P 9 A multi-modal in vivo staging approach to amyotrophic lateral sclerosis. (May 2022)

• Record Type: Journal Article
• Authors: Behler, A.; Müller, H.P.; Lulé, D.; Ludolph, A.C.; Kassubek, J.
• Is Part Of: Clinical neurophysiology. Volume 137(2022)
• Page Start: e19
• Page End: e20
• Publication Date: 2022-05
• Subjects: Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2022.01.040
• Languages: English
• ISSNs: 1388-2457

Abstract

Abstract : Introduction: The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be classified as a four-stage propagation scheme. An in vivo transfer of these stages using diffusion tensor imaging (DTI) in specific tract systems has been established [1]. Since cognitive functions are closely linked to microstructural changes, an analogous classification into four cognitive stages, with high congruence to DTI stages, was demonstrated [2]. Alterations in oculomotor functions in ALS can be characterized by two stages in oculomotor parameters [3]. The objective of the current study is to show congruence of methods by combining neuroimaging, cognitive testing, and video-oculography (VOG) and to potentially improve in vivo staging classification. Methods: A total of 4 microstructural, 2 cognitive, and 9 oculomotor parameters were obtained from each of 193 patients with ALS. To this end, patients underwent VOG und cognitive testing using Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The regional fractional anisotropy (FA) of the tract systems involved in ALS [1] were studied using a tract-of-interest (TOI)-based approach. After z-standardization of all parameters, principal component analysis was performed. Hierarchical and k -means clustering of principal components was used to obtain an optimal cluster solution. Results: After reducing the considered parameters to four uncorrelated principal components, the patients were iteratively merged using pairwise distances. A division of patients into four clusters was used for further analysis. These clusters were different with regard to FA values during the progression of ALS-associated tract systems. Cluster 1 showed the highest FA values and thereby the best performances in executive VOG (e.g. performing correct anti-saccades) and cognitive tests, whereas ALS patients in cluster 4 showed lower FA values, lower ECAS scores and worse executive VOG performance. Patients in clusters 2 and 3 showed lower FA values compared to cluster 1 and higher FA values compared to cluster 4, while cognitive and executive VOG performance were altered only in cluster 2 compared to cluster 1. Conclusion: Cluster analysis of multimodal parameters, incorporating DTI, neuropsychologic testing, and VOG, showed high congruence of methodological approaches in ALS. References [1] Kassubek J et al. J Neurol Neurosurg Psychiatry 2018; 89:374-381. [2] Lulé D et al. Cortex 2018; 101:163-171. [3] Gorges M et al. PLoSOne 2015; 10:e0142546.