Brain metabolism in Rett syndrome: age, clinical, and genotype correlations.
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 < or = p < or = 0.11) and the lowest NAA/Cr ratio (0.029 < or = p < 0.14).


CONCLUSIONS
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.
Horská
Alena
A
Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. ahorska@jhmi.edu
Farage
Luciano
L
Bibat
Genila
G
Nagae
Lídia M
LM
Kaufmann
Walter E
WE
Barker
Peter B
PB
Naidu
SakkuBai
S
D000293:Adolescent; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007223:Infant; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011522:Protons; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D011522:Protons; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine