Current Progress in CNS Imaging of Myotonic Dystrophy

Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results toward the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. It may be related to the fact that most of the reported studies included only small numbers of subjects, sometimes even not separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies

Current Progress in CNS Imaging of Myotonic Dystrophy

Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results towards the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. This heterogeneity may support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies

Tracking the brain in myotonic dystrophies: A 5-year longitudinal follow-up study

ObjectivesThe aim of this study was to examine the natural history of brain involvement in adult-onset myotonic dystrophies type 1 and 2 (DM1, DM2).MethodsWe conducted a longitudinal observational study to examine functional and structural cerebral changes in myotonic dystrophies. We enrolled 16 adult-onset DM1 patients, 16 DM2 patients, and 17 controls. At baseline and after 5.5 ± 0.4 years participants underwent neurological, neuropsychological, and 3T-brain MRI examinations using identical study protocols that included voxel-based morphometry and diffusion tensor imaging. Data were analyzed by (i) group comparisons between patients and controls at baseline and follow-up, and (ii) group comparisons using difference maps (baseline–follow-up in each participant) to focus on disease-related effects over time.ResultsWe found minor neuropsychological deficits with mild progression in DM1 more than DM2. Daytime sleepiness was restricted to DM1, whereas fatigue was present in both disease entities and stable over time. Comparing results of cross-sectional neuroimaging analyses at baseline and follow-up revealed an unchanged pattern of pronounced white matter alterations in DM1. There was mild additional gray matter reduction in DM1 at follow-up. In DM2, white matter reduction was of lesser extent, but there were some additional alterations at follow-up. Gray matter seemed unaffected in DM2. Intriguingly, longitudinal analyses using difference maps and comparing them between patients and controls did not reveal any significant differences of cerebral changes over time between patients and controls.ConclusionThe lack of significant disease-related progression of gray and white matter involvement over a period of five years in our cohort of DM1 and DM2 patients suggests either a rather slowly progressive process or even a stable course of cerebral changes in middle-aged adult-onset patients. Being the first longitudinal neuroimaging trial in DM1 and DM2, this study provides useful additional information regarding the natural history of brain involvement

Renzi score for obstructed defecation syndrome - validation of the portuguese version according to the COSMIN checklist

Recently, the Obstructed Defecation Syndrome score (ODS score) was developed and validated by Renzi to assess clinical staging and to allow evaluation and comparison of the efficacy of treatment of this disorder.CONTEXTO: Recentemente, o Score de Distúrbios Evacuatórios (SDE) foi desenvolvido e validado por Renzi para avaliação e comparação da eficácia do tratamento dos doentes com esta patologia. Objetivo - O nosso objetivo é validar uma versão portuguesa do SDE de acordo com as orientações da checklist de COSMIN. MÉTODOS: O SDE foi traduzido para o português, cumprindo as orientações para validação cultural. Indivíduos com distúrbio evacuatório e controlos saudáveis foram convidados a responder ao SDE numa fase inicial, 2 semanas e 3 meses depois, respetivamente. Foi avaliada a consistência interna, confiabilidade, erro de medição, validade de conteúdo e constructo, responsividade e interpretabilidade. RESULTADOS: Foram entrevistados 113 indivíduos (77 doentes; 36 controlos saudáveis) na fase inicial. O SDE foi aplicado novamente aos 77 doentes, 2 semanas depois, e a 30 doentes, 3 meses depois. Relativamente à consistência interna, a análise fatorial confirmou a unidimensionalidade e o coeficiente α de Cronbach foi 0,77, suportando homogeneidade dos itens. O kappa quadrático ponderado de 0,89 estabeleceu a reprodutibilidade teste-reteste. Considerando o erro de medição, a mudança mínima detectável a nível individual foi 2,66 e a nível de grupo foi 0,30. A validade do constructo foi avaliada através do coeficiente de correlação de Spearman entre o SDE e o score total (-0,32) e físico (-0,43) do SF-36. Em termos de validação clínica, verificou-se uma diferença significativa de 11 pontos entre as médias dos doentes e controlos. A responsividade foi confirmada pelo coeficiente de correlação de -0,86 entre a mudança do score e a evolução clínica, avaliados após 3 meses. Através da curva ROC, a mudança mínima importante foi 2,00 e a AUC foi 0,97. Não foram observados efeito-chão efeito-tecto. CONCLUSÃO: Este projeto permitiu validar a versão portuguesa do SDE de Renzi. É possível agora utilizar esta ferramenta na avaliação de distúrbios evacuatórios em doentes falantes de língua portuguesa.(undefined