David Rintell

The association between cognitive impairment and quality of life in patients with early multiple sclerosis

Cognitive deficits are common in patients with multiple sclerosis (MS) and may be observed early in the course of the disease. Current knowledge about the association between cognitive impairment and health-related quality of life (HQOL) in patients with early MS is limited. We used a well-established battery of cognitive tests and standardized HQOL measures to examine the associations between overall and domain-specific cognitive performance and quality of life in patients with early MS. Ninety-two patients with CIS or MS diagnosed in the previous three years participating in the CLIMB Natural History Study underwent a neurologic examination, neuropsychological evaluation and quality of life assessment. Associations between cognitive scores and HQOL measures were examined. There were no differences between cognitively impaired versus unimpaired subjects on any of the HQOL measures. After controlling for depression, scores on tests of information processing speed were significantly associated with several measures of HQOL including physical well-being, fatigue, and social support. In all cases, correlations between HQOL and cognitive measures were mild. These findings were observed in patients with limited cognitive impairment and minimal physical disability. Our results suggest that cognitive remediation programs aimed at improving cognitive skills may also improve quality of life for patients with early MS.

Work Productivity in Relapsing Multiple Sclerosis: Associations with Disability, Depression, Fatigue, Anxiety, Cognition, and Health-Related Quality of Life

OBJECTIVES To characterize work productivity in relapsing multiple sclerosis (MS) by using a work productivity scale and to identify associations between work productivity and disability, depression, fatigue, anxiety, cognition, and health-related quality of life. METHODS Three hundred seventy-seven subjects with a clinically isolated syndrome or relapsing remitting MS participated in the study. Subjects underwent neurological examinations and completed patient-reported outcome and cognitive measures. Subjects also completed the Work Productivity and Activity Impairment Questionnaire: General Health to quantify absenteeism (missing work because of health problems), presenteeism (impairment while working), overall work impairment, and daily activity impairment attributable to health problems. Univariate correlations and multivariate models were used to determine the associations between each work productivity variable and clinical, patient-reported outcome, and cognitive measures. RESULTS Seventy-six percent of subjects were employed. Fourteen percent of working subjects reported absenteeism, and 47% reported presenteeism. The mean work time lost because of absenteeism was 4%, and the mean work time lost because of presenteeism was 12%. Absenteeism was not significantly associated with disease or patient-reported outcome measures. Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. No associations were observed between presenteeism and disease duration or cognitive function. CONCLUSIONS Subjects with clinically isolated syndrome/relapsing remitting MS reported substantial work productivity losses due to presenteesim. Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life. It is possible that the early identification and treatment of fatigue and mental health symptoms may improve productivity while working and extend employment for individuals with MS.

Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis

Background: Little is known about long-term cognitive and patient-reported outcomes of pediatric-onset multiple sclerosis (POMS). Objective: The objective of this paper is to compare cognitive and patient-reported outcomes in adults with POMS vs. adult-onset MS (AOMS). Methods: We compared standardized patient-reported measures MSQOL54, MFIS, CES-D and SDMT in adult patients with MS onset prior to and after age 18, using data gathered in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Results: Fifty-one POMS and 550 AOMS patients were compared. SDMT scores were significantly lower in POMS after adjusting for age (−7.57 (−11.72, −3.43; p < 0.001), but not after adjusting for disease duration. Estimated group difference demonstrated lower normative z scores in POMS vs. AOMS in unadjusted analysis (−0.74 (95% CI: −1.18, −0.30; p = 0.0009) and after adjusting for disease duration (−0.60; 95%CI: −1.05, −0.15; p = 0.0097). Findings were unchanged in a subset of POMS diagnosed prior to age 18. In unadjusted and adjusted analyses, no significant differences were observed in health-related quality-of-life, fatigue, depression or social support between POMS and AOMS. Conclusions: Younger age of onset was associated with more impairment in information-processing speed in adults with POMS compared to AOMS, and remained significant when controlling for disease duration in age-normed analysis. The two groups were similar in terms of patient-reported outcomes, suggesting similar qualitative experiences of MS.

