Diagnostic value of proton mr spectroscopy and diffusion weighted MR imaging in inherited childhood neurodegenerative brain diseases

PURPOSE: Magnetic resonance (MR) imaging is highly sensitive in the detection of white matter lesions. However, MR imaging has a limited specificity with regard to the pathologic conditions that underlie signal intensity abnormalities in the white matter. For all types of pathologic disorders, T1 and T2 relaxation times become longer. Quantitative MR techniques, such as diffusion-weighted MR imaging (DWI) and proton MR spectroscopy (MRS), may provide more insight into underlying pathologic changes in the white matter. The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurodegenerative brain diseases. METHODS: Retrospective study group was consisting, 22 patients (16 male, 6 female; mean age, 7,8 months; age range, 10 days to 171 months). All patients underwent DWI and/or MR spectroscopy at our instutision for a neurodegenerative brain diseases between 2002 and 2006 years. Diagnoses were confirmed on the basis of clinic, laboratory and genetic tests. Disorders included in the study were metachromatic leukodystrophy (n=4), van der Knaap disease (n=4), Leigh disease (n=2), mitochondrial encephalopathy (n=1), maple syrup urine disease (n=2), Canavan disease (n=2), glutaric aciduria type-1 (n=1), L-2-hydroxglutaric aciduria (n=1), Pelizaeus-Merzbacher disease (n=1), galactosemia (n=1), Tay Sachs disease (n=1), Xlinked adrenoleukodystrophy (n=1), rhizomelic chondrodysplasia punctata (n=1). All patients were examined with a 1,5 T MR unit equipped with in a standard head coil. Eighteen patients evaluated with MRS and DWI, 2 patients with only DWI and 2 patients with only MRS. Single and multivoxel proton MRS was carried out and N-acetylaspartate (NAA)/Cr(creatine), Choline(Cho)/Cr, Myoinositol(mI)/Cr, Glutamine-Gluatamate(Glx)/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. DW images sets were evaluated by two radiologists, taking into account of abnormal signal intensity areas, diffusion properties and ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects (Mann Whitney U for age groups and Fisher Exact test for sex groups). Metabolite ratios and ADC values were compared between study and control groups with a Mann Whitney U test. P values less than 0,05 were considered to indicate a statistically significant difference. RESULTS: Mild and moderate motor mental retardation, loss of tendon reflexes and spasticity are common clinical signs of most of our patients. The most important neurologic finding of 4 patient who had mitochondrial encephalopathy and maple syrup urine disease was neonatal encephalopathy. One patient with Pelizaeus-Merzbacher disease had nystagmus. Two patient with Canavan disease had normal head circumference and NAA/Cr ratios was elevated. One patient with galactosemia had galactitol peak at 3,7 ppm. Spectroscopy of maple syrup urine disease showed resonances related to branched chain amino acids at 0,9 ppm. Four patient with van der Knaap disease had macrocephaly and searched for Canavan disease but NAA levels was not normal or elevated. Two patient with mitochondrial encephalopathy and one patient with maple syrup urine disease had severe lactat elevation. The other patients had not spesific peaks but metabolite ratios allowed recognize the pathogenesis of the diseases such as hypomyelination, active demyelination and gliosis. In 1 patients with mitochondrial encephalopathy and 2 patients with maple syrup urine disease with acute neurologic symptoms, restricted diffusion was detected on DWI. Different diffusion properties (increased and decreased) were seen only in one Glutaric aciduria Type 1 lesions. Remaining patients? brain lesions were having high ADC values compared to normal values. The control groups selection was confirmed with statistical analysis. When metabolite ratios obtained from white matter lesions compared with age and sex matched control subjects only NAA/Cr was significantly different from normal subjects (p<0.05). Calculated ADC values of abnormal diffusion areas were significantly different from normal subjects (p<0.05). CONCLUSIONS: Proton MRS resolves altered brain metabolites in neurodegenerative brain disorders. DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurodegenerative diseases which can give detailed information about neurochemistry of affected brain areas and helps to modify treatment regimens.