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Presents summaries that are intended as a guide to scientific activity, mainly for lay readers. `Newer Magnetic Resonance Techniques and Disease Activity in Multiple Sclerosis: New Concepts and New Concerns,' by M. Filippi et al; `The Effect of Cross-Talk on MRI Lesion Numbers and Volumes in Multiple Sclerosis Using Conventional and Turbo Spin Echo,' by M. Filippi et al; `Comparing the Ability of Various Composite Outcomes to Discriminate Treatment Effects in MS Clinical Trials,' by De Goodkin et al.

These summaries are intended as a guide to current scientific research activity, mainly for lay readers. They contain less technical terminology and jargon than the orginal articles and provide explanations for that which is retained. The uneven length of the summaries is not a measure of their relative importance, but is due to a variation in the difficulty of explaining complex technical concepts or lengthy experimental protocols and results. The purpose of a summary is to alert, interest and inform the reader. For comprehensive details of the issues, methods, results and interpretations you are strongly advised to refer to the original article. Remember also that the published results of any single investigation should not be considered as definitive, or be interpreted in isolation, or reported out of context. Progress in the understanding of MS, as in any other field of science requires critical debate and often must await independent confirmation of findings. [ABSTRACT FROM AUTHOR]

Background: Economic burden studies can provide insights into the drivers leading to increasing healthcare costs. It can also provide a more holistic view of how diseases impact the welfare of patients and their families. Having concrete estimates of the economic burden across multiple diseases can help policymakers determine which diseases are economically more burdensome. This study aimed to review and summarise comprehensively economic burden studies across multiple diseases in the Nordic countries between 2000 and 2020. Methods: According to the 2020 PRISMA statement, a systematic literature review was conducted in PubMed, CINAHL, Academic Search Premier and Global Health databases using key terms related to the economic burden of any disease in Denmark, Finland, Greenland, Iceland, Norway and Sweden. Grey literature was also reviewed. Results: A total of 10,050 potential titles and abstracts were identified and screened, and 254 full-text papers that met the inclusion criteria were evaluated by two independent reviewers. Of these, 119 articles were included in a qualitative synthesis. Twenty-nine had clearly defined comparison groups, thus able to attribute the costs to the disease. Large variations concerning methodology and cost components were noted. Across diseases, the economic burden ranged from EUR 1668 per patient annually for chronic obstructive pulmonary disease to EUR 93,041 for multiple sclerosis. However, estimates varied widely, even within each disease. Conclusions: Our review highlights the need for more comparable economic burden studies. Future studies should focus on applying robust methodology and homogeneous cost-reporting methods to inform policymakers about which diseases are economically more burdensome. [ABSTRACT FROM AUTHOR]

These summaries are intended as a guide to current scientific research activity, mainly for lay readers. They contain less technical scientific terminology and jargon than the original articles and provide explanations for that whch is retained. The uneven length of the summaries is not a measure of their relative importance, but is due to a variation in the difficulty of explaining complex technical concepts or lengthy experimental protocols and results. The purpose of a summary is to alert, interest and inform the reader. For comprehensive details of the issues, methods, results and interpretations you are strongly advised to refer to the original article. Remember also that the published results of any single investigation should not be considered as definitive, or be interpreted in isolation, or reported out of context. Progress in the understanding of MS, as in any other field of science requires critical debate and often must await independent confirmation of findings. [ABSTRACT FROM AUTHOR]

Research shows that patients can have values and use practices that are different from those envisioned by technology developers. Using sociomaterialism as an analytical lens, we show how patients negotiated with digital self-monitoring in the context of a scientific study. Our paper draws on interviews with 26 patients with the chronic neurological disease multiple sclerosis (MS) who were invited to use an activity tracker and a self-monitoring app for a period of 12 months as part of their everyday life. Our study aims to fill a gap: relatively little is known about how digital self-monitoring becomes materialized in the everyday lives of patients with chronic diseases. We show that patients engaged in digital self-monitoring because they are eager to participate in research to contribute knowledge that will benefit the larger community of patients rather than to improve their personal self-management. Although respondents adhered to digital self-monitoring during the study, it is not self-evident that they would do so for private self-monitoring purposes. It became clear that respondents did not necessarily perceive digital self-monitoring as useful for their self-management practices due to their established knowledge and routines. Moreover, respondents referred to the inconvenience of having to perform self-monitoring tasks and the emotional burden of being reminded of the MS because of the digital self-monitoring. We conclude by indicating what could be considered when designing scientific studies, including the suitability of conventional study designs for evaluating technologies used daily by patients and the challenge of integrating patients' experiential knowledge into scientific practices. [ABSTRACT FROM AUTHOR]

