White matter impairment in Rett syndrome: diffusion tensor imaging study with clinical correlations.
OBJECTIVE
RTT, caused by mutations in the methyl CPG binding protein 2 (MeCP2) gene, is a disorder of neuronal maturation and connections. Our aim was to prospectively examine FA by DTI and correlate this with certain clinical features in patients with RTT.


METHODS
Thirty-two patients with RTT underwent neurologic assessments and DTI. Thirty-seven age-matched healthy female control subjects were studied for comparison. With use of a 1.5T MR imaging unit, DTI data were acquired, and FA was evaluated to investigate multiple regional tract-specific abnormalities in patients with RTT.


RESULTS
In RTT, significant reductions in FA were noted in the genu and splenium of the corpus callosum and external capsule, with regions of significant reductions in the cingulate, internal capsule, posterior thalamic radiation, and frontal white matter. In contrast, FA of visual pathways was similar to control subjects. FA in the superior longitudinal fasciculus, which is associated with speech, was equal to control subjects in patients with preserved speech (phrases and sentences) (P = .542), whereas FA was reduced in those patients who were nonverbal or speaking only single words (P < .001). No correlations between FA values for tracts and clinical features such as seizures, gross or fine motor skills, and head circumference were identified.


CONCLUSIONS
DTI, a noninvasive technique to assess white matter tract pathologic features, may add specificity to the assessment of RTT clinical severity that is presently based on the classification of MeCP2 gene mutation and X-inactivation.
Mahmood
A
A
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Bibat
G
G
Zhan
A-L
AL
Izbudak
I
I
Farage
L
L
Horska
A
A
Mori
S
S
Naidu
S
S
D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011446:Prospective Studies; D015518:Rett Syndrome / Q000235:genetics / Q000473:pathology*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013788:Thalamus / Q000473:pathology; D014795:Visual Pathways / Q000473:pathology; D049951:X Chromosome Inactivation
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2