Interferon beta treatment in multiple sclerosis: the European clinical trials

Studies have demonstrated the failure of gut barrier function in all cases of experimental acute diffuse peritonitis. Histobacterioscopy and electron microscopy showed the occurrence of bacteria under the basal membrane, in lymphatic and blood capillaries of the small intestinal villi. Experimental and clinical trials with blood sampling from different regions of the circulation have demonstrated the gut origin polymicrobial bacteremia in 66% of patients and in 75% of experimental animals with acute diffuse peritonitis.     

Current treatment of multiple sclerosis with interferon beta

INTRODUCTION: Demonstration of the efficacy of interferon beta IB in the reduction of outbreaks of multiple sclerosis has led to it being used in Spain. DEVELOPMENT: Discussion of the current situation regarding the use of interferon beta IB in Spain, diagnostic criteria, side-effects and future outlook. CONCLUSIONS: Use of interferon beta IB in Spain has followed criteria established by a Committee of Experts, and there is a lower rate of non-completion of treatment than in the U.S.A. New possibilities arise with the appearance of new drugs which are still awaiting evaluation.     

Human T-cell receptor V beta gene polymorphism and multiple sclerosis

Population-based genetic associations have been reported between RFLPs detected with probes corresponding to the genes encoding the beta chain of the T-cell receptor for antigen (TCRB) and a variety of autoimmune disorders. In the case of multiple sclerosis (MS), these studies have localized a putative disease-associated gene to a region of approximately 110 kb in length, located within the TCRB locus. In the current study, all 14 known TCRBV (variable region) genes within the region of localization were mapped and identified. The nucleotide sequences of these genes were determined in a panel of six MS patients and six healthy controls, who were human-leukocyte antigen and TCRB-RFLP haplotype matched. Nine of the 14 TCRBV genes studied showed evidence of polymorphism. PCR-based assays for each of these polymorphic genes were developed, and allele and genotype frequencies were determined in a panel of DNA samples from 48 MS patients and 60 control individuals. No significant differences in allele, genotype, or phenotype frequencies were observed between the MS patients and controls for any of the 14 TCRBV-gene polymorphisms studied. In light of the extensive linkage disequilibrium across the region studied, the saturating numbers of polymorphisms examined, and the direct sequence analysis of all BV genes in the region, these results suggest that it is unlikely that germ-line polymorphism in the TCRBV locus makes a major contribution to MS susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioelectromagnetic applications for multiple sclerosis

There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.     

Childhood multiple sclerosis

Multiple sclerosis begins before the age of 17 years in 0.4 to 0.5% of the cases, but the diagnosis is exceptionally made before the age of 10 years. Female predominance is more marked in early onset multiple sclerosis. The general features of the disease (clinical expression, progression, prognostic) and the findings of complementary explorations are comparable with those found when the disease begins in adulthood although acute onset and signs of brain stem involvement have been reported. The diagnosis must be made with prudence, especially when progression is slow from the beginning. An analysis of the influence of infective environmental factors and puberty has not provided new insight. Corticosteroids can be used in case of flare-ups. Management requires a multidisciplinary approach to maintain appropriate educational activities.     

New and old treatments for multiple sclerosis

Audiogenic seizures associated with loss of weight, prostration, piloerection, palpebral ptosis and motor deficiency were induced after sound stimulation of determined frequency and amplitude in magnesium-deficient DBA/2 mice. These symptoms were maintained when standard diet conditions (1700 ppm Mg2+) were restored. In contrast, mice were protected from audiogenic seizure in a dose related manner when Crassostrea gigas extract (JCOE) were added to the diet for 10 consecutive days. Although a rational explanation for this protective effect has not yet been determined, it is assumed that it might be due to a chelating complex formed between Mg2+ and taurine, which enhance the uptake of Mg2+.     

