Behavioral Interventions in Multiple Sclerosis

A Biopsychosocial Perspective

C Heesen; S Köpke; J Kasper; J Poettgen; A Tallner; DC Mohr; SM Gold


Expert Rev Neurother. 2012;12(9):1089-1100. 

In This Article

Current status of BI in MS

Exercise Training & Sports

In 2006, we reviewed the current status of exercise training in MS under the provocative title of a 'putatively disease-modifying treatment'. Since then, a few small and short-term new studies, most of them in MS patients with minor disability, have been conducted and several recent reviews and meta-analyses have been published; see Motl and Gosney,[34] Asano et al.[35] and Dalgas et al.[36] (Table 1).

Based on these studies, a shift has occurred moving away from the old paradigm that physical activity might be detrimental in MS.[37] In fact, there is now clear evidence that exercise improves quality of life, mood and motor performance including walking speed and distance, muscle strength and coordination.[34,38,39] In addition, exercise seems to be one of the two approaches that can improve fatigue.[40]

In contrast to the well-established symptomatic effects of exercise in MS, the impact of exercise on the disease process itself has not been studied directly, and Dalgas and Stenager[41] concluded that there is only "the possibility of a disease-modifying potential". Positive effects of exercise training on cognitive functioning and the potentially underlying 'neuroprotective' pathways have received increased attention in aging and psychosomatic research.[42,43] While the exploration of exercise as a therapy for cognitive dysfunction in MS is clearly warranted,[44] only Oken et al. have so far examined cognitive functioning following exercise training in MS and, unfortunately, found no effects, possibly due to the low-intensity training in their study.[45] Recently, however, new evidence from cross-sectional studies supported the rationale for exercise in MS.[46,47] In a series of studies, Prakash et al. compared active and inactive MS patients on MRI. The cohort included 21 patients with minor disability. While major disease factors such as disease duration and disability were comparable, more active patients showed higher gray matter densities as measured by intensity on T1-weighted images. Additionally, diffusion-tensor imaging subtraction images show areas of higher fiber track integrity in trained individuals. Interestingly, morphological changes were associated with information processing as measured by the Symbol-Digit-Modalities test. In addition, the group could demonstrate in another cohort[46] that trained patients had higher resting state connectivity in hippocampal connections correlating with a better performance on memory tests. However, this evidence should be considered preliminary since the cohorts were small and no intervention effects have been studied.

To date, very few studies have addressed the major research challenges regarding exercise and MS as outlined by Rietberg et al.[48] or Rasova et al..[49] Most importantly, these concern the exact composition and intensity of the training depending on disease stage, the maintenance and adherence issue, and the heterogeneity of the outcomes used. Another important task for future research is to develop biopsychosocial approaches to initiate and maintain physical activity participation in individuals with MS. Here, the first promising results have been reported for internet-based interventions that warrant further investigation.[50]

Patient Information Interventions

The unbiased, neutral and understandable presentation of scientific evidence has been referred to as evidence-based patient information (EBPI),[51] which allows patients to make 'informed choices' for important healthcare decisions. Ideally, this should be combined with evidence-based decision support using decision aids[52] and/or decision coaches.[53]

Recently, Bunge et al.[31] summarized the main principles of EBPI comprising, for example, information about the quality of evidence concerning a potential decision, reporting of patient-oriented outcome measures, presentation of numerical data, equal presentation of positive and negative effects, as well as provision of 'meta-information'; for example, about potential conflicts of interest. Coulter and Ellins[54] have shown in a systematic review that the provision of EBPI can improve risk knowledge, use of health services, health behavior and health status, although the evidence base remains weak.

In MS, few studies have rigorously studied the effects of patient information. Since 2001, we have evaluated risk communication and decision-making in MS based on the concept of EBPI aiming to facilitate informed patient choice such as allowing patients to make treatment decisions based on their individual disease concepts and not simply on physicians' recommendations. We recently summarized our own controlled studies[55] and are currently systematically reviewing the evidence in a Cochrane review.[56] Apart from assessing outcomes closely related to information provision, such as knowledge, satisfaction with care and decisional conflict as well as enhanced quality of life, only four of the eight included trials[57–60] also assessed behavioral change. Only one of these clearly showed an effect on behavior: a patient education program about relapse management in MS.[59] Here, after attending a 4-h group education session and provision of a preparatory information booklet, educated patients reported fewer steroid treatments, fewer inpatient treatments and more high-dose oral steroid treatments (Figure 1). Additionally, there were fewer encounters and telephone calls with physicians supporting the concept of enhanced self-management abilities. Finally and importantly, as a possible result of improved self-management and gain of control, educated patients showed significantly fewer relapses (1.9 in the intervention group vs 2.7 in the control group) in 2 years of follow-up. In 2010, Solari et al. published a trial intervening at the stage of MS diagnosis. Provision of an additional hour with a physician and a structured DVD-based information aid lead to substantial improvements in disease knowledge as well as in satisfaction with care, which persisted up to 6 months (Table 2).[61]

Figure 1.

Effects of relapse self-management training. Displayed are relapse treatment regimens in (A) the control group (n = 73) and (B) the intervention group (n = 77).
iv.: Intravenous.
Data taken from [59].

