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At least 109 records · Page 6Linked to original sources
PubMed1995

Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.

Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.

Adjuvants, Immunologic↗
PubMed1977

[Serum antibodies to cytoplasmic antigens of the human brain in patients with multiple sclerosis and amyotropic lateral sclerosis].

In order to eliminate antibodies to water soluble proteins of the human brain which were preliminary divided into 10 fractions of DEAE-cellulose, the authors studied the serum of 30 patients with disseminated sclerosis and 30 patients with lateral amyotrophical sclerosis and determined their antithymic serum activity. The antibides were detected only to protein fractions 1,2 and 10. There was a tendency towards a more frequent detection of antibodies with an increase of the severity of the disease. It was not possible to determine antibodies with an increase of the severity of the disease. It was not possible to determine any correlation between the amount of antibodies and such clinical indices as the degree of severity, duration, form of the disorder, age and sex of the patients. The cytotoxic index of the patients was significantly higher than that in normals. The authors also found a correlation between the antibodies in the serum cytoplasmatic brain proteins and antithymic activity of the same sera.

Adolescent↗
PubMed1996

[Multiple sclerosis and amyotrophic lateral sclerosis. The development of concepts of their etiology and pathogenesis].

The analysis of the results of investigations concerning etiology and pathogenesis of multiple sclerosis and amyotrophic lateral sclerosis performed in Institute of Neurology of Rus. Acad. Med. Sci. There were three main periods of the researches determined mainly by theoretical achievements. For the last years the standards of such investigations have approached fundamental levels and corresponded to the trends of world science.

Academies and Institutes↗
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↗
PubMed1999

Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis.

The PRISMS (Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis) trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon-beta1a in 560 patients from 22 centers in 9 countries with clinically definite or laboratory-supported relapsing-remitting multiple sclerosis. The patients were randomized to receive recombinant interferon-beta1a (Rebif), 22 microg (6 mIU), 44 microg (12 mIU), or placebo, given subcutaneously, three times weekly for 2 years. All patients underwent biannual proton density/T2-weighted magnetic resonance imaging scans to determine the overall magnetic resonance imaging disease activity and burden of disease, and a cohort of 205 patients had 11 initial monthly proton density/T2-weighted and gadolinium-enhanced/T1-weighted magnetic resonance imaging scans. Over the 2 years, the placebo group showed a progressive median increase in burden of disease of 10.9%, whereas the 22-microg group and 44-microg group showed median decreases of 1.2% and 3.8%, respectively. The number of T2 active lesions and percentage of scans showing T2 activity on the biannual scans were also significantly reduced in both treatment groups compared with placebo, with a clear dose-effect favoring the 44-microg dose over the 22-microg dose. In the subgroup undergoing initial monthly scanning, this reduction in activity became statistically significant 2 months after the start of treatment. These results provide strong, objective evidence to support the positive clinical results of reduction in relapses and delay in disease progression. In addition, they also demonstrate a significant dosage effect, favoring the 44-microg dose.

Adult↗
PubMed1990

Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.

Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.

Adult↗
PubMed1977

Biochemical findings in multiple sclerosis IV. Isoelectric focusing of the CSF gamma globulins in multiple sclerosis (262 cases) and other neurological diseases (272 cases).

Despite enormous efforts to find a specific laboratory test for multiple sclerosis, agar gel electrophoresis of the CSF proteins has remained the next to the best one. This study presents evidence that thin layer polyacrylamide isoelectric focusing of the CSF gamma globulins is by far superior for this purpose. In effect, about 91% of the 262 multiple sclerosis patients studied had oligoclonal fractions present in the very alkaline region of the pH gradient. Of the same group of patients only 65% did show pathological results when studied by agar gel electrophoresis. Of the 272 CSF samples from patients suffering from other neurological diseases, only about 7% showed the presence of oligoclonal bands in the same region of the pH gradient, when submitted to isoelectric focusing.

Adolescent↗
PubMed1979

Attempts to reproduce amyotrophic lateral sclerosis in laboratory animals by inoculation of Schu virus isolated from a patient with apparent amyotrophic lateral sclerosis.

