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Disease-Modifying Therapies During the COVID-19 Outbreak

 To access the article and evaluation online, go to https://www.highmarksce.com/mscare.

 The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, pharmacists, researchers, and other health care providers involved in the study and management of patients with multiple sclerosis (MS).

Review current research, including limitations, of the potential cognitive impacts of polypharmacy and anticholinergic burden in individuals with MS.

Evaluate potential cognitive risks associated with polypharmacy and anticholinergic burden using tools such as the Drug Burden Index to guide decision-making in the development of comprehensive treatment plans.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Intellisphere, LLC. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education, the Accreditation Council for Pharmacy Education, and the American Nurses Credentialing Center, to provide continuing education for the health care team.

This activity was planned by and for the health care team, and learners will receive 1.0 Interprofessional Continuing Education credit for learning and change.

 The CMSC designates this journal-based activity for a maximum of 1.0 

. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

 The CMSC designates this enduring material for 1.0 contact hour of nursing continuing professional development (1.0 in the area of pharmacology).

This knowledge-based activity (UAN JA4008165-9999-24-004-H01-P) qualifies for 1.0 contact hour (.01 CEUs) of continuing pharmacy education credit.

 The CMSC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. The activity is designated for 1.0 AAPA Category 1 CME credits. PAs should only claim credit commensurate with the extent of their participation.

 It is the policy of the CMSC to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated.

, has served as physician planner for this activity. He has disclosed no relevant financial relationships. 

, has disclosed not relevant financial relationships. 

, has disclosed financial relationships with Atara Biotherapeutics, Biogen, Bristol Myers Squibb, Immunic, Novartis, Pipeline, Roche, Sanofi, TG Therapeutics, and UCB (researcher). Authors 

Joanie Huebner, PhD; Jade Robichaud, BA; Julia S. Cozart, MA;

, have disclosed no relevant financial relationships.

At the time of this research and authorship, author 

, disclosed no relevant financial relationships. Subsequent to the selection of this paper for publication and continuing education credit, she began an employee relationship with Astra Zeneca.

, CMSC, and Intellisphere, LLC who are in a position to influence content have disclosed no relevant financial relationships. 

 CMSC continuing education director, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships.

Release Date: March 1, 2024; Valid for Credit through: March 1, 2025

(1) Review the continuing education information, including learning objectives and author disclosures.

(3) Complete the evaluation, which is available at https://www.highmarksce.com/mscare.

Statements of Credit are awarded upon successful completion of the evaluation. There is no fee to participate in this activity.

 This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the US Food and Drug Aadministration. The CMSC and Intellisphere, LLC do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Intellisphere, LLC.

 Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.

Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS.

We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models.

Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (

 < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR

Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

From the Department of Community and Family Medicine, University Health Lakewood Medical Center, University of Missouri–Kansas City, Kansas City, MO (JH); Department of Biomedical and Health Informatics, School of Medicine, University of Missouri–Kansas City, Kansas City, MO (JR, JSC, JMB); Department of Psychology, University of Missouri–Kansas City, Kansas City, MO (JSC); Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, MO (CB); Department of Neurology, University of Kansas Medical Center, Kansas City, KS (SGL); and the Departments of Neurology and Psychiatry, University Health Truman Medical Center, Kansas City, MO (JMB). 

Joanie Huebner, PhD, University Health Lakewood Medical Center, 7900 Lee’s Summit Rd, Kansas City, MO 64139, USA; 

The authors would like to express our thanks to those who worked alongside us to make this research possible. In particular, we extend our gratitude to Joan McDowd, PhD, and Joah Williams, PhD, for their support, suggestions, and feedback.

Sharon Lynch, MD, has reported receiving funding in multicenter MS drug trials from Anokion, Atara Bio, Bristol Myers Squibb, Celgene, EMD Serono, Novartis, Roche, Sanofi, and TG Therapeutics. All other authors disclosed no relevant financial relationships at the time of the research and writing of this publication. Subsequent to the selection of this paper for publication and continuing education credit, Crystal Burkhardt, PharmD, began an employee relationship with Astra Zeneca.

This study was financially supported by awards from the UMKC Women’s Council Graduate Assistance Fund: the Mary F. Merryman Award in Memory of Grace Greenwood Duncan, the Martha Jane Starr Award, and Frances E. Clark Merit Recipient award.

Portions of the results of this study were presented as a poster at the European Committee for Treatment and Research in Multiple Sclerosis; October 2022; Amsterdam, The Netherlands.

