International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cerebellar Gray Matter Alterations in Huntington Disease: A Voxel-Based Morphometry Study.

Neuropathological and neuroimaging studies in Huntington disease (HD) have suggested a role for the cerebellum. Our goal was to perform a detailed evaluation of cerebellar morphology. We performed the Unified HD rating scale (UHDRS) and Montreal cognitive assessment (MOCA) in 26 HD patients and 26 healthy controls. We created a two-sample test to analyze cerebellar gray matter (GM) differences between groups and another to correlate GM alterations with UHDRS and MOCA, corrected for age, expanded cytosine-adenine-guanine repeats, and disease duration using the spatially unbiased atlas template (SUIT)-SPM-toolbox which preserves anatomical detailing. We found increased GM density in the anterior cerebellum compared to controls. Higher GM density in the postero-superior lobe correlated with mood symptoms. Worse motor function and better cognitive function correlated with GM changes in the posterior cerebellum (false discovery rate (FDR) correction p < 0.05 and k > 100 voxels). In this detailed study of the in vivo cerebellar morphology in HD, we observed GM changes in regions involved in sensorimotor integration, motor planning, and emotional processing, supporting cerebellar involvement in the neuropathological process of HD.

A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3.

Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically-confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high-resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3-T scanner. We used Tract-Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel-based morphometry of infratentorial structures. T2-relaxometry of cerebellum was performed with in-house-developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel-based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2-relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients.

Is Diffusion Tensor Imaging a Good Biomarker for Early Parkinson's Disease?

Objectives: To assess white matter abnormalities in Parkinson's disease (PD). Methods: A hundred and thirty-two patients with PD (mean age 60.93 years; average disease duration 7.8 years) and 137 healthy controls (HC; mean age 57.8 years) underwent the same MRI protocol. Patients were assessed by clinical scales and a complete neurological evaluation. We performed a TBSS analysis to compare patients and controls, and we divided patients into early PD, moderate PD, and severe PD and performed an ROI analysis using tractography. Results: With TBSS we found lower FA in patients in corpus callosum, internal and external capsule, corona radiata, thalamic radiation, sagittal stratum, cingulum and superior longitudinal fasciculus. Increased AD was found in the corpus callosum, fornix, corticospinal tract, superior cerebellar peduncle, cerebral peduncle, internal and external capsules, corona radiata, thalamic radiation and sagittal stratum and increased RD were seen in the corpus callosum, internal and external capsules, corona radiata, sagittal stratum, fornix, and cingulum. Regarding the ROIs, a GLM analysis showed abnormalities in all tracts, mainly in the severe group, when compared to HC, mild PD and moderate PD. Conclusions: Since major abnormalities were found in the severe PD group, we believe DTI analysis might not be the best tool to assess early alterations in PD, and probably, functional and other structural analysis might suit this purpose better. However it can be used to differentiate disease stages, and as a surrogate marker to assess disease progression, being an important measure that could be used in clinical trials. HIGHLIGHTS DTI is not the best tool to identify early PDDTI can differentiate disease stagesDTI analysis may be a useful marker for disease progression.

Does Side of Onset Influence the Pattern of Cerebral Atrophy in Parkinson's Disease?

BACKGROUND: Imaging studies have revealed widespread neurodegeneration in Parkinson's disease (PD), but only a few considered the issue of asymmetrical clinical presentations. OBJECTIVE: To investigate if the side of onset influences the pattern of gray matter (GM) atrophy in PD. METHODS: Sixty patients (57.87 ± 10.27 years) diagnosed with idiopathic PD according to the U.K. Brain Bank criteria, 26 with right-sided disease onset (RDO) and 34 with left-sided disease onset (LDO), were compared to 80 healthy controls (HC) (57.1 ± 9.47 years). We acquired T1-weighted images on a 3 T scanner. Images were processed and analyzed with VBM8 (SPM8/Dartel) on Matlab R2012b platform. Statistic assessments included a two-sample test (family-wise error p < 0.05) with extent threshold of 20 voxels. RESULTS: Compared to HC, LDO patients had GM atrophy in the insula, putamen, anterior cingulate, frontotemporal cortex, and right caudate, while the RDO group showed atrophy at the anterior cingulate, insula, frontotemporal, and occipital cortex. CONCLUSION: This study revealed widespread GM atrophy in PD, predominantly in the left hemisphere, regardless of the side of onset. Future investigations should also consider handedness and side of onset to better characterize cerebral involvement and its progression in PD.

