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      Impairment of oculomotor functions in patients with early to advanced amyotrophic lateral sclerosis

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          Abstract

          Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive oculomotor function by means of an eye tracking test battery between three groups: advanced ALS patients in iLIS (n = 22), patients in early to middle ALS stages (n = 44) and healthy subjects (n = 32). Patients with ALS showed significant deteriorations in oculomotor functions, with stronger impairments in iLIS. More specifically, ALS patients produced visually guided prosaccades with longer latencies and more frequent hypometria compared to healthy subjects. Longest latencies were obtained in iLIS patients, with a stronger prolongation for vertical than for horizontal prosaccades. ALS patients made more antisaccade errors and generated antisaccades with longer latencies. Smooth pursuit was also impaired in ALS. In the earlier ALS stages, bulbar onset patients presented stronger antisaccade and smooth pursuit deficits than spinal onset patients. Our findings reveal a relevant deterioration of important oculomotor functions in ALS, which increases in iLIS. It includes impairments of reflexive eye movements to loss of executive inhibitory control, indicating a progressing pathological involvement of prefrontal, midbrain and brainstem areas. The assessment of oculomotor functions may therefore provide clinically relevant bio- and progression marker, particularly in advanced ALS.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00415-023-11957-y.

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          Most cited references61

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          Amyotrophic Lateral Sclerosis

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            The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III).

            The ALS Functional Rating Scale (ALSFRS) is a validated rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis (ALS). One weakness of the ALSFRS as originally designed was that it granted disproportionate weighting to limb and bulbar, as compared to respiratory, dysfunction. We have now validated a revised version of the ALSFRS, which incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support. The Revised ALSFRS (ALSFRS-R) retains the properties of the original scale and shows strong internal consistency and construct validity. ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile, indicating that the quality of function is a strong determinant of quality of life in ALS.
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              Stages of pTDP-43 pathology in amyotrophic lateral sclerosis.

              To see whether the distribution patterns of phosphorylated 43kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition of neuropathological stages. pTDP-43 immunohistochemistry was performed on 70 μm sections from ALS autopsy cases (N = 76) classified by clinical phenotype and genetic background. ALS cases with the lowest burden of pTDP-43 pathology were characterized by lesions in the agranular motor cortex, brainstem motor nuclei of cranial nerves V, VII, and X-XII, and spinal cord α-motoneurons (stage 1). Increasing burdens of pathology showed involvement of the prefrontal neocortex (middle frontal gyrus), brainstem reticular formation, precerebellar nuclei, and the red nucleus (stage 2). In stage 3, pTDP-43 pathology involved the prefrontal (gyrus rectus and orbital gyri) and then postcentral neocortex and striatum. Cases with the greatest burden of pTDP-43 lesions showed pTDP-43 inclusions in anteromedial portions of the temporal lobe, including the hippocampus (stage 4). At all stages, these lesions were accompanied by pTDP-43 oligodendroglial aggregates. Ten cases with C9orf72 repeat expansion displayed the same sequential spreading pattern as nonexpansion cases but a greater regional burden of lesions, indicating a more fulminant dissemination of pTDP-43 pathology. pTDP-43 pathology in ALS possibly disseminates in a sequential pattern that permits recognition of 4 neuropathological stages consistent with the hypothesis that pTDP-43 pathology is propagated along axonal pathways. Moreover, the finding that pTDP-43 pathology develops in the prefrontal cortex as part of an ongoing disease process could account for the development of executive cognitive deficits in ALS. © 2013 American Neurological Association.
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                Author and article information

                Contributors
                Andreas.Hermann@med.uni-rostock.de
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                15 September 2023
                15 September 2023
                2024
                : 271
                : 1
                : 325-339
                Affiliations
                [1 ]Department of Neurology, Technische Universität Dresden, ( https://ror.org/042aqky30) Dresden, Germany
                [2 ]Verkehrspsychologie, Fakultät Verkehrswissenschaften, Technische Universität Dresden, ( https://ror.org/042aqky30) Dresden, Germany
                [3 ]Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Dresden, Dresden, Germany
                [4 ]Interactive Minds Research, Interactive Minds Dresden GmbH, Dresden, Germany
                [5 ]Precision Neurology and Cluster “Precision Medicine in Inflammation”, University of Lübeck, ( https://ror.org/00t3r8h32) Lübeck, Germany
                [6 ]Department of Neurology, University of Rostock, ( https://ror.org/03zdwsf69) Rostock, Germany
                [7 ]Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock/Greifswald, Rostock, Germany
                [8 ]Engineering Psychology and Applied Cognitive Research, Technische Universität Dresden, ( https://ror.org/042aqky30) Dresden, Germany
                [9 ]Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, ( https://ror.org/03zdwsf69) Rostock, Germany
                [10 ]Translational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University of Rostock, ( https://ror.org/03zdwsf69) Rostock, Germany
                Author information
                http://orcid.org/0000-0002-8047-5983
                Article
                11957
                10.1007/s00415-023-11957-y
                10770212
                37713127
                8febada2-8d3c-4d2d-9820-7e74e4381306
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 June 2023
                : 17 August 2023
                : 18 August 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100014840, Gemeinsame Bundesausschuss;
                Award ID: 01VSF16026
                Award ID: 01VSF16026
                Award ID: 01VSF16026
                Award ID: 01VSF16026
                Award ID: 01VSF16026
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: 13GW0482
                Award ID: 13GW0482
                Award ID: 13GW0482
                Award ID: 13GW0482
                Award Recipient :
                Funded by: Universitätsmedizin Rostock (8980)
                Categories
                Original Communication
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Neurology
                amyotrophic lateral sclerosis,eye movements,oculomotor function,eye tracking communication systems,executive function,saccades

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