Individuals with multiple sclerosis (MS) experience a wide array of symptoms caused by focal lesions and diffuse neurodegeneration in the central nervous system. It is common for patients to use a disease-modifying therapy (DMT) to slow disease progression as well as treatments for a variety of physical, cognitive, and emotional symptoms.

 For this reason, polypharmacy is a considerable concern for individuals with MS.

Polypharmacy refers to the concurrent use of multiple medications

; it is most commonly quantified in the literature as 5 or more daily medications. Evidence suggests that polypharmacy is associated with adverse health outcomes in those of advanced age, including increased falls, cognitive impairment, and hospitalizations due to drug adverse events.

 Certain types of medications, including those with anticholinergic properties, are particularly hazardous.

 Compared to older adults, individuals with MS represent a similar yet unique population that is vulnerable to polypharmacy effects, yet the literature on this topic is sparse. Our previous research suggests that polypharmacy is associated with subjective cognitive difficulties in MS; however, a consistent relationship with objective cognitive measures was not observed.

Cognitive abnormalities often emerge as a direct consequence of MS disease pathology, affecting between 40% to 70% of patients.

 Notably, difficulties with cognition can arise at any stage of the disease and tend to persist or worsen over time.

 Common cognitive domains affected in MS include information progressing speed, executive function, and working memory, and these deficits can consequently impair visuospatial abilities and verbal fluency.

 Cognitive symptoms are linked to a range of adverse outcomes in MS, such as problems with activities of daily living, employment, and completing daily household tasks.

The present study examines the relationship between polypharmacy and objective cognitive performance in adults with MS while accounting for demographic and disease-related factors. We hypothesized that polypharmacy would be negatively associated with cognitive performance, such that people taking more medications would demonstrate poorer performance on objective measures of cognition. We also explored whether anticholinergic burden scales could predict cognitive performance after controlling for relevant covariates.

We recruited 90 participants with MS through a large MS specialty clinic affiliated with the University of Kansas Medical Center. Additional recruitment methods included referrals and flyers posted in the clinic. Participants received a $25 Amazon gift card as compensation for their participation. Criteria for inclusion included (1) a confirmed MS diagnosis based on established criteria

 from a board-certified neurologist; (2) no nervous system disorder other than MS; (3) no severe sensory, motor, physical, or neurological impairment that would make participation in the study insurmountable; (4) no history of learning disability; (5) no MS relapse and/or corticosteroid treatment within 4 weeks of evaluation; and (6) access to stable internet in a private location for Zoom teleconferences.

Study personnel approached patients with MS while they were attending their routine clinical visits. Upon introduction and a brief description of the research, study personnel assessed patients’ interest in study participation and asked additional screening questions. Eligible and interested patients provided written informed consent, gave their contact information, and scheduled a time to complete the study assessment and questionnaires with the researcher. Out of an abundance of caution during the COVID-19 pandemic, all data collection occurred via telehealth. A battery that could be administered virtually was compiled and included measures across several domains of cognitive functioning that are commonly affected in patients with MS, such as information processing speed, executive functioning, and working memory. The validity and reliability of online assessments using our selected measures has been established in adults with and without cognitive impairment,

 Participants completed the cognitive assessment portion via Zoom or by telephone if online audio/video connectivity was poor. To ensure that mode of test administration did not unduly influence participant test performance, method of participation was examined as a covariate in analyses. Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the University of Missouri–Kansas City.

 All procedures were approved by the institutional review boards of the University of Missouri–Kansas City and the University of Kansas Medical Center.

Participants provided a complete list of all medications used daily (including both prescription and over-the-counter drugs), which were tallied to yield the total number of medications (med count). Medications prescribed as prn were only included in analyses if the participant reported taking the medication within 24 hours prior to the testing session. For each medication, participants provided the dosage, frequency, route of administration, date/time of last dose taken, and percentage of doses missed.

The Anticholinergic Burden Calculator (www.anticholinergicscales.es) was used to derive numerical values and qualitative labels (eg, low/medium/high risk) for 3 rating scales thought to be associated with cognitive functioning

 the Anticholinergic Cognitive Burden (ACB) Scale,

 For each scale, higher scores indicate increased possibility of anticholinergic impact.

Verbal memory was assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R).

 We assessed sequential set-shifting with the oral Trail Making Test (OTMT), trials A (processing speed; OTMT-A) and B (executive functioning; OTMT-B).

