Quantitative H-1 MR spectroscopic imaging in early Rett syndrome

Objective: To determine cerebral regional concentrations of N-acetyl aspart ate (NAA), total choline (Cho), and total creatine (Cr) in Rett syndrome (R S) using H-1 magnetic resonance spectroscopic imaging (MRSI). Background: T he biochemical defect underlying RS is unknown. Because in vivo MRSI can de tect important cerebral metabolites, MRSI has a potential to reveal impairm ent of regional cerebral metabolism in RS noninvasively. Methods: High-reso lution, multislice H-1 MRSI was carried out in 17 girls with RS. The contro l group consisted of nine healthy children. Results: In patients with RS, a verage Cho concentration was 12% higher (p < 0.005) and average NAA concent ration 11% lower (p < 0.0001) compared with the control group. Regional met abolic differences included significantly lower NAA concentration in the fr ontal gray and white matter, insula, and hippocampus in RS; no difference i n regional Cho and Cr concentrations were found. A 20 to 38% higher Cho:NAA ratio in frontal and parietal gray and white matter, insular gray matter, and hippocampus (p < 0.05) and a 14 to 47% lower NAA:Cr ratio in frontal co rtical gray matter, parietal and temporal white matter, insula, and putamen (p < 0.05) were found in subjects with RS compared with controls. Patients with seizures had higher average concentrations of Cho, Cr, and NAA compar ed with those without seizures (8-19%, p < 0.05). Conclusion: Metabolic imp airment in RS involves both gray and white matter and particularly involves frontal and parietal lobes and the insular cortex. Loss of NAA most likely reflects reduced neuronal and dendritic tree size; increased Cho concentra tion may result from gliosis.