Two Cases Of Anti-glutamic Acid Decarboxylase Antibody-associated Neuroimmune Disease And Literature Review

Background And Objective:The symptoms of anti-glutamic acid decarboxylase(GAD)65 antibody-associated neuroimmune diseases are complex and overlapping,and the clinical manifestations are extremely rare.The main phenotypes include stiff-person syndrome(SPS),cerebellar ataxia(CA),limbic encephalitis(LE)and epilepsy.There is a lack of systematic criteria for diagnosis,treatment and prognosis.Anti-GAD65 antibody-associated encephalitis involving the whole cerebral cortex and subcortex and anti-GAD65 antibody-associated CA combined with SPS are even less common.In this paper,we analyzed one case of diffuse cortical and subcortical involvement of anti-GAD65 antibody-associated encephalitis and one case of anti-GAD65 antibody-associated CA combined with possible SPS,and summarized the clinical features and regression of anti-GAD65 antibody-associated encephalitis and antiGAD65 antibody-associated CA combined with SPS by searching relevant literature.Methods By analyzing 2 patients with anti-GAD65 antibody-associated neuroimmune disease and searching in several Chinese and English databases by relevant keywords and search formula,case articles related to adult anti-GAD65 antibody-associated panencephalitis and anti-GAD65 antibody-associated CA combined with SPS published from 2000 to February 2023 were included to summarize their clinical features,auxiliary examination,diagnosis,treatment and prognosis.Results A total of 8 articles on cases of adult anti-GAD65 antibody-associated panencephalitis and 12 articles on cases of anti-GAD65 antibody-associated CA combined with SPS were included.Including case 1 of this paper,there were 12 patients with anti-GAD65 antibody-associated panencephalitis,with a male-to-female ratio of 1:3 and a median age at presentation of 39.5 years,mostly with acute or subacute onset,and only 1 patient reported a combination of autoimmune diseases.10(10/12)patients had different types of seizures as their first symptom,and 6(6/12)patients had severe impairment of consciousness.All 12 patients showed multiple cortical and subcortical abnormal signals in the cerebral hemispheres on cranial MRI,among which 7(7/12)patients had lesions mainly involved near the midline of the brain(frontal,parietal and occipital lobes),which improved after active immunotherapy;5(5/12)patients mainly involved the medial temporal lobe and hippocampus,which left seizures and higher neurological dysfunction even after active treatment.A total of 17 patients with antiGAD65 antibody CA combined with SPS were included in 12 articles,with a male-to-female ratio of 6:11 and a median age of onset of 50 years.11 patients(11/17)had a combination of systemic autoimmune disease,mostly subacute or chronic progression with progressive exacerbation,and CA and SPS could occur simultaneously or sequentially,with the longest reported interval being 11 years.15 patients(15/17)had only improvement in stiffness after active treatment,with no relief of cerebellar symptoms.Conclusion GAD65 antibody-associated panencephalitis is more common in young and middle-aged women,and rarely complicated with other autoimmune diseases.The onset of antiGAD65 antibody-associated panencephalitis is acute or subacute,with different types of seizures as the first manifestation,often accompanied by severe disturbance of consciousness.The prognosis of anti-GAD65 antibody-associated panencephalitis involving the midline of the brain(frontal,parietal and occipital lobes)is good,while the prognosis of anti-GAD65 antibody-associated panencephalitis involving the medial temporal lobe and hippocampus is poor.GAD65 antibody associated CA combined with SPS is common in middle-aged and elderly women,and most of them are accompanied by T1DM,subacute or chronic onset,and continuous exacerbation.Most of CA combined with classical SPS,which may occur simultaneously or successively,has a long course of disease,poor response to immunotherapy,and poor prognosis.