 The Digit Span test is a subtest of the Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV).

 Measures of verbal fluency included both semantic and phonemic fluency tasks.

 All measures utilized have been validated for use in individuals with MS.

Participants completed the Patient-Determined Disease Steps (PDDS),

 a self-reported measure of disability based on motor and ambulatory dysfunction. The PDDS has 9 levels that range from 0 (normal) to 8 (bedridden). PDDS scores correlate strongly with the Expanded Disability Status Scale (EDSS) and are a valid patient-reported outcome of disability in individuals with MS.

We assessed the presence of comorbid health conditions via the Comorbidity Questionnaire for MS, which is validated for use in individuals with MS.

 A supplementary list of comorbidities was also produced to account for other common conditions experienced in the MS population, such as sleep disorder and genitourinary disease; the additional comorbidities were drawn from Cumulative Illness Rating Scale

; Comorbid Medical Conditions Questionnaire

; Self-Administered Comorbidity Questionnaire

; and the discussion section of “Validation of a Self-Report Comorbidity Questionnaire for MS.”

 For each patient-reported comorbid condition, follow-up questions included, “What year were you diagnosed?” and “Is this condition currently being treated?” The total number of comorbid conditions per person was tallied to yield a comorbidity score.

Participants reported the month and year of their MS diagnosis as well as their MS subtype (subtype confirmed by SGL). Demographic information included age, sex, education, ethnicity, and employment status.

A composite variable was created for all cognitive measures (ie, HVLT-R Learning, digit span forward [DSF], digit span backward [DSB], OTMT-A, OTMT-B, Phonemic Fluency, and Semantic Fluency) to reduce the number of analyses and thereby decrease the likelihood of family-wise error. This was achieved by transforming the raw scores to standardized z scores, summing the z scores for each measure, and dividing by 7 (ie, the total number of tests). We used negative z scores for OTMT-A and OTMT-B, as higher scores indicate slower performance. This statistical approach has been used frequently in the literature.

 We obtained zero-order correlations using Spearman rank correlation (

); bootstrapping was performed for 1000 samples, yielding 95% CIs for each correlation. Stepwise regression analyses estimated the predictive utility of the polypharmacy indices on the objective cognitive measures. For each model, multiple checks for potential violations of the assumptions for regression analysis were performed. We assessed the normality of residuals by examining predicted probability plots. The assumption of independent errors was checked by examining the Durbin-Watson test statistic. Homoscedasticity was assessed by visual inspection of scatterplots of the predicted values and residuals. We assessed multicollinearity by examining variance inflation factor values.

Analyses were conducted using IBM SPSS Statistics for Windows, Version 27.0. The threshold for statistical significance was set at 

 (all supplemental material is available in a PDF at the end of the online article) illustrates the enrollment of participants in the study. Demographic and clinical data are presented in 

, respectively. The study sample included 90 adults with MS. Participants were mostly female (78.9%), White (87.8%), and diagnosed with RRMS (73.3%). Average participant age was 50.71 ± 11.68 years. The median level of disability as measured by PDDS was 2 (IQR = 1, 4). On average, participants took 4.78 ± 3.67 daily medications (range 0-14), and 44.4% (n = 40) met the criteria for polypharmacy. The most common drug categories reported in the sample were DMTs (n = 50, 55.6%), analgesics (n = 42, 46.7%), and antidepressants (n = 40, 44.4%). The most common specific medications in the sample were baclofen (n = 26, 28.9%), gabapentin (n = 17, 18.9%), and levothyroxine (n = 14, 15.6%).

On average, participants reported 3.39 ± 2.87 comorbidities (range 0-13). The most frequent comorbidities were hypertension (n = 28, 31.1%), depression (n = 28, 31.1%), hyperlipidemia (n = 27, 30%), anxiety (n = 17, 18.9%), and migraine (n = 16, 17.8%).

All polypharmacy indices were significantly correlated with each other, with moderately strong (

 displays the correlations between the polypharmacy indices and cognitive performance. Six participants completed the cognitive testing by telephone due to connectivity problems. There were no significant differences in performance based on mode of administration. A greater degree of polypharmacy and anticholinergic burden was associated with worse cognitive performance, with values ranging from 

 < .001 (DBI). Post hoc correlations (Table 1) between the polypharmacy scales and each cognitive test were performed to assess whether specific domains of cognition were driving the significant relationships. The polypharmacy indices were more consistently associated with measures of processing speed, attention, and phonemic fluency.

