Automated Assessment of the Substantia Nigra Pars Compacta in Parkinson's Disease: A Diffusion Tensor Imaging Study.

The substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr) are differentially affected in Parkinson's disease (PD). Separating the SNpc and SNpr is challenging with standard magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) allows for the characterization of SN microstructure in a non-invasive manner. In this study, 29 PD patients and 28 healthy controls (HCs) were imaged with 1.5T MRI for DTI. Images were nonlinearly registered to standard space and SNpc and SNpr DTI parameters were measured. ANCOVA and receiver operator characteristic (ROC) analyses were performed. Clinical associations were assessed with Spearman correlations. Multiple corrections were controlled for false discovery rate. PD patients presented with significantly increased SNpc axial diffusivity (AD) (1.207 ± 0.068 versus 1.156 ± 0.045, p = 0.024), with ROC analysis yielding an under the curve of 0.736. Trends with Unified Parkinson's Disease Rating Scale (UPDRS) III scores were identified for SNpc MD (rs = 0.449), AD (rs = 0.388), and radial diffusivity (rs = 0.391) (all p < 0.1). A trend between baseline SNpr MD and H&Y change (rs = 0.563, p = 0.081) over 2.9 years of follow-up was identified (n = 14). In conclusion, SN microstructure shows robust, clinically meaningful associations in PD.

Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox.

The "male-female health-survival paradox" evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the "sex-frailty paradox". The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

Combined Assessment of Diffusion Parameters and Cerebral Blood Flow Within Basal Ganglia in Early Parkinson's Disease.

Diffusion tensor imaging (DTI) is a sensitive tool for detecting brain tissue microstructural alterations in Parkinson's disease (PD). Abnormal cerebral perfusion patterns have also been reported in PD patients using arterial spin labeling (ASL) MRI. In this study we aimed to perform a combined DTI and ASL assessment in PD patients within the basal ganglia, in order to test the relationship between microstructural and perfusion alterations. Fifty-two subjects participated in this study. Specifically, 26 PD patients [mean age (SD) = 66.7 (8.9) years, 21 males, median (IQR) Modified Hoehn and Yahr = 1.5 (1-1.6)] and twenty-six healthy controls [HC, mean age (SD) = 65.2 (7.5), 15 males] were scanned with 1.5T MRI. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) maps were derived from diffusion-weighted images, while cerebral blood flow (CBF) maps were computed from ASL data. After registration to Montreal Neurological Institute standard space, FA, MD, AD, RD and CBF median values were extracted within specific regions of interest: substantia nigra, caudate, putamen, globus pallidus, thalamus, red nucleus and subthalamic nucleus. DTI measures and CBF were compared between the two groups. The relationship between diffusion parameters and CBF was tested with Spearman's correlations. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant, while uncorrected p-values <0.05 were considered a trend. No significant FA, MD and RD differences were observed. AD was significantly increased in PD patients compared with HC in the putamen (p = 0.005, pFDR = 0.035). No significant CBF differences were found between PD patients and HC. Diffusion parameters were not significantly correlated with CBF in the HC group, while a significant correlation emerged for PD patients in the caudate nucleus, for all DTI measures (with FA: r = 0.543, pFDR = 0.028; with MD: r = -0.661, pFDR = 0.002; with AD: r = -0.628, pFDR = 0.007; with RD: r = -0.635, pFDR = 0.003). This study showed that DTI is a more sensitive technique than ASL to detect alterations in the basal ganglia in the early phase of PD. Our results suggest that, although DTI and ASL convey different information, a relationship between microstructural integrity and perfusion changes in the caudate may be present.

Combined DTI-fMRI Analysis for a Quantitative Assessment of Connections Between WM Bundles and Their Peripheral Cortical Fields in Verbal Fluency.

Diffusion tensor imaging (DTI) tractography and functional magnetic resonance imaging (fMRI) are powerful techniques to elucidate the anatomical and functional aspects of brain connectivity. However, integrating these approaches to describe the precise link between structure and function within specific brain circuits remains challenging. In this study, a novel DTI-fMRI integration method is proposed, to provide the topographical characterization and the volumetric assessment of the functional and anatomical connections within the language circuit. In a group of 21 healthy elderly subjects (mean age 68.5 ± 5.8 years), the volume of connection between the cortical activity elicited by a verbal fluency task and the cortico-cortical fiber tracts associated with this function are mapped and quantified. An application of the method to a case study in neuro-rehabilitation context is also presented. Integrating structural and functional data within the same framework, this approach provides an overall view of white and gray matter when studying specific brain circuits.

Assessment of immune reconstitution to Pneumocystis carinii in HIV-1 patients under different highly active antiretroviral therapy regimens.

The introduction of protease inhibitors (PIs) gave a dramatic drop in AIDS-related opportunistic events, mainly due to induced immune reconstitution. Discontinuation of prophylaxis against Pneumocystis carinii is considered safe when CD4 > 200 cells/mm(3). Ideally, we should have specific functional tests for HIV-1-related decisions. We examined viro-immunological profiles, clinical outcome and lymphocyte proliferation (LP) to P. carinii and other antigens in 108 subjects: 28 AIDS presenters with P. carinii pneumonia (PCP) (CD4 < 200 cells/mm(3)), 22 untreated asymptomatic HIV-1-infected patients (CD4 > 200 cells/mm(3)), 44 HIV-1-infected patients immune-reconstituted on antiretroviral regimens and 14 HIV-1-uninfected healthy controls. As regards viral load, there was no significant difference in therapy duration, nadir, or actual CD4, CD8, natural killer or B cell counts in immune-reconstituted patients receiving protease inhibitor (PI)-based versus those receiving PI-sparing antiretroviral regimens. Among subjects showing abnormally low P. carinii-specific LP, three patients receiving a non-nucleoside reverse transcriptase inhibitor (nNRTI) developed PCP despite having CD4 > 250 cells/mm(3). P. carinii-specific LP could be considered for doubtful situations, i.e. for a safer clinical decision of discontinuing or restarting prophylaxis in patients with a low CD4 nadir or experiencing a sudden CD4 decrease under highly active antiretroviral therapy (HAART). HIV-1 PIs, having in vitro aspecific effects against Pneumocystis, could play a clinically significant anti-opportunistic role, thus offering a further benefit in heavily immunosuppressed patients during early stages of antiretroviral therapy.