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Background It has been suggested that polymorphisms in the WT1 gene modulate the effect of IFN- β treatment in multiple sclerosis ( MS) through regulation of the relationship between IFN- β and vitamin D. Objective To examine whether WT1 modulates the relationship between IFN- β and vitamin D in a longitudinal study with repeated assessment of vitamin D before and after initiation of IFN- β. Methods In a prospective study of 85 patients with relapsing remitting MS, 25-hydroxyvitamin D was measured at month 0, 1, 3, 6, 7, 9, 12, 18 and 24. None of the patients used any immunomodulatory treatment at inclusion, and all started IFN- β treatment at month 6. Results The mean concentrations of seasonally adjusted 25-hydroxyvitamin increased slightly (3.1 ± 1.2 nmol/l, P = 0.008) after initiation of IFN- β. The association between IFN- β treatment and 25-hydroxyvitamin D was similar in patients carrying any of the two alleles in the WT1 SNPs (rs10767935 and rs5030244) recently reported to modulate this relationship. Conclusions In this prospective study with repeated measurements of 25-hydroxyvitamin D before and during treatment with IFN- β, we did not find that genetic variation in WT1 plays any role in regulating the relationship between IFN- β and serum 25-hydroxyvitamin D. [ABSTRACT FROM AUTHOR]

Background/Aim: 25-Hydroxyvitamin D (25(OH)D) levels are suggested to influence the susceptibility and risk of disease progression in multiple sclerosis (MS). Seasonal fluctuation of 2S(OH)D levels may differ in magnitude between individuals. The purpose of this paper was to model the seasonal fluctuation of vitamin D in Norwegian MS patients and to examine to which extent one single 25(OH)D measurement predicts the level at other time points throughout the year. Methods: During December 2004 and July 2008, 762 serum samples were collected from 92 Norwegian relapsing-remitting MS patients. Time series analysis and multi-variate modelling techniques were used to model seasonal fluctuations and intra- and inter-individual variations in 25(OH)D values. Results: Most patients reached their lowest 25(OH)D level in March/April and the highest in July/August. There were substantial intra-individual variations in the ex tent of seasonal fluctuation, with 36.6% of explainable variation in seasonally adjusted 2S(OH)D levels (on a logarithmic scale) attributable to the patient level. The remaining 63.4% could be accounted for by sources of inter-individual variation. Both the total and inter-individual variabilities were lowest in February, and the prediction interval in this month was up to 26% narrower compared to other months. The prediction intervals would be at least 21% wider with only one observation available per patient. Conclusions: The seasonal fluctuations of 25(OH)D levels in Norwegian relapsing-remitting MS patients are subject to pronounced intra- and inter-individual variation. The most representative measurements of 25(OH)D levels are taken in February. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is the most common demyelinating disease and characterized by immunological changes. Oligoclonal bands of IgG in CSF not seen in corresponding serum have been used for many years as part of the diagnostic criteria. However, considerably less is known about the role of IgM, despite several studies showing marked changes to IgM metabolism in MS. Bands of oligoclonal IgM (o-IgM) are more difficult to determine than oligoclonal IgG, thus limiting their study, and there is no agreement as to whether o-IgM in CSF should be part of the clinical work-up of MS. Nevertheless, there is a possibility that such bands might provide a prognostic marker if a cut-off could be established., Materials and Methods: In this pilot study, paired samples of CSF and serum from 37 patients with relapsing-remitting MS (RRMS) and 57 controls with no subsequent signs of neurological disease were analysed for total IgM, and bands of o-IgM were visualised by isoelectric focusing and western blot. Patient records were used to compare mean changes in Expanded Disability Status Scale (EDSS) over a maximum of 17 years., Results: None of the controls displayed extra o-IgM in CSF compared to corresponding serum, whereas additional o-IgM band(s) were seen in CSF in most patient samples (70%). After five years of disease, there was a significant difference in the EDSS between patients with no extra o-IgM compared to patients with at least one extra o-IgM band. This difference increased over time. If a cut-off of two or more extra bands of o-IgM in CSF was applied, this difference was not found., Conclusion: These exploratory data suggest that o-IgM support the prognostic potential for RRMS, and though tentative, the occurrence of any bands of o-IgM restricted to CSF seems to result in poorer prognosis. Despite the small size of the groups, the data infer that the absence of CSF-restricted o-IgM is good news for the patient. The results need to be reproduced in a more comprehensive study., Competing Interests: Declaration of Competing Interest No conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity., Objective: To investigate the association between ALA levels and disease activity., Methods: We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a., Results: In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37-0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48-1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34-1.16) and new relapses (OR: 0.49, 95% CI: 0.22-1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results., Conclusion: We found that higher levels of ALA were associated with lower disease activity in MS-patients.