A linear regression was used to examine whether polypharmacy indices predicted composite cognitive performance while controlling for other variables known to be associated with both polypharmacy and cognition. Age, education, disease duration, and comorbidities were entered as covariates in the first block. Polypharmacy indices were entered in the second block using a stepwise method (

). The initial model containing the covariates was significant and explained nearly 20% of the variance in cognitive composite scores, 

 = .003) were both significant predictors in the model. In the second model, DBI was retained and associated with an additional 12% of explained variance (

 = .119). These results suggest that an individual’s score on the DBI can predict a significant portion of variance in the cognitive composite score, such that for every unit of increase on the DBI index, the cognitive composite z score decreases by .209.

Few studies have directly examined polypharmacy in the MS population, and none have examined the potential utility of anticholinergic burden scales in predicting objective cognitive performance. Approximately 44% of the present sample met the criteria for polypharmacy, and DMTs were the most frequently used medications. However, the most commonly reported medication was baclofen, a skeletal muscle relaxant that is commonly used to treat spasticity in MS (and, notably, has considerable anticholinergic properties).

The relationship between anticholinergic medications and cognitive adverse effects in advanced age is well documented across a variety of clinical conditions.

 However, this phenomenon warrants further attention in the MS population. Anticholinergic medications are the first-line treatment for common MS symptoms, such as bladder dysfunction. In a comparison of patients with MS who were and were not using anticholinergic medication for bladder symptoms, Cruce and colleagues reported that anticholinergic users performed significantly worse on measures of processing speed and verbal learning when compared with nonusers.

 This effect remained robust after controlling for age, gender, and disability. More recently, Morrow et al

 used a prospective matched-cohort study to examine the effect of anticholinergic medication on objective cognitive performance in an MS sample. Cases and controls completed a comprehensive neurocognitive battery prior to starting anticholinergic medications and again after 12 weeks. While controls improved on the cognitive measures (consistent with practice effects), the performance of individuals taking anticholinergic medication remained unchanged.

This is the first study to utilize anticholinergic burden scales in the MS population. We compared the number of daily medications to scales that estimate the amount of anticholinergic burden in each participant’s medication regimen. While the ACB and ADS apply numeric ratings to broad lists of medications based on relative anticholinergic activity, the DBI accounts for both sedative and anticholinergic effects and adjusts for medication dosages. We anticipated that scores on these scales (as well as the number of medications) would be highly correlated. This was confirmed, with Spearman correlation coefficients yielding large effect sizes. Of the 3 anticholinergic scales utilized in this study, the DBI yielded the strongest relationship with total number of medications (

Each anticholinergic scale was significantly correlated with the cognitive composite score with moderate to large effect sizes. When examining the relationships between the polypharmacy indices and individual cognitive measures, all scales were correlated with measures of processing speed, attention, and phonemic fluency. This is consistent with the patterns of impaired cognitive performance reported in the studies by Cruce et al

We then entered all 4 polypharmacy indices in a linear regression to predict cognition, while accounting for the effects of age, disease duration, education, and number of health comorbidities, as these factors are known to be associated with cognitive performance. Our results suggest that the DBI may be useful in predicting objective cognitive performance in adults with MS, as it accounted for roughly 12% of additional variance in cognition above and beyond known covariates. No other polypharmacy index was retained in the regression analysis. Compared to the other polypharmacy indices, the DBI may be best suited to predict cognitive problems due to the inclusion of sedative effects and medication dosage in its calculation of anticholinergic burden.

The relationship between DBI and cognitive performance is inconsistent in the literature. One report found that higher DBI scores were associated with poorer performance on a brief cognitive screening tool in a sample of community-dwelling men ages 70 and older.

 However, another study with a very similar sample found no significant relationship between the DBI and measures of cognitive performance.

 In a sample of diabetic adults, researchers found that DBI scores were associated with poorer memory performance, but only among older adults (> 55 years) in the sample.

 It is possible that such heterogeneous results are attributable to variance in study samples and methods of cognitive assessment.

The current findings are somewhat contrary to our previous work, which found very few differences in objective cognition based on polypharmacy status.

 This discrepancy may be a function of the different cognitive measures utilized in the studies. In our 2014 study, participants completed a battery of assessments during a traditional paper-and-pencil testing session.

