Fatigue and Cognitive Impairment in Multiple Sclerosis

Fatigue and cognitive impairment are 2 of the most common health problems associated with multiple sclerosis (MS). Recent MS studies evaluate the nature of these 2 conditions not just as side effects of MS, but as chronic conditions with varying degrees of severity based on objective assessment and self-perception. At the 29th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis, 2 posters presented the findings of observational studies which explored fatigue and cognition in MS. In the first poster discussed here, Joan Thelen, University of Missouri, Kansas City, presents the effects of polypharmacy on fatigue and self-reported cognition in MS patients. In the second, Matteo Pardini, MD, Department of Neurosciences, University of Genoa, Italy, presents a study on the seemingly paradoxical relationship between persistent subjective fatigue and task-related performance in MS.

In her poster, Thelen investigates the relationship between polypharmacy, fatigue, and cognition in MS. For this observational study, 86 patients provided their current list of medications and completed 8 questionnaires, half of which were self-evaluations, and the other half objective neuropsychological tests. Scores were compared to MS patients without polypharmacy treatment, and healthy controls.

The 4 self-report measures indicated a significant difference in fatigue levels and cognitive ability between MS patients with polypharmacy and the other 2 groups. MS patients with polypharmacy treatments reported more fatigue, processing speed difficulties, and memory problems than MS patients without polypharmacy. Furthermore, a mutlivariate analysis of covariance (MANCOVA) revealed that polypharmacy status had a significant effect on MS patients’ self-report measures, an important factor to consider when looking at comparisons of the 4 objective assessments where the only considerable difference between identified polypharmacy patients and non-polypharmacy patients was in cognition.

Dr Pardini’s study, on the other hand, ascribes significance to fatigue perception, particularly in its relationship with MS. Pardini’s poster presents findings for an observational study which evaluated the relationship between persistent subjective fatigue and task performance in relapsing-remitting MS patients (RRMS). The study examined both motor behavioral and neuroanatomical levels through a task-related exercise and MRI.

To carry out their study, Pardini and his team recruited 14 RRMS with minimal disability (EDSS ≤ 2). Before beginning the exercise, a patient’s fatigue perception was evaluated with the Modified Fatigue Impact Scale (MFIS), a quantitative, self-report questionnaire. The patient’s temporal accuracy (TA) was then measured by a rhythm exercise whereby the patient attempted to maintain a consistent tempo with a metronome using a finger-to-thumb motion. Temporal accuracy was assessed with concurrent MRI through the use of an MR-compatible engineered glove.

As a scatter plot on the poster demonstrates, motor behavioral exercise results indicated a positive relationship between MFIS score and TA, as increased persistent subjective fatigue was associated with higher temporal accuracy. This reveals a potential “paradox” in the relationship between fatigue perception and task performance.

Neuroanatomical results were equally as significant. Functional MRI data (fMRI), with TA as a covariate, showed that “only the right cerebellar hemisphere positively correlated with increasing TA.” Further, with MFIS score as a covariate, fMRI indicated that MFIS score had a positive relationship with the left orbitofrontal cortex (OFC) and the right cerebellum. In summary, then, the neuroanatomical study showed that MFIS-related OFC activation positively correlated with TA-related cerebellar activation.

Dr Pardini furthers the discussion by noting that the OFC is functionally-related to sensorimotor processing, motivation, and self-evaluation, all important factors in persistent subjective fatigue. The observed association between neurology and behavior, as Pardini puts it, “point to a possible adaptive role for fatigue as the subjective correlate of increased resource demand for motor activities.”