Search

Background:Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. Objective:To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. Methods:We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 (n=2156) and 2009 (n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Results:Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939-3101 for patients and US$16,302-18,928 for payers. Conclusion:Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them.

BACKGROUND: The main clinical determinants of quality of life (QOL) 5 years after clinically isolated syndrome (CIS) are Expanded Disability Status Scale (EDSS) score and conversion to clinically definite multiple sclerosis (CDMS). The aim of this study was to determine the demographic, clinical, and magnetic resonance imaging (MRI) factors associated with QOL 10 years after CIS. METHODS: Controlled High Risk Avonex® Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS) 10-year patients were assessed for CDMS, EDSS score, MRI T2 activity, brain parenchymal fraction, and patient-reported QOL. Associations were evaluated using analysis of variance models. RESULTS: A second clinical event consistent with CDMS and higher EDSS scores at years 5 and 10 were associated with lower 36-item Short Form Health Status Survey (SF-36) Physical Component Summary scores at year 10 (P < .01). Patients with earlier onset of CDMS had worse patient-reported Physical Component Summary, SF-36 Mental Component Summary, fatigue, and pain scores at year 10 than patients with later or no onset of CDMS. Neither initial randomization group nor any MRI metrics assessed at baseline or during follow-up were associated with QOL at 10 years. CONCLUSIONS: These results support the development of therapies for patients with CIS that significantly reduce the risk of conversion to CDMS and the progression of physical disability to milestones as low as EDSS scores of 2.0.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ~10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan-rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Examined drug and alcohol use and social background to determine their relationship to adolescent suicide attempts. Survey of 2,690 adolescents revealed that young women, farm residents, and in general, drug users were more likely to report suicide attempt. Women who were frequent alcohol users and heavy users of marijuana were more prone to suicide attempt than their male counterparts. (Author)

Approximately 85% of multiple sclerosis (MS) cases begin as clinically isolated syndromes (CIS). Results from the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS) demonstrated that, in patients with CIS, treatment with intramuscular (IM) interferon beta-1a (IFNβ-1a) 30 μg once weekly delayed conversion to clinically definite MS (CDMS) in the total population and in subgroups based on presenting syndromes and baseline magnetic resonance imaging (MRI) characteristics. Changes to clinical and MRI risk classification of presenting symptoms in recent studies prompted reanalysis of CHAMPS data. Presenting syndromes were assessed using a derived algorithm that stratifies patients into mono- or multifocal categories based on functional system scores. The ability of IM IFNβ-1a to delay progression to CDMS in subgroups based on clinical presentation and MRI characteristics was assessed. Reanalysis of CHAMPS patients showed that 30% could be classified by clinical criteria as having multifocal disease at baseline. IM IFNβ-1a initiated at a first demyelinating attack delayed CDMS in monofocal patients (P = 0.0013), patients with or without gadolinium-enhancing lesions (P = 0.0007, P = 0.0405) and patients with at least nine T2 lesions at baseline (P = 0.0044). These data confirm that IM IFNβ-1a delays conversion to CDMS in patients with CIS. [ABSTRACT FROM AUTHOR]

Abstract: Background: Difficulty walking is the most visible sign of disability among persons with multiple sclerosis (MS). However, little is known about mobility aid use by persons with MS living in the community. Objectives: To explore perceptions of mobility problems related to MS and patterns of mobility aid use by persons with MS residing in communities across the United States. Methods: We conducted a 30-minute telephone survey in mid-2007 with 703 community-dwelling, working-age adults who self-reported having MS. We identified potential survey respondents using membership lists of the National Multiple Sclerosis Society, oversampling individuals living in zip codes with relatively high poverty rates. All analyses, including calculation of simple percentages, used sampling weights to produce population estimates. The overall response rate was 73.4%. Survey questions asked basic information about all mobility aids used by respondents and details about up to two different aids. We used multivariable polychotomous logistic regression to predict use of various mobility aids accounting for demographic and disease characteristics. Results: In questions about the previous 2 weeks, needing to concentrate on walking because of MS was the most common problem cited (weighted percent = 79.3%), followed by MS making standing more difficult (69.9%), increased effort needed to walk (59.0%), and needing to hold onto furniture, walls, or someone''s arm when walking indoors every day (40.0%). Among the 703 respondents, 434 (weighted percent = 60.5%) reported using at least one mobility aid; the majority of these individuals reported using more than one type of aid. Manual wheelchairs were the most common mobility aid (63.4%), followed by canes (56.7%), power wheelchairs (36.7%), and scooters (32.2%). Among those using three or more different types of mobility aids, the large majority used manual wheelchairs (88.2%), followed by canes (65.4%). Persons who are married or living with partners were much less likely to use powered equipment than those who were never married (adjusted odds ratio [AOR] = 0.32; 95% CI: 0.13–0.82). Women were much less likely than men to use powered equipment (AOR = 0.40; 95% CI: 0.21–0.75). Conclusion: The vast majority of persons with MS who use at least one mobility aid own more than one type and about half own three or more different types of mobility aids. Persons with MS appear to “mix and match” different devices to suit their specific mobility needs. Given restrictive health insurance coverage policies for mobility aids, these findings raise questions about how persons acquire and pay for higher-technology mobility aids. [Copyright &y& Elsevier]

