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Objective:To explore functional brain region changes and their correlation with behavioral variables based on amplitude of low-frequency fluctuation (ALFF) analysis using resting-state functional MRI (rs-fMRI) in patients with spinocerebellar ataxia type 3 (SCA3).Methods:In this prospective study, patients with SCA3 and healthy controls (HC) were recruited by Southwest Hospital, Army Medical University from May 2017 to March 2022. All subjects completed the scale for assessment and rating of ataxia (SARA), the international cooperative ataxia rating scale-posture and gait (ICARS-p&g), the rapid verbal retrieval (RVR) and Montreal cognitive assessment (MoCA). Meanwhile, the subjects underwent structural MRI and rs-fMRI scans. The MRI data were processed by DPABI software based on MATLAB. The normalized ALFF values of the two groups were compared using two-sample t-test, and the changes of ALFF values in the brain regions of SCA3 and HC groups were analyzed with the t-test of partial correlation coefficient. Spearman correlation analysis was used to evaluate the relationship between the ALFF values of abnormal brain area and the score of neurobehavioral scale in SCA3. Results:Compared with HC group, ALFF significantly increased in the left cerebellum (Crus1, Crus2, 4_5, 6, 7b, 8, 9), right cerebelum_9, left fusiform gyrus and vermis_8; while ALFF significantly decreased in the vermis_4_5 in patients with SCA3. Correlation analysis showed that ALFF values in the left cerebellar_8 were negatively correlated with RVR scores ( r=-0.293, P=0.035), ALFF values in the left cerebellar_9 were negatively correlated with MoCA scores ( r=-0.324, P=0.019), ALFF values in the right cerebellar_9 were negatively correlated with RVR scores ( r=-0.401, P=0.003) in the SCA3 patients. ALFF in the vermis_8 was positively correlated with SARA scores ( r=0.308, P=0.026) and ICARS-p&g scores ( r=0.313, P=0.024) in the SCA3 patients. Conclusion:There are significant changes in ALFF values in the cerebellum and left fusiform gyrus in patients with SCA3, and the changes of ALFF values are closely related with communication, cognitive and movement disorders.
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Objective: Spinocerebellar ataxia type 2, an orphan disease also known as spinocerebellar degeneration, is characterized by a degenerative process of the cerebellum and spinal cord. Method Biographical review of a Japanese woman known as Aya Kitou, using a qualitative approach of discourse analysis to identify resilience capacity, based on Boris Cyrulnik's Biopsychosocial model. Results Description based on the detailed experience reported in Aya´s diary; the areas to achieve resilience are identified (internal resources, sociocultural significance and social support system) Conclusion Although the progression of the clinical condition compromised Aya"s functional capacity, limiting her autonomy and quality of life, it was evidenced that thanks to strong social networks individuals are more likely to achieve resilience, although the prevalence of social values and meanings upon the patient creates greater social anxiety and a greater feeling of inferiority and incapacity.
Objetivo A ataxia espinocerebelar tipo 2, uma doença órfã também conhecida como degeneração espinocerebelar, é caracterizada pelo processo degenerativo do cerebelo e da medula espinhal. Método Revisão biográfica de mulher japonesa conhecida como Aya Kitou, a partir de uma abordagem qualitativa, baseada na análise do discurso, para identificar a capacidade de resiliência, a partir do modelo biopsicossocial de Boris Cyrulnik. Resultados Descritos com base nas vivências detalhadas de seu diário, são identificadas as áreas para alcançar resiliência (recursos internos, significado sociocultural e sistema de suporte social). Conclusão Embora a progressão do quadro clínico tenha comprometido sua capacidade funcional, limitando sua autonomia e qualidade de vida, evidenciou-se que, graças às fortes redes sociais, tem mais chance de alcançar resiliência, embora, com a prevalência de valores e significados sociais sobre ela, haja maior ansiedade social e maiores sentimentos de inferioridade e incapacidade.
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Qualité de vie , Ataxies spinocérébelleuses , Résilience psychologique , Intelligence émotionnelle , Modèles biopsychosociauxRésumé
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.
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Humains , Activités de la vie quotidienne , Ataxies spinocérébelleuses , Indice de gravité de la maladieRésumé
Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.
