Naila Makhani

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.

Cyclophosphamide therapy in pediatric multiple sclerosis

Objective: To review our multicenter experience with cyclophosphamide in the treatment of children with multiple sclerosis (MS). Methods: Retrospective chart review of children with MS treated with cyclophosphamide. Demographic, clinical, treatment, and MRI parameters were collected. Results: We identified 17 children with MS treated with cyclophosphamide. All but one had worsening of Expanded Disability Status Scale scores or multiple relapses prior to treatment initiation. Children were treated with one of three regimens: 1) induction therapy alone; 2) induction therapy with pulse maintenance therapy; or 3) pulse maintenance therapy alone. Treatment resulted in a reduction in relapse rate and stabilization of disability scores assessed 1 year after treatment initiation in the majority of patients. Longer follow-up was available for most cases. Cyclophosphamide was well tolerated in most patients. However, side effects included vomiting, transient alopecia, osteoporosis, and amenorrhea. One patient developed bladder carcinoma that was successfully treated. Conclusions: Cyclophosphamide is an option for the treatment of children with aggressive multiple sclerosis refractory to first-line therapies. Recommendations regarding patient selection, treatment administration, and monitoring are discussed.

Viral exposures and MS outcome in a prospective cohort of children with acquired demyelination.

Epstein–Barr virus (EBV) infection is associated with increased multiple sclerosis (MS) risk. Recently, cytomegalovirus (CMV) infection has been proposed as a protective factor against MS development. We determined EBV, herpes simplex virus, varicella-zoster virus and CMV seroprevalence in 247 prospectively followed children with acquired demyelinating syndromes (ADS). Remote EBV infection was more common in children with MS than those with monophasic ADS while CMV infection was more common in children with monophasic ADS. Children displaying evidence of remote EBV without CMV infection were at highest risk of subsequent MS diagnosis. Viral infection repertoire detected at ADS provides important prognostic information.

A Twist on Lyme: the Challenge of Diagnosing European Lyme Neuroborreliosis

ABSTRACT Lyme neuroborreliosis is a tick-borne illness with central and peripheral nervous system manifestations. Clinical features and methods for accurate diagnosis differ across world regions owing to different causative Borrelia species. The importance of these distinctions is highlighted by a 12-year-old Canadian girl who acquired Lyme neuroborreliosis in Europe.

Glatiramer acetate–induced acute hepatotoxicity in an adolescent with MS

Glatiramer acetate (GA), a synthetic copolymer, is a frequently used first-line treatment for relapsing-remitting multiple sclerosis (RRMS). Probable autoimmune hepatotoxicity during GA treatment has been reported,1–4 but GA hepatotoxicity in the absence of positive autoimmune markers has not previously been described. Here, we report GA-induced hepatotoxicity in a pediatric patient with multiple sclerosis (MS).

Diagnosing neuromyelitis optica.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disorder typically characterized by attacks of recurrent optic neuritis and transverse myelitis. Advances in magnetic resonance imaging techniques and the discovery of the relatively specific NMO IgG biomarker have led to improved diagnostic accuracy and greater recognition of the broad clinical spectrum of aquaporin 4-related autoimmunity. Brain lesions in NMO typically follow the distribution of aquaporin 4 expression and may be symptomatic. Prompt diagnosis of NMO and NMO spectrum disorders has important therapeutic implications given the high risk of recurrent attacks and consequent severe disability, especially in childhood-onset disease.

MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Radiologically isolated syndrome in children Clinical and radiologic outcomes

Objective: To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed “radiologically isolated syndrome” or RIS). Methods: Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS. Results: We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%–60%) in a median of 2.0 years (interquartile range [IQR] 1.0–4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%–76%) in a median of 1.1 years (IQR 0.5–1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4–86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4–43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex. Conclusions: We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.

International Pediatric MS Study Group Global Members Symposium report

The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, “The World of Pediatric MS: A Global Update,” in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders. While these criteria currently identify clinical and MRI features for a particular diagnosis, advances in biomarkers may prove to be useful in the future. An update was also provided on environmental factors associated with pediatric MS risk and possibly outcomes, notably vitamin D deficiency. However, optimal vitamin D intake and its role in altering MS course in children have yet to be established. Regarding MS outcomes, our understanding of the cognitive consequences of early-onset MS has grown. However, further work is needed to define the course of cognitive function and its long-term outcome in diverse patient samples and to develop strategies for effective cognitive rehabilitation specifically tailored to children and adolescents. Finally, treatment strategies were discussed, including a need to consider additional drug treatment options and paradigms (escalation vs induction), although treatment should be tailored to the individual child. Of critical importance, clinical trials of newer MS agents in children are required. Although our understanding of childhood MS has improved, further research is needed to have a positive impact for children and their families.