This paper offers new insights into the promotion of the Exercise is Medicine (EIM) framework for mental illness and chronic disease. Utilising the Syndemics Framework, which posits mental health conditions as corollaries of social conditions, we argue that medicalized exercise promotion paradigms both ignore the social conditions that can contribute to mental illness and can contribute to mental illness via discrimination and worsening self-concept based on disability. We first address the ways in which the current EIM framework may be too narrow in scope in considering the impact of social factors as determinants of health. We then consider how this narrow scope in combination with the emphasis on independence and individual prescriptions may serve to reinforce stigma and shame associated with both chronic disease and mental illness. We draw on examples from two distinct research projects, one on exercise interventions for depression and one on exercise interventions for multiple sclerosis (MS), in order to consider ways to improve the approach to exercise promotion for these and other, related populations. [ABSTRACT FROM AUTHOR]

Background Recognizing the need for more evidence-based multiple sclerosis (MS) rehabilitation, in the mid-2000s several initiatives were undertaken to explore why there had been a paucity of such research and to determine strategies to reverse this pattern. Expert-Opinion-Paper In 2004 the National Multiple Sclerosis Society (NMSS) convened an expert opinion panel, reviewed evidence-based MS rehabilitation research, and published the paper on the web. It was concluded that much of the MS rehabilitation carried out was based on experience, with little research backing it up. Increasing the Quality and Quantity of MS Rehabilitation Research Largely as a result of the conclusions of the Expert-Opinion-Paper, the NMSS convened a conference of a large number of MS and rehabilitation experts in New York in May, 2005. This conference made many recommendations of ways to increase the quantity and quality of MS research. State of the Science Conference In September, 2006, a follow-up conference was held in Washington, D.C… This conference, primarily sponsored by the University of Washington Multiple Sclerosis Rehabilitation Research and Training Center (MS RRTC), focused on some of the under-studied "hidden" disabilities present in persons with MS. This paper discusses the details and recommendations of these latter two conferences. [ABSTRACT FROM AUTHOR]

This paper describes an unusual clinically isolated syndrome of inflammatory demyelination that was characterized by a right VI nerve palsy and right internuclear ophthalmoparesis (INO), along with an unusual form of dissociated nystagmus. Magnetic resonance imaging (MRI) revealed an isolated lesion within the right dorsomediolateral pontine tegmentum. Four years later, the subject developed a partial sensory transverse myelitis, confirming clinically definite multiple sclerosis (MS). This paper extends the range of isolated syndromes associated with MS. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a rescue treatment in multiple sclerosis (MS) patients not responding to first- or second-line therapies. To date, most of the treated cases had a secondary progressive disease course. However, patients with high inflammatory activity, but no secondary progression of the disease, could be candidates to take greater advantage of AHSCT. In this paper, we report two cases with very active, relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic resolution to disease activity. [ABSTRACT FROM AUTHOR]

Fractures resulting from osteoporosis are a major cause of morbidity and mortality in the developed world. People with multiple sclerosis experience reduced mobility and are susceptible to falls. Glucocorticoid use and reduced mobility are known risk factors for osteoporosis. This paper is a review of osteoporosis in people with multiple sclerosis, looking at its prevalence, risk factors and possible mechanisms. We also review management guidelines for osteoporosis in the general population and use these to propose guidelines for osteoporosis management amongst multiple sclerosis patients. A number of studies have examined the incidence of reduced bone mineral density amongst people with multiple sclerosis; the majority provide convincing evidence that bone mineral density is significantly reduced in multiple sclerosis patients. The most significant risk factors appear to arise from the chronic disease process of multiple sclerosis and not from glucocorticoid use. There are currently no guidelines or consensus as how best to treat osteoporosis amongst multiple sclerosis patients despite their being at an increased risk. We propose an algorithm for the screening and treatment of osteoporosis in people with multiple sclerosis. [ABSTRACT FROM PUBLISHER]

Natalizumab, a humanized monoclonal antibody directed against α4-integrin is a first-in-class disease-modifying therapy for the treatment of relapsing multiple sclerosis. Natalizumab is highly effective but has been associated with a risk of progressive multifocal leukoencephalopathy. Since the efficacy of natalizumab in relapsing forms of multiple sclerosis is viewed as superior to first-line agents, a growing number of neurologists are using natalizumab as the treatment of choice for patients with worsening MS. Owing to the recently reported cases of progressive multifocal leukoencephalopathy, a panel of neurologists met in February 2009 to discuss best practices for the use of natalizumab, with the goal of developing consensus-based recommendations on patient management to minimize the risk of progressive multifocal leukoencephalopathy. The panel consisted of a cross section of academic and community neurologists from the United States who treat multiple sclerosis in large centers and have extensive experience with natalizumab (approximating 2000 patient-years combined experience). This paper summarizes the panel's recommendations on the following: (1) appropriate patient selection for natalizumab; (2) routine monitoring and management of adverse events during natalizumab therapy; and (3) clinical vigilance monitoring and risk reduction for progressive multifocal leukoencephalopathy. [ABSTRACT FROM AUTHOR]

