People with multiple sclerosis (MS), a progressive disease of the central nervous system (CNS), experience symptoms of demyelination such as muscle stiffness, paralysis of the involved extremities, fatigue, cognitive impairment, and psychological problems (Keller & Stone, 2009). These changes affect their occupational performance and social participation and necessitate medical and rehabilitative interventions. This article focuses on occupational therapy interventions aimed at impairment (e.g., exercise, cognition, emotional regulation), including programs (e.g., inpatient and outpatient rehabilitation) in which an occupational therapy practitioner was one member of the team. Part 1 focused on interventions within the scope of occupational therapy aimed at activity and participation (Yu & Mathiowetz, 2014).

Articles included in this review were the result of searches for articles published from January 2003 to May 2011. Detailed information about the methodology and a complete list of databases and search terms can be found in the article “Method for the Systematic Reviews on Occupational Therapy and Neurodegenerative Diseases” in this issue (Arbesman, Lieberman, & Berlanstein, 2014).

In addition to evaluating each article using the critically appraised paper format, we used the evaluation guidelines described in MacDermid (2004)  to provide quantitative ratings of the quality of each study. The first author rated the first 10 articles, and the second author checked for agreement. Any disagreements were resolved through discussion. Then the first author completed all of the reviews, and the second author randomly selected articles to check. The few disagreements were resolved again through discussion. A study scoring >80% of the total score (38 of 48) was considered to be of high quality. A study scoring 24–37 was considered to be of medium quality. Systematic reviews and meta-analyses were assigned a score of 48 because they represent the highest level of evidence. We calculated an average score for each intervention category to indicate the pooled strength of an intervention. Strong evidence of an intervention category was defined as an average score ≥38; moderate evidence was an average score of 24–37.

Of the 70 studies relevant to the focused question on occupational therapy–related interventions for people with MS, 42 were categorized as interventions aimed at the impairment level (i.e., client factors and performance skills). The targets of intervention were further classified as follows:

• Specific mental functions, including cognition (2 Level I and 6 Level II) and emotional regulation (5 Level I and 1 Level II)

• Motor and praxis skills, including exercise (14 Level I, 2 Level II, and 7 Level III) and motor training (3 Level I, 1 Level II, and 1 Level III; American Occupational Therapy Association, 2008).

Supplemental Table 1 (available online at http://ajot.aotapress.net; navigate to this article, and click on “Supplemental Materials”) contains summarized information of selected studies with the highest quality scores (MacDermid, 2004). However, two articles were not referenced in this article because one, a Level I study, investigated exercise adherence and the other, a systematic review article, did not specifically focus on occupational therapy interventions.

The cognition category consisted of interventions using computerized cognitive training (1 Level I and 2 Level II) and memory training (1 Level I and 4 Level II). Moderate evidence from high-quality studies supports the effectiveness of home-based, individualized, and computerized cognitive training programs for people with MS in improving cognitive function (average quality rating = 40, pooled sample size = 204). Moderate evidence of medium quality supports the effectiveness of memory training for this population (average quality rating = 33.8, pooled sample size = 230). Included studies demonstrated immediate effects in improving attention or memory performance. However, the long-term effects of these interventions and the relationship between improvement of client factors, performance skills, and functional performance remain unclear.

Individualized and computerized cognitive training programs may be an option for home-based intervention. Solari et al. (2004)  compared the effects of 8 wk of RehaCom memory and attention retraining with RehaCom visuoconstructional and visuomotor coordination retraining. Both groups showed immediate and short-term (16-wk) improvements in cognitive function measured by the Brief Repeatable Battery of Neuropsychological Tests (BRBNT). However, the memory and attention retraining group had significantly greater improvement in phonemic retrieval compared with the control group. Flavia, Stampatori, Zanotti, Parrinello, and Capra (2010)  reported immediate effects of 3 mo of training with RehaCom on information processing and decision making measured by the BRBNT. Shatil, Metzer, Horvitz, and Miller (2010)  indicated that people with MS may benefit from the 12-wk home-based, individualized, and computerized CogniFit Personal Coach program in improving memory performance. However, none of these studies explored the relationship between cognitive improvement and functional performance. Moreover, the long-term effect of computer-based training programs on cognitive function remains untested.

Several studies examined the effect of memory training for people with MS. Goverover, Chiaravalloti, and DeLuca (2008)  reported that participants who used self-generated functional task steps experienced better recall of the task steps and better actual task performance than those who were simply provided the task steps. Visualization and intermittent practice had immediate effects on learning (Chiaravalloti, DeLuca, Moore, & Ricker, 2005; Goverover, Hillary, Chiaravalloti, Arango-Lasprilla, & DeLuca, 2009), whereas no effect was found for knowledge of performance feedback (reminding; Chiaravalloti, Demaree, Gaudino, & DeLuca, 2003). Brenk, Laun, and Haase (2008)  suggested that a 6-wk home-based cognitive training may have an effect on short-term and working memory. No definite conclusions can be drawn regarding the effects of memory training for people with MS because of the diversity of training procedures used in these studies.

