Using Objective and Subjective Measures of Cognition to Predict Instrumental Activities of Daily Living Abilities in Multiple Sclerosis.

BACKGROUND: Cognitive impairment, difficulty performing basic activities of daily living (ADLs) and instrumental ADLs (IADLs), depression, and fatigue are common among individuals with multiple sclerosis (MS). Some associations between these symptoms are known; however, many of their relationships remain unclear. This study investigated the contributions of subjective and objective cognition, depressive symptom severity, and fatigue on ADLs and IADLs. METHODS: Participants (N = 217) were individuals with MS from a comprehensive MS center, participating in a larger study characterizing upper extremity function in MS. Outcome measures of ADL and IADL abilities were the Functional Status Index-Assistance (FSI-A) and Functional Status Index-Difficulty (FSI-D) and the Test D'évaluation Des Membres Supérieurs de Personnes Âgées (TEMPA). Predictors were objective cognition (Symbol Digit Modalities Test; SDMT), subjective cognition (Performance Scales©-Cognition; PS-C), depressive symptom severity (Center for Epidemiologic Studies Depression Scale; CES-D-10), and fatigue (Modified Fatigue Impact Scale; MFIS-5). Correlations were conducted, followed by hierarchal linear regressions. The SDMT and PS-C were entered into separate models. RESULTS: After controlling for demographics, the SDMT significantly predicted the TEMPA and FSI-A, while the PS-C predicted only the FSI-D. The CES-D-10 predicted the FSI-D even after accounting for PS-C and SDMT, while the MFIS-5 only predicted the FSI-D when the SDMT was included. Neither the CES-D-10 nor MFIS-5 significantly predicted the FSI-A or TEMPA. CONCLUSIONS: The way an individual with MS perceived their symptoms significantly contributed to their reported difficulty with functional tasks, while only their objective cognitive functioning predicted ADL and IADL performance and the level of assistance they would require.

Perceived health- related quality of life in persons with multiple sclerosis with and without a vascular comorbidity.

PURPOSE: Vascular comorbidities are prevalent and can contribute to adverse health outcomes in persons with multiple sclerosis (PwMS). Understanding the association between vascular comorbidities and health-related quality of life (HRQOL) among PwMS may be beneficial in improving outcomes and disease management. This cross-sectional study aimed to examine the relationship between vascular comorbidities and the different dimensions of HRQOL in PwMS. METHODS: Participants (n = 185) were PwMS recruited from a community-based comprehensive MS care center. Demographics, comorbid conditions, and disability level were collected via a self-report REDCap survey, with the 29-item Multiple Sclerosis Quality of Life (MSQOL-29) as the outcome measure. Regression models were used to examine the association between vascular comorbidities and the MSQOL-29, controlling for age, gender, ethnicity, level of education, marital status, MS subtype, disease duration, and disability. RESULTS: Approximately 35% reported at least one vascular comorbidity, with the most common being hypertension (27.0%), followed by hyperlipidemia (24.9%) and diabetes (8.1%). After factoring in for demographics and disability, having a vascular comorbidity was associated with lower physical HRQOL (ß = - 10.05, 95% CI: - 28.24, 23.50), but not mental HRQOL (ß = - 2.61, 95% CI: - 10.54, 5.32). Hypertension was negatively associated with several dimensions of HRQOL, including Physical Function, Change in Health, Health Perceptions, Energy, and Health Distress. CONCLUSIONS:  Having at least one vascular comorbidity is associated with lower physical HRQOL, independent of demographics and level of physical disability. Focus should be directed to the physical burden and challenges vascular comorbidities may cause on the lives of PwMS.

Establishment of regression-based normative isometric strength values for major lower limb muscle groups in persons with multiple sclerosis.

BACKGROUND: Limb weakness is a major impairment that affects mobility in persons with multiple sclerosis (PwMS). Specifically, lower limb (LL) weakness can greatly affect gait and balance, while increasing fall risk and decreasing quality of life. Numerous studies have compared LL strength of PwMS to healthy controls, however none have objectively measured strength in all major LL joints (hip, knee, and ankle) in a large number of PwMS. Additionally, while discrete normative values exist for knee extensors in PwMS, there has yet to be regression-based normative isometric strength values for all major LL muscle groups. Therefore, this study aimed to develop gender-specific regression-based normative prediction equations, with 95% confidence intervals, for maximal isometric peak torque of major LL muscles in PwMS. A secondary aim was to characterize the prevalence of LL weakness in PwMS, defined as ≥ 2 SD below values reported for healthy individuals. METHODS: A convenience sample of 175 (women: n = 135) PwMS participated in a prospective, cross-sectional study where isometric peak torque of hip flexors, extensors, and abductors, knee flexors and extensors, and ankle plantarflexors and dorsiflexors were measured using the Biodex System 4 Pro-Dynamometer®. Demographics (age, height, and weight) and disease characteristics (disease duration and disability) were collected. Performances were separated for each muscle group into strongest limb and weakest limb. For each gender, regression-based equations were generated for the LL muscle groups by limb with age, height, weight, disability, and disease duration as the covariates. Descriptive statistics were used to examine the frequency of LL weakness by gender and disability level. For comparison purposes, age-stratified (<30, 30-39, 40-49, 50-59, 60-69, >70 years) and disability-stratified (mild, moderate, and severe ambulant) discrete peak torque values were also generated for each gender. RESULTS: Regression-based normative data are presented for men and women, accounting for age, height, weight, disability, and disease duration. Men were significantly stronger (P < 0.001) than women for all LL, with the men's models accounting for a greater percent of muscle strength variation than women's models for all muscle groups, except for hip extension. Disability was inversely related to strength in all of the models. LL weakness was prevalent in hip flexion (m: 47.5%; w: 63.0%) and extension (m: 92.5%; w: 88.1%), knee extension (m: 30.0%; w: 33.3%) and flexion (m: 25.0%; w: 34.8%), and ankle plantarflexion (m: 15.0%; w: 10.4%) and dorsiflexion (m: 100.0%; w: 96.3%). PwMS with mild disability had a high prevalence of ankle dorsiflexion (94.9-100.0%) and hip extension (81.4-90.0%) weakness. CONCLUSIONS: This study is the first to provide regression-based normative data of bilateral strength in all major LL muscle groups and clinically useful prevalence data on the occurrence of weakness in these muscles. Of note, PwMS had a high prevalence of ankle dorsiflexion and hip extension weakness even when they were only mildly disabled. These findings can help guide the direction of future interventions and treatments to improve muscle function in PwMS.

Effect of Backward and Forward Walking on Lower Limb Strength, Balance, and Gait in Multiple Sclerosis: A Randomized Feasibility Trial.

BACKGROUND: Backward walking (BW) interventions have improved gait and balance in persons with stroke, cerebral palsy, and Parkinson disease but have not been studied in persons with multiple sclerosis (MS). We examined the feasibility of a BW intervention and how it affected strength, balance, and gait vs forward walking (FW) in persons with MS. METHODS: Sixteen persons with MS with a Patient-Determined Disease Steps (PDDS) scale score of 3 to 5 (gait impairment-late cane) were randomized to the FW (n = 8) or BW (n = 8) group. Participants did 30 minutes of FW or BW on a treadmill 3 times per week for 8 weeks (24 visits). Enrollment, adherence rate, and safety were tracked. The Timed Up and Go test, Six-Spot Step Test, single-leg stance, and abbreviated Activities-specific Balance Confidence scale were used to measure balance. Hip and knee flexion and extension strength (isometric peak torque), gait speed, and spatiotemporal gait parameters were measured. A 2×2 factorial multivariate analysis of covariance was used to examine changes in strength, balance, and gait, with the PDDS scale score as the covariate. RESULTS: Treatment adherence rate was 99.7%, with no safety concerns. After controlling for baseline differences in disability (PDDS scale score; P = .041), the BW group improved dominant hip flexion strength preintervention to postintervention compared with the FW group (F 1,13 = 9.03; P = .010). No other significant differences were seen between groups. CONCLUSIONS: This was the first study to look at BW as an intervention in persons with MS. Based on its feasibility, safety, and significant finding, BW should be studied in a larger, definitive trial in the future.

Establishing the Test-Retest Reliability and Minimal Detectable Change of the Multiple Sclerosis Resiliency Scale.