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Objective:To explore the phenotype and molecular genetic features of spinocerebellar ataxia type 2 (SCA2) cases with ATXN2 intermediate-length CAG-repeat expansion.Methods:Fragment analysis by capillary electrophoresis was performed to detect the dynamic mutations in the samples of the probands in 1 383 pedigrees with autosomal dominant inherited ataxia in Research Center for Motor Disorders and Neurogenetic Diseases, Department of Neurology, China-Japan Friendship Hospital from 2005 to 2018. The clinical and genetic features of individuals carrying the ATXN2 intermediate-length CAG-repeat expansion were carefully analyzed.Results:Two hundred and three individuals (including the probands and members of their families) in 163 families carried the expanded CAG repeats in ATXN2 gene, among which 107 individuals in 93 families carried the intermediate-length CAG-repeats. Within 20 parent-child pairs, the CAG repeats increased 0-28 copies in 16 pairs with paternal inheritance, and 0-4 copies in 4 pairs with maternal inheritance.Conclusions:For suspected SCA2 cases, ATXN2 gene testing should be performed on the parental members and adult offspring members in the family. Dynamic mutations testing is essential to identify the individuals with ATXN2 intermediate-length repeat expansion, which is very important for genetic counseling.
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Objective:To identify the morphological alterations in the Golgi apparatus of skin fibroblasts in spinocerebellar ataxia type 3 (SCA3) patients.Methods:In this study, 3 SCA3 patients and 3 healthy volunteers were obtained in the First Affiliated Hospital of Zhengzhou University from 2016 to 2020. The cytosine, adenine, and guanine repeats of 3 SCA3 patients were 14/76, 20/80 and 21/82, respectively. Tissue mass culture was used to amplify skin fibroblasts derived from SCA3 patients and healthy volunteers. Cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry, respectively. Western blotting and immunofluorescence assay were used to detect the protein expression of ataxin-3, Golgi reassembly stacking protein 2 (GORASP2), and Golgi matrix protein 130 (GM130) in the skin fibroblasts. The morphology of the Golgi apparatus in skin fibroblasts was detected using transmission electron microscopy.Results:Tissue culture of skin fibroblasts of both SCA3 patients and healthy volunteers was successfully established. The patient-derived dermal fibroblasts expressing mutant ataxin-3 protein exhibited reduced cell viability ( t=5.06,P=0.007), increased apoptosis ( t=3.77, P=0.020), fragmentation of the Golgi apparatus, increased expression of GM130 ( t=5.23, P=0.006), and decreased expression of GORASP2 ( t=4.35, P=0.012). Transmission electron microscopy revealed that the Golgi apparatus was disorganized in skin fibroblasts. Conclusion:Fragmentation of the Golgi apparatus occurs in the skin fibroblasts of SCA3 patients, and abnormal morphology and structure of the Golgi apparatus may be involved in the pathogenesis of SCA3.
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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.
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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.
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Ataxie cérébelleuse , Réadaptation , Stimulation transcrânienne par courant continuRésumé
Introducción: Cuando se piensa en estudiar el cerebelo es posible que lo primero que viene a la mente sean las siguientes preguntas: ¿cuáles son sus enfermedades?, ¿cómo se expresan clínicamente? y quizás, ¿cómo es su estructura y cuáles las funciones de este órgano? Objetivo: Examinar las principales características anatómicas y funcionales del cerebelo y relacionarlas con su expresión clínica cuando enferma, así como comentar sobre su abanico de etiologías en el niño. Métodos: Las fuentes de búsquedas fueron las bases de datos computarizadas: PubMed, Ebsco y SciELO. Se utilizaron las palabras clave: cerebelo, ataxia, erores congénicos del metabolismo y ataxias, ataxias episódicas, enfermedades progresivas del sistema nervioso y ataxias; en idioma español e inglés. Resultados: El cerebelo recepciona múltiples informaciones y las envía a diversas estructuras cerebrales por medio de las cuales modula la excitabilidad de estas estructuras y sus sistemas descendentes. Este órgano organiza, dirige, coordina múltiples funciones que se traducen en fuerza, tiempo y secuencia. El cerebelo enfermo impide que la persona ejecute sus funciones y movimientos de forma uniforme y coordinada; puede resultar afectado por un amplio abanico de posibilidades etiológicas, genéticas o adquiridas y enfermarse todo o parte de él. Consideraciones finales: El cerebelo cumple importantes funciones dentro del sistema nervioso, tiene una expresividad muy típica cuando está enfermo. El uso adecuado de las nuevas técnicas de estudios por imágenes y genéticas, entre otras, permiten al pediatra clínico estar en mejores condiciones para el diagnóstico de sus afecciones y tratamiento oportuno(AU)
