Multiple Sclerosis: Schwid SR

Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA, Cutter GR, Freedman MS, Kappos L, Lublin FD, McFarland HF, Metz LM, Miller AE, Montalban X, O'Connor PW, Panitch H, Richert JR, Petkau J, Schwid SR, Sormani MP, Thompson AJ, Weinshenker BG, Wolinsky JS. · Department of Neurology, Free University Medical Center in Amsterdam, PO Box 4075, 1007 MB Amsterdam, The Netherlands. · Neurology. · Pubmed #18362273 No free full text.

Abstract: The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

Schwid SR, Cutter GR. · No affiliation provided · Neurology. · Pubmed #16534098 No free full text.

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Schwid SR, Murray TJ. · No affiliation provided · Neurology. · Pubmed #15824329 No free full text.

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Caine ED, Schwid SR. · No affiliation provided · Neurology. · Pubmed #12221154 No free full text.

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Schwid SR, Bever CT. · No affiliation provided · Neurology. · Pubmed #11425925 No free full text.

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Schwid SR, Trotter JL. · No affiliation provided · Neurology. · Pubmed #10802772 No free full text.

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Schwid SR, Noseworthy JH. · No affiliation provided · Neurology. · Pubmed #10449101 No free full text.

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Mehta LR, Dworkin RH, Schwid SR. · Neuroimmunology Unit, University of Rochester Medical Center, 601 Elmwood Avenue, Box 605, Rochester, NY 14586, USA. · Nat Clin Pract Neurol. · Pubmed #19194388 No free full text.

Abstract: Considerable interest has been shown in the potential anti-inflammatory effects of polyunsaturated fatty acids (PUFAs) in multiple sclerosis (MS) and other autoimmune inflammatory disorders. Studies suggest a modest association between consumption of low levels of unsaturated fat and an increased incidence of MS. Moreover, in vitro and in vivo studies have demonstrated that omega-3 and omega-6 PUFA supplementation can reduce immune-cell activation via a number of complex pathways. Noncontrolled and controlled clinical trials of PUFA supplementation in patients with MS have, however, provided mixed results. These studies had important limitations in design and selection of outcome measures, and these factors might partially explain the inconsistent results. We propose that the potential role of PUFAs as disease-modifying, anti-inflammatory treatments for MS should be revisited in proof-of-concept trials that use accepted MRI outcome measures.

O'Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH. · Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Pain. · Pubmed #17928147 No free full text.

Abstract: Pain is common in patients with multiple sclerosis (MS), but estimates of its prevalence have varied widely. The literature describing pain in MS patients spans four decades and has employed a range of different methodologies. We undertook a systematic review in order to summarize current understanding of the association between MS and pain and provide a basis for the design and interpretation of future studies. The point prevalence of pain in patients with MS is nearly 50%, and approximately 75% of patients report having had pain within one month of assessment. Pain adversely affects most aspects of health-related quality of life, including functional domains such as the ability to work. The presence of pain in patients with MS is associated with increased age, duration of illness, depression, degree of functional impairment, and fatigue. Several different types of pain are found in patients with MS, including extremity pain, trigeminal neuralgia, Lhermitte's sign, painful tonic spasms, back pain, and headache. Putative mechanisms of pain in patients with MS are discussed, and a classification of pain in MS is proposed. Few randomized clinical trials of treatments for MS pain have been conducted, and the limitations of current knowledge regarding approaches for treating MS pain are discussed. Suggestions for future studies that would increase understanding of the natural history, mechanisms, and treatment of pain in patients with MS are presented.

Schwid SR, Covington M, Segal BM, Goodman AD. · Department of Neurology, University of Rochester Medical Center, NY, USA. · J Rehabil Res Dev. · Pubmed #12051465 No free full text.