Natalizumab is the first α4-integrin antagonist indicated for the treatment of relapsing multiple sclerosis (MS). Natalizumab has been shown to delay the accumulation of physical disability and reduce relapses. In two large, double-blind, randomized, placebo-controlled, phase 3 clinical trials, natalizumab was effective as a monotherapy as compared with placebo, and in combination with interferon b as compared with placebo and interferon β. Natalizumab in combination with glatiramer acetate was also effective in a phase 2 clinical trial when compared with placebo and glatiramer acetate. Natalizumab monotherapy achieved a 68% relative reduction in annualized relapse rate, and 42% and 54% reductions in disability progression sustained for 12 and 24 weeks, respectively. In a subset of patients with highly active disease, natalizumab proved more effective, decreasing relapse rates by 81% and progression of disability (sustained for 24 weeks) by 64%. Natalizumab-treated patients experienced significant improvements in quality of life, as measured by the Short Form-36, as well as a 35% reduction in risk of clinically significant vision loss. Recent analyses also have demonstrated the potential for natalizumab to induce a state of 'no disease activity' and actual improvement in physical disability. The purpose of this paper is to review evidence for the efficacy of natalizumab, and put its use in MS into perspective. [ABSTRACT FROM AUTHOR]

The objective in this paper is to compare the cumulative incidence and incidence density of therapy-related acute myeloid leukaemia in two cohorts of patients with multiple sclerosis treated with mitoxantrone, and with previously reported data in the literature. Six new cases of acute myeloid leukaemia were observed by prospectively following two Spanish series of 142 and 88 patients with worsening relapsing multiple sclerosis and secondary-progressive disease treated with mitoxantrone. A literature review shows 32 further cases of acute myeloid leukaemia reported, 65.6% of which are therapy-related acute promyelocytic leukaemia. Five cases in the cohorts fulfilled the diagnostic criteria for acute promyelocytic leukaemia, and one patient was diagnosed with pre-B-acute lymphoblastic leukaemia. Acute myeloid leukaemia latency after mitoxantrone discontinuation was 1 to 45 months. The accumulated incidence and incidence density was 2.82% and 0.62%, respectively, in the Valencian cohort, and 2.27% and 0.44% in the Catalonian cohort. In the only seven previously reported series, the accumulated incidence varied from 0.15% to 0.80%. The real incidence of acute myeloid leukaemia after mitoxantrone therapy in the multiple sclerosis population could be higher as evidenced by the growing number of cases reported. Haematological monitoring should continue for at least 5 years after the last dose of mitoxantrone. These data stress the necessity of re-evaluating this risk. [ABSTRACT FROM AUTHOR]

Patients with clinically isolated syndrome (CIS) by definition do not have multiple sclerosis (MS) but are at risk of developing it. While studies show earlier immunomodulating drug use is effective, treatment must consider likely patient prognosis. In this paper we review current diagnosis, prognosis, and treatment literature for patients with CIS within Latin American clinical settings. Latin American MS experts, convened by ACINDES (The Civil Association for Research and Development in Health), reviewed current CIS (and early MS) literature and drew consensus conclusions. Three subgroups addressed separate questionnaires on CIS issues: prognosis, diagnosis, and treatment. MRI can contribute to predicting MS risk in patients with CIS; in Latin America, investigation of haplotype presence associated with CIS would be appropriate. McDonald's criteria and subsequent revisions enable earlier, more accurate MS diagnosis. Type A evidence exists supporting all leading immunomodulating MS drugs for effective treatment of CIS with a high risk of conversion to MS. In conclusion, patients with CIS are usually young, with often-limited symptomatic manifestations, and must be adequately prepared to receive preventive treatment. This consensus review should contribute to the dialogue between physicians and patients. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis (MS) is considered rare in China and reports on MS in the English literature are few. Methods A systematic literature search for articles with MS was made, particularly for papers published in the Chinese medical journals from mainland China. Results In China, the first case of MS was described in the medical records from Xiehe hospital in 1926, and the first autopsy case of MS was reported from Huashan hospital in 1957. Although reports on MS based on the information from hospital case-series have been increased gradually in the recent decades, there is no national surveillance on MS frequency in the population and population-based surveys on MS were few in China. Generally for Chinese patients with MS the mean age at onset of MS is around 30 years, with a few cases younger than 20 years; the most frequent site of the lesions in the central nervous system, based on the clinical symptoms or signs, is the spinal cord (usually more than 60%); there are few patients with a family history of MS; almost all patients are treated with corticosteroids. Reported prevalence rates of MS from population surveys in China are rather low (1-2 per 100,000) and higher in females than in males, which are comparable with the results from other populations in Asia. Conclusion The clinical and epidemiological aspects of MS in China are, in general, similar to that from other populations in Asia. Epidemiological studies and national surveillance on MS are required in China. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) has revolutionized the diagnosis and management of patients with multiple sclerosis (MS). Conventional MRI metrics are employed as primary endpoints in proof-of-concept clinical trials evaluating new drugs for MS and as secondary endpoints in definitive phase III trials. Metrics derived from non-conventional MRI techniques are now emerging and hold significant promise since they appear to be more correlated with the most disabling features of MS. However, none of these has been approved for use as a surrogate endpoint for accumulation of physical disability, which is the most important clinical endpoint of this disease. Taking into account the large numbers of patients needed, the extensive exposure to placebo, and the relatively long duration required for phase III clinical trials to show a meaningful effect on progression of disability, the need for a valid, reliable, and objective paraclinical marker of disease evolution cannot be overemphasized. This paper reviews the most up-to-date data regarding MRI techniques, their relationship with central nervous system pathology, as well as with clinical endpoints, and proposes future insights into the use of MRI metrics as surrogate endpoints in clinical trials of MS. [ABSTRACT FROM AUTHOR]

