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PubMed1986

Interferon induction, 2'-5' oligo A synthetase and lymphocyte subpopulations in out-patients with multiple sclerosis in a longitudinal study.

Nine patients with multiple sclerosis, four with relapsing-remitting disease, and five with chronic progressive disease, together with eight healthy control, were followed for nearly a year with monthly clinical and laboratory examinations. Alpha- and gamma-interferon was induced in lymphocytes with different viruses and PHA, no differences were found between healthy controls and multiple sclerosis patients. The alpha- and gamma-interferon induced enzyme 2'-5' oligo A synthetase in lymphocytes was found to have a tendency to be lower in multiple sclerosis patients than in healthy controls. When medians of ratios of helper/suppressor blood lymphocytes in multiple sclerosis patients were compared with healthy controls, the same results were found, although higher values of ratios were found among the patients and the highest value was found in a patient with chronic progressive disease. No correlation to disease activity could be found in interferon inductions, 2'-5' oligo A synthetase concentrations and ratios of OKT4/OKT8. In particular no change in ratio was found in relation to five exacerbations taking place in the four multiple sclerosis patients with acute relapses.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Desferrioxamine in chronic progressive multiple sclerosis: a pilot study.

Chronic progressive Multiple Sclerosis is refractory to many conventional treatments. We performed a pilot study testing desferroxamine (DFO) as a candidate in the treatment of chronic progressive Multiple Sclerosis. DFO was given daily by 8 h subcutaneous infusions at a dose of 2 grams daily for 7 days, followed by 1 gram daily for 7 days. Eighteen of 19 individuals completed the full dose of 21 grams. One patient was unable to complete the course due to nausea. No acute deterioration of neurological status was seen during the administration of DFO. No worsening of vision or hearing was noted except that the one patient who was unable to tolerate the medication had a transient reduction in hearing. All patients had a local redness at the injection site. None of the patients had any sudden worsening during or shortly after the treatment. This pilot study suggests that DFO is relatively well tolerated by Multiple Sclerosis patients when given in a short course of therapy.

Adult↗
PubMed1992

The morbidity of multiple sclerosis.

Although the clinical course of multiple sclerosis is benign in up to one-third of patients, it is important to recognize the high rate of morbidity in others. Most individuals pass through a remitting phase but in a significant proportion the clinical manifestations subsequently recur, persist or slowly progress, and disability accumulates with time. Here we describe the frequency and spectrum of morbidity in a population based cohort of patients with multiple sclerosis. These statistics will guide those providing health care resources and planning services for patients with multiple sclerosis.

Adolescent↗
PubMed1986

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Canada↗
PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗
PubMed2006

Sex ratio of multiple sclerosis in Canada: a longitudinal study.

BACKGROUND: Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change. METHODS: Since environmental risk factors seem to act early in life, we calculated sex ratios by birth year in 27 074 Canadian patients with multiple sclerosis identified as part of a longitudinal population-based dataset. FINDINGS: The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3.2:1 in Canada. Year of birth was a significant predictor for sex ratio (p<0.0001, chi(2)=124.4; rank correlation r=0.84). INTERPRETATION: The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene-environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed pound1 million per case in the UK.

Adult↗
PubMed1983

The changing neurourologic pattern of multiple sclerosis.

The changing clinical course of multiple sclerosis is a hallmark of the disease. The neurourologic findings in this disorder have been well documented in the literature but the occurrence of urodynamic changes with time has been mentioned only briefly. Ten men and 8 women had 2 or more urodynamic evaluations, consisting of cystometrography and perineal floor needle electromyography during 2 months to 6 years (mean 25 months). The initial urodynamic patterns included a normal study in 1 patient, detrusor areflexia in 7 and detrusor hyperreflexia in 10 (5 with vesicosphincter dyssynergia). Re-examinations were done for persistent or new symptoms. The urodynamic pattern changed in 10 patients (55 per cent), including cystometrographic changes in 7, newly developed neuropathic changes on electromyography in 5 and changes in detrusor-sphincter interaction in 9 (with 5 new cases of vesicosphincter dyssynergia). Of the 8 patients who did not demonstrate a urodynamic change 5 had vesicosphincter dyssynergia that persisted on followup. Vesicosphincter dyssynergia was the predominant pattern noted on re-evaluation, acting as a urodynamic indicator of progressive multiple sclerosis. Careful neurourologic assessment should be performed routinely in the followup of multiple sclerosis patients who are unresponsive to treatment or who manifest new symptoms.

