Quality of life in individuals with spinocerebellar ataxia type 10: a preliminary study / Qualidade de vida em indivíduos com ataxia espinocerebelar tipo 10: estudo preliminar

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".

Expansión anormal de hexanucleótido en gen C9orf72 en una familia con demencia frontotemporal y cuadros asociados / Abnormal expansion of C9orf72 gene in familial frontotemporal dementia

Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND) may share similar pathogenic mechanisms. An abnormal hexanucleotide expansion in C9orf72 gene is the most common genetic abnormality of these conditions and explains their concurrence in the same family. We report a 77-year-old female presenting with non-fluent aphasia leading to mutism and a mild Parkinsonism. A magnetic resonance imaging showed a severe atrophy of frontal and temporal lobes. Several family members of the patient suffered of atypical Parkinsonism, lateral amyotrophic sclerosis and dementia. We identified an abnormal hexanucleotide expansion in the C9orf72 gene in the proband. To the extent of our knowledge, this is the first time that this diagnosis is confirmed in our country. The knowledge of the genetic basis of neuro degenerative disorders improves diagnosis and opens expectatives for future treatments of these disabling conditions.

Spinocerebellar ataxia type 10 in the South of Brazil: the Amerindian-Belgian connection / Ataxia espinocerebelar tipo 10 no sul do Brasil: a conexão Ameríndia-Belga

Spinocerebellar ataxia type 10 (SCA10) is a rare form of autosomal dominant ataxia found predominantly in patients from Latin America with Amerindian ancestry. The authors report the history of SCA10 families from the south of Brazil (the states of Paraná and Santa Catarina), emphasizing the Belgian-Amerindian connection.

A ataxia espinocerebellar tipo 10 (AEC10) é uma forma rara de ataxia cerebelar autossômica dominante, encontrada predominantemente em pacientes da América Latina, de origem Ameríndia. Os autores relatam a história de famílias com AEC10 do sul do Brasil (estados do Paraná e Santa Catarina), enfatizando a conexão Ameríndia-Belga.

Recent advances in clinical and genetic research of spinocerebellar ataxia type 36 / 中华医学遗传学杂志

Non-coding expansion spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases characterized by "CTA/CTG", "ATTCT", "TGGAA" expansion in non-coding region of the causative gene. Until now, 5 subtypes including SCA8, SCA10, SCA12, SCA31 and SCA36 have been mapped. Recently, the causative mutation for SCA36, namely intronic hexanucleotide GGCCTG expansion in NOP56 gene, has been identified in Japanese and Spanish pedigrees in succession. Compared with other subtypes of SCAs, there are certain distinctive characteristics for SCA36. The clinical and genetic features of SCA36 are reviewed in this paper.

Clinical Characteristics, Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.</p><p><b>METHODS</b>In this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.</p><p><b>RESULTS</b>We found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.</p><p><b>CONCLUSIONS</b>Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.</p>

Manifestaciones neuropsiquiátricas y cognitivas en demencia frontotemporal y esclerosis lateral amiotrófica: dos polos de una entidad común / Overlapping features of frontotemporal dementia and amyotrophic lateral sclerosis

Recent genetic and neuropathologic advances support the concept that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are overlapping multisystem disorders. While 10-15% of ALS patients fulfil criteria for FTD, features of motor neuron disease appear in approximately 15% of FTD patients, during the evolution of the disease. This overlap has been reinforced by the discovery of Transactive Response DNA Binding Protein 43 kDa (TDP43) inclusions as the main neuropathologic finding in the majority of ALS cases and almost a half of FTD cases. Also, an expansion in the intron of C9ORF72 (chromosome 9p21) has been identified in families affected by ALS, ALS-FTD and FTD. This review provides an update on the recent genetic and neuropathologic findings of ALS and FTD and a characterization of their clinical presentation forms, based on the current diagnostic criteria. Finally it underscores the importance of having a national registry of patients with ALS and FTD, to provide an earlier diagnosis and a multidisciplinary care.

Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families

OBJECTIVE: Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias. METHODS: We studied 150 patients from 104 families with spinocerebellar ataxias who had received molecular genetic testing for spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17, and dentatorubral-pallidoluysian atrophy. A statistical analysis of the results was performed using basic descriptive statistics and the correlation coefficient (r), Student's t-test, chi-square test, and Yates' correction. The statistical significance level was established for p-values <0.05. RESULTS: The results show that the most common subtype was spinocerebellar ataxia 3, which was followed by spinocerebellar ataxia 10. Moreover, the comparison between patients with spinocerebellar ataxia 3, spinocerebellar ataxia 10, and other types of spinocerebellar ataxia revealed distinct clinical features for each type. In patients with spinocerebellar ataxia 3, the phenotype was highly pleomorphic, although the most common signs of disease included cerebellar ataxia (CA), ophthalmoplegia, diplopia, eyelid retraction, facial fasciculation, pyramidal signs, and peripheral neuropathy. In patients with spinocerebellar ataxia 10, the phenotype was also rather distinct and consisted of pure cerebellar ataxia and abnormal saccadic eye movement as well as ocular dysmetria. Patients with spinocerebellar ataxias 2 and 7 presented highly suggestive features of cerebellar ataxia, including slow saccadic ocular movements and areflexia in spinocerebellar ataxia 2 and visual loss in spinocerebellar ataxia 7. CONCLUSIONS: Spinocerebellar ataxia 3 was the most common subtype examined, followed by spinocerebellar ataxia 10. Patients with spinocerebellar ataxia 2 and 7 demonstrated highly suggestive features, whereas the phenotype of spinocerebellar ataxia 3 patients was highly pleomorphic and spinocerebellar ataxia 10 patients exhibited pure cerebellar ataxia. Epilepsy was absent in all of the patients with spinocerebellar ataxia 10 in this series.