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

Aditi Pandey (Centre of BioMedical Research, India)

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. There is no definite cure for this condition; the seizures can be managed to some extent through medical, dietary and sometimes surgical interventions. LGS is also frequently refractory to anti-seizure medication (ASM).
We report NMR-based metabolomic profile in LGS and its association with clinical parameters. Children between 2-18 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. 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.
Spectra were recorded on 800 MHz NMR spectrometer and eight 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 downregulated in LGS. Glutamate was 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. In view of significant perturbations in glutamate, the effect of anti-glutamatergic ASM may be explored in controlling seizures and brain damage.