Sarah A. Morrow

Incidence and prevalence of multiple sclerosis in Europe: a systematic review.

BackgroundMultiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality.MethodsA comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study.ResultsThere were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates.ConclusionsDespite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

Incidence and Prevalence of Multiple Sclerosis in the Americas: A Systematic Review

Background: The incidence and prevalence of multiple sclerosis (MS) varies considerably around the world. No previous study has performed a comprehensive review examining the incidence and prevalence of MS across the Americas. The purpose of this study was to systematically review and assess the quality of studies estimating the incidence and/or prevalence of MS in North, Central and South American regions. Methods: A comprehensive literature search was performed using MEDLINE and EMBASE from January 1985 to January 2011. Search terms included ‘multiple sclerosis’, ‘incidence’, ‘prevalence’ and ‘epidemiology’. Only full-text articles published in English or French were included. Study quality was assessed using an assessment tool based on recognized guidelines and designed specifically for this study. Results: A total of 3,925 studies were initially identified, with 31 meeting the inclusion criteria. The majority of studies examined North American regions (n = 25). Heterogeneity was high among all studies, even when stratified by country. Only half of the studies reported standardized rates, making comparisons difficult. Quality scores ranged from 3/8 to 8/8. Conclusion: This review highlights the gaps that still exist in the epidemiological knowledge of MS in the Americas, and the inconsistencies in methodologies and quality among the published studies. There is a need for future studies of MS prevalence and incidence to include uniform case definitions, employ comparable methods of ascertainment, report standardized results, and be performed on a national level. Other factors such as sex distribution, ethnic make-up and population lifestyle habits should also be considered.

The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis

Oral prednisone 1might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses.

Cognitive impairment in multiple sclerosis: clinical, radiologic and pathologic insights.

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS) that has only recent gained considerable attention. Clinical neuropsychological studies have made apparent the multifaceted nature of cognitive troubles often encountered in MS and continue to broaden our understanding of its complexity. Radiographic studies have started to decipher the neuroanatomic substrate of MS‐related cognitive impairment and have shed light onto its pathogenesis. Where radiographic studies have been limited by inadequate resolution or non‐specificity, pathological studies have come to the fore. This review aims to provide an overview of the nature of cognitive impairment typically seen in MS and to explore the literature on imaging and pathological studies relevant to its evolution. In particular, the relative contributions of gray (ie, cerebral cortex, hippocampus, thalamus and basal ganglia) and white matter to MS‐related cognitive impairment will be discussed and the importance of interconnectivity between structures highlighted. The pressing need for longitudinal studies combining standardized neuropsychometric, paraclinical and radiographic outcomes obtained during life with post‐mortem tissue analysis after death is presented.

Characterizing cognitive function during relapse in multiple sclerosis.

Objective: To characterize neuropsychological (NP) test performance during multiple sclerosis (MS) relapse and recovery. Methods: Clinical status was assessed with NP testing and Expanded Disability Status Scale (EDSS) in 24 relapsing patients, and 24 individually-matched, stable controls. All presented with cognitive symptoms as indicated by patient, clinician or caregiver perceived decline, but were free of optic neuritis, ataxia and upper extremity weakness that could compromise NP testing. The presence of enhancing magnetic resonance imaging (MRI) lesions was considered confirmatory of relapse. Relapsing patients were treated with corticosteroids. NP testing and EDSS were compared to pre-relapse baseline levels, and three-month, post-relapse, follow-up. Results: Analyses revealed significant decline on the Symbol Digit Modalities Test (SDMT) (p=0.005) and worsening on EDSS (p=0.019). Impairment was observed at the point of relapse in cases but not controls. The groups were no longer different at three-month follow-up. The increment of decline on SDMT was 3.5 raw score points, or roughly 6%. Conclusions: This is the first study to assess NP status changes during MS relapse using well established, reliable metrics. The presence of a clinically meaningful event is substantiated by decline in NP testing, observed or reported cognitive change, and in a subset of patients, gadolinium-enhancing MRI lesions.

Association Between Gadolinium Contrast Exposure and the Risk of Parkinsonism

Association Between Gadolinium Contrast Exposure and the Risk of Parkinsonism Gadolinium-based contrast agents are used for enhancement during magnetic resonance imaging (MRI). Safety concerns have emerged over retained gadolinium in the globus pallidi.1,2 Neurotoxic effects have been seen in animals and when gadolinium is given intrathecally in humans.1 In July 2015, the US Food and Drug Administration stated that it was unknown whether gadolinium deposits were harmful. The substantia nigra (affected in Parkinson disease) directs voluntary movement via signals to the globus pallidi. Consequences of damage to the globus pallidi may include parkinsonian symptoms.3 We conducted a population-based study to assess the association between gadolinium exposure and parkinsonism.

