Cerebrospinal Fluid Level of Glutamic Acid Decarboxylase (GAD) Antibody in Patients with Encephalitis

Abstract

Background: Assaying the Glutamic Acid Decarboxylas( GAD) antibody in patients with encephalitis in cerebrospinal fluid and blood serum and its role in autoimmune encephalitis in children. Objective: This study Aimed at screening for GAD antibody in CSF of children presenting with acute encephalitis with non bacterial cause mostly autoimmune.Participants and methods: study is a pilot prospective study, conducted in the Pediatric department, Children’s Hospital, Ain Shams University.Fifty patients diagnosed with encephalitis exhibited at least one sign of parenchymatous brain dysfunction such as altered consciousness personality or behavior change, seizure, paresis, or ataxia. Encephalitis was defined as the presence of encephalopathy plus at least two of four findings: (1) fever (body temperature>38C); (2) abnormal cerebrospinal fluid examination (pleocytosis>5 white blood cells/mL and/or increased protein content>40 mg/dL) with negative cerebrospinal fluid culture; (3) abnormal electroencephalography findings compatible with encephalitis such as diffuse or focal slow activity, or periodic lateralized epileptiform discharges; and (4)abnormal results of neuroimaging, including computed tomography and magnetic resonance imaging (10), ,with age ranged from 6-144 Months; followed up In the period from September 2014 till March 2016.Basic clinical evaluation and laboratory investigations were done, GAD antibody level was measured in CSF and blood serum. Results: GAD receptor antibody titer was done in CSF which range from (36 -368 ng/l) with median of 64.83 (57.93-74.48), while in serum it range from (42.76-900) ng/l) with median 89.5(58.62-154.5).It was found that 6/50 (12%) patients had high GAD receptor antibody titer were high in CSF. The other 44/50 (88%) patients had low GAD antibody titer. In serum samples of twinty patients we had 8/20 (40%) patients had high GAD antibody titer and the rest were low GAD antibody titer 12/20 (60%).Significant occurrence of DCL, hospitalization plus mechanical ventilation and long term sequel were detected in patients with high GAD antibody titer. EEG findings; Two patients showed generalized epileptogenic activity, one patient had diffuse cortical dysfunction and two patient had multifocal epileptiform discharge and the rest of patients had normal finding. Eighty six precent had normal MRI findings,While 7 patients (14%) had non specific findings;3 patients had transient cortical meningeal enhancment,2 patients had high intensity in medial temporal lobe,one had abnormal signal intensity in medial temporal lobe and one patient had global brain atrophy. Conclusion: GAD Abs are directed against an intracellular antigen. The proposed pathogenic mechanisms of neurological disease in patients with antibodies directed against intracellular proteins is not clear. The present study emphasizes the importance of studying the CSF of patients with encephalitis suspected to be mediated by GAD autoimmunity.Both serum and CSF level must be assessed simultaneously as CSF level may change rapidly with fluctuation of disease. There are great efforts to be done to define the role of these GAD antibodies and to determine how they affect central nervous system function. These studies must be carried out so that appropriate treatments can be provided for the growing number of patients with possible antibody-mediated conditions.