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PubMed1980

Interaction of multiple sclerosis serum with liposomes containing ganglioside GM1.

Multiple sclerosis serum contains a factor or factors capable of releasing sequestered [14C]glucose from liposomes containing GM1, the major ganglioside present in human central nervous system myelin. Although some control sera can also release large quantities of liposomal glucose, multiple sclerosis and control sera differ in the mechanism of this release. Liposomal damage by multiple sclerosis serum does not appear to be complement mediated, but shares certain releasing characteristics of cholera toxin.

Adult↗

PubMed2000

The current state of multiple sclerosis genetic research.

INTRODUCTION: Multiple sclerosis (MS) is the most common genetic disease of the nervous system with onset usually in young adulthood. Four genome-wide searches in different Caucasian populations for MS susceptibility loci have been performed, but none reported any linkage at a level that would be regarded as significant according to current criteria. Significant linkage of MS to allelic variants of the major histocompatibility (MHC) locus on chromosome 6p21 has been established although its overall contribution to MS susceptibility has proven difficult to quantify. The objective of this review is not only to provide the reader with an update of MS genetics research, but also to provide a basic knowledge of the techniques being employed to map MS susceptibility genes. The different methodologies are discussed, and specific studies are reviewed in context. METHODS: This review is based on findings from original articles, however, the results of recent candidate gene studies are intended to update previous review articles. RESULTS: There remains no concrete non-MHC locus for MS, although there are enough findings of sufficient interest to warrant further investigation and optimism. Stratification of genome scan data based on MHC class II suggests that it interacts differentially with non-MHC loci and that it contributes moderately to disease susceptibility. Candidate gene studies have continued to return negative and ambiguous results, and follow-up fine mapping of suggestive linkages from the UK genome scan has proven unsuccessful in identifying significant linkages. Genetic analysis of crosses between mouse strains that are differentially susceptible to experimental allergic encephalomyelitis (EAE) has yielded linkages corresponding to putative MS susceptibility loci. However, recent successes in transgenic mice may provide an alternative to EAE, regarded by some as a poor model of MS. CONCLUSION: The first whole genome search for a common human disease was performed over five years ago, and it is now clear, from the lack success in this field, that the genetic complexity of these traits has been underestimated. The genome-wide searches for MS susceptibility genes have suffered from insufficient statistical power, which has probably been compounded by disease and genetic heterogeneity. Studies in isolated populations and better laboratory and clinical definitions of disease are both steps in the right direction to solving these problems. Not withstanding the negative effects of genetic heterogeneity, pooling of resources for meta-analyses may provide the increase in statistical power required for detection of loci that exert a moderate or small effect on disease predisposition.

Animals↗

PubMed2001

Multiple sclerosis and age at infection with common viruses.

Increased risk of multiple sclerosis has been reported among individuals with a history of measles and other common childhood diseases during adolescence, infectious mononucleosis, or exposure to the canine distemper virus. We investigated these associations in a case-control study nested within the Nurses' Health Study (121,700 women traced since 1976) and the Nurses' Health Study II (116,671 women traced since 1989). Age at diagnosis of common viral diseases and birth order were obtained through a questionnaire. Our results include 301 cases with multiple sclerosis and their (up to six) matched controls. Except for infectious mononucleosis, which was a moderate risk factor (odds ratio = 2.1, 95% confidence interval = 1.5-2.9), we found little association between history of common viral diseases or exposure to canine distemper virus and risk of multiple sclerosis. We did find a relation between mumps after 15 years of age (odds ratio = 2.3, 95% confidence interval = 1.2-4.3) or measles after age 15 years of age (odds ratio = 2.8, 95% confidence interval = 0.8-9.1) and multiple sclerosis. Birth order was not materially related to multiple sclerosis. Our findings support the hypothesis that individuals who suffered from infectious mononucleosis, a marker of late infection with the Epstein-Barr virus, have an increased risk of multiple sclerosis. Late infection with other common viruses may also be associated with increased risk.

Adult↗

PubMed1999

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Adjuvants, Immunologic↗

PubMed2006

Managing the symptoms of multiple sclerosis: a multimodal approach.

