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Aims: Machado–Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is the most common autosomal dominantly‐inherited ataxia worldwide and is characterised by the accumulation of mutant ataxin‐3 (mutATXN3) in different brain regions, leading to neurodegeneration. Currently, there are no available treatments able to block disease progression. In this study, we investigated whether carbamazepine (CBZ) would activate autophagy and mitigate MJD pathology. Methods: The autophagy‐enhancing activity of CBZ and its effects on clearance of mutATXN3 were evaluated using in vitro and in vivo models of MJD. To investigate the optimal treatment regimen, a daily or intermittent CBZ administration was applied to MJD transgenic mice expressing a truncated human ATXN3 with 69 glutamine repeats. Motor behaviour tests and immunohistology was performed to access the alleviation of MJD‐associated motor deficits and neuropathology. A retrospective study was conducted to evaluate the CBZ effect in MJD patients. Results: We found that CBZ promoted the activation of autophagy and the degradation of mutATXN3 in MJD models upon short or intermittent, but not daily prolonged, treatment regimens. CBZ up‐regulated autophagy through activation of AMPK, which was dependent on the myo‐inositol levels. In addition, intermittent CBZ treatment improved motor performance, as well as prevented neuropathology in MJD transgenic mice. However, in patients, no evident differences in SARA scale were found, which was not unexpected given the small number of patients included in the study. Conclusions: Our data support the autophagy‐enhancing activity of CBZ in the brain and suggest this pharmacological approach as a promising therapy for MJD and other polyglutamine disorders. [ABSTRACT FROM AUTHOR]

Background: The natural history of neurodegeneration in spinocerebellar ataxia type 3/Machado Joseph disease is still unclear. Here, we built a long-term longitudinal clinical and neuroimaging study to address this point.Methods: Twenty-three patients with spinocerebellar ataxia type 3/Machado Joseph disease and 22 healthy controls underwent 3T MRI twice 5.0 years apart. T1 and diffusion tensor imaging sequences were obtained. We used T1 multiatlas, diffusion tensor imaging multiatlas, SpineSeg, and CERES-SUIT for cerebral gray and white matter, spinal cord and cerebellar analyses, respectively. Clinical severity was assessed with scale for assessment and rating of ataxia. Analysis of covariance evaluated longitudinal between-group changes. Effect sizes were calculated for each significant result.Results: Progressive volumetric abnormalities were most evident in the cerebellum (Lobule X and Crus II; effect size, 2.0), followed by the basal ganglia (effect size, 0.7). The cerebellar peduncles had the largest white-matter diffusivity changes (effect size, 1.29). Scale for assessment and rating of ataxia-related effect size was 0.82. We failed to identify progressive spinal cord abnormalities.Conclusions: Longitudinal changes in spinocerebellar ataxia type 3/Machado Joseph disease are more evident in the cerebellum and connections, followed by the basal ganglia. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Molecular imaging has proven to be a powerful tool to elucidate degenerated paths in a wide variety of neurological diseases and has not been systematically studied in hereditary spastic paraplegias.Objectives: To investigate dopaminergic degeneration in a cohort of 22 patients with hereditary spastic paraplegia attributed to SPG11 mutations and evaluate treatment response to l-dopa.Methods: Patients and controls underwent single-photon emission computed tomography imaging utilizing 99m Tc-TRODAT-1 tracer. A single-blind trial with 600 mg of l-dopa was performed comparing UPDRS scores.Results: Reduced dopamine transporter density was universal among patients. Nigral degeneration was symmetrical and correlated with disease duration and motor and cognitive handicap. No statistically significant benefit could be demonstrated with l-dopa intake during the trial.Conclusion: Disruption of presynaptic dopaminergic pathways is a widespread phenomenon in patients with SPG11 mutations, even in the absence of parkinsonism. Unresponsiveness to treatment could be related to postsynaptic damage that needs to be further investigated. [ABSTRACT FROM AUTHOR]

