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Objective: The potential of magnetic resonance imaging (MRI) as a technical biomarker for cerebral microstructural alterations in neurodegenerative diseases is under investigation. In this study, a framework for the longitudinal analysis of diffusion tensor imaging (DTI)-based mapping was applied to the assessment of predefined white matter tracts in amyotrophic lateral sclerosis (ALS), as an example for a rapid progressive neurodegenerative disease.Methods: DTI was performed every 3 months in six patients with ALS (mean (M) = 7.7; range 3 to 15 scans) and in six controls (M = 3; range 2–5 scans) with the identical scanning protocol, resulting in a total of 65 longitudinal DTI datasets. Fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), radial diffusivity (RD), and the ratio AD/RD were studied to analyze alterations within the corticospinal tract (CST) which is a prominently affected tract structure in ALS and the tract correlating with Braak’s neuropathological stage 1. A correlation analysis was performed between progression rates based on DTI metrics and the revised ALS functional rating scale (ALS-FRS-R).Results: Patients with ALS showed an FA and AD/RD decline along the CST, while DTI metrics of controls did not change in longitudinal DTI scans. The FA and AD/RD decrease progression correlated significantly with ALS-FRS-R decrease progression.Conclusion: On the basis of the longitudinal assessment, DTI-based metrics can be considered as a possible noninvasive follow-up marker for disease progression in neurodegeneration. This finding was demonstrated here for ALS as a fast progressing neurodegenerative disease.

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative process affecting upper and lower motor neurons as well as non-motor systems. In this study, precentral and postcentral cortical thinning detected by structural magnetic resonance imaging (MRI) were combined with clinical (ALS-specific functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit number index, MUNIX) biomarkers in both cross-sectional and longitudinal analyses.Methods: The unicenter sample included 20 limb-onset classical ALS patients compared to 30 age-related healthy controls. ALS patients were treated with standard Riluzole and additional long-term G-CSF (Filgrastim) on a named patient basis after written informed consent. Combinatory biomarker use included cortical thickness of atlas-based dorsal and ventral subdivisions of the precentral and postcentral cortex, ALSFRS-R, and MUNIX for the musculus abductor digiti minimi (ADM) bilaterally. Individual cross-sectional analysis investigated individual cortical thinning in ALS patients compared to age-related healthy controls in the context of state of disease at initial MRI scan. Beyond correlation analysis of biomarkers at cross-sectional group level (n = 20), longitudinal monitoring in a subset of slow progressive ALS patients (n = 4) explored within-subject temporal dynamics of repeatedly assessed biomarkers in time courses over at least 18 months.Results: Cross-sectional analysis demonstrated individually variable states of cortical thinning, which was most pronounced in the ventral section of the precentral cortex. Correlations of ALSFRS-R with cortical thickness and MUNIX were detected. Individual longitudinal biomarker monitoring in four slow progressive ALS patients revealed evident differences in individual disease courses and temporal dynamics of the biomarkers.Conclusion: A combinatory use of structural MRI, neurophysiological and clinical biomarkers allows for an appropriate and detailed assessment of clinical state and course of disease of ALS.

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Zusammenfassung Um den bislang unaufhaltsamen Verlust motorischer Nervenzellen bei der amyotrophen Lateralsklerose (ALS) quantitativ zu erfassen, sind sog. MUNE-Verfahren (von engl.: motor unit number estimation) eingesetzt worden. Diese scheinen den Verlauf einer ALS besser abzubilden als klinische Scores oder neurophysiologische Standardverfahren, sind daf?r aber sehr zeitaufw?ndig. Letzteres ist bei einem neuen Verfahren nicht der Fall, dem MUNIX (von engl.: motor unit number index). Das Funktionsprinzip von MUNIX ist intuitiv nicht unmittelbar eing?ngig. Hier wird daher versucht, die Funktion von MUNIX m?glichst verst?ndlich zu beschreiben. Der Einsatz von MUNIX bei Patienten mit ALS hat gezeigt, dass MUNIX ?hnlich sensitiv wie MUNE den Verlauf der Erkrankung abbildet. Es ist aber noch unklar, ob MUNIX tats?chlich die Anzahl von Vorderhornzellen wiedergibt oder ob andere Einfl?sse, wie z.?B. eine Pyramidenbahnl?sion, die MUNIX-Werte nicht wesentlich beeinflussen.