Strong evidence from high-quality studies supports interventions targeting emotional regulation for people with MS (average quality rating = 42.3, pooled sample size = 363). Group interventions based on cognitive–behavioral therapy (CBT) had positive effects for people with MS in reducing depression (Forman & Lincoln, 2010; Mohr, Hart, & Goldberg, 2003; Thomas, Thomas, Hillier, Galvin, & Baker, 2006). Interventions that combine education, multidisciplinary focus, goal setting, homework assignments, and discussion forums may provide added benefit for people with MS (Malcomson, Dunwoody, & Lowe-Strong, 2007). A group psychotherapeutic intervention and a social discussion group had similar beneficial effects on mood, self-efficacy, and resiliency compared with an information booklet group (Rigby, Thornton, & Young, 2008). Although individualized CBT had a positive effect on overall fatigue and fatigue severity, marginal significance was reported to differentiate its efficacy from a supportive–expressive group intervention and sertraline treatment (Mohr et al., 2003).

Evidence supporting the effect of relaxation and stress management interventions in improving emotional disturbances is limited because of poor methodological quality (Hughes, Robinson-Whelen, Taylor, & Hall, 2006; Malcomson et al., 2007).

Strong evidence from high-quality studies supports physical activity training (average quality rating = 42.3, pooled sample size = 1,410), strong evidence from medium-quality studies supports aerobic exercise (average quality rating = 34.1, pooled sample size = 275), and moderate evidence from medium-quality studies supports resistance training (average quality rating = 35.8, pooled sample size = 253) and yoga (average quality rating = 37.0, pooled sample size = 87) for people with mild to moderate MS. No studies reported symptom exacerbation attributable to exercise. Most proposed exercise protocols involved high training intensity of three times per week. However, various durations were used, ranging from 3–20 wk for clinic-based training to 6 mo for home-based protocols. Higher attrition rates were reported in studies with longer intervention durations. The most common type of training was aerobic exercise with or without additional training; however, the effect sizes varied (−0.29–3.50 for body function, −0.06–−0.48 for activity measures, and −0.36–2.56 for quality of life; Asano, Dawes, Arafah, Moriello, & Mayo, 2009).

Physical activity programs were beneficial for people with MS in improving muscle power, exercise endurance (Bjarnadottir, Konradsdottir, Reynisdottir, & Olafsson, 2007; Fragoso, Santana, & Pinto, 2008; Rietberg, Brooks, Uitdehaag, & Kwakkel, 2005), and mobility-related activities (walking ability; Freeman & Allison, 2004; Geddes, Costello, Raivel, & Wilson, 2009; Romberg et al., 2004). Greater effects were found when professionals were present, such as in inpatient and outpatient settings (Snook & Motl, 2009).

Aerobic exercise training included unloaded leg cycling, treadmill walking, and aquatic exercise (Ratchford et al., 2010; Roehrs & Karst, 2004; Schulz et al., 2004; Sosnoff, Motl, Snook, & Wynn, 2009; Surakka et al., 2004). Some programs used aerobic exercise combined with progressive resistance exercise. These programs demonstrated strong immediate effects in improving walking distance or endurance. Some studies indicated positive relationships between improved personal abilities and improvement in self-perceived quality of life or fatigue impact (Bjarnadottir et al., 2007; Cakt et al., 2010; McCullagh, Fitzgerald, Murphy, & Cooke, 2008; Rietberg et al., 2005; Roehrs & Karst, 2004).

Progressive resistance training for 6 to 8 wk significantly improved lower-extremity strength, walking speed, and walking endurance in people with mild to moderate MS (Ayán Pérez, Martín Sánchez, de Souza Teixeira, & De Paz Fernández, 2007; Cakt et al., 2010; DeBolt & McCubbin, 2004; de Souza-Teixeira, Costilla, Ayán, García-López, González-Gallego, & de Paz, 2009; Dettmers, Sulzmann, Ruchay-Plössl, Gütler, & Vieten, 2009; Romberg et al., 2004; White et al., 2004).

Yoga was found to be beneficial in improving balance (Freeman & Allison, 2004; Oken et al., 2004) and selective attention ability (Velikonja, Curić, Ozura, & Jazbec, 2010). However, because of different types of yoga used and a small pooled sample size, no conclusion can be drawn regarding the effects of yoga for this population.

