Cerebrospinal fluid N-glycans as potential biosignatures for developmental and epileptic encephalopathy in children

Area of Science:

• Neurology
• Biochemistry
• Glycomics

Background:

• Epilepsy is a leading childhood neurological disorder with diagnostic challenges.
• Glycosylation impacts neuronal function and neuroinflammation, but its role in pediatric epilepsy is understudied.
• Understanding glycan profiles is crucial for advancing pediatric epilepsy diagnosis and prognosis.

Purpose of the Study:

• To investigate differential N-glycan signatures in plasma and cerebrospinal fluid (CSF) of pediatric epilepsy patients.
• To identify specific N-glycans associated with focal epilepsy, generalized epilepsy, and developmental and epileptic encephalopathies (DEE).
• To evaluate the diagnostic potential of N-glycan profiles for pediatric epilepsy, particularly DEE.

Main Methods:

• Collected plasma and CSF samples from pediatric epilepsy patients and controls.
• Utilized N-glycome profiling to analyze glycan signatures.
• Developed discriminative models to identify distinct glycan profiles.
• Analyzed the N-glycan biosynthetic network and correlations with protein and sugar levels.

Main Results:

• Distinct N-glycome profiles were identified in plasma and CSF, differentiating epilepsy patients from controls.
• A common set of 11 N-glycans was identified in both fluids for epilepsy detection.
• Elevated mannosylation and mono-sialylation in CSF were significant in DEE cases.
• High mannosylated and mono-sialylated N-glycans showed strong diagnostic potential for DEE.
• Sialylation, galactosylation, and bisection were key in the transition from control to DEE states.

Conclusions:

• N-glycosylation changes in CSF serve as potential biosignatures for pediatric epilepsy, especially DEE.
• Glycoprotein N-glycome profiling warrants further investigation for disease classification and clinical stratification.
• These findings offer new avenues for improving the diagnosis and management of pediatric epilepsy.