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Results for “SCLEROSIS, MULTIPLE”

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PubMed2003

Neutralizing antibodies against IFN-beta in multiple sclerosis: antagonization of IFN-beta mediated suppression of MMPs.

Neutralizing antibodies (NAb) against interferon-beta (IFN-beta) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFN-beta on clinical and MRI measures. The expression of the interferon acute-response protein, myxovirus resistance protein A (MxA) is a sensitive measure of the biological activity of therapeutically applied IFN-beta and of its reduced bioavailability due to NAb. However, MxA may not be operative in the pathogenesis of multiple sclerosis or the therapeutic effect of IFN-beta. Instead, matrix metalloproteinases (MMPs) are increased in brain tissue, CSF and blood circulation of multiple sclerosis patients and function as effector molecules in several steps of multiple sclerosis pathogenesis. One of the molecular mechanisms by which IFN-beta exerts its beneficial effect in multiple sclerosis is reduction of MMP-9 expression and increase of its endogenous tissue inhibitor, TIMP-1. Quantitative PCR measurements of MMP-2 and MMP-9, TIMP-1 and TIMP-2, and MxA were performed in peripheral mononuclear cells from clinically stable multiple sclerosis patients with relapsing remitting disease course after short-term and long-term treatment with IFN-beta. IFN-beta therapy down-regulated the expression of MMP-9 and abolished that of MMP-2 in long-term, but not short-term treated multiple sclerosis, while levels of MxA were increased in both instances. The presence of NAb reversed these effects, i.e. led to reduced MxA and increased MMP-2/MMP-9 expression levels compared with NAb- patients. In contrast, expression of TIMPs in peripheral blood mononuclear cells remained unaffected by IFN-beta therapy and the presence of NAb. While MxA is able to detect the biological action and reduced bioavailability of IFN-beta on the basis of single injections, only MMP-9 shows quantitative correlation with the NAb titre. Together with evidence that an imbalance between MMP and TIMP expression is a crucial pathogenetic feature in multiple sclerosis, these findings support the concept of a significant role of NAb in reducing the therapeutic efficacy of IFN-beta.

Antibodies↗

PubMed2003

Multiple sclerosis presenting as neurological decompression sickness in a U.S. navy diver.

A case of clinically definite multiple sclerosis presenting as neurological decompression sickness is presented. A 23-yr-old U.S. Navy diver experienced onset of hypesthesia of the left upper trunk approximately 19 h after making two SCUBA dives. She did not seek medical attention until 3 wk later, at which time she was diagnosed with possible neurological decompression sickness. She was treated with hyperbaric oxygen, but demonstrated no improvement. Further evaluation led to the diagnosis of multiple sclerosis. This case underscores the potential similarity in neurological presentation between multiple sclerosis and decompression sickness. The differential diagnosis of neurological decompression sickness, particularly in atypical cases, should include multiple sclerosis. The appropriateness of medically clearing multiple sclerosis patients for diving is discussed.

Adult↗

PubMedDate not supplied

[Multiple sclerosis in childhood: a report of 2 clinical cases].

Multiple sclerosis is a rare finding in pediatric age. The onset of the disease may be in adolescence or pre-adolescence. It is important that pediatricians know the diagnostic criteria and clinical course of multiple sclerosis in childhood. We describe the case reports of two children, a 11- and a 14-years-old girls and review the literature of the last 5 years on multiple sclerosis in childhood.

Adolescent↗

PubMed1984

Multiple sclerosis immune complexes: an analysis of component antigens and antibodies.

Serum immune complexes were isolated from 21 patients with multiple sclerosis and 23 control subjects, who were normal or had other neurological diseases, and then probed for neurotropic viral and brain-reactive components. Multiple sclerosis complexes contained antibody to herpes simplex (13 cases), measles (8 cases), cytomegalovirus (5 cases), and rubella virus (5 cases). In some complexes, herpes simplex or cytomegalovirus antigen was detected along with antibody. Myelin basic protein or antibody to myelin basic protein was found in the complexes of 7 patients with multiple sclerosis and 2 patients with other neurological diseases. Serum complexes containing antibody reactive with galactocerebroside and ganglioside were present in 12 patients with multiple sclerosis and 3 with other neurological diseases. Over 60% of the multiple sclerosis group had IgM and IgA serum complexes, including 5 patients with very high IgA complex levels. This study suggests that patients with multiple sclerosis have ongoing systemic virus production with resultant immune complex formation. In addition, they often have serum complexes that contain brain-reactive components.

