Leszek Stawiarz

Seasonal patterns in optic neuritis and multiple sclerosis: a meta-analysis.

To quantify and characterize seasonal variation in monosymptomatic optic neuritis (MON) onsets, multiple sclerosis (MS) onsets and MS exacerbations (MSE), a meta-analysis was performed, using established methods and pooling weighted information obtained from nine reports on MON, six reports on MS onsets and nine reports on MSE, which fulfilled specific criteria for report quality and data homogeneity. The results suggested that MON, MS onsets and MSE in the Northern hemisphere present a similar pattern with highest frequencies in spring and lowest in winter. These differences were highest for MS onsets, 45% with 95% CI 36-55%, and lowest for MSE, 10% with 95% CI 7-13%, statistically significant and robust, insensitive to an alternative seasonal definition, not unduly influenced by any single primary study, and supported by fail-safe N calculations. Random variation, misclassification and publication bias were less likely to account for the reported generalized seasonal patterns.

The Swedish MS registry - clinical support tool and scientific resource

The Swedish MS registry (SMSreg) is designed to assure quality health care for patients with multiple sclerosis (MS). It has been active since 2001 and web‐based since 2004. It runs on government funding only and is used in all Swedish neurology departments. The SMSreg currently includes data on 14,500 of Swedens estimated 17,500 prevalent patients with MS. One important function of SMSreg, to which participation is voluntary, is to serve as a tool for decision support and to provide an easy overview of the patient information needed at clinical visits. This is its core feature and explains why the majority of Swedish MS specialists contribute data. Another success factor for SMSreg is that entered data can be readily accessed, either through a query function into Excel format or through a set of predesigned tables and diagrams in which parameters can be selected. Recent development includes a portal allowing patients to view a summary of their registered data and to report a set of patient‐reported outcomes. SMSreg data have been used in close to 100 published scientific reports. Current projects include an incidence cohort (EIMS), post‐marketing cohorts of patients on novel disease‐modifying drugs (IMSE), and a prevalence cohort (GEMS). As these studies combine physical sampling and questionnaire data with clinical documentation and possible linkage to other public registries, together they provide an excellent platform for integrated MS research.

Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg).

Background: Sex ratio in multiple sclerosis has been reported from several geographical areas. The disease is more common in women. In Europe the female-to-male ratio varies from 1.1 to 3.4. A recent study from Canada has reported a significant increase, with time, in female-to-male ratio in multiple sclerosis over the last 100 years. Objective: The aim of this study was to analyse any change in sex ratio in multiple sclerosis in the Swedish population. Methods: Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset. Results: In the analysis of sex ratio by year of birth there were 8834 patients (6271 women and 2563 men) born between 1931 and 1985. The mean women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p = 0.298, n = 11). The number of patients analysed by year of onset was 9098 during the time period 1946 until 2005. The mean women-to-men ratio was 2.57. No significant change in women-to-men ratio (Spearman’s rho = −0.007, p = 0.983, n = 12) with time was observed. Conclusion: There is no evidence for an increasing women-to-men ratio with time amongst Swedish multiple sclerosis patients.

Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden

Objective To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden. Methods A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing–remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (€1 = 9.25 SEK). Results In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was €38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial. Conclusions This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.

Regression analysis of metabolite concentrations estimated from localized proton MR spectra of active and chronic multiple sclerosis lesions

Localized short echo time magnetic resonance (MR) spectra were obtained from patients with multiple sclerosis of relapsing‐remitting or secondary chronic‐progressive course and from healthy controls. Automated analysis using model spectra, sensitivity correction, and subtraction of partial ventricular volume yielded tissue concentrations of metabolites that were in line with findings of previous studies. Additional findings were increased creatine in chronic lesions and increased myo‐inositol in normal‐appearing white matter. Regression analysis was performed to reveal concomitant changes of metabolite concentrations. Differences in the correlations between cholines and myo‐inositol suggest increased expression of myo‐inositol in chronic lesions or of cholines in active, contrast‐enhanced lesions. A correlation between N‐acetyl‐aspartate and creatine, which is probably due to extracellular edema, was observed in active but not in chronic lesions. Creatine and cholines correlated in chronic lesions, which may be the result of gliosis. The consequences of these findings for the interpretation of absolute concentrations and creatine ratios are discussed. Magn Reson Med 43:102–110, 2000.