A virus isolated from the CSF of a patient who had amyotrophic lateral sclerosis for 7 years, and prolonged pleocytosis in the CSF, was adapted to suckling mouse brain by subsequent serial blind passages. This Schu virus belongs to the tick-borne encephalitis complex of the genus Flavivirus (Togaviridae). Suckling mouse brain homogenate of the 13th passage was used for transmission experiments in various species of laboratory animals. Golden hamsters infected subcutaneously fell ill after a number of months, lost weight, and had paresis of the legs. Histologically they had petechial hemorrhages in different parts of the CNS and inflammatory changes in the gray substance of the spinal cord. Pilot studies with repeated inoculations of small doses of different flavivirus strains suggest a course of the disease in experimental animals which resembles slow-virus infections insofar as no encephalitis is produced and degenerative changes of the anterior horn cells prevail over inflammatory signs in the spinal cord. After intracerebral application of Schu virus, cynomolgus monkeys developed the typical lesions of togavirus panencephalitis with epileptic seizures, ataxia, and paresis. After subcutaneous application, the virus seems to spread along peripheral nerves to anterior spinal roots and spinal cord, where mainly motor neurons of the anterior horn are damaged, and from there to the brain. The histological findings are such that one may assume the disease of the patient was due to the infection with the virus isolated from his CSF. Therefore, the hypothesis may be advanced that at least some of the cases diagnosed as amyotrophic lateral sclerosis are due to a togavirus infection.

Amyotrophic Lateral Sclerosis↗
PubMed1978

Multiple sclerosis: demyelination and myelination inhibition of organotypic tissue cultures of the spinal cord by sera of patients with multiple sclerosis and other neurological diseases.

Sera from 44 patients with Multiple Sclerosis, of three patients with neurological syndromes compatible with Multiple Sclerosis, of 34 patients suffering from other neurological diseases and of 25 pregnant healthy young women were tested for their demyelinating activity in myelinated tissue cultures. In order to leave the investigators unprejudiced, all sera were coded and intermixed with controls of rabbit EAE serum which had a potent demyelinating capacity. Demyelination was graded (from 0--4), heat lability at 56 degrees C (complement dependency?) was also tested with each serum. Only demyelination of a degree of 2 and more, which was abolished by heating to 56 degrees C, was counted as positive. Six of the 44 sera from MS patients (13.6%), 19 of 37 sera from neurological patients and none of the healthy young women demyelinated. Thus, serum demyelination of tissue cultures seems to be a nonspecific indicator of chronic disease of the nervous system and is of considerable general neurological interest, but does not indicate a demyelinating disease. Myelination inhibition was not observed with any of the human sera tested for it.

Animals↗
PubMed2002

[The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation standard for multiple sclerosis].

The MSDS (multiple sclerosis documentation system) has been developed at the Department of Neurology, Technical University of Dresden, Germany, during the last 4 years. The first version of this database application has been in use since October 2000. The MSDS manages information on MS patients, their treating physicians, patient history (symptoms, other diseases, biographical history, family history, habits, medication), clinical signs, results of laboratory examinations (blood chemistry, autoantibodies, borrelia serology, evoked potentials, cranial and spinal cord magnetic resonance imaging), clinical scores relevant for MS, and biosamples. In principle, MSDS allows online data input and semiautomatically generates reports to all general practitioners and neurologists treating the respective patient. Patient information sheets and internal treatment guidelines are part of the system. During a 3-month evaluation, the first version of MSDS was tested at eight university multiple sclerosis ambulatory care units and one general neurology hospital. The overall judgement was favorable. Suggestions for changes and improvements, as well as practical experiences, were considered when developing MSDS 2.0, which will be available by the end of 2001.

Ambulatory Care↗
PubMed2006

Multiple sclerosis associated with systemic sclerosis.

Multiple sclerosis (MS) has been increasingly reported in association with other autoimmune diseases not primary affected the nervous system. The coexistence of MS and systemic sclerosis (SSc) has been rarely described. We report here the case of a 46-year-old female patient with longstanding MS since the age of 26, who developed SSc 12 years later. Her MS was of the relapsing-remitting type, but the definite diagnosis was not made until the age of 33. MS diagnosis was based on medical history, magnetic resonance imaging (MRI) studies and positive cerebrospinal fluid analysis. One year after the diagnosis of MS, she developed Raynaud's phenomenon, skin tightness and hypopigmented patches, suggestive of scleroderma. Further investigation with laboratory studies, including serology, hand and chest X-rays, and chest computerized tomography scan confirmed the SSc diagnosis. Our report highlights the interesting association between MS and SSc that may be due to an overlapping pathogenetic mechanism for both processes.

Adult↗
PubMed1999

Interferon beta treatment in relapsing-remitting multiple sclerosis: a post-marketing study in Lombardia, Italy. Multiple Sclerosis Centers of Lombardia, Italy.