Adult↗
PubMed1995

Abnormalities in posturography and estimations of visual vertical and horizontal in multiple sclerosis.

Twenty-seven patients with mild multiple sclerosis were tested with the dynamic posturography protocol used in the NeuroCom Equitest procedure. The purpose of this study was to determine if the standard test procedure elicited a pattern of responses that would suggest the possibility of multiple sclerosis during differential diagnosis of a patient with dysequilibrium. In addition, the patients' ability to align a light bar to vertical and horizontal was tested with the head erect and with the head tilted 45 degrees to the right and left shoulder. There was a pattern of abnormality in the Equitest motor coordination tests. Only one patient produced normal scores in both the latency and adaptation tests. No pattern of error was noted in the sensory organization tests. In the visual alignment tests, only 3 of the 27 patients tested produced values that were within normal limits for the three different head positions. Visual alignment and the motor coordination tests are not specific for multiple sclerosis, but poor performance probably indicates a disruption of the integration of visual, vestibular, and somatosensory information. Although patients with early multiple sclerosis and patients with purely vestibular disorders often have similar complaints, they have quite different profiles of abnormalities in posturography testing.

Diagnosis, Differential↗
PubMed2005

Evoked potential studies in the antiphospholipid syndrome: differential diagnosis from multiple sclerosis.

BACKGROUND: The CNS manifestations of the antiphospholipid syndrome (APS) can mimic multiple sclerosis both clinically and radiologically. OBJECTIVE: To compare evoked potential studies in APS patients and patients with multiple sclerosis with similar neurological disability. METHODS: 30 APS patients with CNS manifestations and 33 patients with definite multiple sclerosis and similar neurological disability underwent studies of visual evoked potentials (VEP), somatosensory evoked potentials (SSEP) in the upper and lower limbs (UL, LL), and sympathetic skin responses (SSR) in the upper and lower limbs. RESULTS: The neurological manifestations in the APS patients included stroke (n = 17), transient ischaemic attacks (n = 10), and severe headache with multiple white matter lesions on brain MRI (n = 3). Abnormal SSEP (LL), and SSR (UL; LL) were seen in APS patients (37%, 27%, and 30%, respectively) but VEP and UL SSEP were rarely abnormal (10% and 6%, respectively in APS v 58% and 33% in multiple sclerosis; p = 0.0005, p = 0.008). Mean VEP latencies were more prolonged in multiple sclerosis (116 ms v 101 ms, p<0.001). Only one APS patient had abnormal findings in all three evoked potential studies, compared with seven patients in the multiple sclerosis group (p = 0.04) CONCLUSIONS: Abnormal VEPs are uncommon in APS in contrast to multiple sclerosis. Coexisting abnormalities in all other evoked potentials were similarly rare in APS. In patients with brain MRI findings compatible either with multiple sclerosis or APS, normal evoked potential tests, and especially a normal VEP, may support the diagnosis of APS.

Adult↗
PubMed1989

Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis.

Thirty untreated patients with clinically definite chronic progressive multiple sclerosis were matched with 10 patients with clinically stable definite multiple sclerosis and 16 patients with other neurological diseases. A group of 12 normal control (NC) volunteers was matched to these groups. All patients with chronic progressive multiple sclerosis and normal control subjects were analyzed for the concanavalin A suppressor assay, mitogen stimulation, and phenotyping of peripheral blood mononuclear cells. In addition, serum was analyzed for interleukin-2 levels. Results of mitogen stimulation studies did not distinguish the groups. Concanavalin A-induced suppression was significantly decreased in the patients with chronic progressive multiple sclerosis (p less than 0.01). Phenotyping of fresh cells showed an elevated CD4: CD8 ratio in the patients with chronic progressive multiple sclerosis. Neither phenotyping nor concanavalin A-induced suppression correlated with or predicted the degree of disability, but the serum levels of interleukin-2 correlated inversely with disability (p less than 0.01) and directly with a poor prognosis after 18 months of observation (p less than 0.05). Serum levels of interleukin-2 decreased as the disease progressed.

