In this large community sample, the severity of multiple sclerosis was more strongly associated with depressive symptoms than was pattern of illness. Clinicians should evaluate depression in patients with recent diagnoses of multiple sclerosis, major changes in functioning, or limited social support.

Approximately a fourth of this sample described having a chronic pain problem characterized by severe pain intensity and significant pain-related interference with activities. Disability due to pain may be more important than previously recognized for the MS population.

There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (> 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy.

Factors associated with falls in persons with MS are similar to those in other populations with neurologic diseases. Despite the high incidence of falls, fewer than 50% of people with MS receive information about prevention of falls from an HCP.

IMPORTANCE Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS.OBJECTIVE To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT. DESIGN, SETTING, AND PARTICIPANTS Hematopoietic Cell Transplantation forRelapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled.INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34 + selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT. MAIN OUTCOMES AND MEASURESThe primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes:(1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events.RESULTS Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176-250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%-89.0%) at 3 years. Progression-free survival and clinical relapse-free survival were 90.9% (90% CI, 73.7%-97.1%) and 86.3% (90% CI, 68.1%-94.5%), respectively, at 3 years. Adverse events were consistent with expected toxic effects associated with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvements were noted in neurologic disability, quality-of-life, and functional scores.CONCLUSIONS AND RELEVANCE At 3 years, HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function. Treatment was associated with few serious early complications or unexpected adverse events.

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Telephone-based physical activity promotion represents a promising approach to treating MDD in MS. Further research is warranted on ways to bolster the impact of the intervention and on mediators of the treatment effect.

Biopsychosocial models of chronic pain that recognize psychological and environmental factors as important aspects of adjustment to pain have been proposed for understanding chronic pain and related suffering in persons with multiple sclerosis (MS), but such models have not been empirically tested. The objective of this study was to test such a model by evaluating the associations of several psychosocial variables (i.e., pain-related catastrophizing, perceived social support, pain beliefs, and pain coping) with pain intensity, pain interference with functioning, and psychological functioning in persons with chronic pain and MS, after controlling for demographic and disease-related factors. Participants were 125 community-dwelling persons with MS and pain who completed a mailed questionnaire that included measures of pain intensity and interference, psychological functioning, catastrophizing, social support, and pain beliefs and coping. The psychosocial variables accounted for an additional 25% of the variance in average pain intensity after controlling for demographic and disease-related variables (p<.001). These variables explained an additional 22% of the variance in pain-related interference (p<.001) and 43% of the variance in psychological functioning (p<.001), after adjusting for demographic and MS-related variables and average pain intensity. Catastrophizing was consistently and independently associated with all criterion measures, whereas social support, pain beliefs, and pain coping were associated with some criterion measures but not others. The results provide empirical support for a biopsychosocial understanding of chronic pain in MS and suggest that specific psychosocial factors (e.g., catastrophizing) may be important regarding adjustment to pain in persons with MS.