Abstract: Fatigue is a very common symptom of multiple sclerosis (MS). Theoretically, fatigue may be related to neuromodulation by soluble products of the autoimmune process or by disruption of central nervous system pathways necessary for sustained activity, but little empirical evidence supports these possibilities. Amantadine, pemoline, and modafanil improved fatigue in placebo-controlled clinical trials, but these studies all had significant limitations. Difficulty measuring fatigue has impeded studies of its characteristics, mechanisms, and therapeutics. Most studies have relied on self-report questionnaires. These may be inappropriate, however, because they can be easily confounded by other symptoms of MS, they are entirely subjective, and they require patients to make difficult retrospective assessments. Studies of fatigue would be improved by including measures of more rigorously defined, quantifiable components of fatigue. For example, motor fatigue can be measured as the decline in strength during sustained muscle contractions. Cognitive fatigue can be measured as the analogous decline in cognitive performance during tasks requiring sustained attention. Lassitude is defined as a subjective sense of reduced energy, and it can be measured with the use of a visual analog diary. These measures provide reproducible results and demonstrate significant differences between MS patients and healthy controls. Dividing fatigue into these components can provide objective assessments that are less likely to be confounded by other symptoms of MS, such as weakness, spasticity, cognitive impairment, and depressed mood.

Cohen JA, Carter JL, Kinkel RP, Schwid SR. · Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Cleveland Clinic Foundation, OH 44195, USA. · J Neuroimmunol. · Pubmed #10426359 No free full text.

Abstract: There is increasing impetus to begin disease-modifying therapy for relapsing multiple (R-MS) early, before the development of irreversible tissue damage and resultant permanent disability. However, all of the currently-approved therapies for relapsing multiple sclerosis are only partially effective for patients as a group. Treatment failure can be due to noncompliance with therapy, intolerable adverse effects, the development of neutralizing antibodies, or non-responsive disease. Neurologists managing patients on disease-modifying therapy for R-MS must remain vigilant for these issues and take appropriate action when necessary.

Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR, Anonymous00039. · University of Rochester, Rochester, NY, USA. · Lancet. · Pubmed #19249634 No free full text.

Abstract: BACKGROUND: Clinical studies suggested that fampridine (4-aminopyridine) improves motor function in people with multiple sclerosis. This phase III study assessed efficacy and safety of oral, sustained-release fampridine in people with ambulatory deficits due to multiple sclerosis. METHODS: We undertook a randomised, multicentre, double-blind, controlled phase III trial. We randomly assigned 301 patients with any type of multiple sclerosis to 14 weeks of treatment with either fampridine (10 mg twice daily; n=229) or placebo (n=72), using a computer-generated sequence stratified by centre. We used consistent improvement on timed 25-foot walk to define response, with proportion of timed walk responders in each treatment group as the primary outcome. We used the 12-item multiple sclerosis walking scale to validate the clinical significance of the response criterion. Efficacy analyses were based on a modified intention-to-treat population (n=296), which included all patients with any post-treatment efficacy data. The study is registered with ClinicalTrials.gov, number NCT00127530. FINDINGS: The proportion of timed walk responders was higher in the fampridine group (78/224 or 35%) than in the placebo group (6/72 or 8%; p<0.0001). Improvement in walking speed in fampridine-treated timed walk responders, which was maintained throughout the treatment period, was 25.2% (95% CI 21.5% to 28.8%) and 4.7% (1.0% to 8.4%) in the placebo group. Timed walk responders showed greater improvement in 12-item multiple sclerosis walking scale scores (-6.84, 95% CI -9.65 to -4.02) than timed walk non-responders (0.05, -1.48 to 1.57; p=0.0002). Safety data were consistent with previous studies. INTERPRETATION: Fampridine improved walking ability in some people with multiple sclerosis. This improvement was associated with a reduction of patients' reported ambulatory disability, and is a clinically meaningful therapeutic benefit.

Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, Cohen R, Marinucci LN, Blight AR, Anonymous00326. · Multiple Sclerosis Center, Chief Neuroimmunology Unit, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Ave., Room 6-8521, Box 605, Rochester, NY 14642, USA. · Neurology. · Pubmed #18672472 No free full text.

