Reliability and Validity of Ratings of Perceived Exertion in Persons With Multiple Sclerosis.

OBJECTIVE: To test the reliability and validity of using the Borg rating of perceived exertion (RPE) scale (ratings 6-20) in persons with multiple sclerosis (PwMS). DESIGN: Nonrandomized repeated measures. SETTING: Research laboratory. PARTICIPANTS: Volunteer sample (N=27) comprised of 16 PwMS (10 women) and 11 age-matched persons without multiple sclerosis (MS) (6 women). Clinical measures included symptomatic fatigue, depression, and MS functional capacity. INTERVENTIONS: A submaximal cycling test was performed to estimate maximal capacity. Participants then pedaled for 2 minutes at 50% and 60% of predicted maximal oxygen consumption per unit time (V˙o2), and physiological measures and RPE were obtained (week 1: response protocol). One week later, participants replicated the prescribed V˙o2 using the RPE range from week 1 (week 2: reproduction protocol). V˙o2, heart rate, and respiratory quotient were measured continuously; RPE and workload were measured every minute; and blood lactate and mean arterial pressure were measured after exercise. MAIN OUTCOME MEASURES: RPE, workload, V˙o2, and heart rate from week 1 to week 2. RESULTS: PwMS had greater fatigue (P<.01) and disability (P<.001). Baseline measures were similar between groups and weeks. During exercise, RPE, workload, V˙o2, and heart rate were similar between groups. Both groups had an intraclass correlation coefficient >.86 for RPE, workload, and V˙o2. The intraclass correlation coefficient was comparatively lower for heart rate for both groups (MS group: .72, non-MS group: .83). RPE was highly correlated with V˙o2 (r=.691, P<.001) and workload (r=.700, P<.001) for the MS group. CONCLUSIONS: Results suggest that RPE can be reliably reproduced, is valid, and may be used in exercise prescription in mildly to moderately impaired PwMS during cycling exercise.

Intention tremor and deficits of sensory feedback control in multiple sclerosis: a pilot study.

BACKGROUND: Intention tremor and dysmetria are leading causes of upper extremity disability in Multiple Sclerosis (MS). The development of effective therapies to reduce tremor and dysmetria is hampered by insufficient understanding of how the distributed, multi-focal lesions associated with MS impact sensorimotor control in the brain. Here we describe a systems-level approach to characterizing sensorimotor control and use this approach to examine how sensory and motor processes are differentially impacted by MS. METHODS: Eight subjects with MS and eight age- and gender-matched healthy control subjects performed visually-guided flexion/extension tasks about the elbow to characterize a sensory feedback control model that includes three sensory feedback pathways (one for vision, another for proprioception and a third providing an internal prediction of the sensory consequences of action). The model allows us to characterize impairments in sensory feedback control that contributed to each MS subject's tremor. RESULTS: Models derived from MS subject performance differed from those obtained for control subjects in two ways. First, subjects with MS exhibited markedly increased visual feedback delays, which were uncompensated by internal adaptive mechanisms; stabilization performance in individuals with the longest delays differed most from control subject performance. Second, subjects with MS exhibited misestimates of arm dynamics in a way that was correlated with tremor power. Subject-specific models accurately predicted kinematic performance in a reach and hold task for neurologically-intact control subjects while simulated performance of MS patients had shorter movement intervals and larger endpoint errors than actual subject responses. This difference between simulated and actual performance is consistent with a strategic compensatory trade-off of movement speed for endpoint accuracy. CONCLUSIONS: Our results suggest that tremor and dysmetria may be caused by limitations in the brain's ability to adapt sensory feedback mechanisms to compensate for increases in visual information processing time, as well as by errors in compensatory adaptations of internal estimates of arm dynamics.

Determinants of low bone mineral density in people with multiple sclerosis: Role of physical activity.

BACKGROUND: People with multiple sclerosis (PwMS) have reduced bone mineral density (BMD), but the causes are unclear. Some factors that may cause reduced BMD in PwMS have been understudied, including physical activity, inflammation, cortisol, symptomatic fatigue, and depression. The aim of this study was to investigate factors that may uniquely contribute to reduced BMD in PwMS as compared to people without MS. We hypothesized that physical activity would be the primary determinant of low BMD in PwMS, with additional contributions from inflammation and sympathetic nervous system activation. METHODS: We tested 23 PwMS (16 women; median EDSS: 2) and 22 control participants (16 women). BMD was measured from the femoral neck and lumbar spine with dual x-ray absorptiometry. Disability was measured with the Expanded Disability Status Scale, and functional capacity was measured with the Multiple Sclerosis Functional Composite. Questionnaires measured symptomatic fatigue and depression. A blood draw was used to measure calcium, phosphate, vitamin D, N-terminal telopeptide, osteopontin, and cytokine markers of inflammation. Physical activity was measured with accelerometry. Salivary cortisol and cardiac heart rate variability also were obtained. All outcome variables were compared between groups with independent samples t-tests. Variables that were different between groups and significantly correlated (Pearson product-moment) with femoral neck BMD, were included in a theoretical model to explain femoral neck BMD. The expected direction of relations in the theoretical model were developed based upon the results of previous research. A Bayesian path analysis was used to test the relations of predictive variables with femoral neck BMD and interrelations among predictive variables, as detailed in the theoretical model. RESULTS: PwMS had lower BMD at the femoral neck than controls (p = =0.04; mean difference: -0.09; 95% CI: -0.2, -0.004; Cohen's d = =0.65), and there was a smaller, statistically non-significant difference in BMD at the lumbar spine (p = =0.07; mean difference: -0.08; 95% CI: -0.17, 0.007; Cohen's d = =0.59). PwMS also had lower functional capacity (p ≤ 0.001; Cohen's d = =1.50), greater fatigue (p<0.001; Cohen's d = =1.88), greater depression (p<0.001; d = =1.31), and decreased physical activity (p = =0.03; Cohen's d = =0.62). Using path analysis to test our theoretical model, we found that disability (standardized estimate= -0.17), physical activity (standardized estimate=0.39), symptomatic fatigue (standardized estimate= -0.36), depression (standardized estimate= -0.30), and inflammatory markers (standardized estimate=0.27) explained 51% of the variance in femoral neck BMD. Inflammatory markers were also predictive of disability (standardized estimate=0.44) and physical activity (standardized estimate= -0.40). Symptomatic fatigue and depression were correlated (r = =0.64). CONCLUSION: Physical activity, symptomatic fatigue, depression, disability, and inflammation all contributed independently to decreased femoral neck BMD in PWMS. Bone metabolism in PwMS is complex. Efforts to increase physical activity and address symptomatic fatigue and depression may improve bone mineral density in PwMS. Future research should investigate the mechanisms through which symptomatic fatigue and depression contribute to reduced BMD in PwMS.

