BREMSO: a simple score to predict early the natural course of multiple sclerosis.

BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

Fluctuations of MS births and UV-light exposure.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review.

BACKGROUND: There is growing consensus that neurologists should consider disease-modifying therapies early in multiple sclerosis (MS). However, there is a subgroup with a natural benign course, in which treatment could be postponed. We sought to determine the frequency of benign MS and early clinical factors that may predict a benign course. METHODS: We performed a systematic review of the existing literature on benign MS, which was defined as minimal or no disability equivalent to a score on the Expanded Disability Status Scale (EDSS) < or = 3.0 at least 10 years after disease onset RESULTS: Only a small number of studies of adequate quality was available. In total there were nine published studies representing 2,204 patients. The estimated frequency of benign MS was 26.7%. Onset with optic neuritis, onset before the age of 40 years, absence of pyramidal signs at presentation, duration of first remission more than 1 year, and only one exacerbation in the first 5 years after onset of MS, were associated with a benign course. CONCLUSIONS: From the existing literature a set of unrelated clinical characteristics emerged that was associated with a benign course of MS. However, there is a need for prospective studies to define more precisely clinical and paraclinical predictors of benign MS.

Mapping of a susceptibility gene for multiple sclerosis to the 51 kb interval between G511525 and D6S1666 using a new method of haplotype sharing analysis.

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of patients and of controls and calculates the difference in mean haplotype sharing between patients and controls. Haplotype sharing was found to be significantly greater among patients than among controls in a region of 1.1 Mb between markers G511525 and TNFalpha. The involvement of this region is also supported by association analysis and the transmission/disequilibrium test (TDT). Within this region, HSS, which is largely independent of association and TDT, indicated the interval of 51 kb between G511525 and D6S1666 as that most likely to contain a susceptibility gene for MS. As DQB1 is the sole gene known in this interval at present, the results of our analysis suggest that this gene plays a role in the pathogenesis of MS.

Health care utilization by people with multiple sclerosis in The Netherlands: results of two separate studies.

PURPOSE: For chronically ill persons it is assumed that they make heavy demands on health care services. In the literature one hardly finds any publications to substantiate or refute this assumption. The main purpose of our study is to describe the health care utilization of people with multiple sclerosis (MS) in the Netherlands and its relationships with severity and duration of the disease. METHODS: Two different samples of persons with MS were used. In the first sample (University Hospital Groningen) severity of MS was based on medical judgement, while in the second sample (Dutch Multiple Sclerosis Society) severity was self-reported. In both samples, use of health care facilities was assessed with a mail questionnaire. RESULTS: The methods for determining severity resulted in different distributions for severity of MS. However, the results were quite similar with respect to health care utilization. It appeared that the severity of MS was related to the number of professional caretakers MS-patients had contact with during one year. Duration of MS seemed not to be related to the number of caretakers. Only for specific caretakers, most notably GP, physiotherapist, home help and ergotherapist, the contact frequency increased with severity of MS. No such relationship was found between the frequency of contact with the neurologist and severity of MS. CONCLUSIONS: People with MS do not make a heavy demand on health care facilities in general but only on certain health care provisions. This is in contrast with the general notion that all chronically ill make a heavy demand on health care facilities in general.

Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis.

Despite reports that influenza vaccination appears to be safe in multiple sclerosis there is uncertainty which patients may benefit from it. By using a questionnaire we compared the effects of influenza illness (1995-1996 season) and influenza vaccination (autumn of 1996) on neurologic symptoms in patients with multiple sclerosis registered in the Groningen Multiple Sclerosis Data Bank. No clinically relevant effects were reported in 53 patients with primary progressive multiple sclerosis, either following vaccination or the illness. In a group of 180 patients with relapsing multiple sclerosis, an exacerbation occurred within the following 6 weeks in 33% after influenza illness, whereas it occurred in only 5% after vaccination. The exacerbation rate following influenza illness was significantly higher regardless of whether patients were essentially restricted to wheelchair or not. Because of a substantial greater risk of relapse after influenza illness than after vaccination, annual influenza vaccination should be offered routinely to all patients with relapsing multiple sclerosis.

Space-time clustering of multiple sclerosis cases around birth.

OBJECTIVES: To investigate whether infectious events around birth and during early infancy are likely to be of relevance in MS pathogenesis. SUBJECTS AND METHODS: Data are available from two regions in The Netherlands: Groningen (n=320) and Rotterdam (n=226). Simultaneous clustering in birth date and birth location of MS cases is tested by the methods of Mantel, Knox and Jacquez. RESULTS: No evidence was found for a space-time interaction between place and time of birth. CONCLUSION: Perinatal infectious events are unlikely to be a major factor in determining MS susceptibility.

A patient with vertebrobasilar transient ischaemic attacks and provokable basilar steal.

In a 65-year-old woman with vertebrobasilar transient ischaemic attacks (TIAs) and subclavian steal, a steal phenomenon in the basilar artery could be demonstrated by transcranial Doppler sonography after provocation with postischaemic hyperaemia of the arm on the affected side. It was not possible to provoke symptoms or signs at the time. The significance of finding a steal phenomenon in the basilar artery even in a patient with a history of vertebrobasilar TIAs is discussed.

Chronic epidural haematoma. A non-typical course of extradural haemorrhage.

4 Patients with chronic epidural haematoma are presented. Emphasis is placed a) clinically on symptoms of an intracranial hypertension and b) on the C.T.-scan demonstrating the presence of a homogeneous clot. At operation the findings were a clotted haematoma encapsulated on the dural side and the still leaking blood vessel.