Clinical predictors of cognitive impairment and psychiatric complications in Parkinson's disease.

OBJECTIVE: To estimate the clinical and demographics aspects that may contribute to cognitive impairment and psychiatric symptoms in Parkinson's disease (PD). METHOD: All patients answered a structured standardized clinical questionnaire. Two movement disorders specialists performed the following scale: Unified Parkinson's disease rating score (UPDRS), the modified Hoehn and Yahr staging, Schwab and England Scale, SCOPA cognition (SCOPA-COG), SCOPA-Psychiatric complications (SCOPA-PC) and Non-Motor Symptoms Scale (NMSS). We built a generalized linear model to assess predictors for the SCOPA-COG and SCOPA-PC scores. RESULTS: Almost 37% of our patients were demented as per SCOPA-COG scores. Level of education and the UPDRS-Subscale III were predictors of cognitive impairment. Higher scores in domain 3 of NMSS and male gender were associated with psychiatric complications as assessed per the SCOPA-PC. CONCLUSION: Level of education and disease severity are predictors of dementia in PD. Psychiatric complications are more commonly observed in men.

White Matter Microstructure in Idiopathic Craniocervical Dystonia.

BACKGROUND: Dystonias are hyperkinetic movement disorders characterized by involuntary muscle contractions resulting in abnormal torsional movements and postures. Recent neuroimaging studies in idiopathic craniocervical dystonia (CCD) have uncovered the involvement of multiple areas, including cortical ones. Our goal was to evaluate white matter (WM) microstructure in subjects with CCD using diffusion tensor imaging (DTI) analysis. METHODS: We compared 40 patients with 40 healthy controls. Patients were then divided into subgroups: cervical dystonia, blepharospasm, blepharospasm + oromandibular dystonia, blepharospasm + oromandibular dystonia + cervical dystonia, using tract-based spatial statistics. We performed a region of interest-based analysis and tractography as confirmatory tests. RESULTS: There was no significant difference in the mean fractional anisotropy (FA) and mean diffusivity (MD) between the groups in any analysis. DISCUSSION: The lack of DTI changes in CCD suggests that the WM tracts are not primarily affected.

Infratentorial gray matter atrophy and excess in primary craniocervical dystonia.

BACKGROUND: Primary craniocervical dystonia (CCD) is generally attributed to functional abnormalities in the cortico-striato-pallido-thalamocortical loops, but cerebellar pathways have also been implicated in neuroimaging studies. Hence, our purpose was to perform a volumetric evaluation of the infratentorial structures in CCD. METHODS: We compared 35 DYT1/DYT6 negative patients with CCD and 35 healthy controls. Cerebellar volume was evaluated using manual volumetry (DISPLAY software) and infratentorial volume by voxel based morphometry of gray matter (GM) segments derived from T1 weighted 3 T MRI using the SUIT tool (SPM8/Dartel). We used t-tests to compare infratentorial volumes between groups. RESULTS: Cerebellar volume was (1.14 ± 0.17) × 10(2) cm(3) for controls and (1.13 ± 0.14) × 10(2) cm(3) for patients; p = 0.74. VBM demonstrated GM increase in the left I-IV cerebellar lobules and GM decrease in the left lobules VI and Crus I and in the right lobules VI, Crus I and VIIIb. In a secondary analysis, VBM demonstrated GM increase also in the brainstem, mostly in the pons. CONCLUSION: While gray matter increase is observed in the anterior lobe of the cerebellum and in the brainstem, the atrophy is concentrated in the posterior lobe of the cerebellum, demonstrating a differential pattern of infratentorial involvement in CCD. This study shows subtle structural abnormalities of the cerebellum and brainstem in primary CCD.