Diagnosis and management of multiple sclerosis: case studies.

Although substantial capabilities have emerged in the ability to globally manage patients who have MS, clinicians continue to be confronted with formidable challenges. Reduction in disease activity and its impact on dis-ability progression remains the central objective of disease-modifying therapy and most current MS research initiatives. Nevertheless, the principal factors that determine the day-to-day limitations on functional capabilities(activities of daily living, work performance, quality of life, and so forth)are a derivative of the pathophysiology of the disease process itself. The substrate for these limitations is inherent in the pathology of demyelination and axonal dysfunction. Identifying measures that can optimize the performance and fidelity of axonal conduction mechanisms may translate into a reduction in MS-related symptoms. Chronic neurologic disease management (with MS representing a signature example) can be optimized when all members of the care team (including patients and their families) collaborate in the co-ordination of interdisciplinary care models that address all aspects of suffering.

Endovascular therapy for chronic cerebrospinal venous insufficiency in multiple sclerosis.

Recent reports have emerged suggesting that multiple sclerosis (MS) may be due to abnormal venous outflow from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI). These reports have generated strong interest and controversy over the prospect of a treatable cause of this chronic debilitating disease. This review aims to describe the proposed association between CCSVI and MS, summarize the current data, and discuss the role of endovascular therapy and the need for rigorous randomized clinical trials to evaluate this association and treatment.

Extrapyramidal symptoms with concomitant use of amitriptyline and amiodarone in an elderly patient.

BACKGROUND: Amitriptyline is a tricyclic antidepressant useful for the treatment of depression. Amiodarone is a class III antiarrhythmic agent used for the treatment of cardiac dysrhythmias. OBJECTIVE: The objective of the current report is to describe the case of a previously asymptomatic patient receiving amitriptyline who developed extrapyramidal symptoms within 1 month of initiating concomitant treatment with amiodarone for atrial fibrillation. CASE SUMMARY: An 82-year-old, right-handed, white woman was brought to the medical center's emergency department with speech difficulty suggesting stroke. She was noted to have continuous orobuccal dyskinesias, upper and lower extremity shaking, and dry mouth. Once it was determined that no other focal neurologic findings indicated stroke, her medications were reviewed. The patient had been taking amitriptyline 50 mg/d for the past year for insomnia without any adverse events. However, 1 month before presentation, she also initiated treatment with amiodarone 200 mg/d for atrial fibrillation and had developed the symptoms of concern shortly thereafter. The patient's amitriptyline treatment was discontinued and she received benzotropine for extrapyramidal symptoms from amitriptyline toxicity. She experienced complete resolution of dysarthric speech and limb shaking within 2 days. A total score of 7 was achieved using Naranjo's adverse drug reaction causality algorithm, suggesting amitriptyline was a probable cause of these adverse events. CONCLUSION: This was a probable case of extrapyramidal symptoms in an elderly woman who began using amiodarone while also taking amitriptyline.

Factors that influence adherence with disease-modifying therapy in MS.

BACKGROUND: The complexity and cost of injection treatment can represent a formidable challenge for patients affected by a chronic illness, particularly those whose treatment is primarily preventative and only modestly effective on the more conspicuous symptomatic aspects of the disease process. The aim of this investigation was to identify which factors most influenced nonadherent behavior with the available disease-modifying injection therapies for multiple sclerosis (MS). METHODS: A multicenter, observational (three-wave) study using surveys was developed and administered to patients with MS through the World Wide Web. Healthcare providers at 17 neurology clinics recruited patients for the study. RESULTS: A total of 798 patients responded to the baseline wave of the study (708 responded to all three waves). The nonadherence rates for all patients (missing one or more injections) across these waves remained relatively stable at 39%, 37%, and 36%, respectively. The most common reason participants listed for missing injections was that they simply forgot to administer the medication (58%). Other factors including injection-site reactions, quality of life, patients' perceptions on the injectable medications, hope, depression, and support were also assessed in relation to adherence. CONCLUSIONS: This study characterizes factors that are associated with failure to fully adhere with disease modifying injection therapy for MS and underscores the principles associated with optimizing adherence and its implications for effective treatment of the disease process in MS.