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Background: Cognitive impairment occurs in 40%–70% of persons with multiple sclerosis (MS). Objective: To examine the effectiveness of natalizumab compared with other disease-modifying treatments (DMTs) on improving cognition as measured by the Symbol Digit Modalities Test (SDMT). Methods: Data were collected as part of Swedish nationwide phase IV surveillance studies (2007–2020). An increase in SDMT score by ⩾10% of the difference between maximum score possible (110) and the baseline value was defined as cognitive improvement. The likelihood of improvement was compared between natalizumab-treated individuals and individuals treated with other DMTs using mixed effect logistic regression. Trend in odds of improvement was investigated using slope analyses. Results: We included 2100 persons with relapsing-remitting MS treated with natalizumab and 2622 persons treated with other DMTs. At 6 months, 45% reached improvement. The natalizumab group showed largest odds of improvement during follow-up (odds ratio: 2.3, 95% confidence interval (CI): 1.5–3.5). The odds of improvement increased by 7% (95% CI: 6–7) per month of natalizumab treatment. The equivalent estimate was 4% (95% CI: 2–5) for other monoclonal antibodies and nonsignificant for oral or platform therapies. Conclusion: Treatment with natalizumab or other monoclonal antibodies is associated with a significantly faster likelihood of cognitive improvement than platform or oral DMTs.

Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied. Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls. Using logistic regression models, subjects with different HHV-6A antibody levels, environmental exposures, and lifestyle habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential interactions between high HHV-6A antibody levels and common environmental exposures and lifestyle factors were evaluated on the additive scale. Results: High HHV-6A antibody levels were associated with increased risk of developing MS (OR = 1.5, 95% CI = 1.4–1.6). Regarding MS risk, significant interactions were observed between high HHV-6A antibody levels and both smoking (attributable proportion (AP) = 0.2, 95% CI = 0.1–0.3), low ultraviolet radiation (UVR) exposure (AP = 0.3, 95% CI = 0.1–0.4), and low vitamin D levels (AP = 0.3, 95% CI = 0.0–0.6). Conclusion: High HHV-6A antibody levels are associated with increased MS risk and act synergistically with common environmental/lifestyle risk factors for MS. Further research is needed to investigate potential mechanisms underlying the interactions presented in this study.

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into secondary progressive disease was increased among smokers when self-reported smoking history, but not presumed cotinine levels, was used to define smokers. Defining smoking by cotinine levels without distinguishing between different sources of nicotine may lead to severely biased estimates of the association between smoking and both MS risk and progression.

Background: Evidence for the association between body mass index (BMI) and multiple sclerosis (MS) among men remains mixed. Objective and methods: Swedish military conscription and other registers identified MS after age of 20 years and BMI at ages 16–20 years ( N = 744,548). Results: Each unit (kg/m2) BMI increase was associated with greater MS risk (hazard ratio and 95% confidence interval = 1.034, 1.016–1.053), independent of physical fitness (1.021, 1.001–1.042). Categorised, overweight and obesity were associated with statistically significant raised MS risk compared to normal weight, but not after adjustment for physical fitness. Conclusion: MS risk rises with increasing BMI, across the entire BMI range.

Background: In multiple sclerosis (MS), various aspects of cognitive function can be detrimentally affected, thus patients’ employment and social functioning is commonly impacted. Objective: To analyse income among MS patients in relation to cognitive function, assessed with the Symbol Digit Modalities Test (SDMT). Methods: A cross-sectional study including 2080 MS patients was conducted linking national register-based data. Descriptive statistics and a two-part model were used to estimate differences in earnings and social benefits. Results: MS patients in the highest SDMT score quartile earned more than twice annually compared to patients in the lowest quartile, whereas patients in the lowest quartile received three times more income through social benefits. The difference in earnings and benefits across the SDMT performance quartiles remained statistically significant after adjusting for various clinical and socio-demographic variables, including physical disability. The corrected prevalence ratios for MS patients in the highest quartile for having income from earnings and benefits were 1.40 (95% confidence interval (CI): 1.29–1.49) and 0.81 (95% CI: 0.71–0.90), respectively, when compared to the patients in the lowest quartile. Conclusion: Cognitive function affects the financial situation of MS patients negatively and independently of physical disability. This warrants cognitive testing as a routine measure in health care services for MS patients.

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p −16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p avg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p −16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.