 Of these measures, polypharmacy was associated with poorer performance on a measure of prospective memory; however, no other cognitive measures were significantly related to polypharmacy. Due to safety concerns during the COVID-19 pandemic, the present study utilized a different set of cognitive tasks that were appropriate for virtual administration.

Besides utilizing different measures than our 2014 study, the present investigation also computed a composite score based on standardized z scores of the individual cognitive measures, rather than examining each test separately. We also accounted for comorbidities using a more standardized method than in our previous investigations. The most frequently reported comorbidity was hypertension, consistent with our previous research.

Another notable difference between the present study and our prior work is the composition of the study samples. Our 2014 study was a secondary data analysis of an investigation examining DMT adherence that followed participants for 8 weeks after an initial in-person assessment visit. In contrast, the present study consisted of just 1 virtual study visit and did not require the use of a DMT. It is possible that individuals who agreed to participate in the more intensive study vary systematically from those who participated in the current study, which was less demanding of participants’ time and energy.

We recognize several limitations in this study. Generalizability of our results may be limited, given our study sample and the exclusion criteria used in participant recruitment. We excluded individuals with severe motor, sensory, cognitive, or physical impairments that would make study participation insurmountable. Participants were required to have no nervous system disorder other than MS, no history of learning disability, and access to a computer or tablet with a stable internet connection. It is possible that individuals who agreed to participate in the study differ in certain characteristics compared to individuals who declined to participate, such as free time/availability, aversion to cognitive testing, or capacity to engage with technology. The use of virtual data collection due to COVID-19 precautions limits the generalizability of our results to certain demographic groups. For instance, individuals with lower degrees of technological literacy (whether due to older age, poorer cognitive functioning, or socioeconomic status) may be less likely to access and accurately navigate online applications.

Due to the study’s inclusion and exclusion criteria, our sample included relatively few people with more severe disability. This is noteworthy, as individuals with a progressive disease course tend to demonstrate greater cognitive impairment than those with RRMS

 and are more susceptible to polypharmacy and comorbidities.

 Similarly, our sample included relatively few adults over 70 years of age. It is well established in the literature that increased age is associated with polypharmacy and comorbidities, and age-related physiological changes make older adults especially vulnerable to adverse effects related to polypharmacy and anticholinergic medication use.

Another limitation is related to the virtual data collection method, which precluded the use of certain cognitive tests that are relevant in MS. For instance, measures with visual components are ubiquitous in the traditional assessment of cognition in MS. However, we could not utilize such tests in this study, as we had no way to standardize screen sizes on participants’ computers/tablets or similarly control the testing environment to the degree that is standard in face-to-face assessment. This limitation prevented our ability to measure aspects of visuospatial functioning or utilize certain tests that are known to be sensitive to cognitive impairment in MS. Future studies would benefit from a more comprehensive test battery that includes visually mediated measures, ideally administered in person.

We acknowledge that, due to this study’s correlational and regression-based design, causality cannot be directly addressed. However, ethical implications would preclude methodologies involving randomization of participants to polypharmacy conditions. Alternatively, future longitudinal studies that randomly assign participants to medication review or adjustment may be useful in determining the causal nature of these findings and further inform clinical care. If such studies demonstrate improved cognitive outcomes following medication reduction or reduced anticholinergic load, it may be beneficial to establish clinical guidelines that balance the pros and cons of multidrug therapies and anticholinergic medication use to treat the symptoms of MS. Other potential benefits of reduced medication burden may include reduced medication costs and improved treatment adherence, as demonstrated in other clinical populations.

Overall, our study provides sufficient evidence to suggest that polypharmacy is associated with poorer objective cognitive performance in MS. Furthermore, our results point to the DBI as a useful tool for predicting cognition based on an individual’s medication list. Broadly, clinicians and researchers should account for polypharmacy and anticholinergic effects when evaluating cognition in MS. Tools such as the DBI can allow for quick calculation of anticholinergic burden, which may be clinically addressed by performing a medication review with patients. Although the complex issue of polypharmacy in MS warrants further study, the current findings provide a springboard for future research and clinical considerations.

Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis

This study aims to evaluate the feasibility of an occupation-based intervention (OBI) on dexterity and occupational performance for people with multiple sclerosis (MS) and to gather preliminary efficacy data.

In this feasibility study, 2 women with MS participated in 12 OBI sessions that focused on increasing upper extremity function. The Canadian Occupational Performance Measure, 9-Hole Peg Test, Expanded Disability Status Scale, Montreal Cognitive Assessment, and Fatigue Severity Scale (FSS) were used as outcome measures. The scores of these assessments are reported descriptively.

