Vitamin D, HLA-DRB1 and Epstein-Barr virus antibody levels in a prospective cohort of multiple sclerosis patients.

BACKGROUND AND PURPOSE: Our objective was to study the association between serum levels of anti Epstein-Barr virus nuclear antigen 1 (EBNA-1) antibody and 25-hydroxyvitamin D (25(OH)D) in a prospective cohort of patients with relapsing-remitting multiple sclerosis. METHOD: The study comprised 90 patients with relapsing-remitting multiple sclerosis, all participants in a randomized clinical trial of ω-3 fatty acids (the OFAMS study). Repeated, paired measurements of serum 25(OH)D and serum EBNA-1 immunoglobulin G (IgG) levels were obtained at baseline and every 6 months for 24 months. The association between serum EBNA-1 IgG and serum 25(OH)D levels was analysed using generalized linear models for hierarchical data. RESULTS: There was a significant variation in EBNA-1 IgG antibody level between sampling months (Fdf 11 = 1.8, P = 0.043, one-way anova). There was a negative association between EBNA-1 IgG and 25(OH)D [B = -0.230, 95% confidence interval (CI) (-0.440, -0.023), P = 0.030] and a positive association between EBNA-1 IgG and HLA-DRB1*15 positive status [B = 94.7, 95% CI (2.423, 186.9), P = 0.044]. The association between 25(OH)D and EBNA-1 IgG remained significant after adjusting for the patient's age, gender, HLA-DRB1*15, retinol levels and interferon ß-1a treatment. CONCLUSION: Our study demonstrates monthly differences in EBNA-1 IgG levels and an association between EBNA-1 IgG, 25(OH)D levels and HLA-DRB1*15. These results indicate that EBNA-1 IgG serum levels are affected by genetic and environmental factors that also modulate multiple sclerosis risk.

WT1 and interferon-ß-vitamin D association in MS: a longitudinal study.

BACKGROUND: It has been suggested that polymorphisms in the WT1 gene modulate the effect of IFN-ß treatment in multiple sclerosis (MS) through regulation of the relationship between IFN-ß and vitamin D. OBJECTIVE: To examine whether WT1 modulates the relationship between IFN-ß and vitamin D in a longitudinal study with repeated assessment of vitamin D before and after initiation of IFN-ß. 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-ß 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-ß. The association between IFN-ß 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-ß, we did not find that genetic variation in WT1 plays any role in regulating the relationship between IFN-ß and serum 25-hydroxyvitamin D.

Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients.

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.

Comparison of carbamazepine rash in multiple sclerosis and epilepsy.

OBJECTIVES: Studies on the comorbidity of multiple sclerosis (MS) and allergic disorders have shown conflicting results. Carbamazepine (CBZ) is widely used in MS to control pain. We have compared the incidence of rash from CBZ use in MS and epilepsy. MATERIALS AND METHODS: Consecutive adult patients with MS and epilepsy were studied retrospectively. A detailed survey of medical records concerning CBZ treatment was performed. RESULTS: A total of 495 patients with epilepsy and 442 patients with MS were included. Sixty-five per cent of patients with epilepsy and 20% of patients with MS had used CBZ. In CBZ-exposed patients, rash occurred in 15/89 (17%) in MS and in 43/323 (13%) in epilepsy, a difference which was not significant. Women below 50 years experienced more skin reactions than older women and men. The unadjusted odds ratio (OR) for rash in the MS vs epilepsy group was 1.32 (CI 0.70-2.51, P = 0.40). Adjusting groups for gender and age reduced the OR to 1.11 (CI 0.56-2.19, P = 0.76). CONCLUSION: Compared with epilepsy, which is only rarely caused by immunological mechanisms, the autoimmune disorder MS was not associated with a different occurrence of CBZ skin reactions. The trend towards an increased occurrence of rashes in MS can partly be explained by a higher predisposition to CBZ rash in women of fertile age.

IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

[Neuralgic amyotrophy or an isolated lesion of the anterior interosseal nerve?]. / Neuralgisk amyotrofi eller en isolert lesjon av nervus interosseus anterior?

In this article we describe five patients with acute or subacute weakness of flexor pollicis longus and flexor digitorum profundus. A possible diagnosis of an isolated lesion (entrapment) of the anterior interosseus nerve was considered. However, clinical and neurophysiological findings suggested a diagnosis of neuralgic amyotrophy. Three patients experienced acute shoulder pain at the onset. Sensory loss at the base of the thumb was observed in two patients, and two patients were affected bilaterally. All patients had EMG signs of involvement outside the anterior interosseus nerve innervation area. Low amplitude sensory action potentials were observed in three patients. One patient was operated upon and entrapment was not observed during surgery. Reinnervation was not seen after five months, but was noted in three patients who were investigated 13, 13.5, and 30.5 months after the onset. Thus, the prognosis in this unusual form of neuralgic amyotrophy seems to be rather good, and the length of time before reinnervation supports the theory that the site of the lesion must be located proximally, e.g. in the brachial plexus.

"Cervicogenic headache": clinical manifestation.

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.

Ergotamine in plasma and CSF after i.m. and rectal administration to humans.

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).

The value of dorsal column stimulation in multiple sclerosis.

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.