Background: Elevated antibody levels against Epstein–Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385–420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p 3 supplementation did not affect antibodies against VCA, CMV or VZV. Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

Background: Natalizumab (NTZ) and fingolimod (FGL) are mainly used second line in relapsing–remitting multiple sclerosis (MS), although pivotal trials included mainly treatment-naïve patients. Objective: This study aims to provide real-world data on safety and discontinuation rates. Methods: Using IMSE, a drug monitoring registry for all newer MS drugs in Sweden, we analysed differences in baseline characteristics and 1-year drug survival for patients registered 2011–2013, initiating treatment with NTZ ( n=640) or FGL ( n=876). Among FGL initiators, n=383 (44%) had previously used NTZ (FGLafterNTZ). Results: Compared with NTZ, the FGL cohort was older and more often male (36/38 years, 24%/33% males). Baseline Expanded Disability Status Scale was similar across groups, but MS Severity Score was higher in NTZ patients, and Symbol Digit Modalities Test and MS Impact Scale (MSIS-29) was higher in FGLafterNTZ versus FGLNTZ-naïve patients. Proportion on drug after 1 year was high, NTZ=87%, FGLNTZ-naïve=83% and FGLafterNTZ=76%. Adverse events was the most frequent reason for discontinuing FGL (FGLNTZ-naïve=9%, FGLafterNTZ=12%), and was significantly higher than on NTZ (3%). In contrast, the proportion of patients stopping treatment due to lack of effect was more similar: NTZ=4%, FGLNTZ-naïve=3%, FGLafterNTZ=8%. Conclusion: FGL and NTZ were both well tolerated, but FGL less so than NTZ, especially in patients switching to FGL from NTZ. Group differences were not explained by differences in recorded baseline characteristics.

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( pConclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.

Background In multiple sclerosis various aspects of cognitive function can be detrimentally affected. More than that, patients´ employment and social functioning is likely to be impacted. Objective To determine whether work disability among multiple sclerosis patients could be predicted by the symbol digit modalities test. Methods A register-based cohort study was conducted. Individual data on work disability, operationalised as annual net days of sickness absence and/or disability pension were retrieved at baseline, when the symbol digit modalities test was performed, after one-year and 3-year follow-up for 903 multiple sclerosis patients. The incidence rate ratios for work disability were calculated with general estimating equations using a negative binomial distribution and were adjusted for gender, age, educational level, family composition, type of living area and physical disability. Results After one year of follow-up, the patients in the lowest symbol digit modalities test quartile were estimated to have a 73% higher rate of work disability when compared to the patients in the highest symbol digit modalities test quartile (incidence rate ratio 1.73, 95% confidence interval 1.42‒2.10). This estimate after 3-year follow-up was similar (incidence rate ratio 1.68, 95% confidence interval 1.40‒2.02). Conclusion Cognitive function is to a high extent associated with multiple sclerosis patients’ future work disability, even after adjusting for other factors.

Background: High vitamin D levels have been associated with a decreased risk of developing multiple sclerosis (MS). The most important source of dietary vitamin D is fatty fish. Objective: The objective of this paper is to investigate the association between fish consumption and the risk of MS, including the interaction between fish intake and ultraviolet radiation (UVR) exposure habits. Methods: This study is based on the project Epidemiological Investigation of MS (EIMS), which is a Swedish population-based case-control study. The analysis included 1879 incident cases of MS and 4135 controls. Subjects who reported high fatty fish intake were compared regarding occurrence of MS with those who reported low intake by calculating odds ratio (OR) with 95% confidence interval (CI). Results: Frequent fatty fish intake was associated with decreased occurrence of MS (adjusted OR 0.82 (95% CI 0.68-0.98). There was no significant association between intake of lean fish and MS. Conclusion: Fatty fish intake might decrease the risk for MS. A hypothetical explanation is that intake of fatty fish may compensate for vitamin D deficiency that is associated with increased MS risk.

Background: Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. Objectives: The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS). Methods: This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3–2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a. Conclusions: The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

Background: Possible associations between childbearing patterns and multiple sclerosis (MS) risk have been studied for a long time, with conflicting results. We aimed to investigate the influence of reproductive history on MS risk. Methods: Using a Swedish population-based case-control study involving incident cases of MS (1798 cases, 3907 controls), we calculated odds ratios (OR) for MS comparing parents with childless subjects together with 95% confidence intervals (CI) employing logistic regression. Results: Overall, there was an association between having children and reduced MS risk among both sexes. Subjects who had become parents within five years prior to the index year had a substantially reduced risk of developing MS (OR 0.6, 95% CI 0.5–0.8 for women, and OR 0.4, 95% CI 0.3–0.6 for men). No association between having children and MS risk was observed when more than 10 years had passed since the birth of the last child. We found no association between increasing offspring number and MS risk. Conclusions: The observed association between reproductive history and MS risk is restricted to a limited time period preceding the index year, with similar findings in both sexes, which contradicts biologic impact of pregnancy on MS risk and argues in favor of reverse causality, i.e. that fecundity is affected by yet-undiagnosed MS.

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49.5% in patients < 30 years of age to 66.5% in patients ≥ 60 years of age; p < 0.0001 comparing all age categories), was lower in females than in males (55.8% versus 61.9%; p < 0.0001) and was not affected by prior immunosuppressant or natalizumab use.

Background: A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies. Objective: The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients. Methods: Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1–4 antibodies using ELISA and ImmunoCAP®. Results: Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time. Conclusions: The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1–4 antibodies could be used to discriminate between transiently and persistently positive patients.