Abstract: OBJECTIVE: To examine the efficacy and safety of three different doses of sustained-release fampridine in people with multiple sclerosis (MS). METHOD: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study recruited 206 participants at 24 centers in the United States and Canada. After a single-blind, 2-week placebo run-in, participants were randomly assigned to receive fampridine (10, 15, or 20 mg twice daily) or placebo for 15 weeks. The primary efficacy variable was percent change in walking speed based on the timed 25-foot walk. RESULTS: Trends for increased walking speed were consistent across dose groups vs placebo, but not significant, on the prospective analysis. An increase from baseline in lower extremity strength during the 12-week stable-dose period was seen in the groups receiving 10- and 15-mg doses, compared with placebo (p = 0.018 and 0.003). There were no significant changes in other secondary assessments. Post hoc analysis revealed subsets of participants in each dose group with walking speeds during the treatment period that were consistently faster than during the nontreatment period. There were significantly more "consistent responders" in the drug-treated groups than in the placebo group (36.7% compared with 8.5%). Consistent responders showed significantly greater improvement in self-assessed ambulation on the 12-Item MS Walking Scale than did nonresponders. Fampridine was generally well tolerated. Severe and serious adverse events were more frequent at the highest dose. CONCLUSIONS: This phase 2 study suggests that a subgroup of patients, when treated with fampridine, experiences a clinically relevant improvement in walking ability, which is sustained for at least 14 weeks.

Schwid SR, Decker MD, Lopez-Bresnahan M, Anonymous00347. · Department of Neurology, University of Rochester, Rochester, NY, USA. · Neurology. · Pubmed #16380621 No free full text.

Abstract: Immunologic response was assessed prospectively using influenza vaccine in 86 patients with multiple sclerosis (MS) who were taking interferon beta-1a and 77 patients who were not taking interferon. Blood samples were assayed for hemagglutination inhibition (HI) titers 0, 21, and 28 days after immunization. The two groups were similar in the proportion of patients achieving an HI titer of 40 or greater, the prespecified primary end point and on all secondary indicators of immune response.

Schwid SR, Thorpe J, Sharief M, Sandberg-Wollheim M, Rammohan K, Wendt J, Panitch H, Goodin D, Li D, Chang P, Francis G, Anonymous00131, Anonymous00132. · Department of Neurology, University of Rochester, Rochester, NY 14642, USA. · Arch Neurol. · Pubmed #15883267 links to  free full text

Abstract: BACKGROUND: The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-1a therapy with 44 microg 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 microg 1 time weekly (QW). OBJECTIVE: To determine the effect of changing the dosage from 30 microg QW to 44 microg TIW in this extension of the EVIDENCE Study. DESIGN/PATIENTS: Patients with relapsing MS originally randomized to interferon beta-1a, 30 microg QW, during the comparative phase of the study changed to 44 microg TIW, whereas patients originally randomized to 44 microg TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks. MAIN OUTCOME MEASURE: The within-patient pretransition to post-transition change in relapse rate. RESULTS: At the transition visit, 223 (73%) of 306 patients receiving 30 microg QW converted to 44 microg TIW, and 272 (91%) of 299 receiving 44-microg TIW continued the same therapy. The post-transition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-microg TIW (P = .03). The change was greater in those increasing dose and frequency (P = .047). Patients converting to the 44-mug TIW regimen had fewer active lesions on T2-weighted MRI compared with before the transition (P = .02), whereas those continuing the 44-microg TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-1a therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy. CONCLUSIONS: Patients receiving interferon beta-1a improved on clinical and MRI disease measures when they changed from 30 microg QW to 44 microg TIW.

Schwid SR, Petrie MD, Murray R, Leitch J, Bowen J, Alquist A, Pelligrino R, Roberts A, Harper-Bennie J, Milan MD, Guisado R, Luna B, Montgomery L, Lamparter R, Ku YT, Lee H, Goldwater D, Cutter G, Webbon B, Anonymous00214. · University of Rochester, Rochester, NY, USA. · Neurology. · Pubmed #12821739 No free full text.

