Clinical Heterogeneity Of Anti-GAD65 Antibody-associated Seizure

Objective:The clinical manifestations,positive auxiliary examination results,treatment and prognosis of anti-GAD65 antibody associated epileptic seizure were analyzed,and the clinical heterogeneity was summarized,so as to improve the understanding of this disease and provide reference for timely clinical diagnosis and treatment.Methods:The patients with suspected Autoimmune encephalitis(AE)were collected from May 2018 to December 2019,and the patients with positive anti-neuronal antibody were screened out.The patients with positive anti-GAD65 antibody in serum and cerebrospinal fluid and epileptic seizure were further screened for retrospective analysis and follow-up.The patient’s history,seizure type,antiepileptic medications,and immunotherapy regimen were evaluated by a senior neurologist.The basic information and clinical data of the subjects were analyzed.The basic information of the patients: age,gender,past medical history,family history,etc.Clinical data included: seizure time,seizure characteristics,other neurological symptoms,positive adjuvant test results,medication status,and prognosis.Prognosis was evaluated by modified Rankin(MRS)score.Follow-up evaluations were performed on admission,symptom peak,discharge,3,6 and 12 months after discharge,and the results were collated and analyzed.Results:1.General condition: A total of 800 patients with suspected autoimmune encephalitis were collected for anti-neuronal antibody examination.Among them,80 patients were positive for anti-neuronal antibody,both blood and cerebrospinal fluid were positive for anti-GAD65 antibody,and 5 patients had epileptic seizure during the course of disease(including 1 case with simultaneous positive LGI1 antibody),accounting for 6.25% of the total positive rate of anti-neuronal antibody.Male to female ratio 4:1;Age 18-61 years old(median age 38.2 years old);2 cases(40%)had chronic onset and 3 cases(60%)had acute/subacute onset.2 patients had one or more previous systemic autoimmune diseases,including hyperthyroidism,diabetes,vitiligo,etc.,and 3 patients had no previous medical history.All 3 cases had prodromal symptoms of infection before onset,and 2 cases had no prodromal symptoms.Three patients developed encephalitis symptoms within 15 days of onset of disease,one patient developed cognitive decline and depression 120 days after onset of disease,and one patient showed no progressive symptoms.2.Clinical characteristics: All the 5 patients(100%)presented epileptic seizures,and 2 patients presented systemic tonic-clonic seizures.One patient had focal conscious retention of sensory and autonomic seizures.One case had epileptic status.In one case,the sensory seizure with focal consciousness preservation progressed to the onset of focal consciousness disorder combined with motor symptoms.Attack frequency varies from minutes per episode to 1 month per episode.The EEG of 5 patients(100%)showed extensive and multifocal epileptic discharge in the early stage.All had poor effect on simple antiepileptic therapy.The main manifestations of head MRI abnormality were high FLAIR signal,4 patients(80%)had head MRI abnormality,2 cases involved limbic system,2 cases involved limbic system,cerebral cortex and subcortical white matter.No abnormality was found in 1 case.The CSF white blood cell count increased in 3 patients at the early stage of the disease.CSF protein was slightly elevated in 4 cases.All patients were negative for paraneoplastic antibodies.Other AAbs were positive in 3 cases.3.Treatment plan and prognosis.All patients received antiepileptic,immunoshock and continuous immunotherapy,and 3 patients with acute onset received antiviral therapy at the same time.At discharge,the seizure frequency of 4patients decreased,the encephalopathy symptoms improved,and 1 patient showed progressive aggravation.The prognosis of 3 patients was good at the end of follow-up.Two patients had poor prognosis and one of them died.Patients with chronic epilepsy onset(Patient 1 and Patient 2)had a low MRS score throughout the course of the disease and a good prognosis.All the 4 patients had epileptic relapse in the course of rapid reduction of antiepileptic drugs and hormones.Conclusions:1.Anti-GAD65 antibody associated seizure can be manifested as acute onset of acute symptomatic epileptic seizures secondary to anti-GAD65 antibody associated autoimmune encephalitis and chronic onset of anti-GAD65 antibody autoimmune associated epilepsy;2.The anti-GAD65 antibody related epileptic seizure forms are varied,and the epileptiform discharge in electroencephalogram is multifocal.The effect of antiepileptic therapy alone is poor,and long-term immunotherapy is needed to control the epileptic seizure.The epileptic relapse often occurs when the amount of antiepileptic drugs or hormones is rapidly reduced.3.Patients with acute onset anti-GAD65 antibody associated seizure had a worse prognosis than those with chronic onset.