Smaller brain volumes in Rett girls tied to clinical severity: MRI study
No relationship seen between volume changes and epilepsy
Girls with Rett syndrome have significantly smaller brain volumes across all its regions, regardless of their age, a MRI study shows.
Reductions in the size of certain brain regions were tied to the clinical severity of Rett patients, particularly in gross motor function, such as sitting and walking. Still, scientists found no obvious relationships between brain volume changes and epilepsy.
“Evaluating regional brain volume provides valuable insights into the [disease processes] and can serve as a biomarker for the development of new medical therapies for [Rett],” the scientists wrote. Their study, “Diffuse but Non-homogeneous Brain Atrophy: Identification of Specific Brain Regions and Their Correlation with Clinical Severity in Rett Syndrome,” was published in Brain and Development.
Rett syndrome is a genetic condition that almost exclusively affects girls. It’s marked by various neurological features, including speech problems, stereotypical hand movements, impaired motor function, seizures, autistic features, and breathing irregularities. Microcephaly, or smaller than normal head size, is also a common sign, suggesting a problem with brain development.
Yet, the “relationship between specific neurological abnormalities … and corresponding brain regions has not been fully clarified,” according to scientists in Japan who used MRI to compare brain volumes of 20 girls with Rett, ages 3-18, against those of 25 age-matched healthy girls. In all the cases, Rett was caused by mutations in the MECP2 gene. Epilepsy was reported in 17 patients, 10 of whom were unresponsive to anti-seizure treatment.
Link between brain volume, disease severity
MRI scans revealed that Rett girls had significantly smaller volumes across all the brain regions assessed compared with healthy girls — the cerebral neocortex, cerebral white matter, subcortical gray matter, cerebellum, and brainstem.
After correcting for head size, reduced volume was most prominent in the cerebral neocortex, part of the cerebral cortex, or the brain’s outer layer, where higher cognitive functioning is thought to originate. The cortex was thinner in 46 out of 66 assessed regions, while all 66 cortical regions were significantly smaller in Rett patients than healthy controls.
Small brain volumes were seen in all ages of Rett girls from childhood to adolescence, with no relationships between age and regional volumes across patients or controls.
A statistical analysis found significant correlations between various regional volumes and the clinical severity of Rett patients, as assessed using the Clinical Severity Score (CSS), which evaluates Rett clinical features across 13 categories. Smaller brain regions associated with more severe Rett included the temporal neocortex and amygdala on the right side and the putamen, hippocampus, and the cerebral and cerebellar white matter on the left.
The volume reductions weren’t uniform across all the brain regions and were asymmetric, affecting only one side of the brain.
Within the CSS subcategories, worse gross motor function, or sitting and walking, significantly correlated with multiple smaller regions, including the frontal cortex, parietal cortex, insular cortex, cerebral white matter, and cerebellar white matter.
Still, the researchers found no relationships between brain volume sizes and fine motor skills or communication, possibly due to the “severe impairment of cognitive function in the study population.”
Regarding epilepsy, no significant differences were found in any regional volume, regardless of the treatment response or the time since the onset of epilepsy. Even so, brain volumes tended to decrease with a longer epilepsy duration.
“Significantly smaller volumes were observed in all brain regions at any age from childhood to adolescence in patients with [Rett],” the researchers wrote. “The degree of volume reduction was more prominent in the cerebral cortex.”
The small number of participants was noted as a limitation of the study. As a result, the scientists said they weren’t able to “fully determine the correlation between clinical features such as epilepsy type, genotype [genetic profile], and brain volume.”
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