Introduction: When we think about studying the cerebellum, the first thing that comes to mind may be the following questions: Which are its diseases? How they are clinically expressed? , and perhaps: What is its structure and what functions do this organ has? Objective: Examine the main anatomical and functional characteristics of the cerebellum and relate them to its clinical expression when it becomes ill, as well as comment on its range of etiologies in the child. Methods: Search sources were computerized databases like: PubMed, Ebsco, and SciELO. Keywords used were: cerebellum, ataxia, metabolism congenital errors and ataxias, episodic ataxias, progressive diseases of the nervous system and ataxias; in Spanish and English. Results: The cerebellum receives information and sends it to various brain structures through which it modulates the excitability of these structures and their downstream systems. This organ organizes, directs, and coordinates multiple functions that translate into strength, time and sequence. An ill cerebellum prevents the person from performing their functions and movements in a uniform and coordinated way; it can be affected by a wide range of etiological, genetic or acquired possibilities and make all or part of it ill. Final considerations: The cerebellum performs important functions within the nervous system; it has a very typical expressiveness when it is ill. Proper use of new imaging and genetic study techniques, among others, allows the clinical pediatricians to be better able to diagnose its conditions and timely treatment(AU)
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Humains , Ataxie , Cervelet , Pédiatres , Système nerveuxRésumé
Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10 (SCAR10).Methods:A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected. Friedreich ataxia and other causes of acquired ataxia were excluded, then probands were detected by whole-exome sequencing (WES), and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members. Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results:A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES. The 40-year-old male proband of this pedigree carried compound heterozygous mutations: c.1219-2A>C and c.1163-2A>G of the ANO10 gene, both of which were novel mutations, and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents. Bioinformatic analysis predicted these two mutations were pathogenic. The proband exhibited progressive unsteady walk, dysarthria, mild cognitive impairment. His plasma total coenzyme Q 10 was decreased (0.76 μg/ml). Brain magnetic resonance imaging showed remarkable cerebellar atrophy. Conclusions:Through WES, a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified, which is rare in China. The main clinical manifestation was progressive cerebellar ataxia and cognitive decline, and brain image showed remarkable cerebellar atrophy.
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Spinocerebellar ataxias (SCAs), formerly known as autosomal dominant cerebellar ataxia, are a group of hereditary heterogeneous neurodegenerative disease that contains many subtypes. Spinocerebellar ataxia type 23 (SCA23), one type of SCAs, is caused by mutant prodynorphin (PDYN) gene. A 22-year-old patient was diagnosed with sporadic SCA23 due to gene detection, with a novel identified mutation, PDYN c.647C>T (p.P216L). Located in the dynorphin A-coding-region of PDYN gene, the pathogenic mechanism of the mutation may be relevant to the pathological changes caused by the variant including neurological dysfunction and death of cells. Mild improvement with the patient has been witnessed after active balance and speaking exercise.
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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.