Improving the quality of mental health care in Multiple Sclerosis

OBJECTIVE An exploratory study of mental health treatment of people with multiple sclerosis (MS) to identify hypotheses for future testing. METHODS We mailed surveys to 8750 MS patients in four geographically distributed MS Centers; 3384 completed the survey. We used a modified version of the Experience of Care and Health Outcome Survey™ to assess mental health problems and experiences with mental health treatment and the Kessler 6 scale to identify serious mental illness. RESULTS In the year before the survey, sixty percent of patients reported mental health problems. Less than one half of these individuals received mental health treatment, either from their MS care provider or a mental health professional in the MS Center or the community. Patients generally had good mental health treatment experiences, and felt helped by their treatment, but gave less positive reports about how long it took to be seen, receiving information about treatment options and managing their condition, and phone contact. Care experiences were more positive among those who received care from mental health professionals (compared to medical care providers) and among those receiving mental health treatment in the MS Center (compared to in the community). CONCLUSIONS The unmet need for mental health treatment for people with MS is high. Options for MS care providers to help meet this need include hiring mental health professionals to provide on-site treatment; providing mental health treatment themselves; and referring patients to mental health professionals in the community and collaborating in integrated care. This study provided preliminary data for two related hypotheses that warrant further testing: MS patients will receive better mental health care if their mental health treatment is co-located with their MS care and if it is provided by mental health professionals.

Treatment Satisfaction in Multiple Sclerosis

BACKGROUND Disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) are associated with inconvenient methods of administration, significant side effects, and low adherence rates. This study was undertaken to compare treatment satisfaction in MS patients treated with interferon beta-1a intramuscular (IFNβ-1a IM), interferon beta-1a subcutaneous (IFNβ-1a SC), glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations between treatment satisfaction ratings and adherence to therapy. METHODS Two hundred twenty-six treated MS patients completed the Treatment Satisfaction Questionnaire for Medicine. Multivariable models were used to compare treatment satisfaction across groups. RESULTS There were no statistically significant differences in overall treatment satisfaction. The NTZ group reported greater satisfaction with the ability of the medication to treat or prevent MS than the IFNβ-1a IM group. The NTZ group also reported higher overall convenience scores than the IFNβ-1a IM group and greater satisfaction with ease of use of the medication than the interferon and GA groups. Patients in the IFNβ-1a IM group reported less satisfaction with ease of planning when to use the medication than those in the other groups. Convenience was associated with adherence in IFNβ-1a SC- and GA-treated patients, with lower convenience scores associated with lower adherence. CONCLUSIONS These results may be useful to MS patients and health-care providers facing decisions about DMT use.

Patient reported outcomes in benign multiple sclerosis

Background: Benign MS patients have a mild course of disease and show no or minimal accumulation of disability over time. Little is known about the patient reported outcomes (PROs) in benign MS. Objective: The objective of the study was to compare PROs in benign MS patients and patients with similar disease duration or disability status, and to investigate how the definition of benign MS affected this outcome. Methods: Two groups of Benign MS patients (disease duration ≥15 years, Expanded Disability Status Scale [EDSS] score ≤1.5 [Benign-1.5], or ≤3.0 [Benign-3]) were compared with four other MS groups: disease duration ≥15 years, EDSS score >3.0 (Late-MS); disease duration <15 years, and EDSS score ≤1.5 (Low-EDSS-1.5), or ≤3.0 (Low-EDSS-3); disease duration ≤5 years (Early-MS). PROs included measures of QOL, fatigue, depression, and social support. Cognitive function was also assessed. Results: Both benign groups had better PROs than Late MS patients on all measures (p < 0.05). QOL, depression, and fatigue were significantly different between Benign-1.5 and Early-MS groups (p < 0.01). Benign-1.5 had higher mental health QOL than Low EDSS-1.5, but was otherwise similar. Benign-3 patients had worse depression than Early-MS (p < 0.01), and worse cognition compared with Low-EDSS-3 (p = 0.033). Benign-1.5 had higher QOL and lower fatigue (p < 0.005) than Benign-2-3, and showed a marginally significant difference in cognitive functioning (p = 0.055). Conclusions: Patients with benign MS had better PROs than other groups of MS patients, suggesting that both disease duration and disability influence PROs. The study also showed a difference in PROs based on the way benign MS was defined.

