Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

ALSFRS-R score and subscore distributions (violin graphs) and corresponding GLM comparison for patients’ precentral cortical thickness and ALSFRS-R scores for A–C, global score. D–F, Bulbar. G–I, Arm. J–L, Leg region subscores. Note that while ALFSRS-R subscores are not lateralized, GLM correlations for the left precentral cortex were presumed to be related to right-limb symptoms, and vice versa for the right precentral cortex, as depicted by the orange shading on the silhouette. The color scale (signed log10 P values) indicates decreased cortical thickness with decreasing (less normal) ALSFRS-R scores in red (and vice versa, negative associations in blue). An uncorrected threshold of 1.3 corresponds to a log10 of P = .05. Significant clusters surviving cluster-wise P value correction (P < .05) are outlined in white.

MEP ratio distributions (violin plots) across patients and corresponding GLM comparison for patients’ precentral cortical thickness and electrophysiologic MEP ratios for A and B, Right arm; C and D, Left arm; E and F, Right leg; and G and H, Left leg. Correlations for the left precentral area were performed with right-limb measures, and vice versa for the right precentral area, following the orange shading on the silhouettes. The color scale (signed log10 P values) indicates decreased cortical thickness with decreasing (less normal) MEP ratios in red (and vice versa, negative associations in blue). Uncorrected threshold of 1.3 corresponding to a log10 of P = .05. Significant clusters surviving cluster-wise P value correction (P < .05) are outlined in white.

A and D, Distribution of CSF and serum NfL levels across patients, with corresponding log CSF and serum values represented as a combined histogram-density graph. B and C, GLM comparison for patients’ precentral cortical thickness and log CSF NfL levels. E and F, GLM comparison for patients’ precentral cortical thickness and log serum NfL levels. The color scales in B and C and E and F (signed log10 P values) indicate decreasing cortical thickness with increasing NfL scores in blue (and vice versa, positive associations in red). An uncorrected threshold of 1.3 corresponds to a log10 of P = .05. Note that the negative correlation in the left precentral area is around the premotor cortex. Significant clusters surviving cluster-wise P value correction (P < .05) are outlined in white.