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Large-scale structural alteration of brain in epileptic children with SCN1A mutation
Yun-Jeong Lee1, Mi-Sun Yum1, Min-Jee Kim1
1Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Insights
Children with SCN1A gene mutations causing epilepsy show significant brain development differences, including smaller brain volumes and reduced gray matter in specific regions. These findings highlight large-scale structural changes associated with SCN1A-related epilepsy.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Mutations in the SCN1A gene are linked to epilepsy syndromes like GEFS+ and SMEI.
- Brain imaging in SCN1A mutation patients often shows normal or non-specific findings.
- Investigating brain morphometry differences is crucial for understanding SCN1A-related epilepsy.
Purpose of the Study:
- To investigate differences in brain morphometry between epileptic children with SCN1A gene mutations and healthy controls.
- To identify specific structural brain alterations associated with SCN1A gene mutations in epilepsy.
Main Methods:
- Cortical morphology (thickness, surface area) and brain volumes were measured using FreeSurfer.
- 21 children with epilepsy and SCN1A mutations were compared to 42 age and gender-matched healthy controls.
- Global, subcortical, and regional brain measurements were analyzed.
Main Results:
- Patients with SCN1A mutations had smaller total brain, gray matter, white matter, cerebellar white matter, and subcortical volumes.
- Reduced gray matter volume was observed in bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, and right middle temporal areas.
- Smaller surface area and white matter volume were noted in some of these regions, but regional cortical thickness did not differ significantly.
Conclusions:
- Epilepsy associated with SCN1A gene mutations involves large-scale developmental brain changes.
- These structural alterations may contribute to the core symptoms observed in affected patients.
- Further longitudinal MRI studies are needed to confirm the impact of SCN1A mutations on brain development.
Objective:
Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects.
Methods:
We obtained cortical morphology (thickness, and surface area) and brain volume (global, subcortical, and regional) measurements using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu) and compared measurements of children with epilepsy and SCN1A gene mutation (n = 21) with those of age and gender matched healthy controls (n = 42).
Results:
Compared to the healthy control group, children with epilepsy and SCN1A gene mutation exhibited smaller total brain, total gray matter and white matter, cerebellar white matter, and subcortical volumes, as well as mean surface area and mean cortical thickness. A regional analysis revealed significantly reduced gray matter volume in the patient group in the bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, right middle temporal area with smaller surface area and white matter volume in some of these areas. However, the regional cortical thickness was not significantly different in two groups.
Significance:
This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.