Adipokines secreted by fatty tissue have inflammatory properties and are suggested biomarkers of MS disease activity. To assess this, 88 MS patients were followed with nine repeated measurements of leptin and adiponectin and 12 magnetic resonance imaging (MRI) scans for two years; six months without any immunomodulatory treatment followed by 18 months during interferon-beta (IFNB) treatment. Serum levels of leptin dropped and adiponectin increased upon initiation of IFNB-therapy, but were not associated with clinical or MRI disease activity or with treatment response. Our findings indicate that leptin and adiponectin are not useful as biomarkers of MS disease activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS)., Methods: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months., Results: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non-tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression., Conclusion: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms.

Obesity is a possible risk factor of multiple sclerosis (MS), but the association between obesity and MS disease activity has not been explored. In a cohort of 86 MS patients, 80% of overweight or obese patients (BMI≥25kg/m(2)) had MRI activity compared to 48% of the normal-weight patients (BMI<25kg/m(2)) (p=0.001) during interferon-beta treatment. NEDA-status (no evidence of disease activity) was defined as a composite that consisted of absence of any relapses, sustained disability-progression and MRI-activity. Among normal-weight patients 26% obtained NEDA-status compared to only 13% of patients with BMI >25 (p=0.05). This may indicate that BMI affects interferon-beta treatment response., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To explore if vitamin D modulates interferon-β1a treatment effects in relapsing-remitting multiple sclerosis, we examined relationships between serum vitamin D and magnetic resonance imaging (MRI) activity and ten systemic inflammation markers in 88 patients, before and during treatment. Odds ratios for all MRI parameters were negatively associated with vitamin D levels before therapy, but converged to equally low values irrespective of vitamin D status during treatment. During therapy, similar alterations of MRI activity and inflammation markers were found across patients categorized by mean vitamin D values. This suggests that vitamin D status has no major influence on interferon-β1a treatment effects., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting., Objectives: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response., Methods: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model., Results: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment., Conclusions: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response., (© The Author(s), 2014.)

To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-β1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-β1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-β1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-β1a treatment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Serum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers., Methods: We performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation., Results: After Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers., Conclusions: Serum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.

Background: Evoked potentials are used to detect conduction disturbances in the central nervous system. This paper provides an overview of the areas in which evoked potentials are used in clinical neurophysiological diagnostics, with the emphasis on coma and demyelinating disease., Method: The article is based on a literature search in PubMed and the authors' long experience of neurological and neurophysiological diagnostics., Results: Somatosensory evoked potential (SEP) can be a reliable predictor of failure to regain consciousness as early as 24 hours after anoxic coma has occurred. If coma is caused by a brain trauma, cerebrovascular episode or other neurological disease, information about which sensory brainstem pathways are damaged can be obtained from somatosensory evoked potentials and brainstem auditory evoked potentials (BAEP), which can also be useful for planning rehabilitation. Normal SEP and BAEP findings in cases of coma caused by trauma are associated with a favourable prognosis. Visually evoked potential (VEP) can often reveal signs of a history of optic neuritis. SEP and BAEP can also reveal subclinical lesions in the central nervous system and be a supplementary diagnostic test for multiple sclerosis., Interpretation: The clinical value of SEP and BAEP is high in coma cases. Evoked potentials are also important in intraoperative monitoring. The clinical value of VEP is high when a history of optic neuritis is a deciding factor for a multiple sclerosis diagnosis. Some selected patients who are being assessed for demyelinating disease will benefit from a full EP study.