Adult↗
PubMed1989

Antibodies against the paramyxovirus SV5 are not specific for cerebrospinal fluid from multiple sclerosis patients.

An aetiological agent for multiple sclerosis has not yet been identified. The paramyxovirus SV5 (Simian virus 5) has been suggested as an important cause in some cases. Using antigen immunoblotting with SV5 virus, we confirmed the binding to SV5 of immunoglobulin G from the cerebrospinal fluid of 58% of multiple sclerosis patients, but also found binding in 70% of patients with a variety of neurological disorders where oligoclonal banding was present. This suggests that the antibodies present are not specific for multiple sclerosis and that the SV5 virus is thus unlikely to be of aetiological significance.

Antigens, Viral↗
PubMed1995

Attention related performance in two cognitively different subgroups of patients with multiple sclerosis.

To evaluate the underlying mechanisms of cognitive decline in multiple sclerosis, two clinically and demographically matched multiple sclerosis groups differing in cognitive status were assessed with attention related tasks. In addition to the attention tests recommended by the Cognitive Function Study Group of the American National Multiple Sclerosis Society, a test of sustained attention was used to evaluate the role of possible fatigue on cognitive performance. The cognitively mildly deteriorated group was slower than the cognitively preserved group and the controls on all tests of attention. The mildly deteriorated group did not, however, consistently differ from the other groups in the error scores of the attention tests. The preserved group exhibited slowness at the end of the visual vigilance test, but no deficits were found on the other attention related tests in this group. It is suggested that dissociable kinds of processing slowness are the origin of the deficits found on the attention tests in the two multiple sclerosis groups. Our preserved group exhibited signs of motor and fatigue related slowness, whereas the mildly deteriorated group also had extensive cognitive slowness. As sensitive indicators of cognitive slowness, attentional tests should be included in evaluation of the cognitive status of patients with multiple sclerosis.

Adult↗
PubMed1996

[Painless femoral neck fracture in a patient with multiple sclerosis].

We describe a patient with multiple sclerosis who suffered a painless hip fracture. She was admitted to the hospital three weeks after falling on her left hip. She had been unable to walk after the trauma, but had had no pain. The condition was initially misinterpreted as multiple sclerosis schub. X-ray examination showed fracture of the left femoral neck, and by the time she was admitted to hospital the patient was paretic. She has improved substantially after an operation involving cementless total hip arthroplasty. Painless fractures in patients with multiple sclerosis may be confused with exacerbations of their neurological disease.

Adult↗
PubMedDate not supplied

[Polymorphism of length of tetranucleotide repeat from the 5'-side from the myelin basic protein gene in multiple sclerosis in Russians].

The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5' side from the first exon of MBP in ethnic Russians (126 patients with reliable multiple sclerosis and 142 healthy controls from Central Russia) was analyzed using the case-control method. Upon separation of the tetranucleotide repeat site amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as frequency of allele group B and genotype A/A reliably differs in multiple sclerosis patients and healthy controls. Alleles A and the A/A genotype are associated with the development of multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serospecificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, formed on the basis of the DRB1 phenotype, has shown a reliable increase in the frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No reliable difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., no carriers of any phenotype except DR4 and DR5 were revealed. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is reliably associated only with DR2(15), but not of DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

Base Sequence↗
PubMed1999

[Skin reactions to interferon alpha in a series of 92 patients with multiple sclerosis].

