Spatiotemporal Gait Analysis of Patients with Spinocerebellar Ataxia Types 3 and 10 Using Inertial Measurement Units: A Comparative Study.

Given the high morbidity related to the progression of gait deficits in spinocerebellar ataxias (SCA), there is a growing interest in identifying biomarkers that can guide early diagnosis and rehabilitation. Spatiotemporal parameter (STP) gait analysis using inertial measurement units (IMUs) has been increasingly studied in this context. This study evaluated STP profiles in SCA types 3 and 10, compared them to controls, and correlated them with clinical scales. IMU portable sensors were used to measure STPs under four gait conditions: self-selected pace (SSP), fast pace (FP), fast pace checking-boxes (FPCB), and fast pace with serial seven subtractions (FPS7). Compared to healthy subjects, both SCA groups had higher values for step time, variability, and swing time, with lower values for gait speed, cadence, and step length. We also found a reduction in speed gain capacity in both SCA groups compared to controls and an increase in speed dual-task cost in the SCA10 group. However, there were no significant differences between the SCA groups. Swing time, mean speed, and step length were correlated with disease severity, risk of falling and functionality in both clinical groups. In the SCA3 group, fear of falling was correlated with cadence. In the SCA10 group, results of the Montreal cognitive assessment test were correlated with step time, mean speed, and step length. These results show that individuals with SCA3 and SCA10 present a highly variable, short-stepped, slow gait pattern compared to healthy subjects, and their gait quality worsened with a fast pace and dual-task involvement.

Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings.

Spinocerebellar ataxias (SCAs) have a worldwide average prevalence of 2.7 cases per 100,000 individuals, with significant geographic variability. This study aimed to develop resource-limited strategies to detect and characterize the frequency and genetic-clinical profile of SCAs in an unexplored population from Alagoas State, a low Human Development Index state in northeastern Brazil. Active search strategies were employed to identify individuals with a diagnosis or clinical suspicion of SCAs, and a protocol for clinical and molecular evaluation was applied in collaboration with a reference center in Neurogenetics. A total of 73 individuals with SCAs were identified, with a minimum estimated prevalence of 2.17 cases per 100,000 inhabitants. SCA3 was the most common type (75.3%), followed by SCA7 (15.1%), SCA1 (6.8%), and SCA2 (2.7%). Patients with SCA3 subphenotype 2 were the most predominant. Detailed analysis of patients with SCA3 and SCA7 revealed age at onset and clinical features congruent with other studies, with gait disturbance and reduced visual capacity in SCA7 as the main initial manifestations. The study also identified many asymptomatic individuals at risk of developing SCAs. These findings demonstrate that simple and collaborative strategies can enhance the detection capacity of rare diseases such as SCAs in resource-limited settings and that Alagoas State has a minimum estimated prevalence of SCAs similar to the world average.

Spinocerebellar ataxia in a cohort of patients from Rio de Janeiro.

OBJECTIVE: The objective of this study is to describe the first series of spinocerebellar ataxia (SCA) in Rio de Janeiro, whose population has a high proportion of mixed Portuguese and African ancestry. METHODS: We reviewed the medical records of patients with progressive ataxia evaluated at the Sarah Network of Rehabilitation Hospitals (Rio de Janeiro). Clinical course, genetic tests for hereditary ataxia, brain MRI, and electroneuromyography were analyzed. RESULTS: SCA was confirmed in 128 individuals, one-third of African descendants. SCA3 predominated (83.6%), followed by SCA7 (7%); SCA2 (3.9%); SCA1, SCA6, and SCA8 (1.6% each); and SCA10 (0.8%). Dysphagia, pyramidal signs, and neurogenic bladder occurred frequently. Oculomotor disorders occurred with SCA3, SCA7, SCA2, and SCA1; peripheral neuropathies with SCA3 and SCA1; extrapyramidal syndromes with SCA3, SCA7, and SCA2; bilateral visual impairment with SCA7; and epilepsy with SCA10. Mobility assistance was required in 75% after 11 years and wheelchair in 25%. The Scale for the Assessment and Rating of Ataxia scores at the last follow-up varied from 2 to 37 (median = 14.50) and correlated positively with duration of the disease. In SCA3, a higher CAG repeats correlated with a lower age at onset. African ethnicity was associated with earlier onset, regardless of CAG repeats. The main brain MRI abnormality was cerebellar atrophy, isolated or associated with brainstem atrophy, "hot cross bun" sign, or brain atrophy. Linear T2 hyperintensity along the medial margin of the globus pallidus occurred in SCA3, SCA2, SCA1, and SCA7. ENMG confirmed peripheral neuropathy in SCA3 and SCA1. CONCLUSION: Machado Joseph disease/SCA3 was the most frequent inherited dominant ataxia in Rio de Janeiro. This study revealed new aspects of ethnic influence in the clinical course and new MRI findings.