Depression and fatigue in patients with multiple sclerosis

BACKGROUND Previous research has examined the components of depression and fatigue in multiple sclerosis (MS), but the findings have been inconsistent. The aim of this study was to explore the associations between overall and subscale scores of the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Modified Fatigue Impact Scale (MFIS) as well as the longitudinal changes in scores in a large cohort of MS patients. METHODS MS subjects who completed a battery of patient reported outcome (PRO) measures including the CES-D and MFIS (N=435) were included in our analysis. At the first available MFIS measurement, Pearsons correlation coefficient was used to estimate the association between the CES-D and MFIS in terms of both total scores and subscale scores. In addition, the longitudinal change in each total score and subscale score was estimated using a linear mixed model, and the association between the measures in terms of longitudinal change was estimated using Pearsons correlation coefficient and linear mixed models. RESULTS At baseline, 15% of subjects were classified as high on both depression and fatigue scales, 16% were classified as high on the fatigue scale only, and 9% were classified as high on the depression scale only. There was a high correlation between CES-D and MFIS total scores (r=0.62). High correlations were also observed between the somatic and retarded activity subscales of the CES-D and each of the MFIS subscales (r≥0.60). In terms of longitudinal change, the change over the first year between the CES-D and MFIS total scores showed a moderate correlation (r=0.49). Subjects with high fatigue scores but low depression scores at baseline were more likely than subjects with low baseline fatigue and depression scores to develop high depression scores at follow-up. CONCLUSIONS Our study demonstrated that depression and fatigue in MS share several features and have a similar longitudinal course. But using cut-off scores to define depression and fatigue, our study also found that non-depressed subjects with high fatigue may be at a greater risk for developing depression.

A framework of care in multiple sclerosis, part 2: Symptomatic care and beyond

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

Functional Relapses in Pediatric Multiple Sclerosis

Multiple sclerosis in children is characterized by more frequent relapses than in adult patients. Diagnosing and treating youth with multiple sclerosis present a number of challenges including differentiating organic relapses from functional symptoms. However, there is no literature describing coexistence of functionality in pediatric multiple sclerosis. Here, we report 2 cases in which inconsistency between clinical history, physical examination, imaging, and atypical disease progression led to suspicion of functional relapses. The purpose of this study is to raise awareness of functional relapses, as prompt recognition can prevent overtreatment and iatrogenic risks in children and adolescents with multiple sclerosis. Underlying psychiatric issues also need to be addressed.

Risk attitudes and risk perceptions in individuals with multiple sclerosis

Background Little is known about risk attitudes and risk perceptions in multiple sclerosis (MS). Objectives The objectives of this paper are to investigate the range of risk attitudes and risk perceptions and examine associations between risk attitudes and risk perceptions and demographic and clinical features of the disease. Methods A total of 223 individuals completed a risk questionnaire. Risk attitude was measured using two rating scales and a standard gamble scenario. Risk perception was measured by asking participants to estimate the likelihood of disease progression and the likelihood of minor and serious side effects associated with common MS therapies. Results Participants were risk neutral overall and risk averse on issues related to health and safety. There was a significant association between disease duration and risk attitude, with patients with longer disease duration showing greater tolerance for risk. On the standard gamble scenario, males were significantly more likely to take treatments with a likelihood of death of 1:10,000 or 1:100,000 than females. Individuals with higher disability or a progressive disease course were significantly more likely to expect progression at two, five and 10 years. Conclusion Individuals with MS demonstrate low tolerance for risk. Risk attitudes and perceptions are influenced by some demographic and clinical features of the disease.