According to preliminary data, both participants demonstrated improvements in dexterity, occupational performance, and occupational performance satisfaction. These data suggest that OBI may be implemented effectively in Iran.

OBI improved the functional use of the participants’ upper extremities as well as their occupational performance and satisfaction with their occupational performance in each of the 2 women with MS. This preliminary intervention program should be further tested using randomized controlled trials.

From the Department of Occupational Therapy, School of Rehabilitation, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (SA); Department of Occupational Therapy, School of Rehabilitation Sciences, Rofeideh Rehabilitation Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (NA); Department of Occupational Therapy, Faculty of Rehabilitation, Tabriz University of Medical Sciences, Tehran, Iran (MAK); Department of Occupational Therapy, Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (MR); Department of Occupational Therapy, Charles Sturt University, Bathurst, Australia (MR); Department of Clinical Sciences, School of Rehabilitation Sciences, Rofeideh Rehabilitation Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (MA); Occupational Therapy Program, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA (TKC). 

 Nazila Akbarfahimi, PhD, Koodakyar Ave, Daneshjoo Blvd, Tehran, Iran. Post code: 1985713871; 

People with multiple sclerosis (MS) may confront complex motor, sensory, visual, cognitive, and psychological symptoms.

 In recent decades, numerous studies have focused on lower extremity functioning, gait, and balance changes that occur in the early stages of MS. However, there have been few studies that examine hand and upper extremity function changes in people with MS.

 Approximately three-quarters of people with MS have demonstrated upper extremity dysfunction on 1 or both sides of their bodies.

 Upper extremity dysfunction contributes to reducing the ability to perform activities of daily living and is an important predicator of overall activity and participation within the community,

 possibly resulting in decreased independence and lower quality of life.

Several rehabilitation interventions have been developed to address upper extremity dysfunction, such as exercise training, task-oriented training, sensory training, robotics, and constraint-induced movement therapy. According to a systematic review, however, there is a lack of sufficient evidence of improvement, perhaps because the interventions do not target the upper extremity exclusively.

Occupational therapists are rehabilitation team members who focus on improving occupational performance through occupation-based interventions (OBIs). OBI is a patient-centered practice in which the occupational therapist, in collaboration with the patient, chooses interventions based on the patient’s interests, needs, health, and participation in daily life.

OBI provides a holistic and a strong base for patients to achieve their occupational therapy goals, enhances the ability of therapists to communicate with their patients, and can improve patients’ satisfaction with services.

 However, occupation-based therapies are somewhat culture dependent, so it is necessary to investigate their effectiveness in different cultures.

 Some barriers to using OBI are that therapists lack the knowledge and skills to implement the theory into practice,

 preference for the dominant medical model, patient request, lack of resources, environmental context,

Preliminary evidence supports the effectiveness of OBI for people with some degenerative and neurologic diseases such as stroke or a traumatic brain injury.

 The aim of this study is to describe the development and content of an OBI program focused on hand function that was used to improve the occupational performance of 2 Iranian women with MS.

This feasibility study evaluated the effect of OBI for hand function on 2 women with MS from the Isfahan MS Society. Both volunteers were examined by a neurologist to determine the type of MS they have and their level of disability.

After explanations of the purpose of the study, written consent was obtained from both of the participants and they were assured that their information would be kept confidential. This study was approved by the Ethics Committee of the University of Social Welfare and Rehabilitation Sciences under the code of ethics IR.USWR.REC.1396.319.

Participant 1 was a divorced woman, aged 41 years, with an undergraduate education. Her MS was diagnosed 9 years ago. She has no income or insurance and lives with her mother. According to her report, the strength and coordination of movement in her hands and upper extremities has worsened with the progression of MS symptoms. She needs help in home maintenance and self-care, including bathing and hair brushing.

Participant 2 was a woman, aged 50 years. Her MS was diagnosed 12 years ago. She states that she feels numbness and tingling, and has decreased hand strength and endurance. Sometimes she is responsible for taking care of her grandson and her mother-in-law, who had a stroke. She is independent in all her self-care and mobility activities, but struggles with home maintenance activities.

The Montreal Cognitive Assessment (MoCA) was used because it is more sensitive than the Mini–Mental State Examination in identifying mild cognitive impairment in the general population.