Functionality and disease severity in spinocerebellar ataxias / Relação entre a função e a gravidade nas ataxias espinocerebelares

ABSTRACT Background: Spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by deterioration of balance and functionality that tends to follow disease progression. There is no established link between formal clinical markers for severity and functional/balance scores that could guide rehabilitation teams. Objective: To evaluate the relationship between functional scales and ataxia severity in order to identify cutoff landmarks for functional loss and estimate the mean SARA (Scale for Assessment and Rating of Ataxia) score for the risk ratings for falls on the BBS (Berg Balance Scale). Methods: Consecutive patients with a molecular diagnosis of SCA (total 89: 31 with SCA2 and 58 with SCA3) were assessed for functionality FIM-ADL (Functional Independence Measure-activities of daily living and Lawton-IADL (instrumental activities of daily living), balance (BBS) and disease severity (SARA). Results: The main disability cutoff landmarks were that the need for supervision for FIM-ADL starts with 12 points on SARA and the need for supervision for Lawton-IADL starts with 14 points on SARA. The first items to require assistance were "expression" and "shopping", respectively. At 20 points on SARA, patients were dependent on all FIM and Lawton items. The item with the greatest impact on distinguishing dependents from independents was "means of transport" in Lawton-IADL and the domain "locomotion" in FIM-ADL. The mean SARA score for patients classified as low risk in the BBS was 9.9 points, and it was 17.4 for medium risk and 25.2 for high risk. Conclusions: Analysis on the correlation between the severity of ataxia and functional scales can form an important guide for understanding the progression of functional dependence among individuals with SCAs.

RESUMO Antecedentes: As ataxias espinocerebelares (SCA) são um grupo de doenças neurodegenerativas caracterizadas pela deterioração do equilíbrio e da funcionalidade, que tende a acompanhar a progressão da doença. Não existe uma ligação estabelecida entre os marcadores clínicos formais de gravidade e escores funcionais e de equilíbrio que possam orientar as equipes de reabilitação. Objetivo: Avaliar a relação entre escalas funcionais e de gravidade da ataxia, buscando identificar pontos de corte para a perda funcional relacionados aos escores de gravidade e aos patamares de Risco de Quedas. Métodos: Uma amostra consecutiva de 89 pacientes com diagnóstico molecular de SCA (31-SCA2 e 58-SCA3) foram avaliados para funcionalidade MIF-AVDs (Medida de independência funcional-Atividades da vida diária) e Lawton-AIVDs (Atividades instrumentais da vida diária), equilíbrio (EEB-escala de Equilíbrio de Berg), e gravidade da ataxia (SARA-escala para avaliação e graduação de ataxia). Resultados: Os principais pontos de corte de deficiência foram: com 12 pontos no SARA começa a necessidade de supervisão para MIF-AVDs e com 14 pontos no SARA começa a necessidade de supervisão para Lawton-AIVDs. Os primeiros itens a necessitar de assistência foram "expressão" e "compras", respectivamente. Com 20 pontos no SARA os pacientes eram dependentes em todos os itens MIF/LAWTON. O item com maior impacto na discriminação entre dependentes e independentes foi "meio de transporte" na Lawton e o domínio "locomoção" na MIF. O escore médio no SARA foi de 9,9 pontos para pacientes classificados com baixo risco na EEB, 17,4 para médio risco e 25,2 para alto risco. Conclusões: A análise da correlação entre a gravidade da ataxia e as escalas funcionais pode ser um importante guia no entendimento da progressão da dependência funcional em indivíduos com SCA.

Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations.

Spinocerebellar ataxias (SCAs) conform a heterogeneous group of neurodegenerative disorders with autosomal dominant inheritance. Five of the most frequent SCAs are caused by a CAG repeat expansion in the exons of specific genes. The SCAs incidence and the distribution of polymorphic CAG alleles vary among populations and ethnicities. Thus, characterization of the genetic architecture of ethnically diverse populations, which have undergone recent admixture and demographic events, could facilitate the identification of genetic risk factors. Owing to the great ethnic diversity of the Mexican population, this study aimed to analyze the allele frequencies of five SCA microsatellite loci (SCA1, SCA2, SCA3, SCA6, and SCA7) in eleven Mexican Native American (MNA) populations. Data from the literature were used to compare the allelic distribution of SCA loci with worldwide populations. The SCA loci allelic frequencies evidenced a certain genetic homogeneity in the MNA populations, except for Mayans, who exhibited distinctive genetic profiles. Neither pathological nor large normal alleles were found in MNA populations, except for the SCA2 pre-mutated allele in the Zapotec population. Collectively, our findings demonstrated the contribution of the MNA ancestry in shaping the genetic structure of contemporary Mexican Mestizo populations. Our results also suggest that Native American ancestry has no impact on the origin of SCAs in the Mexican population. Instead, the acquisition of pathological SCA alleles could be associated with European migration.

Caracterización clínico-cognitiva de la ataxia espinocerebelosa tipo 2 / Clinical-cognitive Characterization of Spinocerebellar Ataxia Type 2

RESUMEN Fundamento: la ataxia espinocerebelosa tipo 2 es una enfermedad genética con un patrón de herencia autosómico dominante. Constituye un problema de salud para Cuba, especialmente para la provincia Holguín, que concentra la población enferma y en riesgo más grande que se haya reportado a nivel mundial hasta el momento. Objetivo: caracterizar desde el punto de vista clínico y cognitivo a pacientes con ataxia espinocerebelosa tipo 2 diagnosticados durante los años 2018 y 2019. Métodos: se realizó un estudio retrospectivo a 28 pacientes con ataxia espinocerebelosa tipo 2 diagnosticados en la Clínica para la Investigación y Rehabilitación de las Ataxias Hereditarias de Holguín que permitieron además correlacionarlas en el tiempo. La muestra quedó conformada por 28 pacientes en estadio ligero de la enfermedad a los cuales se les aplicó la Escala para la Evaluación y Calificación de la Ataxia y la Escala de la Evaluación Cognitiva de Montreal para evaluar la progresión de la enfermedad desde el punto de vista clínico y cognitivo respectivamente con un año de diferencia entre los dos muestreos. Resultados: la edad media de los pacientes fue de 50,3 años con ligero predominio del sexo femenino, el tiempo de evolución promedio fue de 9,82 años resultando mayor para el sexo femenino. La edad media de inicio de la enfermedad fue de 39,54 años. Conclusiones: entre las dos evaluaciones existió una progresión de las manifestaciones cerebelosas y se evidenció un deterioro de las funciones cognitivas, dándole por este estudio un importante papel al cerebelo en ambas funciones.

