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Background Flail arm syndrome is a restricted phenotype of motor neuron disease that is characterized by progressive, predominantly proximal weakness and atrophy of the upper limbs. Objective The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from flail arm syndrome patients using a hypothesis-guided tract-of-interest-based approach to identify in vivo microstructural changes according to a neuropathologically defined amyotrophic lateral sclerosis (ALS)-related pathology of the cortico-efferent tracts. Methods DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the neuropathological ALS-propagation pattern for 43 flail arm syndrome patients vs 43 ‘classical’ ALS patients vs 40 matched controls. Results The analysis of white matter integrity demonstrated regional FA reductions for the flail arm syndrome group predominantly along the CST. In the tract-specific analysis according to the proposed sequential cerebral pathology pattern of ALS, the flail arm syndrome patients showed significant alterations of the specific tract systems that were identical to ‘classical’ ALS if compared to controls. Conclusions The DTI study including the tract-of-interest-based analysis showed a microstructural involvement pattern in the brains of flail arm syndrome patients, supporting the hypothesis that flail arm syndrome is a phenotypical variant of ALS.

Background Musculoskeletal complaints are frequent and have large consequences for public health. Information about the prognosis after presentation in general practice is far from complete. Knowledge about determinants of the clinical course of musculoskeletal complaints is essential for management decisions and to inform patients about their prognosis. The purpose of this study is to provide information about the prognosis of musculoskeletal complaints other than low back pain by studying the course of these complaints in general practice and to identify determinants of this course. Methods Patients of 18 years and older, who present in general practice with a new episode of a musculoskeletal complaint of the neck, shoulder, elbow, wrist, hand, arm, hip, knee, ankle or foot, are recruited by their general practitioner (GP). Participants will receive complaint-specific questionnaires by mail at baseline and after 3, 6, 12 and 18 months. The following putative determinants of the course of the complaints will be investigated: sociodemographic characteristics, characteristics of the complaint, psychosocial job characteristics, physical workload, physical activity during leisure time, pain coping, mood, kinesiophobia, social support, optimism. The primary outcomes are perceived recovery, pain, functional status, sick leave and overall quality of life.