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At least 487 records · Page 27Linked to original sources
PubMed1998

Underlying cause of death in Danish patients with multiple sclerosis: results from the Danish Multiple Sclerosis Registry.

OBJECTIVES: To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis. METHODS: The Danish Multiple Sclerosis Registry, which contains virtually all diagnosed cases of multiple sclerosis in Denmark who were alive in 1949 plus cases with onset of multiple sclerosis in the period 1949-93, who have been diagnosed and notified by 1 January 1994, was linked with the Danish Registry of Causes of Death, in which ICD codes for causes of death from the death certificate are stored for all Danish citizens. RESULTS: 6068 register cases of multiple sclerosis, who had died in the period 1951-93, were included. Multiple sclerosis was noted on the death certificate as the underlying cause of death in 55.4%; cardiac or vascular diseases in 17.6%; cancers in 8.6%; respiratory or infectious diseases in 5.1%; other natural causes in 9.5%; accident or suicide in 3.8%. The distribution varied with age at death. Standardised mortality ratios (SMRs) were computed on the basis of the 8142 incident cases, who had onset of multiple sclerosis within the period 1951-93; the SMRs for causes of death other than multiple sclerosis were highest for infectious or pulmonary diseases: 2.46 (95% confidence interval (95% CI) 2.04-2.94); suicide: 1.62 (95% CI 1.29-2.01); cardiac or vascular diseases: 1.34 (95% CI 1.22-1.48); accidents 1.34 (95% CI 1.02-1.71); and significantly lower than unity for cancers: 0.79 (95% CI 0.70-0.90), lower for men than for women. CONCLUSIONS: More than half of the patients with multiple sclerosis die from multiple sclerosis or complications of the disease. Among other causes, patients with multiple sclerosis have an increased risk of dying from heart or vascular diseases but a reduced risk of dying from cancer. An increased risk of death from suicide and accidents can be indirectly attributed to multiple sclerosis. The diminished risk of dying from cancer may be a result of incomplete ascertainment of cancers in disabled patients with multiple sclerosis.

Accidents↗
PubMed1983

In vitro IgG synthesis by peripheral blood lymphocytes of multiple sclerosis patients and normal individuals. Effect of multiple sclerosis and non-multiple sclerosis brain antigens.

In vitro IgG synthesis by peripheral blood lymphocytes cultured for 7 days in serum-free medium was determined by enzyme-linked immunosorbent assay. IgG synthesis by lymphocytes of multiple sclerosis (MS) patients and normal individuals in the presence of MS and non-MS brain antigens and in the absence of brain antigens was investigated. In vitro IgG synthesis by lymphocytes in the absence of any antigen was found to be similar for both groups. Non-MS brain antigens stimulated IgG synthesis by normal lymphocytes but not by MS lymphocytes. MS brain antigens were not found to stimulate IgG synthesis by lymphocytes of either group. The significance of the above-mentioned finding is discussed.

Antigens↗
PubMed1988

Double-masked trial of azathioprine in multiple sclerosis. British and Dutch Multiple Sclerosis Azathioprine Trial Group.

354 patients with multiple sclerosis were randomised to receive either azathioprine 2.5 mg/kg daily or placebo in a double-masked trial. During follow-up of at least 3 years only small differences emerged between the groups. After 3 years the mean deterioration in Kurtzke disability score was 0.62 in the azathioprine group and 0.80 in the placebo group, a difference of 0.18 (95% confidence intervals [CI] -0.15 to +0.52) and in the ambulation index it was 0.84 and 1.25, respectively, difference 0.41 (95% CI 0.03 to 0.80). After 3 years there had been slightly fewer relapses in the azathioprine group (average 2.2) than in the placebo group (average 2.5) but the difference of 0.3 (95% CI -0.2 to +0.9) was not significant. Although the results favour a small beneficial effect from azathioprine the benefit is so small that the use of azathioprine cannot be generally recommended for most patients with multiple sclerosis. Analysis of subgroups (by sex, age, severity, rate of progression, HLA status, relapsing or progressive course) has not revealed any that have shown clear clinical benefit.

Adolescent↗
PubMed2005

Initial evaluations for multiple sclerosis in a university multiple sclerosis center: outcomes and role of magnetic resonance imaging in referral.

OBJECTIVE: To evaluate diagnostic outcomes, especially as they relate to reason for referral, of patients referred to a university-based multiple sclerosis (MS) center for possible MS. METHODS: Retrospective medical record review of all new patient visits to University of Colorado Multiple Sclerosis Center, Denver, from January 1, 2001, to June 30, 2003. RESULTS: Of 281 patients referred to evaluate the possibility of MS, after initial review 33% were diagnosed with MS or possible MS by the McDonald criteria. The rest had other neurological conditions (31.5%), probable psychiatric diagnoses (22.5%), or no clear diagnosis was made (12.5%). Of patients with typical, possible, or atypical demyelinating syndromes, 71%, 27%, and 0%, respectively (P<.001), had MS or possible MS. Of the 63% of patients referred on the basis of clinical symptoms and signs, 46% were diagnosed with MS or possible MS vs 11% of patients referred primarily on the basis of abnormal brain magnetic resonance imaging (MRI) results (P<.001). Of patients referred because of abnormal MRI results who did not have MS or possible MS, 70% had a clear alternative etiology for the abnormal MRI results, including migraine, age older than 50 years, other neurological disease, or hypertension. CONCLUSIONS: A significant percentage of patients referred to a university-based MS center have little or no likelihood of having MS, and many have undiagnosed, untreated psychiatric illness or common conditions with abnormal brain MRI results. With respect to the diagnosis of MS, greater training of primary care professionals, neurologists, and radiologists is necessary.

