Abstracts

Rationale: The International League Against Epilepsy Autoimmunity and Inflammation Taskforce stressed the need to distinguish autoimmune-associated epilepsy (AAE) from acute symptomatic seizures (ASS) secondary to autoimmune encephalitis (AIE). AIE awareness has been increasing rapidly but the concept of AAE is still evolving. We report two patients with antibodies to glutamic acid decarboxylase 65 (GAD65): one with ASS/AIE and the other with AAE.

Methods: Patient-1 is a 55-year-old male with type-1 diabetes and past admissions for ASS due to ethanol withdrawal and hypoglycemia. He presented with convulsive seizures and, after the convulsions stopped, EEG showed 1.5-2 Hz generalized rhythmic sharp and slow wave discharges consistent with nonconvulsive status epilepticus (NCSE). Brain MRI revealed DWI and FLAIR hyperintensities in the tempo-parieto-occipital and mediofrontal cortices. Patient-2 is a 53-year-old woman with a 33-year history of intractable epilepsy. She presented with a 3-week history of delirium, delusions, and hallucinations. Left hemispatial neglect and hemianopsia were also detected on examination. MRI showed DWI and T2-FLAIR hyperintensities in the right parietal and occipital cortices. EEG revealed focal seizures originating from the right parietal region.

Results: AIE was suspected in Patient-1 because of super refractory NCSE and in Patient-2 because of long history of intractable epilepsy without a clear etiology. Cerebrospinal fluid (CSF) was sent to Mayo Clinic for autoantibody testing in both patients. Both patients were treated empirically with steroids: Patient-1 received dexamethasone 10-mg IV for 3 days followed by a 10-day taper and Patient-2 received methylprednisolone 1000-mg IV q24h for 5 days. Both patients responded to IV steroids, both had normal neurological findings on discharge, and both were later found to have elevated CSF GAD65 levels: 3.65 nmol/mL and 18.0 nmol/ml, respectively. Patient-1 remained seizure-free on levetiracetam. Patient-2 continued to have 1 to 2 seizures per month despite therapeutic doses of levetiracetam and lacosamide, hence we started rituximab 1000-mg IV biweekly every 6 months.

Conclusions: Neurologists should be aware of the difference between ASS/AIE and AAE. Both are autoimmune brain disorders with distinct pathophysiology, clinical outcomes, and treatment approaches. ASS/AIE and AAE are similar in that both disorders are driven by autoimmunity involving autoantibodies (anti-GAD65 antibodies in the cases presented). However, patients with ASS/AIE have seizures only in the setting of active inflammation (Patient-1) whereas patients with AAE continue to experience seizures beyond the active inflammatory phase (Patient-2). The tendency for recurrent seizures in AAE is thought to be due to persistent cortical hyperexcitability secondary to structural changes and gliosis driven by T-cell mediated inflammation and neurotoxicity.

Funding: Please list any funding that was received in support of this abstract.: Nothing to disclose.