BACKGROUND: The Multiple Sclerosis Resiliency Scale (MSRS) was designed to assess factors connected to resilience when facing MS-related challenges. Although the MSRS has demonstrated good internal consistency and construct validity, its test-retest reliability has yet to be established. Identifying the minimal detectable change (MDC) of the scale will also improve its utility as an outcome measure for resilience-based interventions. This study aimed to determine the test-retest reliability and MDC of the MSRS. METHODS: Participants were 62 persons with MS who completed the MSRS twice, with a mean ± SD of 16.60 ± 3.97 days (range, 14-30 days) between assessments. Test-retest reliability was evaluated using a 2-way, random-effects, single-measurement intraclass correlation coefficient (ICC), with agreement between time 1 and time 2 visualized with a Bland-Altman plot. The MDC was calculated using the standard error of measurement with a 95% CI. RESULTS: At time 1, the mean ± SD MSRS score was 77.19 ± 11.97 (range, 45.83-97.00); at time 2, the mean ± SD score was 76.38 ± 12.75 (range, 46-98). The MSRS total score had good test-retest reliability (ICC = 0.88), with the subscale ICCs ranging from 0.77 (MS Peer Support) to 0.93 (Spirituality). The MDC for the total score was 11.95. CONCLUSIONS: These findings suggest that the MSRS has good test-retest reliability and that persons with MS with a difference of 12 points or more between assessments have experienced a reliable change. The results support the utility of the MSRS as a potential outcome measure for MS-related resilience.

Quantification of upper limb dysfunction in the activities of the daily living in persons with multiple sclerosis.

BACKGROUND: Dysfunction in upper limb (UL) function has been reported as an important indicator for disease progression in persons with multiple sclerosis (PwMS), thus a relevant outcome in clinical trials. However, standard assessment of UL function is limited to Nine-Hole Peg Test (NHPT) which assesses fine dexterity. This study aimed to deeply endophenotype UL involvement in PwMS and identify the most accurate set of measures needed to capture the complexity of UL dysfunction in the activities of daily living (ADL). METHODS: 257 PwMS underwent an extensive UL assessment using standardized measures of grip strength and endurance, coordination, vibratory and tactile sensation, dexterity, capacity and functionality. Limitation in ADL was defined from an objective perspective using a timed test (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Âgées: TEMPA) and from a subjective perspective using a questionnaire (Disabilities of the Arm, Shoulder and Hand: DASH). Disease severity subgroups were compared utilizing the Kruskal-Wallis test and frequencies determined the prevalence of abnormal UL for each measure. The Jonckheere-Terpstra test compared tested variables with disease severity. Then Receiver operating characteristic (ROC) curve analysis was used to test the accuracy of each tested variable in defining abnormality in the TEMPA and DASH. Cut-off scores were calculated using the Youden index. The predictive value of various tests over TEMPA and DASH were tested using a linear regression analysis. RESULTS: UL dysfunction was highly prevalent in all the modalities tested, even in participants with no/mild disability. Box and Block Test (BBT), finger-nose test (FNT), and NHPT were independently selected with ROC analyses as the most accurate measures in detecting abnormalities in TEMPA and DASH. In multivariate regression models, BBT and FNT, and NHPT all contributed to predicting TEMPA (adj. R2 0.795, P < 0.001), while only BBT and FNT predicted DASH. CONCLUSIONS: UL dysfunction is highly prevalent in PwMS, even when global disability is mild. BBT and FNT are time-efficient and cost-effective measures that complement the NHPT for more precise monitoring of PwMS at all disease stages.

The Role of Cognitive Impairment on Physical Therapy Attendance and Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Many persons with multiple sclerosis (PwMS) experience cognitive impairments, which may affect their ability to engage in physical therapy. There is limited information on how cognitive impairments are associated with PwMS' ability to participate and improve their functional outcomes. This study aimed to assess the relationship between cognitive functioning and PwMS' attendance, total goal attainment, and functional improvement following physical therapy intervention. METHODS: Participants (n = 45) were PwMS who participated in a larger self-management study and enrolled in physical therapy within the past 2 years. Objective cognitive functioning was examined using tests of prospective memory, retrospective memory, working memory, and processing speed, along with a self-report measure. Bivariate analyses were conducted to examine the relationship between cognitive functioning and each physical therapy outcome (session attendance, attaining goals, and changes in functional outcome measures), followed by logistic regressions with age, education, gender, and disability level as covariates. RESULTS: Difficulty learning new verbal information was associated with a greater likelihood of "no showing" one or more of their physical therapy sessions. Reductions in working memory and processing speed were associated with PwMS not meeting all their rehabilitation goals. Despite deficits in new learning, memory, and processing speed, 85.2% of those with pre-/postscores showed improvements in at least one functional outcome measure following physical therapy intervention. DISCUSSION AND CONCLUSIONS: These findings demonstrate the ability for PwMS to make functional motor gains despite the presence of cognitive impairments and highlight the potential contributions of cognitive functioning on attendance and goal attainment of physical therapy intervention.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A362, which includes background, methods, results, and discussion in the authors' own voices).

Risk factors for infusion-related reactions following Ocrelizumab infusion in a community setting: Development of an electronic medical record-based explanatory model.