ABSTRACT Background: spinocerebellar ataxia type 2 is a genetic disease with an autosomal dominant inheritance pattern. It constitutes a health problem for Cuba, especially for the Holguín province, which concentrates the largest sick and at-risk population that has been reported worldwide so far. Objective: to characterize from the clinical and cognitive point of view patients with spinocerebellar ataxia type 2 diagnosed during the years 2018 and 2019. Methods: a retrospective study was carried out in 28 patients with type 2 spinocerebellar ataxia diagnosed at the Holguín Clinic for Research and Rehabilitation of Hereditary Ataxias, which also allowed them to be correlated over time. The sample consisted of 28 patients with a mild stage of the disease to which the Scale for the Assessment and Rating of Ataxia and Montreal Cognitive Assessment Scale were applied to evaluate the progression of the disease from the clinical and cognitive point of view, respectively, with a difference of one year between the two samplings. Results: the mean age of the patients was 50.3 years with a slight predominance of the female sex, the average evolution time was 9.82 years, being longer for the female sex. The mean age of the disease start was 39.54 years. Conclusions: between the two evaluations there was a progression of cerebellar manifestations and a deterioration of cognitive functions was evidenced, giving an important role to the cerebellum in both functions by this study.

New Perspectives of Gene Therapy on Polyglutamine Spinocerebellar Ataxias: From Molecular Targets to Novel Nanovectors.

Seven of the most frequent spinocerebellar ataxias (SCAs) are caused by a pathological expansion of a cytosine, adenine and guanine (CAG) trinucleotide repeat located in exonic regions of unrelated genes, which in turn leads to the synthesis of polyglutamine (polyQ) proteins. PolyQ proteins are prone to aggregate and form intracellular inclusions, which alter diverse cellular pathways, including transcriptional regulation, protein clearance, calcium homeostasis and apoptosis, ultimately leading to neurodegeneration. At present, treatment for SCAs is limited to symptomatic intervention, and there is no therapeutic approach to prevent or reverse disease progression. This review provides a compilation of the experimental advances obtained in cell-based and animal models toward the development of gene therapy strategies against polyQ SCAs, providing a discussion of their potential application in clinical trials. In the second part, we describe the promising potential of nanotechnology developments to treat polyQ SCA diseases. We describe, in detail, how the design of nanoparticle (NP) systems with different physicochemical and functionalization characteristics has been approached, in order to determine their ability to evade the immune system response and to enhance brain delivery of molecular tools. In the final part of this review, the imminent application of NP-based strategies in clinical trials for the treatment of polyQ SCA diseases is discussed.

Aplicação simultânea de estimulação transcraniana por corrente contínua cerebelar anódica para reabilitação do equilíbrio na ataxia cerebelar: relato de caso / Application of add-on anodal cerebellar direct current stimulation for balance rehabilitation in cerebellar ataxia: a case report

INTRODUÇÃO: As ataxias cerebelares são um extenso grupo de doenças que causam diversos distúrbios na marcha e no equilíbrio, e que comprometem seriamente a qualidade de vida, sem opções de tratamento eficazes. A cinesioterapia é a base de programas multifacetados que incorporam mais de um enfoque, como o treinamento de coordenação e equilíbrio. Recentemente, a estimulação transcraniana por corrente contínua (tDCS) sobre o cerebelo surgiu como uma intervenção para melhorar os distúrbios do equilíbrio. OBJETIVO: Descrever a aplicação simultânea de tDCS anódica cerebelar e cinesioterapia, em sessões múltiplas diárias para reabilitação da ataxia cerebelar. MATERIAIS E MÉTODOS: Este relato de caso incluiu um paciente do sexo masculino, de 34 anos, com história de ataxia espinocerebelar há 10 anos. Seus principais objetivos eram melhorar a marcha e o equilíbrio. Ele apresentava ataxia axial e apendicular, dificuldades na marcha e no equilíbrio. O protocolo de estimulação do cerebelo consistiu na aplicação de tDCS por 20 minutos, 2mA, diariamente, durante duas semanas, com ânodo posicionado sobre o ínion e cátodo sobre o músculo deltóide direito. A cinesioterapia simultânea incluiu exercícios funcionais progressivos com objetivo principal de treinamento de equilíbrio. RESULTADOS: A melhora clínica foi particularmente evidenciada por uma redução de 4 pontos na Escala para Avaliação e Graduação da Ataxia após 10 sessões, enquanto a literatura recomenda a eficácia de uma nova terapia que retardaria a progressão da ataxia em 1 ponto por ano. CONCLUSÃO: Nossos resultados sugerem que a associação entre tDCS e cinesioterapia foi eficaz neste paciente; as sessões de tDCS foram seguras e bem toleradas e podem ter desempenhado um papel na melhora nos testes funcionais. Novos estudos controlados envolvendo um número maior de pacientes são necessários para analisar os benefícios destas técnicas combinadas para maximizar a reabilitação motora nesta população.

