FV7. Tract of interest-based DTI analysis in upper and lower motor neuron disease variants of ALS

Abstract

Background It is still a topic of research if specific clinical presentations of motoneuron disease (MND) patients should be classified as amyotrophic lateral sclerosis (ALS) variants, i.e. primary lateral sclerosis (PLS) with predominant upper motor neuron on the one hand and pure lower motor neuron disease (LMND) on the other hand. Objective markers for ALS are to be investigated in these patients. Objective The aim of the study was to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with classical ALS, LMND, and PLS in contrast to healthy controls in order to challenge the hypothesis that brain structural changes according to the neuropathologically defined ALS affectation pattern ( Kassubek et al., 2014 ) can be observed. LMND data were pooled from previous studies at two different study sites (Ulm, Germany and Milano, Italy). Methods DTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors), 42 PLS patients, and 101 ALS patients with a ’classical’ phenotype vs 92 matched controls to identify white matter structural alterations. Results The analysis of predefined tracts-of-interest according to the neuropathological spreading pattern demonstrated regional characteristic alteration patterns (FA reductions) fast LMND progressors and in ALS compared to controls. ( Muller et al., 2018 ) The degree of involvement correlated with the clinical phenotype. PLS also presented substantial tract involvement in the tract-of-interest-based approach. Conclusion In the tract-specific analysis according to the ALS-staging pattern, upper (PLS) as well as lower motor neuron disease (LMND) pathology showed alterations of ALS-related corticoefferent fibers. The neuroimaging results confirm the clinical approach to these phenotypes as ALS variants, in accordance with the latest revision of the El Escorial criteria for ALS, in favour of the consequence to treat these patients like ALS and also to include them into clinical trials of ALS.