 The Cronbach α of the MoCA has been reported as 0.77; a cutoff score of 24 is considered mild cognitive impairment.

The Expanded Disability Status Scale (EDSS) was used to evaluate the severity of the participants’ MS. A higher score on this scale indicates a higher degree of severity.

 The validity and reliability of this tool are adequate.

The Canadian Occupational Performance Measure (COPM) was used to investigate occupational performance.

 It is a valid and reliable tool with acceptable test-retest reliability and content validity that identifies occupational performance problems across the areas of self-care, productivity, and leisure through a semistructured interview.

 A self-rated score of 1 indicates minimum performance and satisfaction with performance, and a score of 10 is the highest score.

The 9-Hole Peg Test (9HPT) is the gold standard tool for evaluating hand dexterity. Interrater and test-retest reliability of this test is high.

 Bertoni et al reported a cutoff point of greater than 1.95 SD of the norm.

The Fatigue Severity Scale (FSS) is a 9-point scale assessing fatigue in people with MS. Lower scores on this scale indicate less fatigue and less impact on everyday life activities. The test-retest reliability of this tool in Iran is 0.93.

 The lowest score possible is 9 and the highest is 63.

Inclusion criteria were a neurologist-determined EDSS score between 3.5 and 5.5 (ie, able to walk independently) and a MoCA score of greater than 24.

Initially, the primary clinical program was developed based on a comprehensive review of OBIs, as well as the biomechanical model and interventions used in rehabilitation of hand and upper extremities with persons with MS.

 The OBI used in this study guides patients through their self-identified goals regarding their occupational hand function. The developed intervention uses the Model of Human Occupation

 (MOHO) to describe occupational performance and participant involvement; motivation for, as well as patterns and performance of, daily tasks; and the fit between occupational goals, participant ability, and capacity in hand function and environment.

 The therapist used MOHO strategies to support the participants, including validating, identifying, giving feedback, advising, negotiating, structuring, coaching, encouraging, and providing physical support.

 were used as components of the intervention. Each session was approximately 1 hour and occurred 2 times a week for 6 weeks. The content of the sessions was based on the participants’ selected goals and priorities based on the COPM (

At the first session, both participants chose their own goals (

). In the second session, the therapist asked them about how they did activities in the past, observed how these tasks were currently performed, and discussed how performance could be improved by asking reflective questions. During the sessions, the emphasis was on self-assessment. The occupational therapist and patient also discussed ways to promote the construction of a daily routine, to return to a healthy routine, to develop positive habits to save energy, to increase ways to be active for a longer time, and methods to prevent fatigue. When the goals were achieved, the next goal was examined. Reevaluation was conducted in the week after attaining the goal.

The validity of the OBI program was investigated in interviews with 5 occupational therapists who had at least 5 years of clinical experience focused on OBI. The experts evaluated the validity of the intervention program rating the simplicity, clarity, relevance, and necessity of the program on a Likert scale. They were asked to recommend suggestions, corrections, or additions. The experts had an average work experience of 10.2 (SD = 3.4) years. Three of them had a doctorate degree, 1 had a master’s degree, and 1 had a bachelor’s degree; 4 were women. Analysis of the experts’ opinions showed that the program was written simply and clearly and that all written content was essential and relevant.

 descriptively summarizes the COPM, 9HPT, and FSS data. MoCA scores indicated mild cognitive impairment for participant 2 and no cognitive impairment for participant 1. Both participants had an EDSS score of 3.5, indicating moderate disability but no walking impairment. Participant 1 and participant 2 achieved their goals in 8 and 10 sessions, respectively, confirmed by the changes in COPM scores. Both participants had an increase of more than 2 points for both performance and satisfaction, indicating that the OBI intervention made a difference in goal obtainment.

The results of this study indicate an improvement in goal performance and performance satisfaction for both participants, as a change of more than 2 points on the COPM

 is clinically meaningful. Likewise, the women’s 9HPT scores reflected improvement in dexterity. FSS scores also indicated reduced fatigue severity for both participants.

In Eastern culture, which includes Iran, people are usually supported by their families during illness, and people with disabilities often come to rely on others for help completing certain tasks and activities of daily living.

 This is juxtaposed with the fact that, in Iran, housework is often performed by women, and women are mostly responsible for caring for other family members. In the context of this study, one of the participants was divorced and the other was responsible for caring for others, so their motivation to achieve maximum hand function was very high.

