Neuroradiological Findings in the Spinocerebellar Ataxias.

Background: The spinocerebellar ataxias (SCAs) are a group of autosomal dominant degenerative diseases characterized by cerebellar ataxia. Classified according to gene discovery, specific features of the SCAs - clinical, laboratorial, and neuroradiological (NR) - can facilitate establishing the diagnosis. The purpose of this study was to review the particular NR abnormalities in the main SCAs. Methods: We conducted a literature search on this topic. Results: The main NR characteristics of brain imaging (magnetic resonance imaging or computerized tomography) in SCAs were: (1) pure cerebellar atrophy; (2) cerebellar atrophy with other findings (e.g., pontine, olivopontocerebellar, spinal, cortical, or subcortical atrophy; "hot cross bun sign", and demyelinating lesions); (3) selective cerebellar atrophy; (4) no cerebellar atrophy. Discussion: The main NR abnormalities in the commonest SCAs, are not pathognomonic of any specific genotype, but can be helpful in limiting the diagnostic options. We are progressing to a better understanding of the SCAs, not only genetically, but also pathologically; NR is helpful in the challenge of diagnosing the specific genotype of SCA.

The genetics of the dystonias--a review based on the new classification of the dystonias.

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

The genetics of the dystonias – a review based on the new classification of the dystonias / A genética das distonias – uma revisão baseada na nova classificação das distonias

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

O conceito e a classificação das distonias foram recentemente revisados. Na nova classificação de 2013, quanto à etiologia, as distonias podem ser subdividas em relação às alterações patológicas, aos danos estruturais, às causas adquiridas e à hereditariedade. Como as distonias hereditárias são clínica e geneticamente heterogêneas, buscamos classifica-las segundo os novos critérios estabelecidos recentemente. Observamos que apesar da nova classificação das distonias ainda ser objeto de discussões e controvérsias, ela pode usada com facilidade, de uma maneira lógica e objetiva, no contexto das distonias hereditárias. Com a descoberta de novos genes poderemos observar se essa classificação continuará sendo efetiva.

Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia.

UNLABELLED: Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. OBJECTIVE: To associate clinical information of patients with dystonia with the TOR1-A gene mutations. METHOD: Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. RESULTS: Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. CONCLUSION: We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia / Avaliação genética para TOR1-A (DYT1) em pacientes brasileiros com distonia

Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia. .

Tem sido mapeada uma série de genes em pacientes com distonia. O gene TOR1-A (DYT1) foi associado a casos de distonia primária. Objetivo Associar os achados clínicos dos pacientes com distonia com mutações em TOR1-A. Método Foram selecionados 88 pacientes com distonia na região cervical (focal, segmentar, multifocal e generalizada) no Setor de Distúrbios do Movimento do Hospital de Clínicas da Universidade Federal do Paraná entre junho de 2008 e junho de 2009. Esses pacientes foram submetidos à avaliação clínica. O DNA foi extraído do sangue periférico e submetido à análise para mutações em TOR1-A através de protocolos padronizados. Resultados A mutação c.907GAGdel foi encontrada em duas pacientes. Ambas tinham história familiar de distonia e iniciaram seus sintomas pelos membros inferiores, evoluindo com generalização. Conclusão Podemos sugerir que a análise para mutações em TOR1-A deve ser realizada em pacientes com distonia de inicio precoce, história familiar e generalização. .

Evolution of the concept of dystonia.

The term dystonia was proposed by Hermann Oppenheim in 1911, but reports of cervical dystonia are finding since the Roman Empire. The differentiation of the dystonia between a neurological and a psychiatric disease turned a lot. Sometimes was proposed, further, the exclusion of the dystonia as a different phenomenon among the movement disorders. The hypothesis of emotional etiology of the dystonias increase in the decade of 1960 and the conclusion of the etiology of dystonia only happened in the decades of 1970 and 1980 with a series of works of Charles David Marsden. These researches defined dystonia as a movement disorder caused by lesion in the basal ganglia. In February of 1984, a committee of members of Scientific Advisory Board of the Dystonia Medical Research Foundation developed the definition for dystonia accepts until 2013 when an international committee developed the new concept.

Evolution of the concept of dystonia / Evolução do conceito de distonia

The term dystonia was proposed by Hermann Oppenheim in 1911, but reports of cervical dystonia are finding since the Roman Empire. The differentiation of the dystonia between a neurological and a psychiatric disease turned a lot. Sometimes was proposed, further, the exclusion of the dystonia as a different phenomenon among the movement disorders. The hypothesis of emotional etiology of the dystonias increase in the decade of 1960 and the conclusion of the etiology of dystonia only happened in the decades of 1970 and 1980 with a series of works of Charles David Marsden. These researches defined dystonia as a movement disorder caused by lesion in the basal ganglia. In February of 1984, a committee of members of Scientific Advisory Board of the Dystonia Medical Research Foundation developed the definition for dystonia accepts until 2013 when an international committee developed the new concept.

