Behavioral manifestations in a Brazilian non-demented C9orf72-negative ALS population.

Cognitive decline and behavioral changes are common features in amyotrophic lateral sclerosis (ALS) and imply worse prognosis as well as increased disease burden for patients and caregivers. Currently, there is a lack of studies regarding behavioral profile in Brazilian ALS cohorts. We assessed the prevalence and profile of behavioral impairment (ALSbi) in a Brazilian non-demented C9orf72-negative ALS cohort according to broad behavioral assessment and the latest consensus. Among 76 initially recruited consecutive ALS patients, 70 were included, including seven ALS type 8 (VAPB-related ALS) individuals. Patients with Frontotemporal Dementia (FTD) diagnosis were excluded. Sixteen ALS patients (23%) were diagnosed as ALSbi. Among ALS type 8 individuals, 2 (28.6%) were diagnosed as ALSbi. Neuropsychiatric Inventory Questionnaire (NPI) total scores did positively correlate with age, but not with other demographic or clinical data. Apathy was the most prevalent finding in the ALSbi subgroup, although the prevalence (20%) was smaller than reported in previous literature. Dysphoria and anxiety were also prevalent findings in the whole ALS cohort. Future studies with larger cohorts and validated ALS-specific tools are needed in order to expand our knowledge.

Sensory ataxia rating scale: Development and validation of a functional scale for patients with sensory neuronopathies.

Sensory neuronopathies (SN) result from dorsal root ganglia damage and manifest with a combination of sensory deficits and proprioceptive ataxia. Characterization of the natural history and development of therapeutic trials are hampered by the lack of clinical scales that capture the whole spectrum of SN-related manifestations. We propose and validate a rating instrument for SN. Three experienced neuromuscular specialists developed items to rate SN. The resultant instrument was later validated by the assessment of the intra-class correlation coefficient, for inter-rater validity in 48 SN patients, and later in a smaller subset of 16 patients to assess its intra-rater validity. Standardized Crombach's alpha and Oblimin rotation analysis were performed to verify internal consistency and items' relationship, respectively. Evaluation of Sensory Ataxia Rating Scale (SEARS)'s external validity was performed by comparison to: scale for the assessment and rating of ataxia (SARA), Beck balance scale (BBS), and INCAT sensory sum score (ISS). A 10-item scale with an intra-class correlation coefficient >0.95 for intra- and inter-rating measurements with a good internal consistency (standardized Cronbach's alpha of 0.83) were observed. There was a normal distribution of the scores without a floor or ceiling effect. A moderate to good correlation between SEARS and SARA, BBS, and ISS was observed. SEARS is a reliable, easy-to-perform and consistent instrument to rate SN. Larger cohorts and multicenter studies are needed to validate its usefulness towards possible treatment trials.

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.

Differences in Cortical Structure and Functional MRI Connectivity in High Functioning Autism.

Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental conditions characterized by deficits in communication and social behaviors. We examined the functional connectivity (FC) of the default mode network (DMN) and its relation to multimodal morphometry to investigate superregional, system-level alterations in a group of 22 adolescents and young adults with high-functioning autism compared to age-, and intelligence quotient-matched 29 healthy controls. The main findings were that ASD patients had gray matter (GM) reduction, decreased cortical thickness and larger cortical surface areas in several brain regions, including the cingulate, temporal lobes, and amygdala, as well as increased gyrification in regions associated with encoding visual memories and areas of the sensorimotor component of the DMN, more pronounced in the left hemisphere. Moreover, patients with ASD had decreased connectivity between the posterior cingulate cortex, and areas of the executive control component of the DMN and increased FC between the anteromedial prefrontal cortex and areas of the sensorimotor component of the DMN. Reduced cortical thickness in the right inferior frontal lobe correlated with higher social impairment according to the scores of the Autism Diagnostic Interview-Revised (ADI-R). Reduced cortical thickness in left frontal regions, as well as an increased cortical thickness in the right temporal pole and posterior cingulate, were associated with worse scores on the communication domain of the ADI-R. We found no association between scores on the restrictive and repetitive behaviors domain of ADI-R with structural measures or FC. The combination of these structural and connectivity abnormalities may help to explain some of the core behaviors in high-functioning ASD and need to be investigated further.

Brain signature of mild stages of cognitive and behavioral impairment in amyotrophic lateral sclerosis.

We aimed to assess the brain signature of cognitive and behavioral impairment in C9orf72-negative non-demented ALS patients. The study included 50 amyotrophic lateral sclerosis (ALS) patients (out of 75 initially recruited) and 38 healthy controls. High-resolution T1-weighted and spin-echo diffusion tensor images were acquired in a 3T MRI scanner. The multi atlas-based analysis protocol and the FreeSurfer tool were employed for gray matter assessment, and fiber tractography for white matter evaluation. Cognitively impaired ALS patients (n = 12) had bilateral amygdalae and left thalamic volumetric reduction compared to non-impaired ALS patients. Behaviorally impaired ALS patients (n = 14) had lower fractional anisotropy (FA) at the fornix in comparison with healthy subjects. These parameters did correlate with cognitive/behavioral scores, but not with motor-functional parameters in the ALS cohort. We believe that basal ganglia and fornix damage might be related to cognitive and behavioral impairment across ALS-frontotemporal dementia continuum. Also, distinct anatomical areas seem to influence the behavioral and cognitive status of these individuals.

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.

Transcultural validation of the ALS-CBS Cognitive Section for the Brazilian population.

Cognitive decline (CD) is common but often under-recognized in ALS due to the scarcity of adequate cognitive screening methods. In this scenario, the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) is the most investigated instrument and presents high sensitivity to identify CD. Currently, there are no validated cognitive screening tools for ALS patients in the Brazilian population and little is known about the frequency of ALS related CD in the country. We assessed the accuracy of the Brazilian Portuguese version of ALS-CBS Cognitive Section (ALS-CBS-Br) for classifying the cognitive status of Brazilian patients compared to a standard neuropsychological battery, and estimated the prevalence of CD in the Brazilian ALS population. Among 73 initially recruited ALS patients, 49 were included. Twenty-four patients were excluded due to severe motor disability, FTD diagnosis or non-acceptance. Ten healthy controls were also included. Ten ALS patients (20%) were diagnosed with executive dysfunction (ALSci) based on the battery results. ALS-CBS-Br scores were significantly lower in the ALSci group (p < 0.001). The scale accuracy in detecting executive dysfunction was 0.906. Optimal cut-off score was 10/20 (specificity 0.872 and sensitivity 0.900). In conclusion, the ALS-CBS-Br may facilitate the recognition of CD in routine clinical care and complement future studies in our population.