Daphne Kos

Origin of Fatigue in Multiple Sclerosis: Review of the Literature

Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). Although numerous studies have tried to reveal it, no definite pathogenesis factor behind this fatigue has been identified. Fatigue may be directly related to the disease mechanisms (primary fatigue) or may be secondary to non—disease-specific factors. Primary fatigue may be the result of inflammation, demyelination, or axonal loss. A suggested functional cortical reorganization may result in a higher energy demand in certain brain areas, culminating in an increase of fatigue perception. Higher levels of some immune markers were found in patients with MS-related fatigue, whereas other studies rejected this hypothesis. There may be a disturbance in the neuroendocrine system related to fatigue, but it is not clear whether this is either the result of the interaction with immune activation or the trigger of this process. Fatigue may be secondary to sleep problems, which are frequently present in MS and in their turn result from urinary problems, spasms, pain, or anxiety. Pharmacologic treatment of MS (symptoms) may also provoke fatigue. The evidence for reduced activity as a cause of secondary fatigue in MS is inconsistent. Psychological functioning may at least play a role in the persistence of fatigue. Research did not reach consensus about the association of fatigue with clinical or demographic variables, such as age, gender, disability, type of MS, education level, and disease duration. In conclusion, it is more likely to explain fatigue from a multifactor perspective than to ascribe it to one mechanism. The current evidence on the pathogenesis of primary and secondary fatigue in MS is limited by inconsistency in defining specific aspects of the concept fatigue, by the lack of appropriate assessment tools, and by the use of heterogeneous samples. Future research should overcome these limitations and also include longitudinal designs.

Evaluation of the Modified Fatigue Impact Scale in four different European countries

Objective: To evaluate the psychometric properties of the Modified Fatigue Impact Scale (MFIS) in four different European countries. Methods: Individuals with definite multiple sclerosis (MS) were selected from centres in Italy (n=50), Spain (n=30), Slovenia (n=50) and Belgium (n=51) and completed the MFIS and the Fatigue Severity Scale (FSS) twice (interval ≤ 3 days). Results: In all four samples, the MFIS demonstrated a good reproducibility (intraclass correlation coefficient ≥ 0.84), with no significant differences between countries (P=0.77). Moderate correlations were found between the MFIS and FSS. No significant correlations were found between the MFIS and age, gender, type of MS, duration of the disease or EDSS score. Factor analysis of all samples (n=181) could not completely confirm the original assumptions concerning the physical, cognitive and psychosocial component. The total score, the physical and the cognitive subscale of the scale were homogeneous (Cronbach’s alpha 0.92, 0.88 and 0.92, respectively), but the psychosocial subscale had a Cronbach’s alpha of 0.65. Conclusions: No cultural or linguistic differences were found in the psychometric properties of the Belgian, Italian, Slovenian or Spanish version of the MFIS. We recommend this scale for research purposes and in clinical practice. Due to the limited value of the psychosocial subscale, we recommend interpreting this subscale with caution.

Multidisciplinary fatigue management programme in multiple sclerosis : a randomized clinical trial

Objective To establish the efficacy of a multidisciplinary fatigue management programme (MFMP) in MS. Method Fifty-one subjects with MS were randomly allocated to group A, who only received the four weeks MFMP, or group B receiving a placebo intervention programme first and the MFMP after 6 months. In both groups, assessment was performed at baseline, 3 weeks and 6 months after the programmes and included Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), MS Self-Efficacy scale (MSSE), Mental Health Inventory (MHI) and Impact on Participation and Autonomy (IPA). Results The MFIS showed a significant change over time (F(4,152) = 3.346, P = 0.012), which was similar in both groups (time*group interaction: F(4,152) = 1.094, P = 0.361). A clinically relevant reduction of MFIS score of 10 points or more was found in 17% of individuals following the MFMP, compared to 44% after the placebo intervention programme (P = 0.06). Compared to no intervention, a significant effect of the MFMP after 6 months (P = 0.003) was found in five participants (31%). No significant changes in FSS, MSSE, MHI and IPA, in both groups, were found. Conclusion Although an additional effect was found, the multidisciplinary fatigue management programme showed no efficacy in reducing the impact of fatigue compared to a placebo intervention programme. Multiple Sclerosis 2007; 13: 996—1003. http://msj.sagepub.com