Background: Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination., Objective: To investigate the association between retinol and disease activity in multiple sclerosis (MS)., Methods: Cohort study of 88 relapsing-remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon β-1a after month 6., Results: Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd(+)) lesions by 49 (8-70)%, new T2 lesions by 42 (2-66)%, and combined unique activity (CUA) by 46 (3-68)% in simultaneous MRI scans, and 63 (25-82)% for new T1Gd(+) lesions, 49 (3-73)% for new T2 lesions and 43 (12-71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd(+) and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid., Conclusion: Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.

Objective: Alpha-tocopherol is the main vitamin E compound in humans, and has important antioxidative and immunomodulatory properties. The aim of this study was to study alpha-tocopherol concentrations and their relationship to disease activity in Norwegian multiple sclerosis (MS) patients., Methods: Prospective cohort study in 88 relapsing-remitting MS (RRMS) patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids (the OFAMS study), before and during treatment with interferon beta. The patients were followed for two years with repeated 12 magnetic resonance imaging (MRI) scans and nine serum measurements of alpha-tocopherol., Results: During interferon beta (IFNB) treatment, each 10 µmol/L increase in alpha-tocopherol reduced the odds (CI 95%) for simultaneous new T2 lesions by 36.8 (0.5-59.8) %, p = 0.048, and for combined unique activity by 35.4 (1.6-57.7) %, p = 0.042, in a hierarchical regression model. These associations were not significant prior to IFNB treatment, and were not noticeably changed by gender, age, body mass index, HLA-DRB1*15, treatment group, compliance, or the concentrations of 25-hydroxyvitamin D, retinol, neutralising antibodies against IFNB, or the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. The corresponding odds for having new T1 gadolinium enhancing lesions two months later was reduced by 65.4 (16.5-85.7) %, p = 0.019, and for new T2 lesions by 61.0 (12.4-82.6) %, p = 0.023., Conclusion: During treatment with IFNB, increasing serum concentrations of alpha-tocopherol were associated with reduced odds for simultaneous and subsequent MRI disease activity in RRMS patients.

Objective: To investigate whether ω-3 fatty acids reduce magnetic resonance imaging (MRI) and clinical disease activity in patients with multiple sclerosis, both as monotherapy and in combination with interferon beta-1a treatment., Design: Multicenter, randomized, double-blind, placebo-controlled clinical trial conducted from 2004 to 2008., Setting: Thirteen public neurology departments in Norway., Participants: Patients aged 18 to 55 years with active relapsing-remitting multiple sclerosis, with a disability score equivalent to 5.0 or less on the Kurtzke Expanded Disability Status Scale. Ninety-two patients were randomized to ω-3 fatty acids (n = 46) or placebo capsules (n = 46)., Interventions: Administration of 1350 mg of eicosapentaenoic acid and 850 mg of docosahexaenoic acid daily or placebo. After 6 months, all patients in addition received subcutaneously 44 μg of interferon beta-1a 3 times per week for another 18 months., Main Outcome Measure: The primary outcome measure was MRI disease activity as measured by the number of new T1-weighted gadolinium-enhancing lesions during the first 6 months. Secondary outcome measures included MRI disease activity after 9 months and 24 months, relapse rate, disability progression, fatigue, quality of life, and safety., Results: The cumulative number of gadolinium-enhancing MRI lesions during the first 6 months were similar in the ω-3 fatty acids and placebo groups (median difference, 1; 95% CI, 0 to 3; P = .09). No difference in relapse rate was detected after 6 (median difference, 0; 95% CI, 0 to 0; P = .54) or 24 (median difference, 0; 95% CI, 0 to 0; P = .72) months. The proportion of patients without disability progression was 70% in both groups (P > .99). No differences were detected in fatigue or quality-of-life scores, and no safety concerns appeared. Serum analyses of fatty acids showed an increase in ω-3 fatty acids (mean difference, 7.60; 95% CI, 5.57 to 7.91; P < .001) in the patients treated with ω-3 fatty acids compared with the placebo group., Conclusion: No beneficial effects on disease activity were detected from ω-3 fatty acids when compared with placebo as monotherapy or in combination with interferon beta-1a. Magnetic resonance imaging disease activity was reduced as expected by interferon beta-1a. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00360906.