INTRODUCTION: Cerebellar ataxias are an extensive group of diseases, which cause many disorders in gait and balance that seriously impair quality of life, and without effective treatment options. Kinesiotherapy is the basis of multifaceted programs that incorporate more than one focus, such as coordination and balance training. Recently, transcranial direct current stimulation (tDCS) over the cerebellum has emerged as an intervention to improve balance disorders. OBJECTIVE: To describe a daily multiple session's simultaneous application of anodal cerebellar tDCS to kinesiotherapy for rehabilitation in cerebellar ataxia. MATERIALS AND METHODS: This case report included a 34-year-old male patient with a 10-year history of spinocerebellar ataxia. His main goals were to improve his walking ability and balance. He presented with axial and appendicular ataxia, impaired gait, and balance. The protocol used to stimulate the cerebellum consisted of twenty-minute tDCS, 2mA, daily applied, over two weeks, with anode positioned over the inion and cathode over the right deltoid muscle. Simultaneous kinesiotherapy included progressive functional exercises with the main objective of balance training. RESULTS: Clinical improvement was particularly evidenced by a 4-point reduction in the Scale for the Assessment and Rating of Ataxia after ten sessions, while literature recommends efficacy of a new therapy that would retard ataxia progression by 1 point per year. CONCLUSION: Our results suggest that the association between tDCS and kinesiotherapy was effective in this patient; tDCS sessions were safe and well-tolerated and may have played a role in improving functional tests. Further controlled studies involving a larger number of patients are needed to analyze the benefits of these combined techniques to maximize motor rehabilitation in this population.

Which Factors in Spinocerebellar Ataxia Type 3 Patients Are Associated with Restless Legs Syndrome/Willis-Ekbom Disease?

There is evidence of a higher prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) in individuals with spinocerebellar ataxia type 3 (SCA3), although the factors underlying this association remain unknown. The present study aimed to determine the prevalence of RLS/WED in SCA3 patients and to investigate which factors of SCA3 patients are associated with presence of RLS/WED. From February to August of 2006, we carried out clinical interviews in 40 controls and 40 SCA3 patients, diagnosed and followed up at Faculty of Medicine of Ribeirão Preto, University of São Paulo. Twenty-seven SCA3 patients were submitted to a detailed clinical protocol, electroneuromyography, blood work up, polysomnography (PSG), suggested immobilization test (SIT), and magnetic resonance image (MRI). RLS/WED was found in 27.5% of SCA3 patients and 2.5% of normal controls (p = 0.003). The factors related to RLS/WED in SCA3 patients were female gender, age at start of the symptoms of ataxia after 30 years, presence of peripheral neuropathy, and documented iron deficiency. Among SCA3 patients, those with RLS showed higher values of maximal discomfort level and discomfort level sum compared to non-RLS individuals on SIT. There is a relation between RLS/WED and SCA3, which seems to be resultant of different factors whose identification could improve the quality of assistance to those patients as well as to promote a better comprehension of the pathophysiology of both RLS/WED and SCA3.

Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review / Evidências e práticas do uso do sequenciamento de nova geração em pacientes com ataxias cerebelares autossômicas dominantes não diagnosticadas: uma revisão

ABSTRACT Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus on searching evidence on the literature, its usefulness in clinical practice and future perspectives.

