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Brain metabolism in rett syndrome: Age, clinical, and genotype correlations
Author(s) -
Horská Alena,
Farage Luciano,
Bibat Genila,
Nagae Lídia M.,
Kaufmann Walter E.,
Barker Peter B.,
Naidu Sakkubai
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21562
Subject(s) - rett syndrome , glutamine , glutamate receptor , medicine , white matter , central nervous system disease , gastroenterology , endocrinology , magnetic resonance imaging , chemistry , biochemistry , amino acid , receptor , radiology , gene
Objective Brain metabolism, as studied by magnetic resonance spectroscopy (MRS), has been previously shown to be abnormal in Rett syndrome (RTT). This study reports the relation of MRS findings to age, disease severity, and genotype. Methods Forty RTT girls (1–14 years old) and 12 age‐matched control subjects were examined. Single‐voxel proton MRS of left frontal white matter was performed. Results NAA/Cr ratios decreased and myoinositol/Cr ratios increased with age in RTT patients (both p < 0.03), whereas these ratios were stable in control. The mean glutamate and glutamine/Cr ratio was 36% greater in RTT patients than in control ( p = 0.043). The mean NAA/Cr ratio was 12.6% lower in RTT patients with seizures compared with those without seizures ( p = 0.017). NAA/Cr ratios decreased with increasing clinical severity score ( p = 0.031). Compared with patients with T158X, R255X, and R294X mutations, and C‐terminal deletions, patients with the R168X mutation tended to have the greatest severity score (0.01 ≤ p ≤ 0.11) and the lowest NAA/Cr ratio (0.029 ≤ p < 0.14). Interpretation Decreasing NAA/Cr and increasing myoinositol/Cr with age are suggestive of progressive axonal damage and astrocytosis in RTT, respectively, whereas increased glutamate and glutamine/Cr ratio may be secondary to increasing glutamate/glutamine cycling at the synaptic level. The relations between NAA/Cr, presence or absence of seizures, and disease severity suggest that MRS provides a noninvasive measure of cerebral involvement in RTT. Ann Neurol 2009;65:90–97