Abstract: BACKGROUND: Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. The therapeutic effects of cooling in patients with MS have not been convincingly demonstrated because prior studies were limited by uncontrolled designs, unblinded evaluations, reliance on subjective outcome measures, and small sample sizes. OBJECTIVE: To determine the effects of a single acute dose of cooling therapy using objective measures of neurologic function in a controlled, double-blinded setting, and to determine whether effects are sustained during daily cooling garment use. METHODS: Patients (n = 84) with definite MS, mild to moderate disability (Expanded Disability Status Scale score < 6.0), and self-reported heat sensitivity were randomized into a multicenter, sham-treatment controlled, double-blind crossover study. Patients had the MS Functional Composite (MSFC) and measures of visual acuity/contrast sensitivity assessed before and after high-dose or low-dose cooling for 1 hour with a liquid cooling garment. One week later, patients had identical assessments before and after the alternate treatment. Patients were then re-randomized to use the cooling garment 1 hour each day for a month or to have observation only. They completed self-rated assessments of fatigue, strength, and cognition during this time, and underwent another acute cooling session at the end of the period. After 1 week of rest, they had identical assessments during the alternate treatment. RESULTS: Body temperature declined during both high-dose and low-dose cooling, but high-dose produced a greater reduction (p < 0.0001). High-dose cooling produced a small improvement in the MSFC (0.076 +/- 0.66, p = 0.007), whereas low-dose cooling produced only a trend toward improvement (0.053 +/- 0.031, p = 0.09), but the difference between conditions was not significant. Timed gait testing and visual acuity/contrast sensitivity improved in both conditions as well. When patients underwent acute cooling following a month of daily cooling, treatment effects were similar. Patients reported less fatigue during the month of daily cooling, concurrently on the Rochester Fatigue Diary and retrospectively on the Modified Fatigue Impact Scale. CONCLUSIONS: Cooling therapy was associated with objectively measurable but modest improvements in motor and visual function as well as persistent subjective benefits.

Schwid SR, Goodman AD, McDermott MP, Bever CF, Cook SD. · Department of Neurology, University of Rochester Medical Center, NY, USA. · Neurology. · Pubmed #11971105 No free full text.

Abstract: As a first step toward understanding which changes should be considered as meaningful, the authors assessed the reliability of quantitative functional tests on 5 consecutive days in 63 patients with MS, determining the range of measurement variability present when patients are clinically stable. Time to walk 25 feet (T25FW) and the 9-hole peg test (9HPT) varied by <20% of individual mean scores on repeated testing. Therefore, a 20% change on these tests can be considered to be the threshold that reliably indicates a true change in function for an individual.

Weinstein A, Schwid SR, Schiffer RB, McDermott MP, Giang DW, Goodman AD, Schwid SI. · Department of Neurology, University of Rochester Medical Center, NY 14642, USA. · Arch Neurol. · Pubmed #10190822 links to  free full text

Abstract: BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.

Mehta LR, Schwid SR, Arnold DL, Cutter GR, Aradhye S, Balcer LJ, Calabresi PA, Cohen JA, Cole PE, Glanzman R, Goelz S, Inglese M, Kapoor R, Kappos L, Kreitman R, Lublin FD, Mann A, Marrie RA, O'Looney P, Polman CH, Ravina BM, Reingold SC, Richert JR, Sandrock AW, Waubant E. · University of Rochester Department of Neurology, Rochester, NY, USA. · Mult Scler. · Pubmed #19389749 No free full text.

Abstract: BACKGROUND: There is considerable interest in tissue-protective treatments for multiple sclerosis (MS). METHODS AND OBJECTIVES: We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods. RESULTS: Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3-6 months after starting treatment) to the final visit 1 year later. Study designs aimed at reducing residual deficits following acute exacerbations are less straightforward, depending greatly on the anticipated rapidity of treatment effect onset. CONCLUSIONS: The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials.