RESUMO As ataxias cerebelares autossômicas dominantes (ACAD) são doenças heterogêneas com fenótipo e genótipo altamente variáveis. Podem ser divididas em ataxia episódica e ataxia espinocerebelar (SCA), sendo este último considerado o protótipo do ACAD. A maior parte das ACAD são causadas por expansões de poliglutaminas, principalmente SCA 1, 2, 3, 6, 7, 17 e atrofia dentatorubro-palidoluisiana (DRPLA). No entanto, 30% dos pacientes permanecem sem diagnóstico após o teste para essas SCA mais comuns. Recentemente, vários estudos têm demonstrado que a nova geração de métodos de sequenciamento são ferramentas úteis para o diagnóstico desses pacientes. Esta é uma revisão sistemática da literatura, com foco em sua utilidade na prática clínica e em perspectivas futuras.

Natural history and epidemiology of the spinocerebellar ataxias: Insights from the first description to nowadays.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant inherited diseases that share the degeneration of the cerebellum and its connections as their main feature. We performed a detailed description of the natural history of the main SCAs, focusing on epidemiology, progression, haplotype analysis and its correlation with founder effect, and perspective of future treatments. References for this review were identified by an in-depth literature search on PubMed and selected on the basis of relevance to the topic and on the authors' judgment. More than 40 SCAs have been described so far. SCA3 is the most common subtype worldwide, followed by SCA2 and 6. To evaluate the natural history and to estimate the progression of the main SCAs, consortiums were created all over the globe. Clinical rating scales have been developed to provide an accurate estimation of cerebellar clinical deficits, evaluating cerebellar and non-cerebellar signs. Natural history studies revealed that SCA1 patients' functional status worsened significantly faster than in other SCA subtypes, followed by SCA3, SCA2, SCA6, and SCA10. Number of CAG repeats, age of onset, and ataxia severity at baseline are strong contributors to the risk of death in most SCAs. Understanding the natural history of SCAs is extremely important. Although these are rare diseases, the impact they have on the affected individual are enormous. The advances in the field of genetics are helping understand neuronal functions and dysfunctions and allowing the study and development of possible therapies.

Volumetric MRI Changes in Spinocerebellar Ataxia (SCA3 and SCA10) Patients.

Spinocerebellar ataxias type 3 (SCA3) and type 10 (SCA10) are the most prevalent in southern Brazil. To analyze the relationships between volumetric MRI changes and clinical and genetic findings in SCA3 and SCA10 patients. All patients in the study had a confirmed genetic diagnosis. Demographic data, ataxia severity (SARA score), and the size of the expanded alleles were evaluated. Nineteen SCA3 and 18 SCA10 patients were selected and compared with a similar number of healthy controls. Patient and control groups underwent the same MRI protocol. The standard FreeSurfer pipeline was used for the morphometric data. Our results show more affected brain structures (volume reductions) in SCA3 patients than in SCA10 patients (15 vs. 5 structures). Volume reductions in brain structures were also greater in the former. The main areas with significant volumetric reductions in the former were the cerebellum, basal ganglia, brain stem, and diencephalon, whereas in the latter, significant volume reductions were observed in the cerebellum and pallidum. While SARA scores and disease duration were more correlated with volume reduction in SCA10, in SCA3, the expansion length (CAGn) correlated positively with cerebellar WM, thalamus, brain stem, and total GM volumes. There was no correlation between expansion length (ATTCTn) and neuroimaging findings in SCA10. Neuroimaging results differed significantly between SCA3 and SCA10 patients and were compatible with the differences in clinical presentation, disease progression, and molecular findings.

Distribution of the CAG Triplet Repeat in ATXN1, ATXN3, and CACNA1A Loci in Peruvian Population.