Sujets)
Humains , Arthrogrypose , Ataxie cérébelleuse/diagnostic , Ataxie cérébelleuse/génétique , Ataxies spinocérébelleuses/diagnostic , Ataxies spinocérébelleuses/génétique , Séquençage nucléotidique à haut débit , GénotypeRésumé
Introducción: La ataxia constituye una alteración en la coordinación de los movimientos, resultado de una disfunción del cerebelo, sus conexiones, así como alteraciones en la médula espinal, nervios periféricos o una combinación de estas condiciones. Las ataxias se clasifican en hereditarias, esporádicas y en adquiridas o secundarias, en las cuales los virus neurotrópicos constituyen los principales causantes. Objetivo: Actualizar los conocimientos relacionados con las ataxias causadas por virus neurotrópicos y los mecanismos neurodegenerativos que pudieran tener relación con la ataxia. Métodos: Se realizó una revisión bibliográfica incluyendo artículos publicados en las principales bases de datos bibliográficas (Web of Sciences, Scopus, SciELO). Se utilizaron las palabras claves: ataxia, virus neurotrópicos, ataxias cerebelosas, ataxias infecciosas, en inglés y español. Análisis e integración de la información: Los virus más conocidos que provocan ataxias infecciosas son el virus de inmunodeficiencia humana, virus del herpes simple, virus del herpes humano tipo 6, virus de la varicela zoster, virus Epstein-Barr, virus del Nilo Occidental, y enterovirus 71, aunque existen otros virus que causan esta afectación. Los mecanismos neuropatogénicos sugeridos son la invasión directa del virus y procesos inmunopatogénicos desencadenados por la infección. Estos virus pueden causar ataxia cerebelosa aguda, ataxia aguda posinfecciosa, síndrome opsoclono-mioclono-atáxico y ataxia por encefalomielitis aguda diseminada. Aunque la mayoría de los reportes de casos informan la evolución satisfactoria de los pacientes, algunos refieren complicaciones neurológicas e incluso la muerte. Conclusiones: Actualmente existe la necesidad de profundizar en el estudio de este tipo de ataxia para favorecer su diagnóstico y tratamiento(AU)
Introduction: Ataxia is an alteration in the coordination of movements caused by a dysfunction of the cerebellum and its connections, as well as alterations in the spinal cord, the peripheral nerves, or a combination of these factors. Ataxias are classified into hereditary, sporadic and acquired or secondary, in which neurotropic viruses are the main causative agents. Objective: Update knowledge about ataxias caused by neurotropic viruses and the neurodegenerative mechanisms which could bear a relationship to ataxia. Methods: A review was conducted of papers published in the main bibliographic databases (Web of Sciences, Scopus, SciELO), using the search terms ataxia, neurotropic virus, cerebellar ataxias, infectious ataxias, in English and in Spanish. Discussion: The best known viruses causing infectious ataxias are the human immunodeficiency virus, herpes simplex virus, human herpesvirus 6, varicella zoster virus, Epstein-Barr virus, Western Nile virus and enterovirus 71, though other viruses may also cause this condition. The neuropathogenic mechanisms suggested are direct invasion of the virus and immunopathogenic processes triggered by the infection. These viruses may cause acute cerebellar ataxia, acute postinfectious ataxia, opsoclonus-myoclonus-ataxia syndrome and ataxia due to acute encephalomyelitis disseminata. Though most case reports describe a satisfactory evolution of patients, some refer to neurological complications and even death. Conclusions: There is a current need to carry out further research about this type of ataxia to improve its diagnosis and treatment(AU)
Sujets)
Humains , Mâle , Femelle , Ataxie cérébelleuse/diagnostic , Ataxie cérébelleuse/épidémiologie , Facteurs de virulenceRésumé
Abstract Subclinical ventilatory dysfunction is observed in individuals with spinocerebellar ataxias (SCA). No studies have correlated ventilatory dysfunction to clinical and functional decline in SCA2. Objective: To evaluate the relationship between the values of peak expiratory flow (PEF), maximum inspiratory pressure (MIP), and presence of respiratory complaints with age, disease duration, age at onset of symptoms, balance scores, independence in basic (ADL) and instrumental (IADL) Activities of Daily Living (ADLs), and severity of ataxia (SARA) in individuals with SCA2. Methods: Cross-sectional study evaluating age, disease duration, age at onset of symptoms, scores in the Berg Balance Scale and in the SARA, Functional Independence Measure and Lawton's scale, values of PEF and MIP, and the presence of respiratory complaints. Results: The study included 36 individuals with SCA2, with a mean age of 42.5±2.4 years, disease duration of 7.6±8.2 years, age 33.7±11.5 years at onset of symptoms, and 9.9±10.3 points in the SARA scale. The lowest PEF values correlated with the longer disease duration (p=0.021). The lowest values of PEF and MIP correlated with greater balance impairment (p=0.019 and p=0.045, respectively), increased degree of dependence in the ADL (p=0.006 and p=0.050, respectively) and IADL (p=0.003 and p=0.001, respectively) scales, and highest severity of ataxia (p=0.00 and p=0.017, respectively). Respiratory complaints were observed in 12 (33.3%) individuals and were not related to age, disease duration, age at onset of symptoms, balance, independence, ataxia severity, or PEF and MIP values. Conclusion: Ventilatory dysfunction, even when asymptomatic, is related to balance impairment, independence, and ataxia severity in individuals with SCA2.
