S60. Case series of anti-GABAb receptor antibody autoimmune limbic encephalitis - clinical data, EEG, brain imaging and treatment outcome

Abstract

Introduction Autoantibodies to extracellular epitopes of neurons and associated neurological disorders, especially autoimmune limbic encephalitis (LE), are increasingly recognized. GABAb receptor antibody associated autoimmune LE often presents with refractory seizures. Timely recognition and diagnosis are critical, as prompt immunotherapy achieves more favorable outcomes. Methods We identified 3 autoimmune LE cases associated with anti-GABAb receptor antibody (Ab). Clinical data was retrospectively obtained and evaluated. Broad neuronal autoantibody panels were also examined. Results The initial clinical presentation of LE was new onset seizures with altered mental status, two patients had prodromal infectious symptoms prior to the onset of seizures. When symptoms evolved, seizures became pharmacologically refractory to anti-epileptics. One patient had convulsive status, and two others had non-convulsive status confirmed by either repetitive EEG tests or continuous EEG monitoring. The patients also presented with behavioral symptoms including agitation, behavioral outbursts, and one patient had hypersomnia. Two patients were with diagnosed with small cell lung cancer prior to the seizure onset, one of whom also had recurrent refractory optic neuritis. The other patient had a negative malignancy workup. CSF studies showed mild pleocytosis with lymphocyte predominance, and two patients were found to have positive oligoclonal bands in CSF. GABAb receptor Abs were found in CSF from all three patients, two patients were also found to have positive GABAb receptor Abs in serum. Other neuronal autoantibodies were also detected, CRMP5 (in serum/CSF from patient with optic neuritis), P/Q, or N-type calcium channel antibodies were found in serum from all three patients. Brain T2/FLAIR signal changes were seen in the temporal lobe and hippocampus in two. The other one patient’s brain MRI was unrevealing. All patients underwent IV Steroid and IVIG or plasma exchange treatment, which helped seizure control and briefly improved mental status. Two patients received further treatment with Rituximab due to persistent cognitive deficits (short term memory loss, poor attention/concentration) or persistent hypersomnia. Rituximab treatment resulted in partial clinical improvement. Though there was no seizure recurrence in these patients followed for 3–9 months, both patients continued to have cognitive deficits and memory loss. Follow-up CSF study showed resolved CSF pleocytosis, however, serum and CSF serology showed persistent positivity of GABAb receptor Abs in these patients. Thus, the patients continued with long term immuno-therapies. Conclusion We report 3 cases of GABAb receptor antibody associated autoimmune LE including one unique case with concurrent CRMP5 associated paraneoplastic optic neuritis. Though coexistence of other neuronal autoantibodies were noted, the neurological presentations in our cohort were likely directly due to the pathogenic effects medicated by GABAb receptor antibodies.