Spinocerebellar ataxia subtypes 1, 3, and 6 (SCA1, MJD/SCA3, and SCA6) are among the most prevalent autosomal dominant cerebellar ataxias worldwide, but their relative frequencies in Peru are low. Frequency of large normal (LN) alleles at spinocerebellar ataxia-causative genes has been proposed to be associated with disease prevalence. To investigate the allelic distribution of the CAG repeat in ATXN1, ATXN3, and CACNA1A genes in a Peruvian mestizo population and examine their association with the relative frequency of SCA1, MJD/SCA3, and SCA6 across populations. We genotyped 213 healthy mestizo individuals from Northern Lima, Peru, for ATXN1, ATXN3, and CACNA1A using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). We compared the frequency of LN alleles and relative disease frequency between populations. We also tested 40 samples for CAT repeat interruptions within the CAG tract of ATXN1. We found no association between disease frequency and population frequency of LN alleles at ATXN1 and ATXN3. All 40 ATXN1 samples tested for CAT interruptions were positive. Frequency of LN alleles at CACNA1A correlates with SCA6 frequency across several populations, but this effect was largely driven by data from a single population. Low frequency of SCA1 and MJD/SCA3 in Peru is not explained by frequency of LN alleles at ATXN1 and ATXN3, respectively. The observed correlation between CACNA1A LN alleles and SCA6 frequency requires further assessment.

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients.

The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are available. The study aims to assess the prevalence, distribution, and neurological features of the Cuban population with hereditary ataxias. A nationwide epidemiological study of hereditary ataxias was conducted in Cuba between March 2017 and June 2018. Patients were scheduled at the Cuban ataxia research center, various hospitals, or at their homes. Demographic and clinical variables were obtained through standardized questionnaires and validated clinical tools. Overall, 1001 patients were diagnosed with hereditary ataxias for a nationwide prevalence of 8.91 cases/100.000 inhabitants. Spinocerebellar ataxia type 2 (SCA2) was the commonest subtype, with highest prevalences at Holguín province (47.86/100.000), and a broad dissemination in the whole country. Most of neurological features were common between all SCA cohorts, but the frequencies of some of them varied between distinct subtypes. Within the SCA2 cohort, significant influences of long mutation size and higher disease duration over the muscle atrophy and oculomotor disorders were observed. Besides, higher disease durations were associated with resting tremor and dysphagia, whereas shorter disease durations were associated with hyperreflexia. The spreading of SCA2 to whole country and the documented raising of its prevalence set the rationales for higher-scope medical care and research strategies, supported in collaborative research networks. The wide epidemiological, clinical, and genetic characterization of this founder SCA2 population identifies this homogeneous cohort as an attractive source for the development of future clinical-genetic and therapeutic researches.

Body composition in Spinocerebellar ataxia type 3 and 10 patients: Comparative study with control group.

Background: Spinocerebellar ataxias (SCAs) are a group of neurodegenerative genetic diseases characterized by movement disorders that can affect nutritional status and body composition. This study sought to assess body composition in SCA3 and SCA10 patients. Methods: Anthropometric assessments and bioelectric impedance analysis were performed in 46 SCA3 and SCA10 patients and 76 controls of both genders. Results: Of the patients, 69.6% had SCA3 and 58.7% were women. SCA3 patients had significantly lower percentages of body fat (%BF) than controls (15.0 ± 6.1 vs. 20.6 ± 7.1; p=0.014) and (22.4 ± 6.9 vs. 30.1 ± 6.0; p<0.001), respectively. Among the women, there was a statistically significant difference in %BF between SCA3 and SCA10 patients (22.4 ± 6.9 vs. 32.4 ± 4.9; p<0.001). Male and female SCA3 patients had significantly lower fat-free mass (FFM) than controls [50.6 kg (46.9-54.7) vs. 58.6 kg (52.6-63.9); p=0.001] and [38.2 kg (35.1-42.6) vs. 42.8 kg (39.7-46.1); p=0.004], respectively. Male SCA10 patients also had lower FFM than controls [51.2 kg (47.1-55.4) vs. (52.6-63.9); p=0.008]. Female SCA10 patients had significantly higher FFM than controls and SCA3 patients [45.0 kg (43.3-45.6) vs. 42.8 kg (39.7-46.1); p=0.004] and [45.0 kg (43.3-45.6) vs. 38.2 kg (35.1-42.6); p=0.004], respectively. There was moderate correlation (-0.42) between disease duration and muscle mass (MM), and weak (-0.38) between SARA (Scale for the Assessment and Rating of Ataxia) and MM in SCA3. In SCA10, there was no significant correlation between these variables. Conclusion: Female SCA3 patients had more body composition changes than female SCA10 patients, mainly in relation to FFM. SCA3 and SCA10 patients need nutritional follow-up to minimize body compartment changes.

