One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson’s disease and 22 control subjects underwent 3-T magnetic resonance imaging with T₂*-weighted, whole-brain T₁-weighted and diffusion tensor imaging scans. The mean R₂* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson’s disease and control subjects. Comparisons were also performed using voxel-based analysis of R₂*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson’s disease displayed significantly higher R₂* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson’s disease from controls. The markers comprising discriminating combinations were R₂* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson’s physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R₂*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson’s disease and, possibly, of other subcortical pathologies.

The purpose of this study was to assess the association between the serial number of gadolinium-enhanced magnetic resonance imaging (MRI) examinations and the signal hyperintensity of the dentate nucleus on unenhanced T1-weighted images in patients with multiple sclerosis (MS) and those with brain metastases (BMs). A group of 38 patients with MS and 37 patients with BM who had undergone at least 2 consecutive enhanced MRI examinations in our institution were examined for this retrospective observational study. The average T1 signal intensity of the dentate nuclei and the pons was obtained, and the dentate nuclei-to-pons (DNP) signal intensity ratio was calculated. These values were compared between patients with less than 6 and 6 enhanced MRI scans or more (eMRI). Relative changes of the DNP were plotted against the number of enhanced MRI scans (eMRIn). A progressive increase in the T1 signal intensity of the DNP ratio was observed both in the MS group and in the BM group. The DNP ratios of the last eMRI scans in the subgroup of patients with 6 eMRI scans or more were significantly higher than those of the first eMRI scan in the MS group (P < 0.001) and in the BM group (P < 0.01). Relative changes of the DNP showed a positive correlation with the eMRIn with a Spearman ρ of 0.96 (P < 0.001) in the MS group and that of 0.88 (P < 0.001) in the BM group. Curve regression analyses of the relative change of DNP ratios showed linear models to best fit the data with r(2) of 0.89 in the MS group and r(2) of 0.74 in the BM group. Our study shows that the increase in the unenhanced T1 signal intensity has a linear relationship with the eMRIn in patients with MS and BM. Indeed, we estimated a linear regression model to fit the progressive increase in T1 signal intensity of the dentate nucleus after multiple enhanced MRI scans. This finding suggests substantial dechelation of gadodiamide in patients with normal renal function, raising further concerns regarding the stability of this agent. Further comparative studies with other gadolinium chelates, specifically both linear and macrocyclic, are strongly recommended.

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5′ of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5′ untranslated regions (5′UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5′UTR of the RELN gene confer vulnerability to autistic disorder.