Resumo Disfunção ventilatória subclínica tem sido observada em indivíduos com ataxias espinocerebelares (SCA). Não existem estudos relacionando disfunção ventilatória ao declínio clínico e funcional na SCA2. Objetivo: Avaliar a relação dos valores de Pico de Fluxo Expiratório (PFE), Pressão Inspiratória Máxima (PIMAX) e presença de queixas respiratórias com idade, tempo de doença, idade de início dos sintomas, escore de equilíbrio, independência para atividades básicas (AVD) e instrumentais (AIVD) de vida diária e gravidade da ataxia (SARA) em indivíduos com SCA2. Métodos: Estudo transversal, considerando: idade, tempo de doença, idade de início dos sintomas, escores nas Escalas SARA, Equilíbrio de Berg, Medida da Independência Funcional e de Lawton, valores de PFE, PIMAX e queixas respiratórias. Resultados: Foram avaliados 36 indivíduos com SCA2 com média de 42,5±2,4) anos de idade, 7,6±8,2 anos de tempo de doença, 33,7±11,5 anos de idade de início dos sintomas e 9,9±10,3 pontos na escala SARA. Os menores valores de PFE estiveram relacionados ao maior tempo de doença (p=0,021). Os menores valores de PFE e PIMAX estiveram relacionados ao maior comprometimento do equilíbrio (p=0,019; p=0,045, respectivamente), maior dependência para ADV (p=0,006; p=0,050, respectivamente) e AIVD (p=0,003; p=0,001, respectivamente) e maior gravidade da ataxia (p=0,006; p=0,017, respectivamente). Foram observadas queixas respiratórias em 12 (33,3%) indivíduos que não estiveram relacionadas à idade, idade de início dos sintomas, tempo de doença, equilíbrio, independência, gravidade da ataxia, ou valores de PFE e PIMAX. Conclusão: A disfunção ventilatória, mesmo quando assintomática, está relacionada ao comprometimento do equilíbrio, à independência e à gravidade da ataxia em indivíduos com SCA2.
Sujets)
Humains , Adulte , Adulte d'âge moyen , Ataxies spinocérébelleuses , Indice de gravité de la maladie , Activités de la vie quotidienne , Études transversalesRésumé
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.
Sujets)
Humains , Mâle , Adulte , Ataxies spinocérébelleuses/complications , Ataxies spinocérébelleuses/diagnostic , Trouble obsessionnel compulsif/diagnostic , Trouble obsessionnel compulsif/thérapie , Dépistage génétique , Démarche ataxique , Dysarthrie , Ataxine-1/génétique , Examen neurologique/méthodesRésumé
RESUMEN El término ataxias cerebelosas hereditarias comprende un amplio espectro de trastornos neurológicos en los cuales la ataxia es el síntoma principal. Conforman un complejo grupo de entidades cuyo reconocimiento es esencial para el correcto asesoramiento genético, el adecuado control clínico y, en algunos casos, el apropiado abordaje terapéutico. La riqueza clínico-semiológica y los avances en la biología molecular han convertido a las ataxias hereditarias en uno de los temas más apasionantes de la neurología. El diagnóstico clínico de los subtipos de ataxias es complicado, por la prominente superposición de fenotipos entre los subtipos genéticos. En este artículo abordamos los principales avances neurofisiológicos, clínicos y genéticos de las ataxias cerebelosas hereditarias.
ABSTRACT The term "Hereditary cerebellar ataxia" comprises a wide spectrum of neurological disorders where ataxia is the main symptom. Hereditary ataxias are a complex group of entities, in which detection is essential for an adequate genetic assessment, satisfactory clinical control and in some cases, a suitable therapeutic approach. Clinical semiology variety and molecular biology advanceshave become hereditary ataxias one of the most interesting subjects inside neurology. Subtypes clinical diagnosis of ataxias is complicated by the salient overlap of phenotypes between genetic subtypes. In this article, we refer to the most important neurophysiological, clinical and genetics advances of hereditary cerebellar ataxias.