Background: Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). Objective: Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. Methods: Serum levels of LIGHT were investigated in four cohorts; 1) MS ( n = 159) and controls ( n = 160) in relation to rs1077667 genotype; 2) MS at relapse ( n = 30) vs. healthy controls ( n = 26); 3) MS ( n = 27) vs. other neurological disease (OND, n = 33); and 4) MS patients before and after one year of treatment with natalizumab ( n = 30). Results: Carriers of the GG genotype had the lowest serum levels of LIGHT ( p=0.02). Serum levels of LIGHT were increased in MS at relapse in two separate cohorts: vs. healthy controls ( p=0.00005) and vs. remission ( p=0.00006), other neurological disease (OND) ( p=0.002) and OND with signs of inflammation (iOND; p=0.00005). Furthermore, serum levels of LIGHT were decreased by natalizumab treatment ( p=0.001). Conclusion: Soluble LIGHT is an inhibitor of T-cell activation and GG carriers of rs1077667, with the highest risk for MS, had the lowest serum levels. The increased levels of LIGHT at times of increased MS activity suggest that soluble LIGHT is protective and may act to limit inflammation.

Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS. Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased. Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without. Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn’s disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset. Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.

Natalizumab is a highly effective immunomodulator in the treatment of multiple sclerosis (MS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), an infection of the central nervous system (CNS) caused by a pathogenic form of the normally benign JC virus (JCV). We searched PubMed and used current data from the natalizumab global safety database to assess risk factors and quantify the risk of PML. Natalizumab treatment duration and prior use of immunosuppressive therapies are established risk factors for development of PML in natalizumab-treated patients. With the development of a reliable and validated assay for detection of antibodies in patients with MS directed against JCV, it is now possible to identify persons who are carriers of JCV. The availability of this assay provides an additional option for risk stratification of PML in patients using or considering natalizumab therapy. Recommendations for clinical management of patients with MS and use of natalizumab are provided based on the presence of these three risk factors. The identification of risk factors that increase the likelihood of PML in natalizumab-treated patients can facilitate benefit–risk discussions between health care professionals and patients. Continued research and data collection will further develop our understanding of PML and the mechanisms by which these risk factors contribute to its development.

Background: Tobacco smoking has consistently been associated with increased risk for multiple sclerosis. However, data has been inconsistent regarding the influence of passive smoking. Objective: The aim was to estimate the influence of passive smoking on the risk for multiple sclerosis. Methods: A population-based case–control study using incident cases of multiple sclerosis was performed in Sweden, and the study population was restricted to subjects who had never smoked (695 cases, 1635 controls). The incidence of multiple sclerosis among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed by calculating the odds ratio with a 95% confidence interval employing logistic regression. Results: The risk for multiple sclerosis was increased among never-smokers who had been exposed to passive smoking (OR 1.3, 95% CI 1.1–1.6) compared to never-smokers who had never been exposed. The risk increased with increasing duration of exposure ( p = 0.003). Conclusions: Exposure to environmental tobacco smoke is associated with an increased risk for multiple sclerosis. Since smoking, but not usage of oral tobacco in the form of moist snuff, is associated with increased risk for multiple sclerosis, we consider that the critical effects of passive smoking may be the result of irritations in the lungs. Hence, further studies would be valuable in order to clarify whether other forms of lung irritation, such as air pollution, contribute to the triggering of multiple sclerosis.

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients ( n = 901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

Background:The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity. Objective:The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS. Methods:Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) ( n = 25) and relapsing–remitting MS (RRMS) ( n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks. Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects. Results:OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02) and RRMS ( p Conclusions:OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.

Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells ( p < 0.05) and peripheral blood mononuclear cells ( p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells ( p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause.

Objective1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML).MethodsThe prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS ( n = 49), CIS ( n = 14) and OND ( n = 53).ResultsA low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus.ConclusionA low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful.

The effect of bovine peripheral nerve myelin (BPM) used for induction of experimental allergic neuritis (EAN) in Lewis rats, on antidepressants' modulation of interferon-gamma (IFN-γ)-induced major histocompatibility complex (MHC) class I and II antigen expression on peritoneal macrophages in EAN rats was studied. Antidepressants with different profiles concerning inhibition of the neuronal reuptake of the monoamines serotonin (5-HT) and noradrenalin (NA), respectively, in concentrations of 10−4 to 10−8 M were used. At the concentration of 1.0 U/ml IFN-γ, most antidepressants significantly enhanced both MHC class I and class II expression, except maprotiline, a selective NA reuptake inhibiting antidepressant that suppressed MHC class I expression. Zimeldine, a selective 5-HT reuptake inhibitor did not affect MHC class II expression. BPM in general had an enhancing effect on modulation of both MHC class I and class II expression by antidepressants. By itself BPM enhanced MHC class I expression, but did not affect class II expression at IFN-γ 1.0 U/ml. The modulating effect of BPM on regulation of MHC expression by antidepressants could be the result of contaminating T cells and release of IFN-γ into cultures. The modulatory effect of antidepressants on MHC expression may to some extent be exerted by the action on 5-HT and/or NA regulation, but also by direct effects of antidepressants on macrophages. They probably play a role in zimeldine-induced Guillain-Barré syndrome in some patients and in the suppression of clinical signs of EAN in Lewis rats reported for some antidepressants.