Diffuse decreased gray matter in patients with idiopathic craniocervical dystonia: a voxel-based morphometry study.

BACKGROUND: Recent studies have addressed the role of structures other than the basal ganglia in the pathophysiology of craniocervical dystonia (CCD). Neuroimaging studies have attempted to identify structural abnormalities in CCD but a clear pattern of alteration has not been established. We performed whole-brain evaluation using voxel-based morphometry (VBM) to identify patterns of gray matter (GM) changes in CCD. METHODS: We compared 27 patients with CCD matched in age and gender to 54 healthy controls. VBM was used to compare GM volumes. We created a two-sample t-test corrected for subjects' age, and we tested with a level of significance of p < 0.001 and false discovery rate (FDR) correction (p < 0.05). RESULTS: Voxel-based morphometry demonstrated significant reductions of GM using p < 0.001 in the cerebellar vermis IV/V, bilaterally in the superior frontal gyrus, precuneus, anterior cingulate and paracingulate, insular cortex, lingual gyrus, and calcarine fissure; in the left hemisphere in the supplementary motor area, inferior frontal gyrus, inferior parietal gyrus, temporal pole, supramarginal gyrus, rolandic operculum, hippocampus, middle occipital gyrus, cerebellar lobules IV/V, superior, and middle temporal gyri; in the right hemisphere, the middle cingulate and precentral gyrus. Our study did not report any significant result using the FDR correction. We also detected correlations between GM volume and age, disease duration, duration of botulinum toxin treatment, and the Marsden-Fahn dystonia scale scores. CONCLUSION: We detected large clusters of GM changes chiefly in structures primarily involved in sensorimotor integration, motor planning, visuospatial function, and emotional processing.

Clinical predictors of cognitive impairment and psychiatric complications in Parkinson’s disease / Preditores clínicos de transtorno cognitivo e complicações psiquiátricas na doença de Parkinson

Objective To estimate the clinical and demographics aspects that may contribute to cognitive impairment and psychiatric symptoms in Parkinson’s disease (PD). Method All patients answered a structured standardized clinical questionnaire. Two movement disorders specialists performed the following scale: Unified Parkinson’s disease rating score (UPDRS), the modified Hoehn and Yahr staging, Schwab and England Scale, SCOPA cognition (SCOPA-COG), SCOPA-Psychiatric complications (SCOPA-PC) and Non-Motor Symptoms Scale (NMSS). We built a generalized linear model to assess predictors for the SCOPA-COG and SCOPA-PC scores. Results Almost 37% of our patients were demented as per SCOPA-COG scores. Level of education and the UPDRS-Subscale III were predictors of cognitive impairment. Higher scores in domain 3 of NMSS and male gender were associated with psychiatric complications as assessed per the SCOPA-PC. Conclusion Level of education and disease severity are predictors of dementia in PD. Psychiatric complications are more commonly observed in men. .

Objetivo Estimar aspectos clínicos e demográficos que podem contribuir para o comprometimento cognitivo e sintomas psiquiátricos na doença de Parkinson (DP). Método Todos pacientes responderam questionário clínico padrão. Duas especialistas em distúrbios do movimento aplicaram as seguintes escalas: Unified Parkinson’s disease rating score (UPDRS), Hoehn and Yahr estágios, Schwab and England Scale, SCOPA cognição (SCOPA-COG), SCOPA-Complicações psiquiátricas (SCOPA-CP) e Escala de sintomas não motores (NMSS). Utilizamos análise multivariada, para avaliar os preditores relacionados ao SCOPA-COG e SCOPA CP. Resultados Aproximadamente 37% dos nossos pacientes foram classificados como dementes utilizando-se os valores obtidos no SCOPA-COG. Nível educacional e a parte III do UPDRS foram preditores de comprometimento cognitivo. Escores elevados no domínio 3 do NMSS e sexo masculino associaram-se com complicações psiquiátricas quando acessadas pelo SCOPA-CP. Conclusão Nível educacional e gravidade de doença são preditores de demência na DP. Complicações psiquiátricas são mais comumente observadas em homens. .