Adult↗

PubMed2000

The genetics of multiple sclerosis.

Epidemiological studies implicate an interplay between genetic and environmental factors in the aetiology of multiple sclerosis. The classical genetic observations suggest that multiple sclerosis is a complex trait in which susceptibility is determined by several genes acting independently or epistatically. The main dividend from understanding the genetic basis of susceptibility in multiple sclerosis will be an improved understanding of the pathogenesis. To date, candidate gene approaches have proved relatively unrewarding other than in establishing the association with alleles of the major histocompatibility complex (MHC). In common with most other complex traits, no major susceptibility gene has been identified through full genome screens but regions of interest have provisionally been identified. An important part of future studies in the genetics of multiple sclerosis will be to resolve the question of disease heterogeneity.

Genetic Predisposition to Disease↗

PubMed1976

Multiple sclerosis and high incidence of a B lymphocyte antigen.

Multiple sclerosis patients were tested for six new antigens present on human B lymphocytes. The group 4 specificity occurred in 83.9% of the 56 patients as compared to 32.5 percent in 72 healthy controls (P less than .003). The antiserums defining the five other B lymphocyte specificities reacted at a lower frequency to B cells from multiple sclerosis patients, showing that increased reactivity to group 4 antiserum was specific. Linkage of a hypothesized multiple sclerosis susceptibility gene with certain haplotypes of HLA-A3, HLA-B7 HLA-DW2, and the new B group 4 can be inferred.

Alleles↗

PubMed1988

Peripheral blood lymphocyte phenotype and function in multiple sclerosis.

T suppressor cell function and phenotype are abnormal in patients with multiple sclerosis, especially during the chronic progressive phase but the sub-populations defined by mitogen stimulation and serological methods may not be identical. In this study, involving 45 patients with multiple sclerosis and 33 controls, there was no correlation between T suppressor function and CD8 cell phenotype in patients with multiple sclerosis or in controls. These phenotypic and functional studies cannot therefore be used interchangeably in the assessment of patients with multiple sclerosis since they provide different information about lymphocyte subpopulations.

Antibody Formation↗

PubMed1990

[Retinal periphlebitis and multiple sclerosis. Incidence, cerebrospinal fluid and results of visual evoked potentials].

In a retrospective study 323 patients with multiple sclerosis were screened for the incidence of retinal periphlebitis. The results of lumbar puncture and the visual evoked potentials were related to the eye disease. Retinal periphlebitis was seen in 19 patients (5.9%). Of the patients with retinal periphlebitis, 79% developed the eye pathology within the first 10 years of multiple sclerosis. The cerebrospinal fluid and visual evoked potentials were no different than the results in a control group of multiple sclerosis patients without periphlebitis. Multiple sclerosis should always be considered as one of the potential underlying diseases in retinal periphlebitis since it is found in 30% before or at the same time as the first neurological symptoms of multiple sclerosis.

Adult↗

PubMed1976

Delayed visual perception and delayed visual evoked potentials in the spinal form of multiple sclerosis and in retrobulbar neuritis.

(1) We have used both subjective and evoked potential tests to study cases of multiple sclerosis with no history of retrobulbar neuritis (spinal patients) and compared them with patients with multiple sclerosis who had experienced an attack of retrobulbar neuritis (RBN). We measured the delay of steady-state evoked potentials (EPs) elicited by flicker in the medium-frequency (13-25 c/s) range, by flicker in the high-frequency (30-60 c/s) range, and by pattern-reversal. We also measured the delay in seeing (perceiving) both an increase of light intensity and a decrease of light intensity. (2) The difference between perceptual delays for the left and right eyes (D s) was abnormal when retrobulbar neuritis affected only one eye (22/22 patients) even when acuity and discs were normal. It might be supposed that this perceptual test would be ineffective when both eyes were affected by retrobulbar neuritis. However, the value of D was abnormal in cases of bilateral retrobulbar neuritis (5/5 patients). Probably the principal reason is that demyelination was patchy in the patients studied. For this same reason the difference between perceptual delays for two sites in the visual field (T s) may also be abnormal. In principle the perceptual delay test can be effective even when both eyes are similarly delayed: abnormal values of T were recorded in 5 spinal patients for whom D was normal. (3) Perceptual delays were measured for an extended group of 19 patients suffering from spinal multiple sclerosis. Taking both D and T into account, the perceptual delay test alone picked out 12/19 spinal patients. The perceptual delay test has the advantage over EP tests that it can detect islands of demyelination as small as 3 degrees diameter, and the apparatus is cheap and straightforward to use. (4) Thirteen patients with spinal multiple sclerosis, including 6 with no ocular signs or symptoms, were examined with a battery of two evoked potential and one perceptual test. Ten patients had clearly abnormal visual delays. Results for the remaining 3 were equivocal. Delay tests can reveal visual damage in most patients who have not experienced an attack of RBN as well as in practically all patients who have experienced an attack. (5) Correlations between the results of the various tests were different in spinal patients and in multiple sclerosis patients who had experienced an attack of retrobulbar neuritis. Flicker EPs, pattern EPs and visual perception were all delayed in every RBN patient, whereas for spinal patients different tests could pick up different patients. Flicker EPs picked up 5/13 spinal patients, pattern EPs 6/13, perceptual delay (D) picked up 4/13 and perceptual delay T picked up 7/13. (6) Delay tests divided spinal multiple sclerosis patients into two fairly distinct groups. In one group pattern EPs and perception were delayed; in the other group flicker EPs were delayed. This grouping corresponded to a clinical distinction between long-standing patients with visual signs and recent patients without visual signs...