Objective: Machado-Joseph disease (SCA3/MJD) is the most frequent spinocerebellar ataxia worldwide and characterized by brainstem, basal ganglia, and cerebellar damage. However, little is known about the natural history of the disease. This motivated us to determine the extension and progression of central nervous system involvement in SCA3/MJD using multimodal magnetic resonance imaging (MRI)-based analyses in a large cohort of patients (n = 79) and presymptomatic subjects (n = 12).Methods: All subjects underwent MRI in a 3T device to assess gray and white matter. To evaluate the cerebral and cerebellar cortices, we used measures from FreeSurfer and SUIT. T1-multiatlas assessed deep gray matter. Diffusion tensor imaging multiatlas was used to investigate cerebral white matter (WM) and SpineSeg to assess the cervical spinal cord.Results: There was widespread WM and cerebellar damage, in contrast to the restricted motor cortex involvement when all patients are compared to age- and sex-matched controls. Presymtomatic patients showed WM microstructural abnormalities mainly in the cerebellar and cerebral peduncles and volumetric reduction of midbrain, spinal cord, and substantia nigra. To assess the disease progression, we divided patients into four subgroups defined by time from ataxia onset. There was a clear pattern of evolving structural compromise, starting in infratentorial structures and progressing up to the cerebral cortex.Conclusion: Structural damage in SCA3/MJD begins in the spinal cord, cerebellar peduncles, as well as substantia nigra and progresses to cerebral areas in the long term. These structural differences reveal some insights into the pathogenesis of SCA3/MJD and suggest a staging scheme to map the progression of the disease. Ann Neurol 2018;84:401-408. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive disorder (gene CHS1/LYST) characterized by partial albinism, recurrent infections, and easy bruising. Survivors develop a constellation of slowly progressive neurological manifestations.Methods: We describe clinical, laboratory, electrophysiological, and genetic findings of a patient who developed an immune-mediated demyelinating neuropathy as the main clinical feature of CHS.Results: The patient presented with subacute flaccid paraparesis, absent reflexes, and reduced vibration sense. Protein and immunoglobulins (Igs) were elevated in the cerebrospinal fluid. Electrodiagnostic tests indicated an acquired chronic demyelinating polyneuropathy. Intravenous Ig and immunosuppressant treatment resulted in neurological improvement. The patient later developed organomegaly and pancytopenia. Bone-marrow smear revealed giant azurophilic granules pathognomonic for CHS. Two novel mutations in the LYST gene were identified through whole exome sequencing [c.7786C>T and c.9106 + 1G>T].Conclusions: This case expands the clinical phenotype of CHS and highlights inflammatory demyelinating neuropathy as a manifestation of the disease. Muscle Nerve 55: 756-760, 2017. [ABSTRACT FROM AUTHOR]

Background: The distinction between sensory neuronopathies (SN), which is by definition purely sensory, and sensory polyneuropathies (SP) and sensory multineuropathies (SM) is important for etiologic investigation and prognosis estimation. However, this task is often challenging in clinical practice. We hypothesize that F-wave assessment might be helpful, since it is able to detect subtle signs of motor involvement, which are found in SP and SM, but not in SN., Objective: The aim of the present study was to determine whether F-waves are useful to distinguish SN from SP and SM., Methods: We selected 21 patients with SP (12 diabetes mellitus, 4 transthyretin familial amyloid polyneuropathy, 4 others), 22 with SM (22 leprosy), and 26 with SN (13 immune-mediated, 10 idiopathic, 3 others) according to clinical-electrophysiological-etiological criteria. For every subject, we collected data on height and performed 20 supramaximal distal stimuli in median, ulnar, peroneal, and tibial nerves, bilaterally, to record F-waves. Latencies (minimum and mean) and persistences were compared across groups using the Kruskal-Wallis and Bonferroni tests. P -values < 0.05 were considered significant., Results: All groups were age, gender, and height-matched. Overall, there were no significant between-group differences regarding F-wave latencies. In contrast, F-wave persistence