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Plasma amino acids in childhood epileptic encephalopathies
C D Ferrie1, S Bird, K Tilling
1Department of Paediatric Neurology, Leeds General Infirmary, Belmont Grove, UK.
Insights
Children with epileptic encephalopathies and their parents show lower aspartate levels, suggesting a potential genetic link in neurotransmitter systems. This finding is particularly noted in cases without focal brain abnormalities on PET scans.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Plasma amino acid abnormalities are observed in epilepsy patients and their relatives.
- Epileptic encephalopathies in children present complex challenges in understanding pathogenesis.
- Cortical glucose metabolism provides insights into brain function in neurological disorders.
Purpose of the Study:
- To investigate plasma amino acid levels in children with epileptic encephalopathies and their parents.
- To correlate these amino acid levels with cortical glucose metabolism patterns assessed by 18-fluorodeoxyglucose positron emission tomography (FDG PET).
- To explore potential genetic links in neurotransmitter systems contributing to childhood epileptic encephalopathies.
Main Methods:
- Prospective study of 28 children with cryptogenic epileptic encephalopathies and their parents.
- FDG PET scans with visual and semiquantitative analysis to identify focal cortical defects.
- Ion exchange chromatography to measure plasma concentrations of 21 amino acids.
- Non-parametric statistical methods and multivariate analysis for data comparison and antiepileptic drug effects.
Main Results:
- Significantly lower plasma aspartate levels were found in children with epileptic encephalopathies and their parents (P < 0.005).
- Lowered aspartate levels were not attributable to antiepileptic drug (AED) treatment.
- Reduced aspartate was specifically observed in children and parents without focal abnormalities on PET scans.
Conclusions:
- Findings suggest a possible genetic abnormality in aspartate neurotransmitter systems in the pathogenesis of childhood epileptic encephalopathies.
- Lowered aspartate may be a biomarker for specific subgroups of epileptic encephalopathies, particularly those without focal PET defects.
- Further research into neurotransmitter system genetics is warranted for understanding and treating these conditions.
Abstract:
Abnormalities in plasma amino acid levels have been noted in patients with various epilepsies, and sometimes also in their first degree relatives. We sought to study plasma amino acid levels in children with epileptic encephalopathies and their parents, relating findings to the pattern of cortical glucose metabolism as determined by 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty-eight children with cryptogenic epileptic encephalopathies were studied prospectively. Cortical glucose metabolism was evaluated by FDG PET with combined visual and semiquantitative analysis used to detect focal cortical defects. The plasma concentration of 21 amino acids in the children and their parents was measured by ion exchange chromatography and compared with control values using non-parametric statistical methods. Multivariate analysis was used to assess antiepileptic drug effects. Children were classified as: Lennox-Gastaut syndrome following infantile spasms (six patients); de-novo Lennox-Gastaut syndrome (eight); severe myoclonic epilepsy in infancy (eight) and myoclonic-astatic epilepsy (two). Four patients remained unclassified. Fourteen patients had focal/multifocal abnormalities on PET scans. The plasma level of aspartate was significantly lower in both the children with epileptic encephalopathies and in their parents (P < 0.005). The lowered aspartate levels could not be accounted for by the antiepileptic drug medication taken by the children. Further analysis showed the lowered aspartate levels to be confined to children and their parents who lacked focal PET abnormalities. These findings suggest a possible genetic abnormality in the aspartate neurotransmitter systems in the pathogenesis of seizures in the childhood epileptic encephalopathies.