Résumé
ABSTRACT Introduction: The clinical assessment of patients with ataxias requires reliable scales. We aimed to translate, adapt and validate the International Cooperative Ataxia Rating Scale (ICARS) into Brazilian Portuguese. Methods: The steps of this study were forward translation, translation synthesis, backward translation, expert committee meeting, preliminary pilot testing and final assessment. Thirty patients were enrolled in the preliminary pilot testing and 61 patients were evaluated for construct validity, internal consistency, intra- and inter-rater reliability and external consistency. Results: This study showed good validity of the construct and high internal consistency for the full scale, except for the oculomotor domain (Cronbach's alpha = 0.316, intraclass correlation coefficients intra- = 82.4% and inter- = 79.2%). A high correlation with the Scale for the Assessment and Rating of Ataxia was observed. We found good intra-rater agreement and relative inter-rater disagreement, except in the posture and gait domain. Conclusion: The present ICARS version is adapted for the Brazilian culture and can be used to assess our ataxic patients.
RESUMO Introdução: A avaliação clínica de pacientes atáxicos requer instrumentos confiáveis. Nosso objetivo foi traduzir, adaptar culturalmente e validar a International Cooperative Ataxia Rating Scale (ICARS) para a língua portuguesa do Brasil. Métodos: As etapas foram tradução, síntese das traduções, retrotradução, comitê de especialistas, pré-teste e avaliação final. O pré-teste foi realizado com 30 pacientes. Outros 61 pacientes foram avaliados para validade do constructo, consistência interna, confiabilidade intra e interexaminadores e consistência externa. Resultados: Este estudo mostrou boa validade do constructo e alta consistência interna para o total da escala, exceto para o domínio Oculomotor (alfa de Cronbach = 0.316, CCIintra = 82.4% e CCIinter = 79.2%). Alta correlação com a Scale for the Assessment and Rating of Ataxia foi observada. Nós encontramos boa concordância intraexaminador e relativa discordância interexaminadores, com exceção dos domínios postura e marcha. Conclusão: Esta versão da ICARS está adaptada para a cultura brasileira e pode ser usada em pacientes com ataxia.
Sujets)
Humains , Mâle , Femelle , Adolescent , Adulte , Adulte d'âge moyen , Jeune adulte , Ataxie/diagnostic , Enquêtes et questionnaires/normes , Psychométrie , Ataxie/classification , Traductions , Indice de gravité de la maladie , Brésil , Comparaison interculturelle , Reproductibilité des résultats , LangageRésumé
ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.
RESUMO As ataxias espinocerebelares (SCA) são um grupo clínico e geneticamente heterogêneo de doenças monogênicas que compartilham ataxia e herança autossômica dominante como características principais. Uma proporção importante de SCAs é causada por expansões de repetição de trinucleotídeos CAG na região de codificação de diferentes genes. Além da heterogeneidade genética, os aspectos clínicos transcendem os sintomas motores, incluindo aspectos cognitivos, eletrofisiológicos e de imagem. Apesar de todo o progresso feito nos últimos 25 anos, os mecanismos que determinam como se dá a morte neuronal mediada por essas expansões instáveis ainda não estão claros. O objetivo deste artigo é revisar, de um ponto de vista histórico, a primeira ataxia geneticamente relacionada com o CAG descrita: SCA 1.
Sujets)
Humains , Histoire du 20ème siècle , Ataxies spinocérébelleuses/génétique , Ataxine-1/génétique , Troubles de la veille et du sommeil/physiopathologie , Imagerie par résonance magnétique/méthodes , Expansion de trinucléotide répété/génétique , Ataxies spinocérébelleuses/histoire , Ataxies spinocérébelleuses/thérapie , Ataxies spinocérébelleuses/imagerie diagnostique , Dépression/physiopathologie , Neuroimagerie/méthodes , Dysfonctionnement cognitif/physiopathologie , Ataxine-1/histoireRésumé
ABSTRACT Spinocerebellar ataxia type 10 (SCA10) is characterized by gait ataxia, dysarthria, nystagmus, epilepsy, reduced cognitive ability and depression, which lead to functional loss and behavioral changes. These signs gradually evolve and may interfere with the physical, emotional, and social aspects of quality of life (QoL). Objective: To assess the self-perception of quality of life and its association with disease duration, severity of ataxia, balance and functional independence. Methods: This study focused on the disease duration, ataxia severity (SARA), balance (Berg Balance Scale), functionality (FIM, Lawton IADL) and QoL (SF-36 v.2) of 15 individuals with SCA10. Results: The population sample consisted of eight females and seven males, with a mean age of 43.8 (± 8.2) years, mean age of symptom onset of 33.1 (± 8.9) years and mean disease duration of 9.8 (± 11.2) years. The mean Berg Balance Scale score was 47.2 (± 12), mean SARA score (n = 14) 11.5 (± 7.3), mean Lawton IADL score 20.4 (± 1.8) and mean FIM score 120.3 (± 5.4). Individuals with SCA10 had a greater impairment of QoL in the "role-physical" domain (p = 0.04). The longer the disease duration (p = 0.02), risk of falling (p = 0.04), severity of ataxia (p = 0.00) and functional dependence in activities of daily living (p = 0.03) and instrumental activities of daily living (p = 0.00), the worse the QoL was in the "physical functioning" domain, with a decrease of 1.62 points for each year of disease duration. Conclusion: In this sample, the greatest impairment of QoL in individuals with SCA10 was observed in "physical functioning" and "physical role".