Adult↗

PubMed1991

Suicidal tendency and multiple sclerosis.

This article examines the relationship between various physiological, psychological, and social variables and suicidal tendency among people with multiple sclerosis. In 1986, a sample of 147 respondents with multiple sclerosis was obtained. The authors studied the absence of social support systems as an important predictor of suicidal tendency in people with multiple sclerosis. Multiple regression is used to assess the independent effects of predictors. Findings suggest family support, hopelessness, and self-perceived religiosity as predictors of suicidal tendency.

Adult↗

PubMed1997

Long-term survival experience of patients with multiple sclerosis.

BACKGROUND: Long-term survival of patients with multiple sclerosis is not well characterized because this disorder is relatively uncommon and subjects must be followed for decades after onset of symptoms. This paper reports comparative mortality experience of the world's largest series on an unselected cohort with multiple sclerosis. RESULTS: Excess mortality varied with age, gender, duration since onset and diagnosis, calender year of onset, and clinical severity. CONCLUSIONS: Compared to the general population in Denmark, patients with multiple sclerosis had less favorable survival experience during long-term follow-up.

Adult↗

PubMed2004

Clinical characteristics of multiple sclerosis in Västerbotten County in northern Sweden.

BACKGROUND: Most clinical data for multiple sclerosis are hospital based-that is, derived from patients referred to clinics specialising in the disease. OBJECTIVES: To present data derived from two population based multiple sclerosis populations, an incidence cohort and a prevalence population, from Västerbotten County, northern Sweden. METHODS: The two populations were identified from multiple sources, and case ascertainment was assured through a personal clinical review, including interviews and examination of the patients. RESULTS: Characteristics at onset for the different clinical subtypes of multiple sclerosis are presented, including the clinical spectrum of the first attack, the anatomical correlation between the first and second attacks, sex distribution, and disability distribution. CONCLUSIONS: Based on the comparison of present and earlier natural history data, multiple sclerosis appears to be a slightly more benign disease than previously recognised.

Adult↗

PubMed2006

Progression of non-age-related callosal brain atrophy in multiple sclerosis: a 9-year longitudinal MRI study representing four decades of disease development.

BACKGROUND: In multiple sclerosis (MS), multiple periventricular lesions are commonly the first findings on MRI. However, most of these MS lesions are clinically silent. The brain atrophy rate has shown better correlation to physical disability, but it is not clear how atrophy develops over decades. Corpus callosum forms the roof of the third and lateral ventricles. The corpus callosum area (CCA) in a midsagittal image is age independent in a normal adult population up to the seventh decade; therefore it can be used as a marker for non-age-related, pathological brain atrophy. OBJECTIVES: To investigate whether and how CCA decreases in size over time in patients with MS. METHODS: In a clinical observational study, 37 patients with MS with a wide range of disease duration at baseline (1-33 years) were followed. Three different MS courses were represented. The mean of individual MRI follow-up was 9 years. Multiple sclerosis severity score (MSSS) was also applied to evaluate disability at baseline and after 9 years of follow-up. RESULTS: A significant decrease in CCA over 9 years (p<0.001) and a persisting association between CCA and the disability status were found. The atrophy rate was similar ever four decades of MS for all MS courses. The mean annual CCA decrease was 9.25 mm2 (1.8%). Surprisingly, atrophy rate did not correlate with sex, disease duration, age at MS onset or MS course. CONCLUSIONS: Serial evaluations of CCA might be a robust method in monitoring a non-age-related decrease in CCA, reflecting progression of irreversible destructive changes in MS.