Using meta-analytic procedures, this study examined the overall effect of exercise training interventions on quality of life (QOL) among individuals with multiple sclerosis (MS). We searched MEDLINE, PSYCHINFO and CURRENT CONTENTS PLUS for the period of 1960 to November 2006 using the key words exercise, physical activity and physical fitness in conjunction with QOL and MS. We further conducted a manual search of bibliographies of the retrieved papers as well as literature reviews and contacted study authors about additional studies. Twenty-five journal articles were located and reviewed, and only 13 provided enough data to compute effect sizes expressed as Cohen's d. One hundred and nine effect sizes were retrieved from the 13 studies with 484 MS participants and yielded a weighted mean effect size of g = 0.23 (95% CI = 0.15, 0.31). There were larger effects associated with MS-specific measures of QOL and fatigue as an index of QOL. The nature of the exercise stimulus further influenced the magnitude of the mean effect size. The cumulative evidence supports that exercise training is associated with a small improvement in QOL among individuals with MS. [ABSTRACT FROM AUTHOR]

In 1868 the German Leopold Ordenstein (1835–1902) published in Paris a doctoral thesis in French language under the patronage of Jean-Martin Charcot (1825–1893). For the first time, multiple sclerosis and Parkinson's disease were clearly recognized as different clinical entities, based on clinical and pathological data. Ordenstein's work represents today a fundamental and often credited, yet still widely unknown, contribution to the history of these two diseases. The present paper delivers a synopsis of this key document. In addition, the life and work of Leopold Ordenstein will be reviewed. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is thought to be an autoimmune disease in which activated T-cells initiate a macrophage mediated destruction of CNS myelin. Bone marrow transplantation (BMT) is currently being evaluated in the treatment of MS in patients with aggressive disease activity. Autologous BMT could potentially reset the immune response to myelin antigens leading to immune tolerance and decreased disease activity. Allogeneic transplantation could reconstitute the immune system potentially arresting the progression of autoimmune disease. The purpose of this paper is to report a patient with MS who underwent allogeneic BMT for chronic myelogenous leukemia (CML) and showed continued evidence of active demyelinating disease by clinical and radiologic criteria over a period of two years. While this is only a single case report with inherent limitations, it suggests that the immune mediated destruction of CNS myelin in MS may not be prevented or aborted by immune system reconstitution, and is consistent with the idea that immune mediated tissue destruction in MS could be targeted against an abnormal antigen. [ABSTRACT FROM AUTHOR]

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxo®) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS. [ABSTRACT FROM AUTHOR]

In the actual scenario of the search for further genetic susceptibility factors, a recent paper noted an SNP in the UCP2 gene as a multiple sclerosis (MS) risk factor. UCP2 is a member of the mitochondrial proton transport family, which uncouples proton entry in the mitochondrial matrix from ATP synthesis. mtDNA haplogroups are also associated with ATP production, and are linked with mitochondrial proton transport. In this work, we studied the UCP2 SNP and the mitochondrial haplogroups distribution in a Spanish MS population, with a population sub-group of Basque-origin patients. Our results confirm the link between UCP2 SNP and MS, and show a slight relation between this SNP and mitochondrial haplogroups. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) has been attributed to different underlying pathological events. The aim of this paper is to present the first case report of a patient with Down's syndrome (DS) who died of a fulminant NMO. A 29-year-old woman with DS developed acute transverse myelitis, with complete visual loss and swollen optic discs. Two days later, she developed quadriplegia, respiratory arrest and died. The anatomical study demonstrated typical findings of DS in the brain without demyelinating lesions. A severe destruction of medulla and cervical cord with a very high degree of demyelination of the optic nerves was typical of monophasic NMO (Devic's disease). Most of the cases of NMO in Cuba are of the relapsing form, but this case report is the first one with monophasic NMO and DS with a very aggressive course. The link of the pathogenetic relationship between DS and NMO remains unclear; it may well be coincidence but the fact that the patient died very shortly after the onset suggests, at least on clinical grounds, that the presence of DS could have accelerated the fatal evolution of NMO. [ABSTRACT FROM AUTHOR]

