Thiago Junqueira Ribeiro de Rezende

MRI Texture Analysis Reveals Deep Gray Nuclei Damage in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is characterized by extensive corticospinal damage, but extrapyramidal involvement is suggested in pathological studies. Texture analysis (TA) is an image processing technique that evaluates the distribution of gray levels between pixels in a given region of interest (ROI). It provides quantitative data and has been employed in several neurodegenerative disorders. Here, we used TA to investigate possible deep gray nuclei (DGN) abnormalities in a cohort of ALS patients.

Dystonia in Machado-Joseph disease: Clinical profile, therapy and anatomical basis.

INTRODUCTIONnDystonia is frequent in Machado-Joseph disease, but several important aspects are not yet defined, such as the detailed clinical profile, response to treatment and anatomical substrate.nnnMETHODSnWe screened 75 consecutive patients and identified those with dystonia. The Burke-Marsden-Fahn Dystonia Rating Scale was employed to quantify dystonia severity. Patients with dystonia received levodopa 600 mg/day for 2 months and were videotaped before and after treatment. A blinded evaluator rated dystonia in the videos. Patients with disabling dystonia who failed to respond to levodopa treatment received botulinum toxin. Finally, volumetric T1 and diffusion tensor imaging sequences were obtained in the dystonic group using a 3T-MRI scanner to identify areas of gray and white matter that were selectively damaged.nnnRESULTSnThere were 21 patients with dystonia (28%): 9 classified as generalized and 12 as focal/segmental. Patients with dystonia had earlier onset and larger (CAG) expansions (28.9 ± 11.7 vs 40.6 ± 11.4; p < 0.001 and 75 vs 70; p < 0.001, respectively). Although group analyses failed to show benefit on levodopa (p = 0.07), some patients had objective improvement. In addition, ten patients received botulinum toxin resulting in a significant change in dystonia scores after 4 weeks (p = 0.03). Patients with dystonia had atrophy at pre- and paracentral cortices; whereas, non-dystonic patients had occipital atrophy. Basal ganglia volume was reduced in both groups, but atrophy at the thalami, cerebellar white matter and ventral diencephali was disproportionately higher in the dystonic group.nnnCONCLUSIONnDystonia in Machado-Joseph disease is frequent and often disabling, but may respond to levodopa. It is associated predominantly with structural abnormalities around the motor cortices and in the thalami.

Nonneurological Involvement in Late-Onset Friedreich Ataxia (LOFA): Exploring the Phenotypes.

Friedreich’s ataxia (FDRA) is the most common inherited ataxia worldwide, caused by homozygous GAA expansions in the FXN gene. Patients usually have early onset ataxia, areflexia, Babinski sign, scoliosis and pes cavus, but at least 25xa0% of cases have atypical phenotypes. Disease begins after the age of 25 in occasional patients (late-onset Friedreich ataxia (LOFA)). Little is known about the frequency and clinical profile of LOFA patients. One hundred six patients with molecular confirmation of FDRA and followed in three Brazilian outpatient centers were enrolled. General demographics, GAA expansion size, age at onset, cardiac, endocrine, and skeletal manifestations were evaluated and compared between LOFA and classic FDRA (cFDRA) groups. We used Mann–Whitney and Fisher tests to compare means and proportions between groups; p values <0.05 were considered significant. LOFA accounted for 17xa0% (18/106) and cFDRA for 83xa0% (88/106) of the patients. There were 13 and 48 women in each group, respectively. LOFA patients were significantly older and had smaller GAA expansions. Clinically, LOFA group had a tendency toward lower frequency of diabetes/impaired glucose tolerance (5.8 vs. 17xa0%, pu2009=u20090.29) and cardiomyopathy (16.6 vs. 28.4xa0%, pu2009=u20090.38). Skeletal abnormalities were significantly less frequent in LOFA (scoliosis 22 vs. 61xa0%, pu2009=u20090.003, and pes cavus 22 vs.75xa0%, pu2009<u20090.001) as were spasticity and sustained reflexes, found in 22xa0% of LOFA patients but in none of the cFDRA patients (pu2009=u20090.001). LOFA accounts for 17xa0% of Brazilian FDRA patients evaluated herein. Clinically, orthopedic features and spasticity with retained reflexes are helpful tips to differentiate LOFA from cFDRA patients.

Longitudinal evaluation of cerebral and spinal cord damage in Amyotrophic Lateral Sclerosis

Objective To evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression. Methods Twenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software). All analyses were corrected for multiple comparisons. The standardized response mean (SRM = mean score change / standard deviation of score change) was calculated for all methods herein employed and used for comparison purposes. Results There were 18 men and mean age at first examination was 51.9 years. Mean ALSFRS-R scores at baseline and follow-up were 34.0 and 29.0, respectively. There was no region with progressive cortical thinning, but there was significant brainstem volumetric reduction (p = 0.001). TBSS analyses revealed progressive increase of AD (axial diffusivity) and MD (mean diffusivity) at the corpus callosum (p < 0.05), whereas SpineSeg showed progressive cord area reduction (p = 0.002). Cervical spinal cord cross-sectional area reduction was the only MRI parameter that correlated with ALSFRS-R change (r = 0.309, p = 0.038). SRM for ALSFRS-R was 0.95, for cord area 0.95, for corpus callosum AD 0.62 and MD 0.65, and for brainstem volume 0.002. Conclusions Structural MRI is able to detect short term longitudinal changes in ALS. Cervical spinal cord morphometry is a promising neuroimaging marker to assess ALS course.