BACKGROUND: Patients with multiple sclerosis (MS) may experience numerous symptoms, including spasticity, fatigue, cognitive dysfunction, depression, bladder dysfunction, bowel dysfunction, sexual dysfunction, and pain. OBJECTIVE: This article reviews the pharmacologic and nonpharmacologic interventions used to manage the symptoms of MS and discusses how interventions for a particular MS symptom may have an impact on other symptoms. METHODS: The English-language literature was reviewed through November 2005 using MEDLINE and the Cochrane Database of Systematic Reviews, with no restriction on year. The search terms included multiple sclerosis, disease-modifying therapies, adverse events, and combinations of multiple sclerosis with terms such as spasticity, fatigue, depression, mood disorders, pain, bladder dysfunction, bowel dysfunction, sexual dysfunction, cognitive dysfunction, and quality of life. RESULTS: The numerous options for the treatment of MS symptoms have shown varying degrees of efficacy and tolerability. Certain symptoms, if left untreated, may precipitate exacerbation of others. For example, spasticity may lead to pain and bladder and bowel dysfunction, whereas fatigue can compromise cognitive function. Similarly, the adverse effects of treatments for certain symptoms may further compromise other aspects of function. For example, the use of antidepressants may lead to sexual dysfunction, and treatments for spasticity and pain may cause sedation, which can worsen fatigue, cognitive dysfunction, and depressed mood. CONCLUSIONS: MS is associated with numerous symptoms that can be adversely affected by each other and by therapeutic interventions. Careful clinical monitoring and individualization of pharmacologic and non-pharmacologic therapies are recommended to manage the symptoms of MS, with the goals of improving or maintaining function and preserving the patient's quality of life.

Cognition Disorders↗

PubMed2006

Serum prolactin level in patients with multiple sclerosis: a case control study.

BACKGROUND: Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system and is considered to be multifactorial with an autoimmune component. Prolactin (PRL) is a neuroendocrine peptide with potent immunomodulatory properties. Hyperprolactinemia enhances several autoimmune disorders and may play a role in the pathogenesis of MS. The aim of this study was to compare serum PRL levels in MS patients with those of healthy controls. MATERIAL/METHODS: There were 43 patients with definite MS and 43 sex- and age-matched healthy controls. Conditions leading to a rise in PRL, such as pregnancy, lactation, and specific underlying diseases and drugs, were excluded. PRL levels were measured in fasting blood samples. For the MS group, disease duration and subtype, clinical manifestations, and expanded disability status scores (EDSS) were also recorded. RESULTS: There were no significant differences in serum PRL levels between the case and control groups in both women and men (376.78+/-231.11 mIU/l in female patients with MS vs. 364.19+/-202.55 mIU/l in female controls, 266.00+/-200.83 mIU/l in male patients with MS vs. 197.25+/-65.25 mIU/l in male controls). We also found no significant relationship between PRL and disease activity, disease duration, and EDSS. CONCLUSIONS: Our findings do not support the hypothesis that MS patients are in a hyperprolactinemic state. However, further studies in more homogenous MS subgroups are needed.

Adult↗

PubMed1991

Prevalence of multiple sclerosis in five rural Suffolk practices.

OBJECTIVE: To determine a point prevalence of multiple sclerosis in part of Suffolk. DESIGN: Multiple source search for patients with multiple sclerosis in five general practices. Patients were reviewed and categorised by using general practice notes. SETTING: Five rural general practices in Suffolk, 12 May 1988. SUBJECTS: 31,379 patients registered with five practices. MAIN OUTCOME MEASURES: Multiple sclerosis diagnosed by a specialist. RESULTS: The search produced a provisional list of 62 eligible patients with multiple sclerosis. Review of case notes showed that 48 had probable disease, 10 early disease, and four possible disease. The probable cases gave a crude prevalence of 153/100,000 population (95% confidence interval 109/100,000 to 196/100,000). CONCLUSIONS: Although the results should be interpreted cautiously because of the small sample size, they suggest that the prevalence of multiple sclerosis in Suffolk is higher than has been estimated from hospital data.

Age Factors↗

PubMed2006

Mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.

BACKGROUND: There are few treatment options for patients with secondary progressive and worsening relapsing-remitting multiple sclerosis. Mitoxantrone is an antineoplastic drug, recently approved for treatment of multiple sclerosis. Mitoxantrone is, however, associated with dose-related cardiotoxicity, which limits its use. OBJECTIVE: To investigate the possible cardiotoxicity of mitoxantrone in multiple sclerosis. METHODS: We studied 96 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis, to evaluate cardiotoxicity within one year of mitoxantrone therapy. This study was performed in the Multiple Sclerosis Clinic of Isfahan University of Medical Sciences from October 2003 through October 2004. Analysis of mitoxantrone therapy (12 mg/m2), in terms of cardiac toxicity, was conducted on patients who received at least 4 doses. Cardiac assessment was carried out every 6 months with electrocardiogram, as well as a spectral and color-flow Doppler echocardiographic examination at the time of enrollment and 6 and 12 months later. RESULTS: Ninety-six patients were assessed over 12 months. There was no evidence of clinically-significant cardiac dysfunction. Three patients had a left ventricular ejection fraction of <10% of the base-line value and three had <50%. CONCLUSION: Mitoxantrone (12 mg/m2) is effective and generally well tolerated by patients with worsening relapsing-remitting and secondary progressive multiple sclerosis. Our findings suggest that the risk for developing cardiotoxicity is low in patients with multiple sclerosis within one year of the treatment with mitoxantrone.

