Camila Piccinin

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.

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.

Multimodal neuroimaging analysis in patients with SYNE1 Ataxia

BACKGROUND The gene SYNE1 is highly expressed in the cerebellum and its dysfunction is related to an autosomal recessive ataxia (SYNE1-ataxia). The disease was firstly considered a pure cerebellar ataxia however, recent studies have described a broader clinical presentation, including motor neuron disease symptoms. OBJECTIVES To investigate cerebellar and potential extra-cerebellar changes in SYNE1-ataxia using multimodal neuroimaging analyses. METHODS Six patients completed clinical and imaging exams, and were compared to age-gender-matched healthy controls. Gray matter was analyzed using FreeSurfer and CERES for brain and cerebellum, respectively. White matter was analyzed with DTI-TBSS while we used SpineSeg for spinal cord analysis. RESULTS We found significantly reduced cortical thickness (p < 0.05, FDR-corrected) in primary and association cortices, and volume reduction in subcortical structures, brainstem and cerebellum. White matter was found disrupted in both brain and cerebellum (p < 0.05, FWE-corrected). These results are consistent with the expression of the SYNE1 mRNA and its encoded protein in the brain. We failed to demonstrate spinal cord changes. CONCLUSIONS SYNE1-ataxia is, therefore, a relatively common cause of recessive ataxia characterized by complex multisystemic neurostructural changes consistent with the phenotypic heterogeneity and neuroimaging configures a potential marker of the disease.