It was determined that the participants could achieve the goals in 12 sessions of evidence-based, occupation-focused, and patient-centered therapy interventions, but both participants achieved their goals in fewer sessions. The intervention emphasized improving hand and upper extremity performance to meet occupational goals. Using OBI, the occupational therapist collaborated with the participants to help them find new ways to perform daily tasks. The collaboration between the therapist and the participant as well as participant feedback at all stages of the intervention was paramount. The intervention plan was continually adjusted and tailored to the needs of the individual. To ease the process of time-consuming goal setting, a semistructured COPM interview and occupational profile were used.

This was a preliminary study. Generalization would require more robust design. For example, participants in this study did not have significant cognitive problems, so future research should include people with different levels of MS severity in all areas.

This study introduces a simple, structured occupational therapy intervention for people with MS. The improvements in occupational performance, occupational satisfaction, and hand dexterity experienced by both participants suggest that OBI has the feasibility to be implemented with individuals with MS in Iran. More research with a larger sample size is needed to establish the effectiveness of this occupational therapy intervention among a wider population with varying degrees of MS severity and impairment.

Occupation-Based Intervention for People With Multiple Sclerosis: A Feasibility Study

Cognitive impairment (CI) is common in multiple sclerosis (MS). Processing speed (PS) is often affected, making it an ideal target for monitoring CI. This study aims to evaluate the association between disease-modifying therapy (DMT) use and intensity and longitudinal changes in Processing Speed Test (PST) scores for individuals with MS.

A retrospective analysis of individual PST scores at a single MS center was conducted. Individuals with 2 or more PST assessments were included. Scores on the PST were compared longitudinally between those who had been on a DMT for 2 or more years and those who had been off a DMT for 2 or more years and between those on high-efficacy DMTs and those on low-/moderate-efficacy DMTs. A linear regression model was approximated to evaluate the rate of cognitive change over time. A propensity score adjustment was conducted using a multivariable logistic regression.

The cohort was 642 individuals, 539 on DMT and 103 off DMT. Median age and disease duration was 49.7 (IQR 42.4-57.9) and 16.6 years (IQR 9.3-23.0) in the DMT group, and 58.9 (IQR 52.2-65.3) and 20.0 years (IQR 14.1-31.4) in the non-DMT group. Both cohorts were predominantly female (75% DMT, 79.6% non-DMT), with a mean of 4 assessments (IQR 3-5), and an average monitoring duration of 1.9 years (1.2-2.4) in the DMT group, and 1.8 years (1.4-2.4) in the non-DMT group. After adjusting for multiple factors, DMT status and intensity were not found to be significant predictors of longitudinal PST change.

Neither DMT status nor intensity was a significant predictor of cognitive processing speed over a period of approximately 2 years. Future prospective studies are needed to further support these findings.

From the Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH,USA (AA, JB); Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA (MA, GM, DO); Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA (KN); Department of Neurology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon (GM). 

Daniel Ontaneda MD, PhD, 9500 Euclid Ave U10, Mellen Center, Cleveland, OH 44116; 

 Dr Amin received a Novartis fellowship award (NGC44741). Dr Macaron has served on advisory boards for Biologix, Genentech-Roche, Merck, and Novartis; received speaker fees from Biologix, Merck, and Novartis; and participated in educational activities for NeurologyLive

 and John Hopkins's e-Literature Review. Dr Ontaneda receives research support from Genentech, Genzyme, National Institutes of Health, National Multiple Sclerosis Society, Novartis Patient Centered Outcomes Research Institute, and Race to Erase MS Foundation. He has received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Janssen, Merck, and Novartis. The other authors have no conflicts of interest.

 Presented as a poster at the European Committee for Treatment and Research in Multiple Sclerosis; October 27, 2022; Amsterdam, The Netherlands.

Multiple sclerosis (MS) is among the most common disabling neurologic diseases in young adults.

 Global disease prevalence continues to rise, with estimates from 2020 approximating 35.9 per 100,000 people.

 Approximately 40% to 70% of individuals with MS demonstrate varying degrees of cognitive impairment (CI).

 Importantly, all forms of MS have been associated with CI, including cognitive deficits in individuals with clinically isolated syndrome (CIS) and radiologically isolated syndrome.

 CI can be disabling even in the early stages of the disease and arises independent of physical disability.

Because it affects social functioning and future employment and often results in increased social isolation, CI predicts quality of life in MS.

Smathorn Thakolwiboon, MD

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