Mikol DD, Barkhof F, Chang P, Coyle PK, Jeffery DR, Schwid SR, Stubinski B, Uitdehaag BM, Anonymous00042. · University of Michigan Medical Center, Ann Arbor, MI 48109-0316, USA. · Lancet Neurol. · Pubmed #18789766 No free full text.

Abstract: BACKGROUND: Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS. METHODS: In this multicentre, randomised, comparative, parallel-group, open-label study, patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were randomised to receive 44 mug subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse. A subpopulation of 460 patients (230 from each group) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume. Treatments were assigned by a computer-generated randomisation list that was stratified by centre. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00078338. FINDINGS: Between February and December, 2004, 764 patients were randomly assigned: 386 to interferon beta-1a and 378 to glatiramer acetate. After 96 weeks, there was no significant difference between groups in time to first relapse (hazard ratio 0.94, 95% CI 0.74 to 1.21; p=0.64). Relapse rates were lower than expected: 258 patients (126 in the interferon beta-1a group and 132 in the glatiramer acetate group) had one or more relapses (the expected number was 460). For secondary outcomes, there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions, although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions (0.24 vs 0.41 lesions per patient per scan, 95% CI -0.4 to 0.1; p=0.0002). Safety and tolerability profiles were consistent with the known profiles for both compounds. The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks. INTERPRETATION: There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome. The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity, which is an important consideration for ongoing and future trials in patients with RRMS.

Thompson JP, Noyes K, Dorsey ER, Schwid SR, Holloway RG. · Department of Neurology, University of Rochester, Rochester, NY, USA. · Neurology. · Pubmed #18663181 links to  free full text

Abstract: OBJECTIVE: To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS). METHODS: We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML). RESULTS: Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%. CONCLUSIONS: A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.

Mehta LR, Samuelsson MK, Kleiner AK, Goodman AD, Anolik JH, Looney RJ, Schwid SR. · Neuroimmunology Unit, Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA. · Mult Scler. · Pubmed #18208886 No free full text.

Abstract: Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system characterized by severe episodes of optic nerve and spinal cord inflammation. NMO-IgG (anti-aquaporin-4) has been recently described as a sensitive and specific marker for NMO. As there have been prior published reports of an association between NMO and systemic autoimmune diseases, the prognostic value of the antibody test in these cases is uncertain. We describe a 47-year old woman with recurrent transverse myelitis and a long-standing history of systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLS). While she did not have a history of optic neuritis, serological testing for the NMO-IgG was positive when she was admitted for her second episode of transverse myelitis. Testing for the NMO-IgG in cases of isolated or recurrent transverse myelitis attributed to current SLE and APLS may help clarify the diagnosis of a distinct disease process likely to cause recurrent and severe disability, warranting more aggressive immunotherapy.

Schwid SR, Panitch HS. · Department of Nuerology, University of Rochester, Rochester, New York 14642, USA. · Clin Ther. · Pubmed #18035202 No free full text.