Multiple sclerosis: a study of chemokine receptors and regulatory T cells in relation to MRI variables

Magnetic resonance imaging (MRI) remains the most valuable tool for monitoring disease activity and progression in patients with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS) with presumably autoimmune etiology. Chemokine receptors have been implicated in MS as key molecules directing inflammatory cells into the CNS. Regulatory (CD4+CD25+) T cells (Tr cells) are important in suppressing autoimmunity, and their absolute or functional deficit could be expected in MS. In the present study, venous blood was obtained from MS patients concurrent with MRI examination of the brain, and expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3 and CXCR4 by CD4 T cells and monocytes, proportions of Tr cells, as well as expression of CD45RO, CD95, CTLA‐4, HLA‐DR and interleukin (IL)‐10 by Tr cells and non‐Tr (CD25−) CD4 T cells was analyzed by flow cytometry. Surface expression of CXCR3 by CD4 T cells was downregulated in the group of patients with high lesion load (LL) on T2‐weighted images and gadolinium (Gd)‐enhancing lesions on T1‐weighted images, compared to the group with high LL and no Gd‐enhancing lesions, and to the group with low LL, suggesting internalization of CXCR3 due to the release of its chemokine ligand (IP‐10/CXCL10) from active MS lesions. Proportions of Tr cells amongst all CD4 T cells, and expression of IL‐10 by Tr cells were increased in the patients with high LL and Gd‐enhancing lesions. These results suggest that there is correlation between MRI parameters, chemokine receptor expression and the status of circulating Tr cells in MS, but further studies need to discriminate between pathogenetically relevant and bystander phenomena.

Incidence of optic neuritis in Stockholm, Sweden 1990–1995: I. Age, sex, birth and ethnic-group related patterns

We studied the incidence of monosymptomatic optic neuritis (MON) in Stockholm county, Sweden and its variation with person-related factors. Patients with suspected or diagnosed MON between January 1, 1990 and December 31, 1995 were referred from ophthalmologists and neurologists to a research registry. The diagnosis was based on accepted clinical criteria only, and verified by an ophthalmologist who examined all the patients. Data were collected by interview using a structured questionnaire. The crude mean annual incidence, based on 147 patients, 118 females and 29 males, diagnosed with MON, was 1.46 per 100,000 person-years, 2.28 for females and 0.59 for males. The corresponding age-adjusted incidences were 1.40, 2.28 and 0.53. The age-specific incidence curve for both sexes suggested a bimodal distribution with peaks at 30-34 years and 45-49 years. The smoothed cumulative incidences in 1 year birth cohorts showed a notchy profile, related to bimodality. The incidence among residents born out of the Nordic countries was low, 0.28 per 100,000. Patients with onset of MON before 40 years of age had a significantly higher frequency of mononuclear pleocytosis in cerebrospinal fluid and shorter duration to conversion to multiple sclerosis. In summary, MON occurred in Stockholm at a relatively low frequency, particularly among males. The presence of particular birth date and birth place related patterns might be etiologically relevant.

Parkinson's disease incidence: magnitude, comparability, time trends

ABSTRACT In this study, we reviewed incidence surveys of Parkinsons Disease (PD) from all over the world, published during the period 1945‐1989, using reported quality criteria. In addition, we compared age‐specific PD incidences from selected observations by stratified analysis. Crude incidences were described for 11 populations, and age‐specific incidences for three of them: Iceland, Rochester (Minn, USA), and Turku (Finland). Effect modification by age was detected: a) by comparing incidences by age at diagnosis with incidence by age at clinical disease onset; and b) when only data on onset of disease was computed. For disease onsets, the incidences in Rochester for the period 1955‐1966, and in Turku (Finland) during the interval 1968‐1970, were lower than that in Iceland for the period 1958‐1960: RR=0.58 95% CI (0.41, 0.83), and RR=0.67 95% CI (0.51, 0.87), respectively. For the Rochester population aged 40‐69 years, a statistically significant 56% decrease in the incidences of Parkinsonism onsets during the period 1945‐1966 was found. Validity problems in comparing PD incidences and the role of PD underdiagnosis were emphasized. We concluded that: a) stratified analysis is more suitable than standardization when comparing incidences for etiological purposes; b) the incidence of PD was highest in Iceland; and c) in Rochester, PD incidence under the age of 70 decreased with time.

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup.

Callosal atrophy in multiple sclerosis is related to cognitive speed

Long‐term changes regarding corpus callosum area (CCA) and information processing speed in cognitive and sensory‐motor tasks have rarely been studied in multiple sclerosis (MS).