Adult↗

PubMed1996

Magnetic resonance imaging in the differential diagnosis and monitoring of the treatment of multiple sclerosis.

Treatments with potentially beneficial effects on the course of multiple sclerosis are now emerging and magnetic resonance imaging techniques are needed which have a high specificity for diagnosing multiple sclerosis, and which can characterize the heterogeneous nature of multiple sclerosis lesions and define disease evolution over time. Differential diagnosis may be improved by the use of gadolinium-enhanced magnetic resonance imaging, high-resolution spinal cord and optic nerve magnetic resonance imaging and non-conventional magnetic resonance imaging techniques. In the monitoring of treatment, a number of different approaches have been used to increase magnetic resonance imaging accuracy in describing and predicting disease activity and evolution. These include optimization of the acquisition and post-processing of data obtained with conventional magnetic resonance imaging techniques (T2-weighted and postcontrast T1-weighted sequences) and the use of newer nonconventional magnetic resonance imaging techniques.

Diagnosis, Differential↗

PubMed2000

Progression of visual evoked potential abnormalities in multiple sclerosis and optic neuritis.

To investigate visual signal processing in patients with optic neuritis, suspected multiple sclerosis, confirmed multiple sclerosis (MS), and optic neuritis combined with MS, pattern reversal visual evoked potentials (VEPs) were recorded in patients and normal subjects. The amplitude and latency of the first positive peak, P100 were determined to assess electrical conduction in patients as compared to normal subjects. Suspected MS patients did not differ from normal subjects in peak latencies or amplitudes. The P100 amplitude was reduced in optic neuritis, confirmed MS and optic neuritis combined with confirmed MS. The P100 and N145 latencies were prolonged in optic neuritis patients and confirmed MS patients as compared to normal subjects. The main characteristic of optic neuritis was P100 amplitude reduction, and of confirmed MS was P100 latency delay. There was a progression of the P100 latency delay and of the P100 amplitude decrement in optic neuritis, confirmed MS, and optic neuritis combined with confirmed MS. These results indicate a progression of demyelination in optic neuritis, confirmed MS, and optic neuritis combined with confirmed MS.

Adolescent↗

PubMed1992

Multiple sclerosis in the Cambridge health district of east Anglia.

A survey of multiple sclerosis (MS) in the Cambridge Health District has identified 374 cases in a population of 288,410, giving a prevalence of 130 per 100,000. A total of 322 cases (86%) had either clinically definite or probable multiple sclerosis on 1 July 1990 (112 per 100,000) and 52 cases (14%) had suspected multiple sclerosis (18 per 100,000.) The incidence during 1989-91 was 5.94 per 100,000 per year. The prevalence figure is higher than in recent surveys from other southern parts of the United Kingdom, but correction for the age and sex characteristics of the at risk population eliminates these differences. The overall prevalence of multiple sclerosis is probably between 108 and 120 per 100,000 in the southern United Kingdom.

Adolescent↗

PubMed1991

Consanguinity and multiple sclerosis in Orkney.

For all patients with multiple sclerosis in Orkney who were alive in 1974 or who had died during 1958 to 1974, pedigree data were analysed. The relationship between their parents, expressed by kinship coefficients, was compared with that between parents of matched controls. The closer relationship between parents of patients suggests that it is the genes that are shared by a patient's parents, and that he inherits from both, that influence his susceptibility to multiple sclerosis.

Consanguinity↗

PubMed1988

Pregnancy and multiple sclerosis.

The effect of pregnancy on the relapse rate of multiple sclerosis has been investigated. Obstetric and relapse histories of 52 women with clinically definite multiple sclerosis were obtained; there were 101 pregnancies of which 85 were at risk of a multiple sclerosis relapse. By comparing the number of relapses in the pregnancy period (9 months of pregnancy and 6 months immediately post partum) with the number in non-pregnancy periods for the same women, no increased risk of relapse during the pregnancy period was demonstrated. However, of the relapses that did occur during the pregnancy period, there was a significant reduction in the number of relapses in the first and second trimesters.

Adult↗

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