Objectives: We explored the stigma that people with multiple sclerosis (MS) experienced in social relationships. Informed by the symbolic integrationist paradigm, this sociological study focuses on the creation of personal identity through interaction with others. The symbolic interactionist account of stigma examines the meaning and reality being negotiated in communication with others. Methods: Fourteen people with MS and their relatives were interviewed. The unstructured interviews were tape-recorded, transcribed and coded in accordance with the procedure of grounded theory. Results: Informants reported being ignored or, in contrast, having people overemphasize MS in interpersonal encounters. Although people tried to act tactfully, these acts were experienced as crucial stigmatizing. Informants were coping to counteract stigmatizing experiences in social relationships. Discussion: People with MS perceive that their bodily performance and impression management is being judged in interpersonal encounters. Being ignored or perceiving that MS is overemphasized indicates the dilemma of managing stigma in social networks. Consequently, during interaction and in social relationships, people with MS experience a sense of 'feeling more ill'. This paper describes strategies of networking to affirm self and identity. [ABSTRACT FROM AUTHOR]

Methylprednisolone plays an important role in the current treatment of multiple sclerosis (MS), particularly in the acute phase of relapse. It acts in various ways to decrease the inflammatory cycle including: dampening the inflammatory cytokine cascade, inhibiting the activation of T cells, decreasing the extravasation of immune cells into the central nervous system, facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha. This paper reviews the most recent observations on these mechanisms both to understand the disease mechanism and its treatment. As more becomes known about these mechanisms, it may become possible to design treatment regimes that are more specific towards both the individual and the disease state. [ABSTRACT FROM AUTHOR]

Using meta-analytic procedures, this study involved a quantitative synthesis of the difference in physical activity among individuals with multiple sclerosis (MS) compared with nondiseased and diseased populations and then examined factors (i.e., moderators) that explain variation in the overall difference in physical activity. We searched MEDLINE, PsycINFO and Current Contents Plus using the key words physical activity, exercise and physical fitness in conjunction with multiple sclerosis; conducted a manual search of bibliographies of the retrieved papers; and contacted study authors about additional studies. Overall, 53 effects were retrieved from 13 studies with 2360 MS participants and yielded a weighted mean effect size (ES) of -0.60 (95% CI= -0.44, -0.77). The weighted mean ES was heterogenous, Q = 1164.11, df=52, P <0.0001. There were larger effects with objective versus self-report measures of physical activity, nondiseased versus diseased populations and primary progressive versus relapsing–remitting MS. The cumulative evidence suggests that individuals with MS are less physically active than nondiseased, but not diseased, populations. [ABSTRACT FROM AUTHOR]

Health-related quality-of-life measures have been increasingly used in research into neurological disorders in recent years. The aim of this paper is to provide an objective appraisal of the evidence in regard to disease-specific quality-of-life measures used in research on health interventions for three degenerative neurological disorders: multiple sclerosis, motor neurone disease/amyotrophic lateral sclerosis and Parkinson's disease. A comprehensive search strategy was developed to include nine relevant electronic databases. Only studies pertaining to patient-based outcome measurements in multiple sclerosis, motor neurone disease and Parkinson's disease were included. We identified 76 eligible studies. As studies consisted of descriptive and cross-sectional survey study designs, results were reported qualitatively rather than in the form of a meta-analysis. Four disease-specific measures were found for Parkinson's disease, 11 for multiple sclerosis and one for motor neurone disease. We conclude that health-related quality-of-life measures are useful in assessing the impact of treatments and interventions for neurological disorders. However, further research is needed on the development of instruments using psychometric methods and on the validation, utilization and responsiveness of instruments to change. [ABSTRACT FROM AUTHOR]

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients. This paper describes these inconsistencies and their sources, and recommends a systematic approach that attempts to reduce the variability in interpreting clinical findings. [ABSTRACT FROM AUTHOR]

The pathogenesis of multiple sclerosis (MS) remains unknown. Although inflammation, demyelination and axonal injury are all involved, the primary pathogenic process is not clear. In this paper we challenge the hypothesis that MS is a primary inflammatory condition, and suggest that axonal damage may occur independently. [ABSTRACT FROM AUTHOR]

A case study is presented which examines the political and organizational processes associated with the attempt by the Department of Health, through its appraisal body NICE, to regulate the introduction of a new drug treatment (beta interferon) for patients with multiple sclerosis on 'cost-effectiveness' grounds. Underpinning this case is a concern to engage critically with the claim that we are witnessing the emergence of a de-regulated contractual form of health care provision within 'postmodernity'. A general assertion of this paper is that New Labour's NHS modernization programme has produced more rather than less central regulation over the activities of health trusts and the work of health care professionals. However, in this case study the Department of Health is shown to have ultimately failed in achieving its goal of regulating the introduction of beta interferon precisely because it involved social and economic factors beyond its direct control. These factors included the clinical needs of patients, the prescribing activities of doctors and the refusal of the pharmaceutical companies to reduce their profit margins. [ABSTRACT FROM AUTHOR]

In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income. [ABSTRACT FROM AUTHOR]

The article introduces the topics published within the issue. The topics include conceptual developments at both societal and individual levels by Adam Carrico and colleagues, importance of clinical and theoretical implications, awareness of the people with multiple scleroses with stigma by Nina Grytten and Per Maseide, and the presentation of the research paper by Rachel Solotaroff and colleagues.