The Validity and Reliability of the Neurogenic Bladder Symptom Score

PURPOSE The neurogenic bladder symptom score is a tool to measure urinary symptoms and consequences in patients with acquired or congenital neurogenic bladder. We describe score validity and reliability. MATERIALS AND METHODS Exploratory factor analysis was used to assess item variability and subscale structure. Reliability was assessed by the Cronbach α and correlation with retest data. Validity was assessed with a priori hypotheses specifying relationships with the AUASS (American Urological Association symptom score), ICIQ-UI (International Consultation on Incontinence-Urinary Incontinence) and urinary specific quality of life SF-Qualiveen questionnaires, and a self-assessed global bladder problem score. Known groups analysis was used to further assess construct validity. RESULTS A cohort of 230 patients with spinal cord injury (35%), multiple sclerosis (59%) and congenital neurogenic bladder (6%) were included in study. Factor analysis suggested 3 neurogenic bladder symptom score domains, including incontinence, storage and voiding symptoms, and consequences. Overall internal consistency was high (Cronbach α=0.89). Test-rest reliability was also excellent with an ICC2,1 of 0.91. Validity was demonstrated by the confirmation of hypothesized correlations with the AUASS, ICIQ-UI and SF-Qualiveen, and significant differences in neurogenic bladder symptom score scores among known groups. Patients with a history of seeing a urologist had a significantly higher mean score, as did those with a higher global bladder problem score (22.1 vs 17.1 and 22.1 vs 12.6, respectively, each p<0.001). CONCLUSIONS The neurogenic bladder symptom score, developed specifically to assess symptoms and consequences associated with neurogenic bladder dysfunction, has appropriate psychometric properties. Depending on the measurement need individual domains may be selected or it can be used as a comprehensive score.

High dose oral steroids commonly used to treat relapses in Canadian MS clinics.

BACKGROUND Glucocorticoid treatment improves the speed of functional recovery of acute multiple sclerosis (MS) relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of administration or the dosage of glucocorticoid, or the particular glucocorticoid prescribed. Recent studies support similarities in the bioequivalence and in the clinical effect of high dose oral corticosteroids for MS relapses. OBJECTIVE This survey aimed to determine the relapse treatment preferences of clinicians in Canadian MS clinics. METHODS Members of the Canadian Network of MS Clinics are linked by an email server. A one page survey was distributed to the group to determine and report use of corticosteroids to manage MS relapses amongst Canadian MS specialists. RESULTS Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys were returned representing 16 clinics. Five doses are most commonly prescribed, usually without a taper. Three or four doses and the use of a corticosteroid taper, however, are not uncommon. Gastric cytoprotection and sedatives are often prescribed for use as needed. CONCLUSION This survey illustrates that when Canadian clinicians with expertise in managing MS treat MS relapses they choose high dose corticosteroids, either oral or i.v. The results therefore represent Canadian practice as these clinicians provide direct patient care and influence care by community neurologists. Until evidence clearly identifies a superior practice all options should be available to clinicians and their patients.

Future MS care: a consensus statement of the MS in the 21st Century Steering Group

The “MS in the 21st Century” initiative was established with the purpose of (1) defining how multiple sclerosis (MS) treatment and standards of care should look in the 21st century; (2) developing a minimum standard of care across the world; and (3) motivating the broad MS community to align standards of care and challenge the current treatment paradigm. The aim was to develop a consensus statement to reach and influence the broader MS community. An expert steering group from Europe and Canada—consisting of neurologists, patient advocates, a pharmacoepidemiologist/pharmacoeconomist, and representatives from national MS centers—participated in a series of workshop-driven meetings between February 2011 and 2012. After three phases of discussions, the steering group identified that the overall vision for future care of MS should be full access to personalized treatment, with reimbursement, to achieve freedom from disease. They constructed seven overall principles that support this vision: personalized care, patient engagement, commitment to research, regulatory body education and reimbursement issues, new endpoints in clinical trials, more therapy options, and MS centers of excellence. This consensus statement outlines the key aspects of the seven principles that need to be addressed. The “MS in the 21st Century Steering Group” hopes that this consensus statement acts as a call to action for healthcare providers and decision-makers to address simultaneously the overarching principles that will guide patient management in order to improve outcomes for people with MS.

The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results

Objective People with multiple sclerosis (MS) are living longer so strategies to enhance long-term health are garnering more interest. We aimed to create a profile of ageing with MS in Canada by recruiting 1250 (5% of the Canadian population above 55 years with MS) participants and focusing data collection on health and lifestyle factors, disability, participation and quality of life to determine factors associated with healthy ageing. Design National multicentre postal survey. Setting Recruitment from Canadian MS clinics, MS Society of Canada chapters and newspaper advertisements. Participants People aged 55 years or older with MS symptoms more than 20 years. Outcome measures Validated outcome measures and custom-designed questions examining MS disease characteristics, living situation, disability, comorbid conditions, fatigue, health behaviours, mental health, social support, impact of MS and others. Results Of the 921 surveys, 743 were returned (80.7% response rate). Participants (mean age 64.6±6.2 years) reported living with MS symptoms for an average of 32.9±9.5 years and 28.6% were either wheelchair users or bedridden. There was only 5.4% missing data and 709 respondents provided optional qualitative information. According to data derived from the 2012 Canadian Community Health Survey of Canadians above 55 years of age, older people with MS from this survey sample are about eight times less likely to be employed full-time. Older people with MS were less likely to engage in regular physical activity (26.7%) compared with typical older Canadians (45.2%). However, they were more likely to abstain from alcohol and smoking. Conclusions Despite barriers to participation, we were able to recruit and gather detailed responses (with good data quality) from a large proportion of older Canadians with MS. The data suggest that this sample of older people with MS is less likely to be employed, are less active and more disabled than other older Canadians.