Adult↗

PubMed1975

Nationwide survey of multiple sclerosis in Japan. Clinical analysis of 1,084 cases.

Between October 1972 and October 1973, the first nationwide survey of the multiple sclerosis group of diseases in Japan was performed by the Multiple Sclerosis Research Committee of Japan, supported by the Japan Ministry of Health and Welfare. Reports on 1,084 patients with the multiple sclerosis group were collected: 509 patients with multiple sclerosis, 82 with Devic's disease, 357 with "multiple sclerosis possible," and 136 with "other or unclassified demyelinating diseases." The natural history in the present nationwide series of multiple sclerosis patients showed considerable similarity to that of patients in Western countries, suggesting that multiple sclerosis in Japan is essentially the same as that in the Western countries. However, the previously reported special characteristics of Japanese multiple sclerosis patients, namely, a higher rate of visual impairment at onset, a higher rate of optic nerve involvement during the course of illness, and a higher rate of Devic's disease, were reconfirmed in the present series.

Adult↗

PubMed1997

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium.

OBJECTIVES: To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. METHODS: Lifetime risks were calculated using the maximum likelihood approach. RESULTS: Vital information was obtained on 674 probands with multiple sclerosis in Flanders and a total of their 26225 first, second, and third degree relatives. Full medical information to allow documentation of multiple sclerosis status was available for 21351 (81.4%) relatives. The age adjusted risk for parents was 1.61 (SEM 0.35)%, for siblings 2.10 (SE 0.36)%, and for children 1.71 (SEM 0.70)%. For aunts and uncles, the risk was 0.66 (SEM 0.13)%. CONCLUSIONS: The risk for first degree relatives of patients with multiple sclerosis in Flanders is increased 10-fold to 12-fold; for second degree relatives, it is increased threefold. This information can be used for risk counselling in families and provides additional support for the role of more than one locus contributing to the susceptibility of multiple sclerosis.

Adult↗

PubMed2006

Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study.

BACKGROUND: Autoimmune mechanisms are thought to have a major role in the pathogenesis of multiple sclerosis. We aimed to identify coexisting autoimmune phenotypes in patients with multiple sclerosis from families with several members with the disease and in their first-degree relatives. METHODS: A total of 176 families (386 individuals and 1107 first-degree relatives) were characterised for a history of other autoimmune disorders. Family-based or case-control analyses were done to assess the association of cytotoxic T-lymphocyte-antigen 4 (CTLA4) and protein tyrosine phosphatase (PTPN22) variants with susceptibility to multiple sclerosis. FINDINGS: 46 (26%) index cases reported at least one coexisting autoimmune disorder. The most common were Hashimoto thyroiditis (10%), psoriasis (6%), inflammatory bowel disease (3%), and rheumatoid arthritis (2%). 112 (64%) families with a history of multiple sclerosis reported autoimmune disorders (excluding multiple sclerosis) in one or more first-degree relatives, whereas 64 (36%) families reported no history of autoimmunity. Similar to index cases, Hashimoto thyroiditis, psoriasis, and inflammatory bowel disease were also the most common disorders occurring in family members. A common variant within CTLA4 was strongly associated with multiple sclerosis in families who had other autoimmune diseases (p=0.009) but not in families without a history of other autoimmune disorders (p=0.90). INTERPRETATION: The presence of various immune disorders in families with several members with multiple sclerosis suggests that the disease might arise on a background of a generalised susceptibility to autoimmunity. This distinct multiple-sclerosis phenotype, defined by its association with other autoimmune diseases, segregates with specific genotypes that could underlie the common susceptibility.

Alleles↗

PubMed1981

[The significance of enlarged retinal veins in the diagnosis of multiple sclerosis: report of a patient (author's transl)].

Multiple sclerosis is a disease of polymorphic presentation and multiple and varied clinical symptoms must be looked for in order to establish a diagnosis, although a definite diagnosis can only be established through post mortem examination. In the early stages, ocular lesions are among the most frequent presenting symptoms and enlarged retinal veins as well as their association with ocular signs such as nystagmus and optic neuritis are characteristic of multiple sclerosis and an important diagnostic sign. In spite of being infrequent, enlarged retinal veins must be looked for when a diagnosis of multiple sclerosis is suspected, with its presentation usually being bilateral, peripherical and with a white band surrounding the retinal veins.

Adult↗

PubMed1998

Neuropsychological aspects of multiple sclerosis.

