. Funding: none