This paper extends on previous data on prognosis in multiple sclerosis (MS), to encompass the entire course of the disease. The first episode suggestive of MS [the clinically isolated syndrome (CIS)] was included as a starting point, and the speed of secondary progression as an end point. Primary progressive MS was not included. Unique preconditions, with one neurological service covering the Göteborg district, allowed for establishing a strictly population-based, essentially untreated 15-year incidence cohort of 308 MS patients who were followed for 25 years. Survival analysis was performed as Kaplan–Meyer graphs, and independent predictors were ascertained by Cox regression analysis. A matrix of several predictors and end points was created. From CIS, a higher risk of developing clinically definite MS (CDMS), secondary progressive course and Disability Status Scale 7 (DSS7) was predicted by efferent tract lesions. However, less than 25% had reached DSS7 25 years after CIS with pure afferent lesions or other favorable predictors. During the first five years, higher relapse frequency, as well as incomplete remission of early bouts, predicted higher risks of secondary progressive course and DSS7 during follow-up to 25 years. However, these early predictors were unable to predict the rate of progression, which seems to contain an element of the disease process unassociated with its early events. Only late predictors, such as a shorter time from onset to secondary progression (1–10 years) and a higher number of functional systems involved at onset of progression predicted a faster progression rate. Predictors from this study could be used to refine historically controlled trials. [ABSTRACT FROM AUTHOR]

Traditional paper-and-pencil neuropsychological batteries used to document cognitive deficits in multiple sclerosis (MS) patients lack timing precision. This makes it difficult to accurately measure psychomotor slowing, a central cognitive symptom of MS. Additionally, traditional batteries lack multiple alternate forms necessary to control for practice effects when assessing cognition over time. Finally, such batteries are lengthy and expensive. Computerized neuropsychological batteries address many of these shortcomings. They measure response time more precisely, require less administration time, include alternate forms, and are ideal for rapid screening/triage. Although there are normative data on the reliability and validity of computerized measures, there have been no controlled validation studies with MS patients. The current study was designed to validate a computerized neuropsychological battery (ANAM) for use with relapsing remitting (RR) MS patients. Prior to initiation of interferon-β-1a (Avonex) treatment, subjects participated in a neuropsychological evaluation consisting of traditional and computerized measures. Moderate-to-high correlations were found between computerized and traditional measures. Computerized tests accurately predicted performance on key traditional tests. The battery was also concordant with traditional measures in identifying RR MS patients with and without neurocognitive impairment. Findings are discussed with respect to increased accuracy and accessibility of neuropsychological evaluations for MS patients. [ABSTRACT FROM AUTHOR]

Beta-interferon (beta-IFN) has a proven treatment effect on relapsing–remitting multiple sclerosis (MS), presumably through its regulatory properties on T-cell activation and cytokine production. This paper examines whether combination therapy of beta-IFN with prednisone would enhance immunoregulatory effects of beta-IFN by measuring serum levels of selected proinflammatory cytokines and soluble T-cell activation markers associated with MS. The selected markers were analyzed in MS patients treated with beta-IFN alone (n = 22) and beta-IFN combined with a low daily dose of prednisone (n =33), as compared with those in 27 healthy controls at baseline and at a three-month interval for one year. The study confirmed that beta-IFN treatment inhibited serum levels of tumor necrosis factor-alpha (TNFα) and intracellular adhesion molecule-1 (IC AM-1) in patients with MS. However, combination therapy did not significantly enhance the inhibitory effect of beta-IFN treatment on the production of TNFα, interleukin (IL)-12, IL-2R, and ICAM-1, while the addition of prednisone antagonized the effect of beta-IFN on up-regulation of IL-10 and soluble CD95. No difference in the occurrence of binding antibodies to beta-IFN was found between the two treatment groups. The findings are important for the understanding of the role of combination therapy in the treatment of MS. [ABSTRACT FROM AUTHOR]

This paper profiles nursing home residents with multiple sclerosis (MS) at the time of admission, including sociodemographic characteristics, health status measures, and treatments received. Admission assessments from the Minimum Data Set are used to create these profiles of residents with MS. There are 9013 admission assessments in the MDS for residents with MS between June 22, 1998 and January 17, 2000 analyzed for this study. Residents with MS are distinctly younger at admission than most nursing home residents, averaging 57.98 years of age. Recently admitted residents with MS are more physically dependent than other nursing home residents and tend to have limited range of motion and loss of voluntary movement. About one in three newly admitted residents with MS had some degree of impaired cognitive function. Over one third of residents with MS were depressed at admission, yet only 11.7% of recently admitted residents with MS were evaluated by a licensed mental health specialist. This prompts concern about the psychosocial well-being of MS residents in nursing homes. [ABSTRACT FROM AUTHOR]