RESUMO A Ataxia Espinocerebelar tipo 10 (SCA10) caracteriza-se pela ataxia da marcha, disartria, nistagmo, epilepsia, redução da capacidade cognitiva e depressão, causando perda funcional e alterações comportamentais. Esses sinais evoluem gradualmente e podem interferir nos aspectos físicos, emocionais e sociais da Qualidade de Vida (QV). Objetivo: Avaliar a autopercepção da qualidade de vida e sua associação com a duração da doença, gravidade da ataxia, equilíbrio e independência funcional. Método: O estudo enfoca a duração da doença, gravidade da ataxia (SARA), equilíbrio (EEB), funcionalidade (MIF, Lawton) e QV (SF-36 v.2) de 15 indivíduos com SCA10. Resultados: A amostra foi composta por oito indivíduos do sexo feminino, com média de idade de 43,8 (± 8,2), de idade de início dos sintomas 33,1 (± 8,9) e de tempo de doença de 9,8 (± 11,2) anos. A média do escore na Berg foi 47,2 (± 12,0), no SARA (n = 14) foi de 11,5 (± 7,3), na escala de LAWTON 20,4 (± 1,8) e na MIF 120,3 (± 5,4) pontos. Os Indivíduos com SCA10 apresentaram maior prejuízo na QV no domínio "Aspectos Físicos" (p = 0,04). Quanto maior a duração da doença (p = 0,02), risco de queda (p = 0,04), gravidade da ataxia (p = 0,00) e maior dependência funcional para AVD (p = 0,03) e AIVD (p = 0,00), pior a QV no domínio "Capacidade Funcional" com decréscimo de 1,62 ponto para cada ano no tempo de doença. Conclusão: Nesta amostra, o comprometimento da QV em indivíduos com SCA10 foi observado nos domínios "Capacidade Funcional" e "Aspectos Físicos".
Sujets)
Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Qualité de vie , Concept du soi , Ataxies spinocérébelleuses/physiopathologie , Valeurs de référence , Indice de gravité de la maladie , Activités de la vie quotidienne , Modèles linéaires , Études transversales , Études prospectives , Enquêtes et questionnaires , Analyse de variance , Expansion de séquence répétée de l'ADN , Évaluation de l'invalidité , Équilibre postural/physiologieRésumé
Background: Ataxia can be classified as genetic, sporadic or acquired. Aim: To report the clinical features of a group of patients with ataxia. Material and Methods: Review of medical records of patients consulting in a specialized center in movement disorders. Those records in which the diagnosis of "ataxia" or "ataxic syndrome" appeared, were selected for the review. Results: Of 4,282 records surveyed, the diagnosis of ataxia appeared in 95. After eliminating repeated or incomplete records, 63 were reviewed. Results: Ataxia was sporadic, genetic and acquired in 27, 22 and 14 patients, respectively. The mean age at presentation for genetic, acquired and sporadic ataxia was 24, 46 and 53 years respectively. All autosomal dominant ataxias were type 3 spinocerebellar ataxia (SCA). Friedrich's ataxia was the most common recessive form. Most sporadic forms of ataxia were multiple system atrophy with predominant cerebellar ataxia (MSA-C) subtype. Conclusions: Considering the heterogeneity of patients with ataxia, we propose a method to approach them.