Obsessive-compulsive disorder in a patient with SCA type 1 / Transtorno obsessivo compulsivo em um paciente com SCA tipo 1

For many years, the cerebellum was thought to be only responsible for balance, movement, planning and execution. Nowadays, it is well accepted that most cerebellar connections are involved in non-motor functions. Herein, we provide a case report in which a 27-year-old Brazilian male, diagnosed with Obsessive-Compulsive Disorder (OCD), has demonstrated cerebellar features that could be connected to Spinocerebellar ataxia type 1 (SCA-1), an autosomal dominant polyglutamine neurodegenerative disorder that had been previously ruled out. Since obsessive compulsive symptoms (OCS) are known to correlate with alterations in the cortico-striato-thalamo-cortical circuitry, we propose a possible association between OCS and SCA onset.

Durante muitos anos, o cerebelo foi considerado responsável exclusivamente pelo controle das funções de equilíbrio, movimento, planejamento e execução. Atualmente, já está consagrada a participação das conexões cerebelares em funções não-motoras. Apresentamos um relato de caso de um paciente de 27 anos de idade, diagnosticado com Transtorno Obsessivo-Compulsivo (TOC). O paciente apresentava sintomas cerebelares compatíveis com o diagnóstico de ataxia espinocerebelar tipo 1 (SCA-1), um distúrbio da poliglutamina, autossômico dominante neurodegenerativo, que havia sido previamente descartado. Como os sintomas obsessivos compulsivos (SOC) são conhecidos por correlacionar-se com alterações nos circuitos cortico-estriato-tálamo-cortical, propomos uma possível associação entre o SOC e o início da SCA.

Spinocerebellar ataxias in Southern Brazil: Genotypic and phenotypic evaluation of 213 families.

OBJECTIVES: To describe and correlate the genotype and phenotype of patients diagnosed with SCAs in southern of Brazil. PATIENTS AND METHODS: Data were collected from the records of our ataxia outpatient clinic. We included 460 patients from 213 families, who were divided into four groups: SCA3, SCA10, Other SCAs and Undetermined. RESULTS: The most frequent type was SCA3 (45.7%), followed by SCA10 (18.3%), SCA2 (6.5%), SCA1 (4.3%), SCA7 (1.8%), and SCA6 (0.65%). The Undetermined group represented 22.8% of all patients. We observed a high frequency of SCA10 when compared to data from other studies, which can be explained by a founder effect in our region. Statistically significant differences were found for several symptoms when comparing SCA groups, especially lid retraction (p < 0.001), ophthalmoplegia (p < 0.001), visual loss (p < 0.001) and slow saccades (p < 0.001) which may help clinically differentiate SCAs and allow neurologists to request the right confirmatory genetic test and define prognosis. Also, the prevalence of epilepsy in SCA10 patients was lower than usual (4.8%), suggesting a genetic variation of the disease. CONCLUSION: Although SCA3 remains the most common, we observed a high frequency of SCA10 in our region. In addition, some symptoms and signs might help differentiate the SCAs.

Sleep Disorders in Hereditary Ataxias.

PURPOSE OF REVIEW: In this review, we aim to describe the main sleep disorders observed in patients with different forms of hereditary ataxias and discuss the main pathophysiological mechanisms. RECENT FINDINGS: Several pathological studies have demonstrated that the degenerative process in patients with hereditary ataxias may involve not only the cerebellum, but also other areas of the nervous system, and explain noncerebellar symptoms, such as sleep disorders. Hereditary ataxias are neurodegenerative disorders with heterogeneous genetic and clinical presentation. This group of diseases usually affects other areas of the nervous system, besides the cerebellum, and noncerebellar signs and symptoms may occur, such as sleep disorders. The main sleep disorders related to hereditary ataxias include REM sleep behavior disorder, insomnia, excessive daytime sleepiness, obstructive and central sleep apnea, periodic leg movement in sleep, and restless legs syndrome.