Circulating metabolomic changes in Lennox-Gastaut syndrome: correlation with clinico-radiological severity

Abstract

Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by multiple types of seizures typically occurring between 1 and 7 years of age, cognitive impairment and characteristic electroencephalographic abnormalities. Circulating metabolomic profile may give insight into the ongoing metabolic pathway abnormalities in these patients, but there is no such study. We report NMR based metabolomic profile in LGS and its association with clinical severity, MRI changes and EEG findings. LGS children between 2 and 18 years were included based on clinical and EEG diagnostic criteria. Detailed neurological examinations, frequency and type of seizures, EEG changes, cranial MRI and NMR based serum metabolomic profile were measured. The Clinical Global Impairment Severity Scale (CGI-S) was used to rate severity of LGS. Twenty-six LGS patients and 11 healthy matched controls were included. The median age of the patients was 6 (range 2–17) years, and 19 were males. Their median CGI-S score was 6, and all had more than one type of seizures. Seven metabolites namely lactate, glucose, glutamate, pyruvate, glutamine, glycine, citrate and creatinine were crucial for discrimination of LGS from the controls, among which glutamate was upregulated and citrate, pyruvate, and glutamine were down regulated in LGS. Glutamate associated with developmental quotient (r = −0.48) and pyruvate with focal seizures (r = 0.47) and cystic encephalomalacia on cranial MRI (p = 0.02). NMR metabolomic profile including glutamate, glutamine, glycine, glucose, pyruvate, lactate, citrate and creatinine can discriminate LGS from the controls. Role of antiglutamatergic drugs may be beneficial in controlling seizures, and needs future study.