Twice-Daily Alertness Test Does Not Accurately Categorize Fatigue in MS

A twice-daily tonic alertness test is not suitable as the sole diagnostic tool for objectifying self-reported fatigue.

A twice-daily alertness test is insufficient in objectively measuring fatigue in individuals with multiple sclerosis (MS), according to study findings published in the Archives of Clinical Neuropsychology.

For individuals with MS, fatigue is a common nonmotor symptom, with a prevalence of up to 90%. Fatigue has been shown to affect sustained performance on motor and cognitive tasks, with implications on employment and retirement. For the study, researchers aimed to validate the ability of a twice-daily alertness test in identifying self-reported MS-related fatigue.

In the retrospective data analysis, the researchers recruited 213 patients (136 women; mean age, 47.34) with relapsing MS from the Neurological Rehabilitation Center in Bonn, Germany from January 2018 to 2021. Individuals with complete testing protocols and no comorbid neurologic diseases were included in the study.

The researchers analyzed participants based on their performance on various neuropsychologic assessments.

[I]t is obvious that the neuropsychological objectification of subjective fatigue solely by means of the twice-daily tonic alertness tests is an insufficient assessment method.

The twice-daily administered Test Battery of Attentional Performance (TAP) recorded tested reaction time (RT) differences between morning tonic alertness (8:30-11:00 a.m.) and afternoon tonic alertness (3:00-4:30 pm.). The researchers instructed the participants not to take naps between those 2 time points. Based on differences between the 2 measurements, alertness performance groups were classified as: improver group (n=40), maintainer group (n=87), and decliner group (n=86). TAP performance was indicative of faster reaction times in the morning when compared with afternoon trials.

The fatigue scale of motor and cognition (FSMC) classified subjective fatigue with cutoff scores signifying no (total score <43), mild (≥43), moderate (≥53), and severe (≥63) fatigue.

Ambulatory ability was recorded using the Expanded Disability Status Scale (EDSS) and the Center for Epidemiologic Studies Depression Scale (CES-D) assessed self-reported depressive symptoms.

Using FSMC scores, the researchers found that 7 (3.3%) patients with MS reported mild fatigue, 25 (11.7%) reported moderate fatigue, and 167 (78.4%) reported severe fatigue.

Multinomial logistic regression (MLR) was used to predict the likelihood of patients belonging to 1 of the performance groups. Considering all tested variables, the final MRL model included the following: morning tonic alertness (P <.001), FSMC (P =.008), EDSS (P =.038), CES-D (P =.161), and gender (P =.057).

In total, 56.8% of the cohort was assigned to the correct group; this correct assignment to alertness was slightly higher than maximum random probably (40.8%).

Of note, afternoon tonic alertness demonstrated the highest potential for differentiation between the 3 performance groups (P <.001).

As this study focused solely on patients with MS, the lack of a control group to compare alertness performance was noted as a limitation.

The researchers noted, “Against this background and the results of this and other studies, it is obvious that the neuropsychological objectification of subjective fatigue solely by means of the twice-daily tonic alertness tests is an insufficient assessment method.” “A nuanced view of the different facets of fatigue and its interrelated factors is important for further research and highly relevant for clinical diagnostic and treatment management,” they concluded.


Weinrich JO, Saliger J, Eschweiler M, Karbe H, Kalbe E, Nielsen J. The relationship between diurnal measures of tonic alertness and self-reported fatigue in persons with multiple sclerosis — a retrospective data analysis. Arch Clin Neuropsychol. doi:10.1093/arclin/acad040