Cerebral infarction associated with moyamoya disease: histogram-based quantitative analysis of diffusion tensor imaging - a preliminary study

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.
Magnetic Resonance Imaging (Impact Factor: 2.09). 08/2008; 26(6):835-40. DOI: 10.1016/j.mri.2008.01.036
Source: PubMed


Moyamoya disease (MMD) is a rare disorder of unknown etiology in which terminal portions of the internal carotid arteries become steno-occlusive, with fine collateral "moyamoya vessels" formed secondarily, resulting in serial ischemic strokes throughout its clinical course. Whole-brain histogram (WBH) of diffusion tensor imaging (WBH-DTI) is an analytical tool whose feasibility has been ascertained in various pathologies. To elucidate whether WBH-DTI could detect any difference between ischemic MMD and normal controls, we examined 27 consecutive MMD patients without hemorrhage and 48 normal controls in this prospective study using a 3.0-T magnetic resonance scanner. WBHs of fractional anisotropy (FA) (WBH-FA) and mean diffusivity (MD) (WBH-MD) were compared among three groups: Group 1, MMD patients with infarct (n=15); Group 2, MMD patients without infarct (n=12); and Group 3, normal controls (n=48). Group 1 showed significantly higher peak height and significantly lower mean value on WBH-FA, as well as significantly lower peak height and significantly higher mean value on WBH-MD, compared with Groups 2 and 3. No significant difference was seen in parameters at either WBH-FA or WBH-MD between Groups 2 and 3. These results might reflect the pathological severity of each group, and WBH-DTI could feasibly detect differences between ischemic MMD with infarction and MMD without infarction and normal controls.

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    ABSTRACT: Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2009. Introdução: A Síndrome de Rett é uma desordem do neurodesenvolvimento ligada ao cromossomo X com um acometimento precoce na infância, que afeta, primariamente meninas. O lobo frontal é particularmente afetado. A base genética da doença, em 80% das meninas acometidas, está cionada às mutações no gene da proteína methyl-CpG binding protein 2 (MeCP2). Casuística e Métodos: Dois grupos de meninas afetadas, que preenchem os critérios clínicos e são positivas para mutações, foram avaliadas com espectroscopia (MRS) e tensor de difusão (DTI). Os dados foram comparados com controles pareados por idade e sexo. O fenótipo foi avaliado pelo perímetro cefálico, história de crises convulsivas, irregularidades respiratórias, alterações de marcha e fala. O genótipo foi avaliado pelo tipo de mutação existente. Os exames de ressonância magnética (RM) foram realizados em aparelho de 1,5T e incluíram avaliação anatômica (sagital T1, axial T2 e axial FLAIR). Quarenta meninas (idade média de 6,1 anos) foram submetidas à MRS uni-voxel, na substância branca do lobo frontal esquerdo, com TE de 35 ms.Foram obtidas as relações de N-acetil-aspartato (NAA), Colina (Co), mio-inositol (mI), Glutamato e Glutamina (Glx) sobre Creatina (Cr) e suas respectivas concentrações. Trinta e duas meninas (idade média de 5,5 anos) foram avaliadas com DTI, obtidos com single-shot echo-planar com SENSE (fator de 2,5), espessura de 2,5 mm, 30 orientações e valor b de 700 s/mm2. As medidas de anisotropia fracionada (FA) foram obtidas com o delineamento manual de dezesseis regiões de interesse nos compartimentos supra e infratentorial. Assimetrias entre os lados foram avaliadas pela medida da FA e pelo índice de lateralidade. Resultados: Os resultados demonstraram que a NAA/Cr diminuiu e a mI/Cr aumentaram com a idade (p<0,03), enquanto essas razões permanecem estáveis no grupo controle. A razão de Glx/Cr foi 36% maior nas pacientes (p=0,043). A razão de NAA/Cr foi 12,6% menor na presença de crises convulsivas (p=0,017). Houve decréscimo da NAA/Cr com a gravidade clínica (p=0,031). A presença da mutação R168X tem pior grau de gravidade clínica (0,01 ? p ? 0,11) e uma razão NAA/Cr mais baixa (0,029 ? p <0,14), quando comparados com outras mutações. Houve redução da FA no joelho e esplênio do corpo caloso, cápsulas interna e externa, cíngulo anterior, radiação talâmica e substância branca frontal. A FA do fascículo longitudinal superior foi semelhante aos controles (p=0,542) e nas pacientes com fala preservada e reduzida (p<0,001) nas pacientes com mutismo. Não houve alteração nos valores de FA na presença de crises convulsivas ou de alterações motoras. Conclusão A redução da NAA/Cr e o aumento do mI/Cr com a idade sugere que haja uma lesão axonal progressiva e reação astrocitária. O aumento do Glx/Cr pode ser secundário ao aumento do ciclo de glutamato e glutamina nas sinapses. As alterações do NAA/Cr na presença de crises convulsivas e associadas à gravidade da doença e a redução da FA nos casos de comprometimento da fala sugerem que a MRS e DTI podem ser úteis na avaliação evolutiva do comprometimento cerebral da Síndrome de Rett. _______________________________________________________________________________ ABSTRACT Introduction Rett syndrome is a X-linked neurodevelopmental disorder that affects almost exclusively girls from early childhood. Frontal lobe is particularly affected. Mutations in the methyl-CpG binding protein 2 (MeCP2) gene are identified in more than 80% of affected girls. Patients and Methods Two groups of patients who fulfill clinical criteria and were positive for MeCP2 mutations underwent for spectroscopy (MRS) and diffusion tensor imaging (DTI) evaluation. Data were compared with age and sex matched controls. Clinical assessments included neurological status, head circumference, and history of seizures, respiratory irregularities, gait, and speech. Genotype assessment was performed by mutation analysis. Magnetic resonance imaging was performed at 1.5T unit and includes anatomical images. Forty girls (mean age 6.1 years) underwent single voxel MRS in the left frontal lobe white matter, TE 35 ms. Individual metabolite ratios were obtained from N-acetylaspartate (NAA), coline (Co), myoinositol (mI), glutamate e glutamine (Glx) over creatine (Cr) and their concentrations. Thirty-two girls (mean 5.5 years) underwent DTI evaluation, data were acquired using single-shot echo-planar with SENSE (reduction factor of 2.5), thickness of 2.5 mm, 30 encoding directions and b value of 700 s/mm2. Fractional anisotropy (FA) was obtained by manually delineated regions of interest of major white matter tracts. Asymmetry between the hemispheres was evaluated by comparison of left and right FA values and laterality index. Results NAA/Cr ratios decreased and mI/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). Patients with the R168X mutation tended to have the greatest severity score (0.01 X ! p ! 0.11) and the lowest NAA/Cr ratio (0.029 ! p <0.14). Significant reductions in FA were noted in the genu and splenium of corpus callosum and external capsule with regional reductions in the anterior cingulated, internal capsule, posterior thalamic radiation, and frontal white matter. Differences of FA in superior longitudinal fasciculus (SLF), which has strong correlation with speech, were noted in RTT with preserved speech (phrases and sentences) where FA in SLF was equal to controls (p=0.542) while FA was reduced (p<0.001) in those who were non-verbal or with single words. No correlation with FA values for tracts associated with seizures, gross or fine motor skills were identified. Conclusion Decreasing NAA/Cr and increasing mI/Cr with age are suggestive of progressive axonal damage and astroglyosis, respectively, whereas increased Glx/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, and also reduction of FA at superior longitudinal fasciculus at impaired speech patients suggest that MRS and DTI may provides a noninvasive measure of cerebral involvement in Rett syndrome.
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