US residents can face serious financial barriers to obtaining prescription medications, including disease-modifying medications for multiple sclerosis (MS). We conducted 30-min telephone surveys with 983 persons with MS nationwide, 21-64 years old, to explore how financial and health insurance concerns affect access to services including MS drugs. Almost everyone (96.3%) had some health insurance. Multivariable logistic regression analyses accounted for demographic, disease and insurance characteristics. Only 10.8% of those <40 years old had never received disease-modifying medications, compared with 41.1% of persons aged 60-64. Among the uninsured, 36.8% reported having never taken these medications, compared with 21.2% of persons with health insurance. Adjusted odds ratio (95% CI) of using these drugs in prior 12 months among the uninsured (compared with insured persons) was 0.28 (0.08, 0.95). Just over 16% of persons with public health plans reported that their insurer initially denied coverage for MS medication. When asked about MS medications in general, 22.3% reported having not filled prescriptions, skipping doses or splitting pills because of cost concerns; 22.4% worried 'a lot' about getting MS medications when they needed them. Substantial fractions of persons with MS confront financial and health plan-related barriers to obtaining MS drugs. [ABSTRACT FROM AUTHOR]

Objective: The anatomic location of subsequent relapses in early multiple sclerosis (MS) appears to be predicted by the first attack location. We sought to determine if genetic polymorphisms associated with MS susceptibility are associated with attack location. Methods: 17 genome-wide association study-identified MS susceptibility polymorphisms were genotyped in 503 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed in multivariate repeated measures analyses (generalized estimating equations with robust standard errors). Results: The IL12A polymorphism was independently associated with increased odds of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009), as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The IL7R polymorphism was associated with reduced odds of attacks involving the brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034). Several other genes showed trends for association with attack location. Conclusions: Some of the MS susceptibility genes may be associated with MS attack location. The IL12A polymorphism is of particular interest given that interferon beta therapy appears to influence IL12 levels. These findings may lead to improved understanding of MS pathogenesis and treatment.

Objective: Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack. Methods: 503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack. Results: The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year. Conclusions: Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.

Background: Patients with clinically isolated syndrome (CIS) and characteristic magnetic resonance imaging (MRI) lesions are at high risk for multiple sclerosis (MS). However, patients with a minimal MRI lesion burden (a low T2-hyperintense [low T2] lesion count) may have borderline formal diagnostic criteria, presenting a clinical management challenge., Objective: Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals., Methods: CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 (first quartile; 2-8 lesions) or higher-T2 (second through fourth quartiles; ≥ 9 lesions) groups using baseline T2 lesion counts. The 5- and 10-year open-label extension of CHAMPS (CHAMPIONS) evaluated conversion to clinically definite MS (CDMS), MRI activity, relapses, and disability., Results: The vast majority of patients showed new disease activity by MRI and/or clinical criteria at 10 years (low-T2 86%; higher-T2 98%). Fewer low-T2 than higher-T2 patients developed CDMS (40% vs. 63%; p = 0.013); low-T2 patients also had fewer new brain lesions, less brain volume loss, and less disability progression., Conclusion: CIS patients with low T2 lesion counts show continued disease activity. However, all assessments of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients., (© The Author(s), 2014.)

Objective: Determine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS) predicted progression to clinically definite multiple sclerosis (CDMS) over the subsequent 30 months in intramuscular interferon beta-1a (IM IFNβ-1a)-treated patients vs placebo-treated patients., Methods: CHAMPS patients were randomized to once-weekly IM IFNβ-1a 30 μg or placebo for up to 36 months. MRI was performed every 6 months until CDMS confirmation. Patient groups were defined based on new T2 and/or Gd+ lesions at 6 months., Results: Thirteen IM IFNβ-1a patients (6.7%) and 24 placebo patients (12.6%) developed CDMS prior to month 6 and did not undergo the 6-month MRI. At 6 months, 29.7% of IM IFNβ-1a-treated patients vs 40.9% of placebo-treated patients were defined as having high MRI activity levels (≥2 new T2 and/or ≥2 Gd+ lesions). In this subgroup, estimated cumulative probabilities of CDMS were similar between groups (HR=0.88 [0.44-1.77], p=0.7227). A significant treatment response was seen for patients with <2 new T2 and <2 Gd+ lesions at 6 months (HR=0.39 [0.19-0.82], p=0.0120)., Conclusion: MRI scans 6 months after IM IFNβ-1a initiation in CIS patients predict early treatment non-response. Standardized scanning and monitoring may facilitate early disease management., (Copyright © 2014 Elsevier B.V. All rights reserved.)

