Brain gray matter changes in children at risk for sudden unexpected death in epilepsy

Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP.

The cerebellar cortex, hippocampus, amygdala, putamen, cingulate, thalamus, and para-hippocampal gyrus showed increased gray matter volumes in epilepsy, and decreased volumes in the posterior thalamus, lingual gyrus, and temporal cortices. The cingulate, insula, and putamen showed significant positive relationships with focal seizure frequency indices using whole-brain voxel-by-voxel partial correlations. Tissue volume changes in selected sites differed in direction from adults; particularly, cerebellar sites, key for hypotensive recovery, increased rather than adult declines.

The volume increases may represent expansion by inflammatory or other processes that, with sustained repetitive seizure discharge, lead to tissue volume declines described earlier in adults.

Children with epilepsy, who are at risk for Sudden Unexplained Death, show changes in brain volume that often differ in direction of change from adults at risk for SUDEP. Sites of volume change play significant roles in mediating breathing and blood pressure, and include areas that serve recovery from prolonged apnea and marked loss of blood pressure. The extent of volume changes correlated with focal seizure frequency. Although the underlying processes contributing to regional volume changes remain speculative, regions of tissue swelling in pediatric brain areas may represent transitory conditions that later lead to tissue loss in the adult condition.