Interferon beta-1b inhibits reactive oxygen species production in peripheral blood monocytes of patients with relapsing-remitting multiple sclerosis

To determine if perforation rate is a function of delayed diagnosis or delayed presentation in childhood acute appendicitis we performed a retrospective casenote review of 101 consecutive children undergoing emergency appendicectomy over a 12-month period. The perforation rate was 7% in those children presenting with symptoms of 1 day or less and was significantly greater (33%, Chi 2 = 9.45, P < 0.01) in those who had had symptoms for more than 1 day at presentation. There was no difference in in-hospital delay between the groups. A high perforation rate was found to be a feature of delayed presentation.     

Depression and multiple sclerosis

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.     

Genetics of multiple sclerosis

The cause of MS is unknown. There is considerable circumstantial evidence that MS is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. At present, it must be acknowledged, however, that our understanding of the pathogenesis of MS is minimal. Very little is known about the genes determining disease susceptibility and perhaps even less is understood about environmental factors that influence penetrance or the geographic distribution. This lack of knowledge results neither from lack of effort nor from a shortage of fertile imaginations. Almost every imaginable hypothesis has, in the past, found some support. The intractability of the problem could well result from its complexity, because answers to testable hypotheses are commonly negative or ambiguous. Today, the opportunity exists for researchers to provide such answers because of recent major developments. The first development is the recognition that MS research requires a relatively large pool of well-ascertained, carefully diagnosed, and longitudinally well-characterized MS patients. The last two developments are the identification and successful application of statistical and molecular genetic techniques carrying sufficient power to allow the exploration of complex traits such as MS.     

Pregnancy and multiple sclerosis

In this review, we summarize the available information on the short- and long-term effects of pregnancy on the course of multiple sclerosis (MS). Published studies that used established criteria for the diagnosis of MS were given more weight than studies in which the criteria for diagnosis were unstated or unclear. Population-based studies were emphasized more than clinic-based studies, unless the clinic base was well defined and thought to be reasonably representative of the MS population in the geographic area. For completeness, small studies were also included but weighted accordingly in our overall conclusions. Methodologic limitations and biases inherent in the study methods are discussed. We conclude that patients with relapsing MS have an increased risk of relapse during the initial 6-month postpartum period. This increased risk does not seem to have a detrimental effect on the rate of developing sustained disability. In fact, a full-term pregnancy may increase the time interval to reaching a common disability endpoint-walking with the aid of a cane or crutch--or to having a secondarily progressive course. Evidence indicates that pregnancy may alter T-lymphocyte functions and cause clinically relevant consequences. The specific biochemical mechanisms responsible for these observations, however, remain undefined. Because of limitations of current knowledge, our conclusions are tentative at best. The data are most applicable to patients with relapsing-remitting MS in its early stages. MS is an unpredictable disease and is only one of many factors that patients must consider when a pregnancy is contemplated.     

Neuroimaging in multiple sclerosis

Neuroimaging in multiple sclerosis is now dominated by MR imaging. This article will focus primarily on conventional MR imaging studies in multiple sclerosis, but will also discuss briefly some of the more recent advances related to MR imaging. Fast spin-echo imaging, fluid attenuated inversion recovery MR studies, three-dimensional volumetric studies, magnetization transfer, and magnetic resonance spectroscopy as it applies to multiple sclerosis are examined.     

Prognosis in multiple sclerosis

Prognosis of the natural course of multiple sclerosis is most often measured on Kurtzke's "expanded disability status scale" (EDSS), a non-linear scale over 20 steps, heavily weighted on mobility. Optic neuritis and sensory disturbances as initial symptoms, lower age at onset of the disease, female sex and a longer interval between relapses are indicators of a more favorable prognosis. As a rule, disability as measured on this scale 5 years after onset corresponds to 3/4 of the disability status after 15 years. The number of relapses diminishes naturally over the course of the disease. Presence and extent of lesions on the initial MRI of the brain in clinically isolated syndromes are valuable predictors of dissemination of the disease process over the following 5-10 years. New therapies (e.g. interferon beta 1b and 1a, copolymer 1) reduce relapse frequency by 1/3 and diminish the extent of pathological lesions in brain MRI, but fail to show (as yet) significant influence on disability.