MEPs and MRI Motor Band Sign as Potential Complementary Markers of Upper Motor Neuron Involvement in Amyotrophic Lateral Sclerosis

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of both upper and lower motor neurons (UMNs and LMNs). Recognizing the involvement of UMNs is challenging because of the absence of reliable biomarkers beyond clinical evaluation.

Aim: To identify a reliable marker of UMN damage in a cohort of patients with ALS referring to the Motor Neuron Disease Clinic of the University Hospital of Padova.

Methods: We retrospectively evaluated the clinical records of 79 patients with ALS and compared the results of various investigations, including the motor-evoked potentials (MEPs), positron emission tomography-magnetic resonance imaging (MRI) and light neurofilaments (NfLs), with the degree of UMN clinical involvement, as assessed by the Penn Upper Motor Neuron Score (PUMNS).

Results: MEPs, considering the central motor conduction time (CMCT) values in both the upper and lower limbs, showed a significant correlation with the relative PUMNS subscores (p = 0.01, ρ = 0.4; and p = 0.005, ρ = 0.45, respectively). Additionally, there was a positive correlation between NfLs and PUMNS values (p = 0.04, ρ = 0.33). The presence of the motor band sign on MRI was associated with higher PUMNS values. Receiver operating characteristic analysis revealed that PUMNS accurately predicted abnormalities in CMCT values (specificity 86%, sensitivity 62%) and the presence of the motor band sign (specificity 58%, sensitivity 80%).

Interpretation: In our cohort of patients with ALS, CMCT values proved to be the most reliable test for assessing UMN involvement, albeit the presence of the motor band sign on MRI showed higher sensitivity.

Keywords: ALS; PET‐MR; PUMNS; upper motor neuron.

FIGURE 1

Frequency distribution of PUMNS values within the studied population. In our cohort, no patients exhibited a PUMNS score exceeding 18 (PUMNS score range, 0–32).

FIGURE 2

Correlation analysis of CSF Log[NfL] concentrations with PUMNS values. Correlations between quantitative variables (PUMNS and NfL) were assessed using the Spearman correlation coefficient (ρ = 0.33, p = 0.04). Triangles indicate increased NF light levels; circles indicate normal NF light levels; the dashed line represents the regression line calculated using the ordinary least squares (OLS) method considering all values.

FIGURE 3

Box plots depicting the distribution of PUMNS lower limb subscore across different levels of CMCT values categorized as normal, abnormal on one side, or abnormal on two sides. ‘Abnormal on one side’ indicates that at least one of the values (right or left) is altered, whereas ‘abnormal on two sides’ signifies that both values (right and left) are altered. The dashed trend lines represent the regression line generated using the OLS method, providing a visual indication of the positive correlation between the increase in the PUMNS lower limb total score and different levels of the CMCT. The Spearman correlation coefficient was used to determine the strength and direction of the correlation (p = 0.01, ρ = 0.4). The median and interquartile range are shown.

FIGURE 4

Box plots depicting the distribution of PUMNS upper limb subscore across different levels of CMCT values categorized as normal, abnormal on one side, or abnormal on two sides. ‘Abnormal on one side’ indicates that at least one of the values (right or left) is altered, whereas ‘abnormal on two sides’ signifies that both values (right and left) are altered. The dashed trend lines represent the regression line generated using the ordinary least squares method, providing a visual indication of the positive correlation between the increase in the PUMNS upper limb subscore and different levels of the CMCT. The Spearman correlation coefficient was used to determine the strength and direction of the correlation (p = 0.005, ρ = 0.45). The median and interquartile range are shown.

FIGURE 5

Box plots illustrating the relationship between PUMNS and the presence or absence of the motor band sign (a) and corticospinal tract (CST) hyperintensity (b). The bold line indicates the median, the box represents the interquartile range, and the whiskers show the minimum and maximum values. Patients with the motor band sign on at least one side had significantly higher PUMNS (p = 0.015), whereas no significant difference was observed for those with CST hyperintensity (p = 0.144). The Wilcoxon–Mann–Whitney test was used to assess data distribution.

FIGURE 6

Box plots illustrating the correlation between PUMNS scores and varying degrees of hypometabolism in the motor cortex. The dashed trend lines represent the regression line generated using the OLS method. No significant difference was observed between hypometabolism levels and PUMNS scores (p = 0.9). The Spearman correlation coefficient was used to evaluate the strength and direction of the correlation. The median and interquartile range are shown.

FIGURE 7

AUC values for the individual tests: NfL, PET‐MRI, and MEPs.