To observe the pattern of recovery after treatment with intravenous Methylprednisolone (i.v. MP) for a relapse of multiple sclerosis (MS), and to determine the best time to plan further interventions such as rehabilitation, we assessed consecutive outpatients (n = 24) treated with i.v. MP for a relapse over a period of 12 weeks. Outcomes measures used were the Expanded Disability Status Scale (EDSS), the Incapacity Status Scale (ISS), the MOS Short Form-36 (SF-36), the Mental Health Inventory (MHI), and the MS-Related Symptom Checklist (MSSCL). There was statistically significant early improvement of EDSS and ISS scores, which was sustained until week 12, and significant improvement of MHI and MSSCL scores between 4 and 12 weeks. Although trends for improvement of scores reflecting the same pattern of recovery were observed with the SF-36 physical and mental composites, these changes did not reach statistical significance. Our results suggest that improvement of impairments and disability after treatment with i.v. MP for a relapse of MS occurs early, while improvement of subjective health status is delayed. Even after maximum improvement is reached, patients are left with multiple symptoms and functional limitations, and may benefit from additional rehabilitative interventions.

Background: Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value., Methods: We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis., Results: During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months., Conclusions: Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.

Objectives: To describe the occurrence of cerebral venous thrombosis in a 40-year-old man whose cerebral event was induced by a poor golf swing, to review the literature on possible mechanisms producing venous thrombosis, and to compare this case with the literature., Background: Headache is the most frequent symptom in patients with cerebral venous thrombosis. However, patients presenting with a headache due to cerebral venous thrombosis are uncommon. The known risk factors for thrombosis include both acquired and genetic factors. When the interaction of these two groups occurs, the magnitude of this interaction is thought to produce a dynamic state that can favor thrombosis. Our case report illustrates that moderate levels of anticardiolipin antibodies together with the mild trauma of a golf swing can induce a cerebral venous thrombosis. This case also suggests that although headache is rarely due to cerebral venous thrombosis, it should be excluded by good medical acumen and testing., Results: Minor trauma induced by a poor golf swing was chronologically related to the development of a progressive cerebral venous thrombosis. The patient had none of the risk factors associated with a predisposition to venous thrombosis: hypercoagulable state, concurrent infection, pregnancy/puerperium, collagen vascular disorder, malignancy, migraine, false-positive VDRL, previous deep vein thrombosis, renal disease, factor V Leiden, or a hematological disorder. There was no anatomical abnormality that would predispose the patient to a cerebral venous thrombosis. The only laboratory abnormality was a moderate anticardiolipin antibody level (25 GPL). The patient was placed on warfarin sodium therapy and is currently without clinical sequela from the venous thrombotic event., Conclusions: Under certain circumstances, minor trauma can induce cerebral venous thrombosis. A review of the literature indicates that cerebral venous thrombosis in the presence of anticardiolipin antibodies and in the absence of systemic lupus erythematosus is a rare event. Previously, only major traumatic events have been reported to be associated with cerebral venous thromboses. The chronological development of cerebral venous thrombosis after a faulty golf swing strongly indicates that given a background of moderate levels of anticardiolipin antibodies, even minor trauma can induce a venous thrombotic event.

Autoimmune diseases are typically characterized by a persistent inflammatory self-recognition process that ultimately leads to chronic progressive disability. Over the past several years we have addressed the fundamental question of why autoimmune diseases are chronic. Our working hypothesis in these studies has been that autoimmunity involves a continuous acquisition of new self-recognition events, thereby providing an inflammatory steady-state that leads to chronicity. This acquired T cell neoautoreactivity is commonly referred to as epitope spreading. By studying multiple sclerosis (MS) and its related animal model, experimental autoimmune encephalomyelitis (EAE), we have found that chronic progression of autoimmune disease is invariably linked to the development of an epitope-spreading process that manifests as a cascade of inflammatory T cell neoautoreactivities to a sequential series of predictable new target self-antigens. However, our most recent observations indicate that the emergence of epitope spreading is accompanied by a concurrent regression of the established primary autoreactivity associated with disease onset. Thus, our studies indicate that progression of autoimmune disease involves a shifting of T cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during progression to chronicity. Our data support the view that the natural development of self-recognition during autoimmune disease may best be understood when considered in the temporal context of an "epitope du jour" and "moving target" perspective.