was able to stratify the groups. Peroneal F-wave persistence was higher, bilaterally, in the SN group compared to SM and SP ( p  < 0.05). In addition, F-waves persistence of the ulnar and tibial nerves was also helpful to separate SN from SP ( p  < 0.05)., Conclusion: F-wave persistence of the peroneal nerves might be an additional and useful diagnostic tool to differentiate peripheral sensory syndromes., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript., Competing Interests: MVP, MVG, MCMC, MRGF, CDM, ARMM, CLM, OJMN, APPMC, ASBO, CCBP, MMJR, FTR, RHS: report no financial disclosures. MCFJ: received honorarium from Pfizer and PTC for financial support for research; Ionis for acting as a principal investigator in clinical trials; Pfizer, PTC and Alnylam for travel expenses related to presentations at medical meetings; Pfizer, PTC and Alnylan for acting as an advisory board member. FAAG, ARMM: received honorarium from Pfizer for travel expenses related to presentations at medical meetings. WMJ: received honorarium from Pfizer, Alnylam and PTC for travel expenses related to presentations at medical meetings, for acting as a principal investigator in clinical trials and/or as a consultant member. MWC: received honorarium from NHI, Prothena, FoldRx, Ionis, Pfizer, Alnylam, PTC, Astra Zeneca, Novonordisk, and Genzyme for travel expenses related to presentations at medical meetings, for acting as a principal investigator in clinical trials and/or as a consultant member., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

In the last few decades, there have been considerable improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy. International guidelines have been published and recently reviewed. A group of Brazilian experts has developed a standard of care based on a literature review with evidence-based graded recommendations in a two-part publication. Implementing best practice management has helped change the natural history of this chronic progressive disorder, in which the life expectancy for children of the male sex in the past used to be very limited. Since the previous publication, diagnosis, steroid treatment, rehabilitation, and systemic care have gained more significant insights with new original work in certain fields. Furthermore, the development of new drugs is ongoing, and some interventions have been approved for use in certain countries. Therefore, we have identified the need to review the previous care recommendations for Brazilian patients with DMD. Our objective was to create an evidence-based document that is an update on our previous consensus on those topics., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Background: Huntington's disease (HD) is a progressive disorder characterized by motor, cognitive and psychiatric features. Cerebellar ataxia is classically considered as uncommon in HD clinical spectrum. Objective: To determine the prevalence of cerebellar ataxia in patients with HD, both in the early and in the late stages of HD. Methods: Seventy-two individuals considered eligible were assessed by two trained doctors, applying the Scale for Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS) for ataxia, the Unified Huntington's Disease Rating Scale (UHDRS) and also, Barthel Index (BI), in order to evaluate functional capacity. Results: Fifty-one patients (70.8%) presented with clinical ataxia at the time of examination (mean time of disease was 9.1 years). Six (8.33%) patients presented with cerebellar ataxia as first symptom. When stratified according to time of disease, a decline in the presence of chorea ( p = 0.032) and an increase in cognitive deficit ( p = 0.023) were observed in the patients as the disease progressed. The presence of ataxia was associated with longer duration of illness and severity of illness (UHDRS) ( p < 0.0001), and shorter Barthel (less functionality) ( p = 0.001). Conclusions: Cerebellar involvement may play an important role in natural history of brain degeneration in HD. The presence of cerebellar ataxia in HD is relevant and it may occur even in early stages, and should be included as part of the motor features of the disease., (Copyright © 2020 Franklin, Camargo, Meira, Pavanelli, Milano, Germiniani, Lima, Raskin, Barsottini, Pedroso, Maggi, Tumas, de Carvalho, de Oliveira, Braga, Souza, Guimarães, Piovesana, Lopes-Cendes, de Azevedo, França, Martinez and Teive.)