O termo distonia foi proposto por Hermann Oppenheim em 1911, porém, quadros de distonia cervical são encontrados desde a antiguidade. A categorização da distonia entre uma doença neurológica ou psiquiátrica mudou muitas vezes sendo proposta, inclusive, a retirada da distonia como um fenômeno distinto entre os distúrbios do movimento. A etiologia emocional das distonias teve grande força na década de 1960 e o fim da discussão etiológica da distonia somente ocorreu nas décadas de 1970 e 1980 com uma série de trabalhos de Charles David Marsden colocando a distonia como um distúrbio do movimento por lesão nos gânglios da base. Em fevereiro de 1984, um comitê formado de membros da Scientific Advisory Board of the Dystonia Medical Research Fundation desenvolveu a definição para distonia aceita até 2013 quando um comitê internacional desenvolveu a definição aceita atualmente.

DYT6 in Brazil: Genetic Assessment and Clinical Characteristics of Patients.

BACKGROUND: Several genes associated with dystonia have been identified. A mutation in one of these, THAP1 (DYT6), is linked to isolated dystonia. The aim of this study was to assess the prevalence of THAP1 gene mutations and the clinical characteristics of patients with these mutations in a clinical population in Brazil. METHODS: Seventy-four patients presenting with dystonia involving the cervical muscles and without mutations in the TOR1A (DYT1) gene or any other movement disorders were recruited at a movement disorders clinic between June 2008 and June 2009. All the patients underwent clinical examination and were screened for mutations of the THAP1 gene. RESULTS: Three patients had the novel p.Gln97Ter THAP1 nonsense mutation in heterozygosis. One of them had no family history of dystonia. Symptoms in this patient first appeared in his right arm, and the condition progressed to the generalized form. The other two patients belonged to the same family (cousins). Symptoms in the first patient started in her right arm at the age of 18 years and the condition progressed to the segmental form. The second patient, who carried the p.Arg169Gln missense mutation, developed dystonia in her left arm at the age of 6 years. The condition progressed to generalized dystonia. DISCUSSION: We conclude that THAP1 mutations are also a cause, albeit uncommon, of segmental and generalized dystonia in the Brazilian population.

Cervical dystonia: about familial and sporadic cases in 88 patients.

Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001). The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01). Generalized cases were more severe in patients with a family history (p<0.01). Sporadic patients had higher levels of pain than familial cases (p<0.05). We expect soon to present the results of genetic analyzes of these patients.

Cervical dystonia: about familial and sporadic cases in 88 patients / Distonia cervical: consideracoes sobre casos esporadicos e familiares em 88 pacientes

Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001). The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01). Generalized cases were more severe in patients with a family history (p<0.01). Sporadic patients had higher levels of pain than familial cases (p<0.05). We expect soon to present the results of genetic analyzes of these patients.

A distonia cervical (CD) afeta a musculatura do pescoço de modo focal ou em combinação com outras partes do corpo. O objetivo deste estudo foi identificar diferenças clínicas entre pacientes com distonia com história familiar e pacientes sem história familiar (esporádicos). Foram selecionados 88 pacientes com DC no Setor de Distúrbios do Movimento entre julho de 2008 e junho de 2009. Somente os pacientes sem diagnóstico etiológico foram admitidos para análise. A idade de início dos sintomas foi mais tardia em pacientes com distonia focal e segmentar do que em pacientes com distonia generalizada (p<0,001). A gravidade dos sintomas foi maior em pacientes com distonia focal esporádicos do que naqueles com história familiar (p<0,01). Os casos generalizados foram mais graves nos pacientes com história familiar (p<0,01). Pacientes esporádicos tiveram níveis maiores de dor em relação aos casos familiares (p<0,05). Esperamos apresentar em breve resultados de análises genéticas desses pacientes.

Botulinum toxin type A and cervical dystonia: a seven-year follow-up.

Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6 ± 6.6 and 17.7 ± 4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD.

Botulinum toxin type A and cervical dystonia: a seven-year follow-up / Toxina botulínica A e distonia cervical: avaliação após sete anos

Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6±6.6 and 17.7±4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD.

A maioria dos casos de distonia cervical (DC) são idiopáticos; injeções locais com toxina botulínica A (BoNT/A) são o tratamento de escolha. O objetivo de nosso estudo foi documentar os efeitos do tratamento a longo prazo da BoNT/A em pacientes com DC idiopática. Foram selecionados 58 pacientes com DC idiopática de março de 2001 a maio de 2002. Desses pacientes, 28 estavam disponíveis para re-avaliação após sete anos. Durante esse período, todos foram submetidos a tratamento regular com injeções de BoNT/A. As informações clínicas dos pacientes e a gravidade da DC (TWSTRS e VAS) na primeira avaliação (2001-2002) e na reavaliação (2008-2009) foram comparadas. Houve uma significante melhora motora detectada pelos resultados da escala TWSTRS, usada para analisar a gravidade clínica (19,6±6,6 e 17,7±4,8; p<0,05). Não houve melhora nos resultados referentes a dor cervical (p=0,43). Em conclusão, BoNT/A foi uma terapêutica de longo prazo efetiva e segura para DC.