Spinal Cord Damage in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder caused by a CAG repeat expansion, characterized by progressive cerebellar ataxia and pyramidal signs. Non-motor and extracerebellar symptoms may occur. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are no data about cord damage in the disease and its clinical relevance. To evaluate in vivo spinal cord damage in SCA1, a group of 31 patients with SCA1 and 31 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was used to quantify disease severity. The groups were significantly different regarding CA (47.26xa0±xa07.4 vs. 68.8xa0±xa05.7xa0mm2, pxa0<xa00.001) and CE values (0.803xa0±xa00.044 vs. 0.774xa0±xa00.043, pxa0<xa00.05). Furthermore, in the patient group, CA presented significant correlation with SARA scores (Rxa0=xa0−0.633, pxa0<xa00.001) and CAGn expansion (Rxa0=xa0−0.658, pxa0<xa00.001). CE was not associated with SARA scores (pxa0=xa00.431). In the multiple variable regression, CA was strongly associated with disease duration (coefficient −0.360, pxa0<xa00.05) and CAGn expansion (coefficient −1.124, pxa0<xa00.001). SCA1 is characterized by cervical cord atrophy and anteroposterior flattening. Morphometric analyses of the spinal cord MRI might be a useful biomarker in the disease.

Differential Pattern of Cerebellar Atrophy in Tremor-Predominant and Akinetic/Rigidity-Predominant Parkinson’s Disease

Parkinson’s disease (PD) is an akinetic-rigid disorder characterized by basal ganglia dysfunction and a possible cerebello-thalamo-cortical circuit involvement. This study aims to investigate the pattern of cerebellar involvement in PD and to assess whether it correlates with clinical parameters. MRI scans were acquired from 50 healthy controls (HC) and 63 patients; 44 were classified as tremor-predominant-PD (PDT) and 19 as akinetic/rigidity-predominant-PD (PDAR). We designed an analysis of covariance including the three groups and contrasted as follows: (1) all 63 PD vs HC, (2) PDT vs HC, (3) PDAR vs HC, and (4) PDT vs PDAR. For a precise evaluation of the cerebellum, we used the SUIT tool for voxel-based morphometry. Applying pxa0=xa00.001 and extent threshold = 20 voxels, the overall PD group vs HC showed decreased gray matter (GM) in the left lobules VI and crus I. The PDT group showed decreased cerebellar GM when compared with HC at left lobules VI, VIIb, and VIIIa; at right lobules Crus I, VIIb, and VIIIb; and vermal lobules VI and VIIIa. When compared with PDAR, PDT also showed a decrease in the left lobules VIIIa (pxa0<xa00.001). There were small clusters of both positive and negative correlation between disease duration and PDT group. The PDAR group showed no cerebellar changes. Our findings support the growing evidence of cerebellar involvement in the pathogenesis of the resting tremor.

SPG11 mutations cause widespread white matter and basal ganglia abnormalities, but restricted cortical damage

SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3u202fT MRI scan. Mean age and disease duration were 29 and 13.2u202fyears respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration.

Structural signature of classical versus late-onset friedreich's ataxia by Multimodality brain MRI

Friedreichs ataxia (FRDA) is the most common autosomal‐recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities, and slowly progressive ataxia. However, some individuals manifest the disease after the age of 25 years and are classified as late‐onset FRDA (LOFA). Therefore, we propose a transversal multimodal MRI‐based study to investigate which anatomical substrates are involved in classical (cFRDA) and LOFA.

Structural signature in SCA1: clinical correlates, determinants and natural history

Spinocerebellar ataxia type 1 is an autosomal dominant disorder caused by a CAG repeat expansion in ATXN1, characterized by progressive cerebellar and extracerebellar symptoms. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are few data about supratentorial/spinal damage and its clinical relevance. We have thus designed this multimodal MRI study to uncover the structural signature of SCA1. To accomplish that, a group of 33 patients and 33 age-and gender-matched healthy controls underwent MRI on a 3T scanner. All patients underwent a comprehensive neurological and neuropsychological evaluation. We correlated the structural findings with the clinical features of the disease. In addition, we evaluated the disease progression looking at differences in SCA1 subgroups defined by disease duration. Ataxia and pyramidal signs were the main symptoms. Neuropsychological evaluation disclosed cognitive impairment in 53% with predominant frontotemporal dysfunction. Gray matter analysis unfolded cortical thinning of primary and associative motor areas with more restricted impairment of deep structures. Deep gray matter atrophy was associated with motor handicap and poor cognition skills. White matter integrity loss was diffuse in the brainstem but restricted in supratentorial structures. Cerebellar cortical thinning was found in multiple areas and correlated not only with motor disability but also with verbal fluency. Spinal cord atrophy correlated with motor handicap. Comparison of MRI findings in disease duration-defined subgroups identified a peculiar pattern of progressive degeneration.

Developmental and Neurodegenerative Damage in Friedreich Ataxia

Friedreichs ataxia (FRDA) is the most common autosomal‐recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities and slowly progressive ataxia. All magnetic resonance imaging (MRI)‐based studies have focused on the evaluation of adult patients. Therefore, we designed a cross‐sectional multimodal MRI‐based study to investigate the anatomical substrates involved in the early stages of FRDA.