BACKGROUND: A significant proportion of multiple sclerosis patients develop cutaneous reactions by interferon beta 1b (IFN-beta). The am of this study was to describe clinically and histologically the cutaneous reactions by IFN-beta. PATIENTS AND METHODS: A series of 92 patients with multiple sclerosis in treatment with IFN-beta was followed. Cutaneous biopsy was performed in cases with persistent lesions. RESULTS: 9 out of 92 patients presented eritematous plaques, 4 cutaneous ulcers and 1 sclerodermiform plaques. Vascular thrombosis was demonstrated in 2 cases. CONCLUSIONS: In patients with multiple sclerosis treated with IFN-beta the persistent skin lesions are more frequent in female patients. Generally is not necessary to stop the treatment.

Adult↗
PubMed1997

New insights into the immunogenetics of multiple sclerosis.

The genetic analysis of multiple sclerosis has been based mainly on candidate gene association studies in selected populations. However, the candidate gene approach, although straightforward, is problematic in diseases of unknown or partially known etiology. With the advent of genomic screening and novel statistical approaches, it is possible now to perform an efficient screen of the entire human genome to identify the genetic components of multiple sclerosis.

Humans↗
PubMed1996

Multiple sclerosis: clinical presentation, diagnosis and treatment.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system and is associated with periods of disability (relapse) alternating with periods of recovery (remission) and often results in progressive neurologic disability. Scientists believe that multiple sclerosis may be a T cell-mediated autoimmune disease. Treatment with high-dose pulses of intravenous methyl-prednisolone is usually associated with a good outcome in the short term. A recent study suggests that interferon beta-1b may decrease the number of relapses in relapsing-remitting multiple sclerosis by 30 percent and also may decrease the development of new central nervous system lesions. Recently, another clinical trial of interferon beta-1a showed a 31 percent reduction in relapse rate and a significant reduction in the average number of active lesions. A third trial showed that 20 mg of copolymer-1, a random polymer of glutamic acid, lysine, alanine and tyrosine, reduced relapses by 21 percent without significant side effects. Further investigation is needed, but these new treatments show great promise in alleviating this difficult clinical problem.

Adrenal Cortex Hormones↗
PubMed2005

Role of return migration in the emergence of multiple sclerosis in the French West Indies.

The emergence of multiple sclerosis in island societies has been investigated only in a few Caucasian populations living in temperate regions. The effect of human migration on the risk of developing this disease is still an open question because of possible genetic selection. We conducted an epidemiological study of the multiple sclerosis population in the French West Indies (Martinique and Guadeloupe), a population which includes large numbers of West Indians who have returned after emigrating to metropolitan France. Standardized incidence ratios (SIRs) for multiple sclerosis among migrants were calculated and their genetic characteristics were compared to those of non-migrants. The crude prevalence of multiple sclerosis was 14.8/10(5) on December 31, 1999 (95% CI: 11.9-17.7); and its crude mean annual incidence for the period July 1, 1999 to June 30, 2002 was 1.4/10(5) (95% CI: 1.0-1.8), confirming its emergence in the French West Indies. Recurrent neuromyelitis optica, which is virtually the only form of multiple sclerosis in black African populations in tropical regions, represented not >17.8% of these cases. During the 1,440,000 person-years of follow-up, 33 incidence cases were identified in migrants. Since the number of expected cases was 19.3, the overall SIR was 1.71 (95% CI: 1.19-2.38; P < 0.01) among migrants. The increase in the SIR was more marked if the stay was made before the age of 15 years (4.05, 95% CI: 2.17-6.83; P < 0.0001). European ancestry in the two migrating and non-migrating populations was similar. Martinique, which has a higher rate of return migration, has a higher prevalence of multiple sclerosis (21.0/10(5) versus 8.5/10(5)) and a higher incidence (2.0/10(5) versus 0.7/10(5)) than Guadeloupe. The emergence of the disease in the French West Indies is of environmental rather than genetic origin. It may be explained either through the introduction by migrants of precipitating environmental factors that operate in a critical way before the age of 15 years, and/or by the recent disappearance from the French West Indies of protective environmental factors acting before this age.

Adolescent↗