BACKGROUND: In 2017, ocrelizumab became the first FDA approved disease modifying therapy (DMT) for primary progressive multiple sclerosis (MS). Although effective, adverse infusion-related reactions (IRR), such as erythema, pruritus, hives, and throat irritation, were frequently reported. OBJECTIVE: To develop an explanatory model of factors associated with increased odds of IRR development to further enhance clinical decision-making when administering ocrelizumab in a community setting. METHODS: A retrospective chart review was performed (n = 422) by extracting patient demographic factors and co-occurring conditions and symptoms from electronic medical records. Bivariate analyses were conducted to examine which demographic and clinical characteristics were associated with IRR development, and variables with a p-value of <.10 were then entered into a logistic regression to create the explanatory model. RESULTS: Being female (odds ratio [OR]: 2.60), Hispanic/Latinx (OR: 3.98), and having a history of a co-occurring tremor (OR: 3.78) were risk factors for increased odds of having an IRR. CONCLUSIONS: These findings may be helpful in guiding clinical practice routines and improving patient expectations regarding the likelihood of IRR development based on their individual demographics and co-occurring conditions and symptoms.

Quantification characteristics of digital spiral analysis for understanding the relationship among tremor and clinical measures in persons with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a degenerative neurological condition causing demyelination and neuronal loss. Tremor, a symptom of MS, is prevalent in 45.0-46.8% NARCOMS registrants. Although several tools to measure tremor exist, few outcomes are quantitative or regularly utilized clinically. NEW METHOD: Introduction of a novel adaptation of the digital spiral drawing to find a quick, sensitive, and clinically useful technique, to predict tremor in persons with MS (pwMS). Digital spiral measures included: Segment Rate (SEGRT), Standard Deviation (SD) of Radial Velocity (VSD-R), SD of Tangential Velocity (VSD-T), SD of Overall Velocity (VSD-O), Mean Drawing Velocity (MNV-O) and Mean Pen Pressure Acceleration (MNA-P). Digital spiral measures were compared with the manual Archimedes Spiral (AS) drawing and the following clinical measures: Finger-Nose Test (FNT), presence of visually observed intention tremor (VOT), Nine-Hole Peg Test (NHPT), and Box and Block Test (BBT). RESULTS: All clinical measures utilized demonstrated significant relationships with all digital variables, except VSD-R. The forward-stepwise regression revealed BBT accounted for the most variance, followed by SEGRT. Comparison with Existing Methods: SEGRT is more sensitive in detecting VOT and better for quantifying tremor than AS. BBT and SEGRT are optimal predictive measures for tremor. CONCLUSIONS: SEGRT has stronger sensitivity and negative predictive value than AS in detecting VOT. All clinical measures (NHPT, FNT, BBT, and AS) were significantly associated with the digital variables (SEGRT, VSD-T, VSD-O, MNV-O, and MNA-P) except for VSD-R. After controlling for Patient Determined Disease Steps (PDDS), BBT and SEGRT are the best predictive measures for tremor.

Changes in Cognitive Processing Speed, Mood, and Fatigue in an Observational Study of Persons With Multiple Sclerosis Treated With Dalfampridine-ER.

OBJECTIVE: Multiple sclerosis (MS) is a degenerative neurological condition that results in impairments in multiple domains including cognition, fatigue, and mood. Dalfampridine-extended release (D-ER) has been approved to improve walking in persons with MS. It is plausible that D-ER could improve cognition, fatigue, and mood through the same mechanisms. We aim to examine effects of D-ER on cognition, depression, mood, and fatigue and to describe how these associations differ among those with and without D-ER related improvements in walking speed. METHODS: Patients with MS at the Mandell Center who were newly prescribed D-ER as part of their standard MS care were invited to participate in this observational pre-post study. Thirty-nine participants with MS were observed for 14 weeks; 31 remained on D-ER for 14 weeks or longer. Of these, 28 were then subdivided based on walk responder status. Cognition was assessed using the SDMT; depression was measured with the CESD. Self-reported cognition, mood, and fatigue were also measured using subscales of the Performance Scales (PS). RESULTS: Among those on drug through 14 weeks, there was significant improvement in the SDMT (P < 0.001) and the PS Fatigue score (P = 0.04). Among those who discontinued drug before 14 weeks, PS Cognition and PS Mood scores significantly improved (P = 0.02). Timed walk responders had significant improvements in SDMT (P < 0.001) and PS Fatigue (P = 0.046) from baseline to week 14. Among timed walk nonresponders, none of the measures significantly changed. CONCLUSIONS: Dalfampridine-extended release may improve cognition and fatigue in persons with MS, especially among timed walk responders.