Cognitive-behavioral & Acceptance-oriented Approaches

Cognitive-behavioral treatment (CBT) has been studied in MS for more than 20 years. Much of the research on CBT in MS has focused on the treatment of depression.[62] Cognitive-behavioral theory posits that cognition, emotion and behavior all interact, such that change in any of the systems might induce changes in the others. When treating patients with chronic illness such as MS, this conceptualization has been extended to include physiological functioning.[63] Enhancing coping strategies in general as well as fatigue management have also been addressed in CBT. In a Cochrane review Thomas et al. concluded that there is some evidence that CBT ameliorates depression and enhances coping strategies in MS in general and particularly in the context of cognitive dysfunction.[64] In 2010, Dennison and Moss-Morris reviewed the status of CBT in MS.[65] Three major achievements in the field have been published since then (Table 3).[66–68]

One of the most elaborate recent CBT studies has been a combined individual face-to-face and telephone intervention to manage fatigue in a randomized controlled trial (RCT) compared with a nonspecific group-based control intervention.[68] Here, the authors could show a substantial improvement of fatigue self-ratings after 8 weeks. On the other hand, very few authors have tried to study the effects of CBT on disease evolution in MS. Providing a rationale for such an approach, Mohr et al. had earlier demonstrated that psychological stress is associated with inflammatory activity on MRI in an observational study.[13] They recently completed the first RCT of a stress management intervention with an MRI outcome.[67] Individual stress-management training during 24 weeks led to significantly fewer new brain lesions on MRI, relative to a wait-list control condition and a higher percentage of patients remaining lesion free during the intervention period. However, effects disappeared rapidly after the end of the intervention. In addition, the study did not clarify whether the effects were due to the specific stress management treatment or whether they were the result of other nonspecific factors such as attention or social support.

Self-management and health promotion are concepts related to CBT. Recently, Plow et al. reviewed studies to enhance self-management.[29] They found 27 studies, 13 of which included RCTs addressing fatigue (n = 12), coping/depression/stress management (n = 10) and medication management (n = 6). Most studies were small and comparisons between different interventions are largely lacking.

Online treatment tools have recently been implemented using CBT approaches with encouraging results. In fact, online tools are highly attractive as they are easily accessible and can be tailored to individuals' resources.[69] However, comparative studies on telephone, face-to-face or group interventions are lacking.

While most CBT interventions aim to enhance active problem-oriented coping strategies, other approaches are more emotion-focused or acceptance oriented. For example, mindfulness, a concept that goes back to the neurobiologist Kabat-Zinn,[70] has been implemented as such an approach in psychiatric conditions. Grossmann et al. recently studied mindfulness in a RCT in MS.[66] Patients trained for approximately 1 h per day for 8 weeks, which resulted in improved quality of life and reductions in depression and fatigue. Unfortunately, neither cognitive measures nor any functional or structural measures (e.g., MRI) were included in this study.

A number of questions regarding CBT interventions remain. It is unclear what the effects of online treatments are relative to standard treatments, and the role they might play in different healthcare delivery systems. It is also unclear whether therapists must be mental health professionals. Both nurses and MS patients have been preliminarily studied as potential treatment providers.[71,72] In addition, questions regarding the psychological mechanisms underlying the therapeutic effects remain: Is it inducing behavior change? Is it working through relationship and empathy? Is it modification of thoughts and feelings? A study by Mohr et al. indicates that a CBT approach might be superior to a just supportive, empathy-oriented approach.[71] Most studies have used samples that excluded more severely disabled, nonambulatory patients so the question of whether and how these interventions might work in advanced MS is an open issue. A major question is how cognitive deficit may influence the therapeutic effects. Here, Mohr et al. indicated that neither brain lesion load nor cognitive impairment are predictors for treatment effectiveness; however, cognitive impairment and greater lesion load did predict poorer maintenance of treatment gains after the cessation of treatment.[73] As research has shown the relevance of social support, more work on the inclusion of peers is needed. Cohort data from Messmer Uccelli et al. indicate that an 8-week guided peer support group did not improve quality of life or depression.[74] However, the train-the-trainer part was only a 1-day course.

Cognitive Training Interventions

Cognitive training might be considered as a special CBT approach aiming at regaining cognitive function. It is often named neuropsychological rehabilitation. Two recent Cochrane reviews assessed cognitive training interventions[75,76] and concluded that, at present, evidence for effectiveness is weak. However, both reviews explain that their conclusions are based on trials of weak methodology and therefore are far from definitive. Rosti-Otajärvi and Hämäläinen[76] analyzed 14 RCTs with acceptable methodology. Cognitive training was found to improve memory span, working memory and immediate visual memory but the evidence was considered 'low level'. Both reviews emphasize the need to increase the methodological quality for future studies. Specifically, Rosti-Otajärvi and Hämäläinen[76] requested:

  • Detailed reporting of the most essential disease variables;

  • Determining the aim of the intervention beforehand and measuring it with the primary measure;

  • Detailed reporting of the contents of the interventions;

  • Detailed reporting of the basic statistics and outcome assessment timing;

  • The use of outcome measures which more extensively reflect everyday functioning and the generalization effects of the interventions, thus enabling the assessment of the achievement of individual rehabilitation aims related to everyday functions;

  • Longitudinal follow-ups to evaluate the permanence of the treatment effects.