Perceived and actual arm performance in multiple sclerosis: relationship with clinical tests according to hand dominance

Background: The real-life relevance of frequently applied clinical arm tests is not well known in multiple sclerosis (MS). Objective: This study aimed to determine the relation between real-life arm performance and clinical tests in MS. Methods: Thirty wheelchair-bound MS patients and 30 healthy controls were included. Actual and perceived real-life arm performance was measured by using accelerometry and a self-reported measure (Motor Activity Log). Clinical tests on ‘body functions & structures’ (JAMAR handgrip strength, Motricity Index (MI), Fugl Meyer (FM)) and ‘activity’ level (Nine Hole Peg Test (NHPT), Action Research Arm test) of the International Classification of Functioning were conducted. Statistical analyses were performed separately for current dominant and non-dominant arm. Results: For all outcome measures, MS patients scored with both arms significantly lower than the control group. Higher correlations between actual arm performance and clinical tests were found for the non-dominant arm (0.63–0.80). The FM (55%) was a good predictor of actual arm performance, while the MI (46%) and NHPT (55%) were good predictors of perceived arm performance. Conclusions: Real-life arm performance is decreased in wheelchair-bound MS patients and can be best predicted by measures on ‘body functions & structures’ level and fine motor control. Hand dominance influenced the magnitude of relationships.

Measuring activity patterns using actigraphy in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease resulting in impairments in motor and mental performance and restrictions in activities. Self‐report instruments are commonly used to measure activity patterns; alternatively, actigraphs can be placed on several parts of the body. The aims of this study were to evaluate the superiority and specificity of actigraph placement (wrist vs. ankle) in subjects with MS and healthy controls and explore the relationship between self‐report and objective activity patterns. A total of 19 subjects with definite MS and 10 healthy volunteers wore actigraphs on the non‐dominant wrist and ankle for three days while they kept a log to register performed activities every. 5 h. Wrist and ankle actigraphs produced similar activity patterns during the most active hours (09∶00–20∶30 h) (ANOVA, time×location interaction: F=.901, df=23, p=.597) in individuals with MS and healthy controls (between subjects factor F=3.275, p=.083). Wrist placement of the actigraphs was better tolerated than ankle placement. Wrist actigraph data corresponded to a higher degree with self‐reported activities of the upper limbs in the early afternoon, whereas ankle data seem to reflect better whole body movements in the later afternoon/early evening. Overall, actigraph data correlated moderately with self‐reported activity (r=.57 for ankle and r=.59 for wrist). The regression model revealed that self‐reported activities explained 44% of the variance in ankle and 50% of wrist data. Wrist and ankle actigraphs produce similar activity patterns in subjects with MS and in healthy controls; however, the placement of actigraphs on the wrist is better tolerated. Ankle actigraphs reflect general movement but underestimate upper body activity. Subjective registration of activity level partly matches with objective actigraph measurement. A combination of both objective and subjective activity registration is recommended to evaluate the physical activity pattern of subjects with MS.

Paced visual serial addition test in multiple sclerosis

The paced auditory serial addition test (PASAT), a subtest of the multiple sclerosis functional composite score (MSFC), is increasingly used in the evaluation of cognitive function in multiple sclerosis (MS). While patient acceptance for the PASAT is low, its visual version, the paced visual serial addition test (PVSAT), is perceived to be better tolerated. The aim of this study was to investigate the interchangeability of PVSAT and PASAT in the evaluation of cognitive function in MS. Twenty-one normal controls and 50 patients with clinically definite MS were tested with PASAT and PVSAT. Both for PASAT and PVSAT, 3 and 2-second versions of two parallel test forms were used. In the PVSAT, the PASAT stimuli were shown on a computer screen. Patients were also tested with the other two MSFC subtests, i.e. the nine-hole pegboard test and timed 25-foot walk test, to calculate MSFC scores. PASAT-3 correlated highly with both PVSAT-3 and PVSAT-2. MSFC-v scores calculated with PVSAT-2 and PVSAT-3 values correlated highly with MSFC scores calculated with PASAT-3 results. The results suggest that the PVSAT can be used as an alternative for the PASAT in the MSFC.

Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review

It is hypothesised that the autonomic nervous system responds differently to various stressors in patients with chronic fatigue syndrome (CFS) compared with healthy controls. The goal is to systematically review the scientific literature addressing the functioning of the autonomic nervous system in patients with CFS.

P300 and treatment effect of modafinil on fatigue in multiple sclerosis

To evaluate the value of visual and auditory P300 for predicting the response of multiple sclerosis-related fatigue to modafinil treatment, 33 patients were treated with 100 mg modafinil once daily for 4 weeks, following a 4-week baseline phase and an optional 8-week extension phase. The main clinical outcome parameter was a decrease in the fatigue visual analogue score (VAS) before and after 4 weeks of treatment. Patients with shorter auditory P300 latency at baseline were more likely to benefit from modafinil treatment. Auditory P300 latency predicted treatment response with a specificity of 76% and a sensitivity of 75% at a cut-off latency of 350 ms. Visual P300 latency could not be used to predict treatment response. Baseline auditory P300 latency predicted treatment response, whereas visual P300 latency did not. Clinical improvement did not correlate with changes in either visual or auditory P300.

Symptom Fluctuations and Daily Physical Activity in Patients With Chronic Fatigue Syndrome: A Case-Control Study

OBJECTIVES To compare the activity pattern of patients with chronic fatigue syndrome (CFS) with healthy sedentary subjects and examine the relationship between the different parameters of performed activity (registered by an accelerometer device) and symptom severity and fluctuation (registered by questionnaires) in patients with CFS. DESIGN Case-control study. Participants were asked to wear an accelerometer device on the nondominant hand for 6 consecutive days. Every morning, afternoon, and evening patients scored the intensity of their pain, fatigue, and concentration difficulties on a visual analog scale. SETTING Patients were recruited from a specialized chronic fatigue clinic in the university hospital, where all subjects were invited for 2 appointments (for questionnaire and accelerometer adjustments). In between, activity data were collected in the subjects normal home environment. PARTICIPANTS Female patients (n=67) with CFS and female age-matched healthy sedentary controls. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Accelerometry (average activity counts, peak activity counts, ratio peak/average, minutes spent per activity category) and symptom severity (intensity of pain, fatigue, and concentration difficulties). RESULTS Patients with CFS were less active, spent more time sedentary, and less time lightly active (P<.05). The course of the activity level during the registration period (P interaction>.05), peak activity, and the staggering of activities (ratio peak/average) on 1 day were not different between groups (P>.05). Negative correlations (-.242 varying to -.307) were observed for sedentary activity and the ratio with symptom severity and variation on the same and the next day. Light, moderate, and vigorous, as well as the average activity and the peak activity, were positively correlated (.242 varying to .421) with symptom severity and variation. CONCLUSIONS The more patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the previous day. The direction of these relations cannot be determined in a cross-sectional study and requires further study.

Self-Report Assessment of Fatigue in Multiple Sclerosis: A Critical Evaluation

SUMMARY Fatigue is among the most common and disabling symptoms of multiple sclerosis. Clinicians usually assess fatigue by asking people to describe and rate their fatigue in a self-report instrument. This paper evaluates the clinical usefulness and the scientific properties of a selection of various self-report instruments for fatigue. To be selected, instruments had to assess fatigue or a related concept, have some published information on reliability and validity, be used in at least one clinical trial of fatigue with people with multiple sclerosis, and demonstrate validity in people with MS. Five fatigue specific scales and four subscales of quality of life instruments were selected and evaluated. In occupational therapy, the fatigue subscales or items of quality of life measurements give limited information about the quality of fatigue. The selection of an instrument may depend on the clinical setting or trial design.