Academic Medical Centers↗
PubMed2000

Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis.

PURPOSE: To determine annual rates of volumetric changes in the whole-brain parenchyma of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) and test the hypothesis that these changes correlate with clinical disability. MATERIALS AND METHODS: A computer-assisted segmentation technique with thin-section magnetic resonance (MR) imaging was used in 36 patients with MS (27 relapsing-remitting, nine secondary progressive) and in 20 control subjects to quantify brain and cerebrospinal fluid volumes. To determine the degree of brain atrophy, the percentage brain parenchyma volume (PBV) relative to that of intracranial contents was calculated. RESULTS: At the beginning of the study, the PBV was smaller in the MS group than in the control group (P = .007); brain parenchyma volumes were similar. The median rate of brain volume loss was 17.3 mL per year in patients with relapsing-remitting MS and 23.6 mL per year in those with secondary progressive MS. There was a negative correlation between brain atrophy and Expanded Disability Status Scale (EDSS) score in patients with secondary progressive MS (r = -0.69, P = .004) and no correlation in patients with relapsing-remitting MS. T2 lesion volume did not correlate with brain atrophy in either group. CONCLUSION: The correlation between brain atrophy and EDSS score was better in patients with secondary progressive MS than in those with relapsing-remitting MS.

Adult↗
PubMed1991

The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group.

To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56). All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.

Adult↗
PubMed2001

Placebo-controlled clinical trials in multiple sclerosis: ethical considerations. National Multiple Sclerosis Society (USA) Task Force on Placebo-Controlled Clinical Trials in MS.

The availability of partially effective therapies for some forms of multiple sclerosis (MS) raises practical and ethical issues for future placebo-controlled clinical trials. An international Task Force of clinicians, statisticians, ethicists and regulators was convened to discuss these issues and develop consensus. The Task Force concluded that placebo-controlled clinical trials in forms of MS for which partially effective therapies exist were ethical, so long as study subjects were fully apprised of the availability of such therapies and were encouraged to pursue them outside of a clinical trial. Patients who decline to utilize available treatments, after proper education and counseling, or those that fail all therapies can be considered to have no treatment alternatives and thus may participate in a placebo-controlled trial.

Ethics, Medical↗
PubMed1998

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.

Alleles↗
PubMed1978

Electroencephalographic studies in multiple sclerosis. Specific changes in benign multiple sclerosis.

EEG changes were analysed in a group of 260 patients with definite multiple sclerosis, 156 women and 104 men, average age 38.8, at different stages of the disease. Among 103 patients with an evolution up to 5 years, 34% had significantly abnormal EEG'S while in 157 patients with an evolution from 5 to 45 years abnormal records were obtained in 47.8%. The larger group showed EEG differences between benign (66 patients), malignant (23 patients) and moderate courses (68 patients) patients. The frequency of abnormal and doubtful EEGs was highest in the benign group (80.4%) and largest in the malignant group (24.1%). The main characteristic in malignant multiple sclerosis in the steadily progressive stage was a flat EEG. There was also a significant correlation between a flat EEG and intellectual deficit. In benign multiple sclerosis the dominant activities were slow (6-10 c/sec) and high voltage (80-180 muV) alpha-theta rhythms spreading all over the cortex, usually associated with "centrencephalic" discharges. A self-limiting effect of lesions around the 3rd ventricle on auto-agressive immunological processes is proposed.

Adult↗
PubMed2004

Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis.

Autologous haematopoietic stem cell transplantation is now a feasible and effective treatment for selected patients with severe autoimmune diseases. Worldwide, over 650 patients have been transplanted in the context of phase I and II clinical trials. The results are encouraging enough to begin randomised phase III trials. However, as predicted, significant transplant-related morbidity and mortality have been observed. This is primarily due to complications related to either the stage of the disease at transplant or due to infections. The number of deaths related to cardiac toxicity is low. However, caution is required when cyclophosphamide or anthracyclines such as mitoxantrone are used in patients with a possible underlying heart damage, for example, systemic sclerosis patients. In November 2002, a meeting was held in Florence, bringing together a number of experts in various fields, including rheumatology, cardiology, neurology, pharmacology and transplantation medicine. The object of the meeting was to analyse existing data, both published or available, in the European Group for Blood and Marrow Transplantation autoimmune disease database, and to propose a safe approach to such patients. A full cardiological assessment before and during the transplant emerged as the major recommendation.

Anthracyclines↗