Patients suffering from multiple sclerosis have a high frequency of cognitive deficits usually attributable to demyelination and axonal loss in the subcortical white matter. Neurologic abnormalities referable to cortical function are uncommon but have been described. The present study describes three patients with clinically definite MS with deficits in cognitive function referable to cortical location. Two of the patients underwent positron emission tomography and showed profound cortical hypometabolism adjacent to subcortical white matter lesions seen on MRI. This paper points out that neurologic deficits referable to cortical sites may be caused by subcortical white matter lesions and that cognitive dysfunction in patients with MS may progress rapidly in the absence of motoria deficits or other evidence of clinical deterioration. Multiple Sclerosis (2000) 6, 50 – 55. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic neuro-inflammatory disease. Its diagnosis and evaluation require a visual assessment in brain magnetic resonance images. This neurological disease is characterized by its unpredictable evolution. The most common form is relapsing–remitting multiple sclerosis, consisting of episodes of neurological dysfunction remitting with a variable degree of recovery. The underlying mechanisms are still unknown and have no mathematical models to explain this spatial and temporal dissemination. The main objective of this paper is to propose an approach based on chaos theory to define the clinical characteristics for lesion progression, principally its evolution. Previous authors have explored the nervous system by accurately modeling their attractors in the phase space and reproducing a non-linear result. This remains to be compared with chaotic attributes. In this work, multiple sclerosis lesions are treated through modeling and calculating of their degree of evolution. This is a retrospective study of cases collected from the National Institute of Neurology Mongi Ben Hmida. It included 74 patients with an age group ranging from 20 to 72 years. Four clinical trials are properly discussed: unstable cases with active lesions may be described by dynamic and non-linear systems presenting higher chaos value compared to ill patients with inactive lesions. On the other hand, the accuracy of chaos demonstration can be favorably affected by the reduced resolution of magnetic resonance images. Therefore, the interest is in preprocessing to improve the eventual results. High accuracy was achieved for the models discussed in this paper (91.97–85.1%). Accordingly, the suitability and practical usefulness of the ‘simple’ pretreatment to achieve multiple sclerosis classification are demonstrated. [ABSTRACT FROM AUTHOR]

Disease progression and irreversible disability in multiple sclerosis results from incomplete recovery from relapses, but most importantly from insidious disease progression. Although magnetic resonance imaging parameters, such as new lesion rate and gadolinium enhancement, reflect inflammation and disease activity they have no bearing on disease progression. Until now the T2 lesion load or disease burden has been relied upon for this, despite its poor relationship with disability measures. This paper looks at the mechanisms responsible for disease progression and discusses the MR techniques now available to reflect these pathological processes. [ABSTRACT FROM AUTHOR]

Urea cycle disorders are a group of inborn errors of metabolism caused by dysfunction of any of the six enzymes or two transport proteins involved in urea biosynthesis. In this paper, we report a patient who presented with neurological dysfunction and coma in the immediate postpartum period. She was misdiagnosed for many years as a case of multiple sclerosis. The importance of reporting this case is to illustrate that the wrong diagnosis of patients as being affected with multiple sclerosis for many years due to magnetic resonance imaging abnormalities rather than the classic relapsing–remitting nature of the disease may lead to catastrophic consequences. The patient was treated with intravenous steroids several times, which is contraindicated in patients with urea cycle disorders as it may precipitate acute hyperammonemic attacks. In addition, the management of urea cycle disorder could have started earlier and avoided multiple admissions to the intensive care unit. We believe that the presence of symmetric hyperintense insular cortical changes are seen in multiple hyperammonemic processes, and in the context of the clinical presentation and high ammonia levels can be suggestive of a urea cycle disorder. For any patient presenting with atypical clinical features, images should be reviewed and discussed in detail with an experienced neuroradiologist. In addition, the ammonia levels should be checked if a urea cycle disorder is suspected. [ABSTRACT FROM AUTHOR]

The weak correlation between inflammatory activity and disease progression in patients with multiple sclerosis has shifted the emphasis from inflammatory monitoring to the investigation of the pathological processes of demyelination, axonal loss, and gliosis. New magnetic resonance imaging (MRI) techniques that have been developed to measure these processes appear very promising. This paper will briefly discuss potential body fluid markers of axonal loss, gliosis and demyelination, as the pathological substrates of brain atrophy, their function and the principles behind their future study in patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination. Although it is widely accepted that demyelination in MS results from an active inflammatory process, the cause of the inflammation is still not completely resolved. Findings in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and observations in human MS have led to the hypothesis that MS is an autoimmune disease mediated by autoreactive T cells with specificity for myelin antigens. The identity of the brain antigen(s) which is (are) the primary target(s) of the autoimmune process is not known, but current evidence indicates that myelin basic protein (MBP) is a likely candidate. In this paper we will overview some of the experimental evidence suggesting that MBP reactive T cells hold a central position in the pathogenesis of MS, and discuss some of the currently tested therapeutic strategies in MS which are directed towards the pathogenic MBP reactive T cells. Although there appears to be no direct correlation between anti-MBP T cell responses and clinical disease activity, some recent observations suggest that monitoring of anti-MBP T cell responses could be helpful to study immunological efficacy of experimental immunotherapies in MS. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries. Methods: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria. Results: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94–97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89–96%) and the overall negative predictive value (NPV) was 99% (95% CI 96–100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases. Conclusions: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries. [ABSTRACT FROM AUTHOR]