Since S. Rao's ["Neuropsychology of Multiple Sclerosis: A Critical Review," A Journal of Clinical and Experimental Neuropsychology, Vol. 85, pp. 503-542] (1986) seminal review, considerable research has been undertaken on the neuropsychological consequences of multiple sclerosis. This review incorporates the research literature of the last decade in presenting an overview of the current state of our knowledge concerning the etiology, course, symptoms, assessment, consequences, and treatment of multiple sclerosis (MS). The concept of subcortical dementia is revisited in light of the most recent literature documenting the neuropsychological deficits in patients with MS. The view that cognitively heterogeneous patient groups may disguise more specific patterns of focal neuropsychological impairment is considered. A critical review of the recent literature is also presented, detailing the degree to which recent research has addressed the areas of research need identified by Rao in 1986. Given recent advances in our knowledge, the need for more attention to be directed toward the evaluation of rehabilitation and psychological intervention is highlighted.

Activities of Daily Living↗

PubMed2005

The appearance of pars planitis in multiple sclerosis.

The aim of the study was to investigate the clinical association of multiple sclerosis and pars planitis (or intermediate uveitis), as well as to determine the incidence of pars planitis in multiple sclerosis patients. During the period of one year authors examined 42 patients with multiple sclerosis divided into two groups. First group consisted of 23 patients with history of optic neuritis and the second group consisted of 19 patients who have never had optic neuritis. The mean age of patients in the first group was 31.7 +/- 5.1 years and in the second group 29.1 +/- 8.1 years. Pars planitis was found in 12 patients with multiple sclerosis. Age, sex and degree of neurological disability had no influence on the appearance of pars planitis. Although optic neuritis is considered to be the most common ocular manifestation of multiple sclerosis, the significant number of patients with multiple sclerosis has pars planitis.

Adult↗

PubMed2006

[Facial palsy as the first syndrome of multiple sclerosis in 16 years old girl].

INTRODUCTION: Multiple sclerosis (MS) is demyelinating disease characterized by scattered neurologic deficits the central nervous system. The large number of scattered lessions produce many clinical symptoms. Facial palsy is rarely ascribed to multiple sclerosis as first syndrome. MATERIAL AND METHODS: 16-years old girl with sequence of features: 1. facial palsy, 2. transitional sudden hearing loss 3. transitory vertigo is presented. In audiologic examination pure tone audiogram, impedance audiometry, ABR and ENG were done. Air and bone thresholds were normal, stapedial reflex was absent and ABR suggested retrocochlear involvement in affected ear. RESULTS: In this case after MRI examination multiple sclerosis was diagnosed. CONCLUSION: ENT specialists should considered MS like a reason of facial palsy.

Adolescent↗

PubMed1992

Lower urinary tract dysfunction in multiple sclerosis.

Previous investigators have shown that in multiple sclerosis failure to empty the bladder was secondary to detrusor-distal sphincter dyssynergia or areflexia. However, our urodynamic evaluation of 46 female and 43 male patients with multiple sclerosis revealed that 63 percent of patients failed to empty their bladders because of a hypocontractile detrusor, and only 6 percent had areflexia. Detrusor-distal sphincter dyssynergia (6%) and bladder neck obstruction (6%) were present in only 12 percent of patients. Hyperreflexia was common (78%) and was associated with hypocontractility in 63 percent of patients. Urgency incontinence was significantly more common in females and voiding difficulty significantly more common in males. Sensation was also reduced in 74 percent of female and 77 percent of male patients. In conclusion, failure to empty the bladder in multiple sclerosis is most commonly associated with hypocontractility, and the combination of hyperreflexia and hypocontractility produces the symptoms of urgency and incomplete emptying.

Adult↗

PubMed1986

[Determination of a factor inhibiting migration of leukocytes to brain antigens, its concentration in serum and spontaneous leukocyte migration in multiple sclerosis].

The authors examined 58 patients with multiple sclerosis and 56 healthy donors. The patients presented elevated production of the migration inhibition factor (MIF) by lymphoid cells to cerebral tissue antigens, most expressed in the acute period of the disease. The blood serum of patients with multiple sclerosis showed inhibitory activity, lymphocytes spontaneously produced the MIF in vitro. Hyperproduction of lymphokins may serve as one of the pathogenetic factors of generalization of the inflammatory process in the central nervous system in patients with multiple sclerosis and indicates impaired regulation of immunity.

Brain↗

PubMed1979

Pes cavus and claw toes deformity in patients with spinal cord injury and multiple sclerosis.

Patients with spinal cord injury or multiple sclerosis were surveyed for the presence of extreme foot deformities and spasticity. Pes cavus and claw toes were found in eight of 80 spastic spinal cord injury and two of 20 multiple sclerosis patients. Pes cavus and claw toes were not found in 29 flaccid spinal cord injury patients. Pes cavus and claw toes were associated with flexor reflexes which could be elicited by pin prick proximal to the knee, suggesting extreme spasticity--and by low excitatory thresholds for the anterior tibialis as indicated electromyographically. Complications of severe spasticity associated with spinal cord injury and multiple sclerosis include pes cavus and claw toes, mediated in part by spasms of the anterior tibialis.

Adult↗