Luiza Piovesana

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.

Pattern of Reduced Functional Connectivity and Structural Abnormalities in Parkinson’s Disease: An Exploratory Study

Background MRI brain changes in Parkinson’s disease (PD) are controversial. Objectives We aimed to describe structural and functional changes in PD. Methods Sixty-six patients with PD (57.94 ± 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM–SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1–1.5], moderate PD (HY 2–2.5), and severe PD (HY 3–5). Results We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks. Conclusion Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak’s proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression.

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 Parkinsons disease (PD). METHOD All patients answered a structured standardized clinical questionnaire. Two movement disorders specialists performed the following scale: Unified Parkinsons 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.

Misdiagnosis of hemifacial spasm is a frequent event in the primary care setting

UNLABELLED Primary hemifacial spasm (HFS) is characterized by irregular and involuntary contraction of the muscles innervated by the ipsilateral facial nerve. Treatment controls symptoms and improves quality of life (QoL). OBJECTIVE Evaluate the initial diagnosis and treatment of HFS prior to referral to a tertiary center. METHOD We interviewed through a standard questionnaire 66 patients currently followed in our center. RESULTS Mean age: 64.19±11.6 years, mean age of symptoms onset: 51.9±12.5 years, male/female ratio of 1:3. None of the patients had a correct diagnosis in their primary care evaluation. Medication was prescribed to 56.8%. Mean time from symptom onset to botulinum toxin treatment: 4.34 ±7.1 years, with a 95% satisfaction. Thirty percent presented social embarrassment due to HFS. CONCLUSION Despite its relatively straightforward diagnosis, all patients had an incorrect diagnosis and treatment on their first evaluation. HFS brings social impairment and the delay in adequate treatment negatively impacts QoL.

Misdiagnosis Of Hemifacial Spasm Is A Frequent Event In The Primary Care Setting.

UNLABELLED Primary hemifacial spasm (HFS) is characterized by irregular and involuntary contraction of the muscles innervated by the ipsilateral facial nerve. Treatment controls symptoms and improves quality of life (QoL). OBJECTIVE Evaluate the initial diagnosis and treatment of HFS prior to referral to a tertiary center. METHOD We interviewed through a standard questionnaire 66 patients currently followed in our center. RESULTS Mean age: 64.19±11.6 years, mean age of symptoms onset: 51.9±12.5 years, male/female ratio of 1:3. None of the patients had a correct diagnosis in their primary care evaluation. Medication was prescribed to 56.8%. Mean time from symptom onset to botulinum toxin treatment: 4.34 ±7.1 years, with a 95% satisfaction. Thirty percent presented social embarrassment due to HFS. CONCLUSION Despite its relatively straightforward diagnosis, all patients had an incorrect diagnosis and treatment on their first evaluation. HFS brings social impairment and the delay in adequate treatment negatively impacts QoL.

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.

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.

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

Objectives: To assess white matter abnormalities in Parkinsons 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 PD DTI can differentiate disease stages DTI analysis may be a useful marker for disease progression

Exploratory structural assessment in craniocervical dystonia: Global and differential analyses

Introduction Our goal was to investigate the cortical thickness and subcortical volume in subjects with craniocervical dystonia and its subgroups. Methods We studied 49 subjects, 17 with cervical dystonia, 18 with blepharospasm or oromandibular dystonia, and 79 healthy controls. We performed a whole group analysis, followed by a subgroup analysis. We used Freesurfer software to measure cortical thickness, subcortical volume and to perform a primary exploratory analysis in the craniocervical dystonia group, complemented by a region of interest analysis. We also performed a secondary analysis, with data generated from Freesurfer for subgroups, corrected by false discovery rate. We then performed an exploratory generalized linear model with significant areas for the previous steps using clinical features as independent variables. Results The primary exploratory analysis demonstrated atrophy in visual processing regions in craniocervical dystonia. The secondary analysis demonstrated atrophy in motor, sensory, and visual regions in blepharospasm or oromandibular dystonia, as well as in limbic regions in cervical dystonia. Cervical dystonia patients also had greater cortical thickness than blepharospasm or oromandibular dystonia patients in frontal pole and medial orbitofrontal regions. Finally, we observed an association between precuneus, age of onset of dystonia and age at the MRI exam, in craniocervical dystonia; between motor and limbic regions and age at the exam, clinical score and time on botulinum toxin in cervical dystonia and sensory regions and age of onset and time on botulinum toxin in blepharospasm or oromandibular dystonia. Conclusions We detected involvement of visual processing regions in craniocervical dystonia, and a pattern of involvement in cervical dystonia and blepharospasm or oromandibular dystonia, including motor, sensory and limbic areas. We also showed an association of cortical thickness atrophy and younger onset age, older age at the MRI exam, higher clinical score and an uncertain association with longer time on botulinum toxin.