When surveying the county of Värmland in Sweden in order to determine the prevalence of multiple sclerosis (MS), we observed an aggregation of MS cases originating from the parish of Lysvik in the local region called Fryksdalen. Our intention was to analyse this cluster thoroughly, confirming the MS diagnosis and seeing if a hereditary or environmental background was plausible.
The medical files were studied and the cases were classified by a neurologist according to Poser's criteria. Hereditary factors were analysed.
Sixteen living cases of MS were found, either living in the parish (n = 6) or born or raised there and had later moved to another place (n = 10). All patients had clinically definite MS. Eleven patients had relatives with MS, all of these being descendants of the Suhoinen family. Another two cases were Suhoinen descendants who did not have relatives with MS. Other common ancestors were also identified. Two cases were adopted. Eleven deceased MS patients from Lysvik were found, 10 of them had Suhoinen ancestry.
We report a cluster of MS cases with a common ancestry indicating heredity for MS in 85% of the cases. Lysvik is a parish where Finnish immigration was pronounced in the 17th century and there has been inbreeding to a certain extent through marriage between cousins. Thus, we interpret this aggregation as possibly being genetically based, and neurogenetic studies are now being performed. However, as two of the cases were adopted environmental factors must also be considered.
Since there are clinical and genetic differences between MS patients with intrathecal oligoclonal bands (OCB+) in the cerebrospinal fluid (CSF) compared with those without (OCB-), the aim was to find out if OCB- patients showed a different pattern of cytokine immune activation compared with OCB+ patients.
The study included 25 MS patients (10 OCB- and 15 OCB+) and 13 controls. A panel of cytokines was measured; IL-1ß, IL-6, IL-8/CXCL8, IL-10, TNF and GM-CSF in serum, CSF and in supernatants from polyclonally stimulated blood mononuclear cells, where also levels of IL-12p40, IL-13, IL-15, IL-17 and IFN-? were measured. The concentrations of soluble (s) VCAM-1 and sCD14 were measured in serum and CSF.
In general, there were no extensive differences in cytokine concentrations between the OCB- and OCB+ groups.
OCB- MS patients do not seem to constitute a separate entity concerning inflammatory parameters measured as cytokine concentrations in CSF and blood.
In several international studies, an increasing women-to-men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age-specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.
OBJECTIVES: The geographic distribution of multiple sclerosis (MS) in Sweden over time was compared in order to analyze homogeneity. METHODS: The distribution of MS was compared among three nationwide resources: 1301 hospital cases 1925-1934; 5425 deaths 1952-1992; and 11,371 disability pension recipients 1971-1994. RESULTS: Distributions by county (lan) were markedly non-homogenous, with greatest variations in the early prevalence series (16-232% of the national mean), less within the death data (75-170%), and least for the disability series (87-128%). Maximal rates for MS in the early prevalence series were found for the cluster of seven counties surrounding the two major lakes of south central Sweden, as well as for one region on the northern shore of the Bay of Bothnia, and another also off the Bay north of Stockholm. CONCLUSION: Though the epidemiologic sources are quite different, they are internally consistent and thus provide three consecutive cross-sectional views of the distribution over time. When considered together the data may be compatible with a thesis of the origin and spread of MS within Sweden from the south-central inland lake regions of the country. Such spread within a half century is too rapid for a genetic cause, including HLA patterns.
Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23-31, 6p24-21, 6q25-27, 14q24-32, 16p13-12 and 17q12-24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24-32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12-24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene-gene interaction was observed.
Earlier studies have indicated an association between multiple sclerosis and environmental factors, especially occupational exposure to solvents. The present study examined such relationships further. From medical files of hospitals in Kalmar and Jönköping, 91 cases of multiple sclerosis, diagnosed in 1983-1988, were identified from population registers corresponding to the catchment areas of the hospitals, and 348 referents were randomly drawn. The cases and referents answered a questionnaire concerning occupational exposure and animal contacts. The men had significantly elevated risks, determined from logistic odds ratios, for solvent exposure, occupational contact with dogs or cats, and leisure-time contact with caged birds. X-ray treatment and previous diseases were risk indicators among the women. For the men and women together, solvent exposure, radiological work, and previous diseases were associated with clearly elevated risks. Although the study concerned rather few subjects, the findings indicate that several exogenous factors might contribute to the development of multiple sclerosis.
Comment In: Scand J Work Environ Health. 1995 Apr;21(2):1507618061
BACKGROUND: Volatile anaesthetics are chemically related to organic solvents used in industry. Exposure to industrial solvents may increase the incidence of multiple sclerosis (MS). AIM: To examine the risk among nurse anaesthetists of contracting MS. METHODS: Nurses with MS were identified by an appeal in the monthly magazine of the Swedish Nurse Union and a magazine of the Neurological Patients Association in Sweden. Ninety nurses with MS responded and contacted our clinic. They were given a questionnaire, which was filled in by 85 subjects; 13 of these were nurse anaesthetists. The questionnaire requested information about work tasks, exposure, diagnosis, symptoms, and year. The number of active nurse anaesthetists was estimated based on information from the National Board of Health and Welfare and The Nurse Union. Incidence data for women in the region of Gothenburg and Denmark were used as the reference to estimate the risk by calculation of the standardised incidence ratio (SIR). RESULTS: Eleven of the 13 nurse anaesthetists were exposed to anaesthetic gases before onset of MS. Mean duration of exposure before diagnosis was 14.4 years (range 4-27 years). Ten cases were diagnosed in the study period 1980-99, resulting in significantly increased SIRs of 2.9 and 2.8 with the Gothenburg and the Danish reference data, respectively. CONCLUSION: Although based on crude data and a somewhat approximate analysis, this study provides preliminary evidence for an excess risk of MS in nurse anaesthetists. The risk may be even greater than observed, as the case ascertainment might have been incomplete because of the crude method applied. Further studies in this respect are clearly required to more definitely assess the risk.
To evaluate the possible relation between exposure to organic solvents and the development of multiple sclerosis, we carried out a best-evidence synthesis of the available information. We found 13 studies with varying methodology that included information on solvent exposure. In 10 of the studies, there were indications of an increased risk of multiple sclerosis in relation to solvent exposure. We made three selections of studies for both pooled analyses and meta-analyses. The relative risk point estimates that we obtained varied from 1.7 to 2.6. Our evaluation is consistent with the hypothesis that organic solvents may be a cause of multiple sclerosis.
To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward.
Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period.
For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013.
A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.