Insufficient evidence supports the effect of exercise in reducing MS-related spasticity (Sosnoff et al., 2009) or disability (Velikonja et al., 2010; White et al., 2004). Additionally, most studies reported immediate effects; only 1 of the 23 exercise-related studies reported the longer term (≥3 mo) efficacy of a 12-wk endurance training (McCullagh et al., 2008). Limited evidence restricts the ability to draw conclusions regarding the short- or long-term efficacy of exercise interventions.

Two studies were aimed at balance training, including motor and sensory strategies (Cattaneo, Jonsdottir, Zocchi, & Regola, 2007) and torso weighting (Widener, Allen, & Gibson-Horn, 2009), and 2 were focused on task-specific training through robot-based rehabilitation (Carpinella, Cattaneo, Abuarqub, & Ferrarin, 2009) and constraint-induced movement therapy (Mark et al., 2008). People with MS may benefit from balance training using motor and sensory strategies. Participants showed improved motor coordination after receiving a robot-based rehabilitation program, and those who received constraint-induced movement therapy demonstrated improvement in all upper-extremity motor function. Although the evidence is limited, task-specific functional training is suggested as an appropriate approach for motor learning for people with MS. No overall conclusion can be drawn for motor training because of the diversity of interventions and the limited studies targeting this population.

The purpose of the second part of the systematic review was to examine evidence for the effectiveness of occupational therapy–related interventions aimed at remediating impairment in cognition, emotional regulation, and motor and praxis skills for people with MS. Most studies reported immediate effects on the targeted outcomes. Few investigated short- and long-term effects of the interventions or the relationships between client factors and functional performance. In addition, most of the studies were conducted by researchers from disciplines other than occupational therapy. More research on the effectiveness of occupational therapy interventions at the impairment level is essential and needs to be conducted by occupational therapists as part of the research team.

People with MS may improve cognitive function through home-based, individualized, and computerized cognitive retraining programs. However, most cognitive retraining interventions in this review showed only immediate effects in improving attention and memory abilities, and insufficient evidence supported the retention of learned abilities. In addition, only 1 study examined functional performance (i.e., activities of daily living) in a natural context (Goverover et al., 2008). Thus, it is unknown whether the demonstrated improvements in memory and attention can be generalized to problem solving in the real world.

CBT-based psychological interventions in a group format had strong supporting evidence for reducing depression in people with MS. Two studies reported 3-mo postintervention efficacy (Forman & Lincoln, 2010; Hughes et al., 2006). Only 1 study investigated the effect of individualized CBT-based intervention, and marginal support was found for this type of intervention in reducing fatigue compared with a supportive–expressive group and sertraline treatment (Mohr et al., 2003). More research investigating the efficacy of CBT-based psychological interventions in an individual format is required. More important, the need remains to evaluate the short- and long-term efficacy of group and individualized CBT-based interventions on psychological variables and functional performance.

Moderate evidence supports the effectiveness of exercise interventions in improving walking performance, endurance, and lower-extremity muscle strength and self-perceived quality of life for participants with mild to moderate MS. No study examined the effect of upper-extremity exercise training for this population. Additionally, it remains unclear whether the effects of exercise interventions persist over the long term.

People with MS often experience symptoms of CNS dysfunction such as spasticity, muscle stiffness, and paralysis of involved extremities. Motor training approaches have been used to address these types of limitation in other populations; however, the limited quantity of this type of study and the diversity of interventions restricted our ability to draw conclusions regarding the effects on people with MS. More research should investigate the effectiveness of interventions that use motor training.

The results of Part 2 of this systematic review indicate that occupational therapists should be cautious about their choice of impairment-based interventions. Interventions included in this review showed immediate effects on the targeted outcomes, but few investigated short- and long-term effects. Moreover, the relationship between client factors, performance skills, and functional performance has not been well explored. In addition, most studies were not conducted by occupational therapy researchers. The need is great for additional research on the efficacy of impairment-level occupational therapy interventions for people with MS.

In summary, the findings of this review have the following implications for occupational therapy practice with people with MS:

• Occupational therapy practitioners should encourage people with MS to develop strategies for recall of task steps and can use individualized and computerized telerehabilitation programs as an extension of cognitive training.

• Practitioners can use group CBT-based intervention to improve depression and self-efficacy in participants with MS. Additional improvement can be expected when CBT-based intervention is combined with goal setting, education, multidisciplinary programs, home assignments, and discussion forums.

• Evidence supports exercise interventions to improve endurance, lower-extremity muscle strength, and walking performance. Occupational therapists may incorporate exercise concepts such as gradual increase, low intensity, and repetition to develop a program involving the whole body for people with MS.

This project was supported in part by the American Occupational Therapy Association. Thanks to Deborah Lieberman and Marian Arbesman for their guidance and support throughout the process of this review.

*Indicates studies that were systematically reviewed for this article.