Background/aim: 25-Hydroxyvitamin D (25(OH)D) levels are suggested to influence the susceptibility and risk of disease progression in multiple sclerosis (MS). Seasonal fluctuation of 25(OH)D levels may differ in magnitude between individuals. The purpose of this paper was to model the seasonal fluctuation of vitamin D in Norwegian MS patients and to examine to which extent one single 25(OH)D measurement predicts the level at other time points throughout the year., Methods: During December 2004 and July 2008, 762 serum samples were collected from 92 Norwegian relapsing-remitting MS patients. Time series analysis and multivariate modelling techniques were used to model seasonal fluctuations and intra- and inter-individual variations in 25(OH)D values., Results: Most patients reached their lowest 25(OH)D level in March/April and the highest in July/August. There were substantial intra-individual variations in the extent of seasonal fluctuation, with 36.6% of explainable variation in seasonally adjusted 25(OH)D levels (on a logarithmic scale) attributable to the patient level. The remaining 63.4% could be accounted for by sources of inter-individual variation. Both the total and inter-individual variabilities were lowest in February, and the prediction interval in this month was up to 26% narrower compared to other months. The prediction intervals would be at least 21% wider with only one observation available per patient., Conclusions: The seasonal fluctuations of 25(OH)D levels in Norwegian relapsing-remitting MS patients are subject to pronounced intra- and inter-individual variation. The most representative measurements of 25(OH)D levels are taken in February., (Copyright © 2012 S. Karger AG, Basel.)

The main criteria of "cervicogenic headache" are considered to be as follows: relatively rare and long-lasting unilateral attacks of severe headache, although seemingly of a non-excruciating character, signs of neck involvement, and lack of "cluster pattern". In the present communication, the clinical manifestations in 11 patients fulfilling these criteria are described. All 11 patients selected in accordance with these criteria proved to be females, the age at onset ranging from 6 to 40 years (mean, 30 years). The mean duration of symptoms was 13 years. Six patients had had previous head/neck injuries. All patients had pain periorbitally, in the temporal region, and in the low occipital region (nape of the neck); less frequent were frontal, parietal, and facial pain and pain in the upper part of the occipital region. The duration of attacks was from 3 h to 3 weeks, and the interval between attacks lasted from 2 days to 2 months. The commonest accompanying phenomena were phonophobia, dizziness, ipsilateral eyelid edema, ipsilaterally blurred vision, and irritability. Some of the patients also had nausea (n = 7) and vomiting (n = 6). On physical examination, slight to moderate reduction of movements in the neck was noted, and five patients had ipsilaterally reduced sensation for touch in the trigeminal area. All the patients except one were severely afflicted. Attacks could, in addition to occurring spontaneously, be precipitated in all patients by head movements or by pressure at specific points in the neck.

Ten patients with definite and one with probable MS, all markedly inflicted, but with a varying degree of motor and bladder dysfunction were subjected to spinal cord stimulation in a controlled study. None of the patients exhibited appreciable fluctuation in symptoms in the pre-study period. Bladder symptoms were most markedly influenced by electrical stimulation. The reduction in hesitancy and urgency was of great importance to the patients. In 9 of 10 patients reduction in voiding frequency took place, the all over reduction being 8%. Maximum extension torque increased by 9% and flexion torque by 29% during the stimulation when compared to the first placebo period. In selected MS patients, i.e. patients with bladder dysfunction and with a certain muscular reserve, electrical spinal cord stimulation may have an indication.

An attempt was made to study the kinetics of penetration of ergotamine across the blood-brain barrier. A single therapeutic dose of ergotamine was given to 18 hospitalized patients; eight patients received 0.5 mg i.m., three patients 4 mg rectally, and seven patients 2 mg rectally. Plasma samples were drawn between 0.25 and 72 h and one CSF sample was taken from each patient between 0.5 and 6.5 h after administration. The ergotamine concentrations were measured using a RIA method. The 0.5 mg intramuscular injection showed the highest plasma levels of ergotamine, with a mean peak concentration of 1.27 ng/ml reached at 0.5 h. The 4 mg rectal administration resulted in mean plasma ergotamine levels of 0.44 ng/ml in the time interval of 0.75-2 h. The 2 mg ergotamine rectally resulted in mean plasma levels of 0.15-0.17 ng/ml 1-8 h after administration of ergotamine. Neither the plasma samples taken after 10 h nor the CSF samples had ergotamine concentrations above the detection limit of the RIA method (0.1 ng ergotamine/ml).