Involvement of cortico-efferent tracts in flail arm syndrome: a tract-of-interest-based DTI study

Angela Rosenbohm,Heiko Braak,Kelly Del Tredici,Albert C Ludolph,Hans-Jürgen Huppertz,Hans-Peter Müller,Jan Kassubek

doi:10.1007/s00415-021-10854-6

Abstract

BackgroundFlail arm syndrome is a restricted phenotype of motor neuron disease that is characterized by progressive, predominantly proximal weakness and atrophy of the upper limbs.ObjectiveThe 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.MethodsDTI-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.ResultsThe 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.ConclusionsThe 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.

Highlights

The neuropathological process underlying amyotrophic lateral sclerosis (ALS) entails abnormal changes of the endogenous and predominantly intranuclear protein TDP43 whichHans-Peter Müller and Jan Kassubek have shared senior authorship.(DZNE), Ulm, Germany progress at different rates, but in a similar sequence of four stages, in ALS patients’ brains [1, 2]
ALS patients may present with phenotypes that differ from the ‘classical’ involvement of the upper and the lower motor neuron (UMN, LMN) according to established diagnostic criteria: on the one hand, the diagnostic criteria for primary lateral sclerosis as a slowly progressive upper motor neuron syndrome have been recently updated [3], whereas, on the other hand, it is recognized that upper motor neuron signs are not always clinically evident [4], such as in progressive muscular atrophy or progressive bulbar palsy
When comparing flail arm syndrome patients and controls, regional fractional anisotropy (FA) reduction was observe in the upper CST; the identical FA reduction pattern was observed in the comparison of ALS patients vs controls

Summary

Introduction

The neuropathological process underlying amyotrophic lateral sclerosis (ALS) entails abnormal changes of the endogenous and predominantly intranuclear protein TDP43 (transactive response DNA-binding protein 43) whichHans-Peter Müller and Jan Kassubek have shared senior authorship.(DZNE), Ulm, Germany progress at different rates, but in a similar sequence of four stages, in ALS patients’ brains [1, 2]. ALS patients may present with phenotypes that differ from the ‘classical’ involvement of the upper and the lower motor neuron (UMN, LMN) according to established diagnostic criteria: on the one hand, the diagnostic criteria for primary lateral sclerosis as a slowly progressive upper motor neuron syndrome have been recently updated [3], whereas, on the other hand, it is recognized that upper motor neuron signs are not always clinically evident [4], such as in progressive muscular atrophy or progressive bulbar palsy This concept of ‘restricted’ phenotypes includes flail arm syndrome, which often begins with asymmetric predominantly proximal deficits of the arms [5]. 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

Methods

Results

Conclusion