The article offers information on the performance of the journal "Multiple Sclerosis" in the year 2008. It is reported that the greatest achievement for this clinical neurology journal was that, its impact factor increased from 2.77 to 3.26 which placed it at the 29th position. Further it is stated that the year 2008 witnessed an increase in quantity and quality of submissions. Also it is reported that the journal saw a 225 percent increase in on-line downloads.

The article focuses on the relationship of fatigue on multiple sclerosis (MS). Fatigue is intrinsic to MS and is the most commonly known symptom of the disease. Fatigue is a sense of exhaustion, lack of energy, or tiredness. Several papers related to fatigue are discussed within the issue of the journal.

Comments on the paper 'Chromosome 19 locus apolipoprotein C-11 association with multiple sclerosis,' which was published in the journal 'Multiple Sclerosis.' Criticisms on the number of patients and controls; Argument against the method of allele grouping employed in the statistical analysis; Association of chromosome 19 locus apolipoprotein C-11 with relapsing-remitting/secondary progressive multiple sclerosis.

There is an evident need for a quantitative laboratory marker for ascertaining disease activity and treatment effects in multiple sclerosis (MS) patients. Activity of the disease process in MS is accompanied by myelin breakdown and appearance of myelin basic protein (MBP) in cerebrospinal fluid (CSF). In this paper MBP in CSF of relapsing-remitting (RR) MS patients is reviewed. MBP in CSF is a fragment containing an epitope corresponding to aminoacid residues 45 – 89 of the native molecule. From several relevant studies about CSF MBP in RR MS the following relations can be concluded: CSF MBP levels in active MS patients are frequently increased (45 – 100%), remain increased until 5 to 6 weeks after onset symptoms and are higher in polysymptomatic exacerbations and correlate with number of gadolinium-enhanced (Gd) lesions on MRI, severity of relapses, EDSS score and CSF intrathecal IgM synthesis. After an intravenous methylprednisolone treatment the increased CSF MBP levels return to normal values and reduction in CSF MBP is related to reduction in EDSS score, number of Gd lesions and CSF intrathecal IgM synthesis. [ABSTRACT FROM AUTHOR]

The authors reflect on the success of the development of the journal regarding multiple sclerosis in Great Britain. They cite that the journal aims to strive for excellence and meet the requirements of the medical community. Moreover, they emphasize the cooperation of the publication with the SAGE team leader Claire Minto.

A letter to the editor is presented in response to the article "Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis," by Biljana D. Beretich and Thomas M. Beretich.

Introduction: This paper reviews the most important articles using data from the Danish Multiple Sclerosis Registry (DMSR) published in the past 25 years. Research topics: These articles include: descriptive epidemiological studies, indicating that the female incidence of multiple sclerosis (MS) in Denmark has increased considerably; follow-up studies on social events, showing that patients at a high rate lose their working ability and their spouses/partners; mortality studies, demonstrating a considerable excess mortality; cause-of-death studies; comorbidity studies; and, most importantly, historical prospective studies identifying some risk factors (e.g. infectious mononucleosis) and refuting others (head trauma and a number of occupational exposures e.g. nurses, utility workers, people exposed to solvents). The most important results are briefly presented. Conclusion: The Danish MS register has proven to be a valuable tool for MS epidemiology and has provided knowledge that could not otherwise be achieved. [ABSTRACT FROM PUBLISHER]

The number of new gadolinium-enhancing lesions discovered via magnetic resonance imaging is a well-established outcome for multiple sclerosis studies, especially Phase II Studies. Due to the high cost of magnetic resonance imaging scans, many investigators select participants for the presence of lesions. While this selection procedure is thought to improve the power of inferences, the effect of screening for baseline activity on parameter estimation and interval coverage has not yet been examined. The objective of this study was to investigate the performance of the negative binomial distribution for modeling lesion count data in multiple sclerosis when patients have been selected for activity on a baseline scan. We performed computer simulations to investigate the influence of the screening process on inferences made using a negative binomial model about treatment effects in two independent samples. We also demonstrate how the statistical properties of screening can be incorporated into trial design. We demonstrate that when the negative binomial distribution is used to model lesion counts, while screening for baseline activity improves point estimation, this practice also has the potential to decrease interval coverage and inflate the Type I error rate. For data that is to be modeled using a negative binomial distribution, screening for baseline activity can create a trade-off between cost effectiveness and a higher than desired false positive rate that must be carefully considered in planning Phase II trials. [ABSTRACT FROM AUTHOR]