Abstract: BACKGROUND: Interferon (IFN)-beta therapy represents an important advance in the management of relapsing multiple sclerosis (MS), but information about the relative benefits and risks of available preparations is limited. OBJECTIVE: This report describes the full results of the Evidence of Interferon Dose-response-European North American Comparative Efficacy (EVIDENCE) study, combining analyses that were previously reported in separate publications for different phases of the study. METHODS: The EVIDENCE study was a multicenter, randomized, assessor-blinded comparison of 2 IFN-beta dosing regimens. In the study, patients with relapsing MS were randomly assigned to SC IFN-beta1a 44 lag TIW (Rebif, Serono Inc., Geneva, Switzerland) or IM IFN-betala 30 mug QW (Avonex, Biogen Idec, Cambridge, Massachusetts) for 1 to 2 years. The primary clinical end point during the comparative phase was the proportion of patients who remained free from relapses; secondary and tertiary clinical end points included the annualized relapse rate and time to first relapse, re- spectively. All clinical and magnetic resonance imaging (MRI) evaluations were performed by blinded assessors. In the crossover phase of the study, patients who were originally randomized to low-dose QW treatment switched to the high-dose TIW treatment for an additional 8 months. Adverse events were determined by spontaneous reporting and monthly laboratory testing during the comparative phase. RESULTS: A total of 677 patients were enrolled in the study and evenly randomized to treatment; 605 patients completed the comparative phase and 439 completed the crossover phase. During the comparative phase, a significantly higher proportion of patients in the high-dose TIW treatment group remained free from relapses when compared with patients in the low-dose QW treatment group (adjusted odds ratio, 1.5; 95% CI, 1.1-2.0; P = 0.023). The high-dose TIW regimen was also associated with a significant reduction in the annualized relapse rate (-17%; P = 0.033) and a prolonged time to first relapse (hazard ratio, 0.70; P = 0.002). MRI measures of disease activity were significantly reduced in the high-dose TIW group compared with the low-dose QW treatment. During the crossover phase, a 50% reduction in mean relapse rates was observed in patients who converted from low-dose QW treatment to high-dose TIW treatment (P < 0.001), with significant concomitant reductions in MRI activity. Injection-site reactions were significantly more common with high-dose TIW treatment than with low-dose QW treatment (85% vs 33%; P < 0.001). Neutralizing antibody formation was more common with high-dose TIW treatment than with low-dose QW treatment (26% vs 3%; P < 0.001). CONCLUSIONS: The comparative phase of the EVIDENCE study found that treatment of MS with SC IFN-beta1a 44 microg TIW was associated with a significant reduction in clinical and imaging measures of disease activity over 1 to 2 years, when compared with IM IFN-betala 30 microg QW treatment. The crossover phase found that patients who changed from low-dose QW treatment to high-dose TIW treatment experienced enhanced benefits of treatment without a substantial increase in adverse events.

Ambrosio F, Boninger ML, Fitzgerald SG, Hubbard SL, Schwid SR, Cooper RA. · Department of Rehabilitation Sciences and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, USA. · J Rehabil Res Dev. · Pubmed #17943681 No free full text.

Abstract: Individuals with multiple sclerosis (MS) report decreased satisfaction with their mobility devices compared with individuals with spinal cord injuries (SCIs). This study (1) investigated the demographic differences between veterans with MS (V-MS) and veterans with SCI (V-SCI) who were issued a wheelchair by the Veterans Health Administration (VHA) and (2) described differences in mobility device prescription. We merged two VHA databases to obtain demographic and wheelchair information for all V-MS and V-SCI in 2000 and 2001. Descriptive information for issued wheelchairs was available for 2,154 V-MS and V-SCI. We found that V-MS were significantly less likely to receive higher quality wheelchairs (manual or power) compared with V-SCI (p < 0.001). The disparity in VHA wheelchair prescription between these two groups indicates a need for further research regarding the assistive device prescription process in these populations.

Dorsey ER, Thompson JP, Noyes K, Dick AW, Holloway RG, Schwid SR. · Department of Neurology, University of Rochester Medical Center, Rochester, NY 14620, USA. · Neurology. · Pubmed #17470756 No free full text.

Abstract: Using published data, we quantified the risk and benefits of natalizumab in relapsing multiple sclerosis using quality-adjusted life years (QALYs) as a metric. Over the first 2 years of therapy, the negative health effects from progressive multifocal leukoencephalopathy were small (loss of 0.001 QALYs) relative to the positive effects on relapses and disability resulting in 0.033 QALYs (12 quality-adjusted days) gained. For context, we performed an analogous calculation for interferon beta-1a, which also had a net health benefit of 0.033 QALYs (12 quality-adjusted days).