The aim of the study was to evaluate the efficacy of interferon beta-1a (IFN-beta-1a) and beta-1b (IFN-beta-1b) in clinical practice for the treatment of relapsing-remitting multiple sclerosis (RR MS). Patients were selected and prospectively monitored according to a predefined protocol. An appropriate form was prepared to collect clinical data of multiple sclerosis patients attending the MS Centers of Lombardia, Italy. On 30 June 1998, 317 patients were treated with IFN-beta-1b and 156 with IFN-beta-1a. Basal expanded disability status scale (EDSS) and relapse frequency were similar in both groups of patients. The annual relapse rate consistently decreased from 1.76 to 0.63 at 1 year and to 0.51 at 2 years for the IFN-beta-1b group and from 1.6 to 1.0 at 1 year for the IFN-beta-1a group. Disability remained stable in most patients. Dropouts (20.5%) were affected by more active disease compared to patients who continued to be treated. This study confirms the efficacy of both treatments, showing a more marked effect than expected from the clinical trials' results, probably due to differences in selection criteria and exclusion of dropouts.

Adjuvants, Immunologic↗
PubMed2001

Multiple sclerosis and multiple sclerosis-associated retrovirus in Sardinia.

The island of Sardinia has a high and increasing incidence of multiple sclerosis (MS). In a search for environmental factors that may account for this anomalously high incidence, we looked for evidence of multiple sclerosis-associated retrovirus (MSRV) that has previously been found in the plasma and cerebrospinal fluid of MS patients. We studied 25 MS patients and 25 matched healthy controls of ascertained Sardinian lineage. Blood samples were processed for extracellular RNA extraction. RNAs underwent reverse transcription/nested polymerase chain reaction (RT-PCR) with primers specific for MRSV-pol gene. We found a striking correlation between MSRV positivity and MS disease, but the virus was found also only in controls (100% and 12% respectively; Fisher's exact test, p<0.00001). It is unclear whether MSRV exerts any pathogenic role in MS. It is possible that this is simply an epiphenomenon, but even then, it may constitute a diagnostic marker.

Female↗
PubMed1983

Epidemiology of multiple sclerosis in U.S. veterans: 2. Latitude, climate and the risk of multiple sclerosis.

An analysis of ten climatic factors and elevation for the counties of birth of 4371 U.S. white male veterans with multiple sclerosis and matched controls has been made in relation to birthplace latitude. The climatic factors include an air pollution index, concentrations of minerals in ground water, measures of annual solar radiation, both in energy per unit area and in hours of sunshine, mean annual periods of high and low temperatures, and measures of annual rainfall and average humidity. These variables all significantly influence the risk of multiple sclerosis when analyzed alone, but when they are adjusted for latitude, their effect is found to be due to their correlation with this variable.

Air Pollution↗
PubMed1975

Monozygous twins discordant for multiple sclerosis. Report of one pair and discussion of possible causes of multiple sclerosis.

One pair of male monozygous twins was examined: only 1 twin had multiple sclerosis. Differences in the life histories of the twins were identified. Haematological, biochemical and microbiological studies were performed. It is possible in theory to determine which environmental factors may have been responsible for the development of multiple sclerosis in 1 twin. Several differences in life history were found in this study.

Diseases in Twins↗
PubMed1994

On the pathogenesis of multiple sclerosis. A revised model of the cause(s) of multiple sclerosis, especially based on epidemiological data.

Data from an epidemiological study are used to analyse the course of multiple sclerosis. It could be proved that the course of MS is not as haphazard as was often supposed. In general the course is described as being a chronic progressive one, in the majority of patients preceded by a relapsing-remitting period. In contrast to the relapsing-remitting phase the chronic progressive phase of the course does not show marks of being an autoimmune process. From recent data obtained by MRI and NMR spectroscopy it can be concluded that the chronic progression of handicaps in multiple sclerosis is related to neuronal and axonal damage. The relation between these different pathogenetic processes should be the aim of further research.

Adult↗
PubMed1993

Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis.

Primary lateral sclerosis (PLS) bears close resemblance to cases of amyotrophic lateral sclerosis (ALS) presenting with spasticity, but histopathological studies have shown significant difference between the two conditions. When the lower motor neurons in cases of ALS and PLS are compared with the equivalent cells of control subjects, morphometric studies indicate significantly decreased size and increased convexity (rounding) of the cell bodies only in ALS. In both disorders there is loss or shrinkage of the largest cortical motor neurons (Betz cells) in the primary motor cortex, though this change is not conspicuous in all cases of ALS. Morphometry reveals in both diseases a general reduction in the sizes of pyramidal cells in the precentral gyrus, indicating that smaller neurons are involved. The cortical motor neurons shrink more in PLS than in ALS. It is concluded that there is clear difference between ALS and PLS. In PLS, quantitative histopathological data show that the neuronal degeneration is confined to long descending pathways, notably the corticospinal system, with no concomitant involvement of lower motor neurons. In ALS, lower motor neuron degeneration occurs in all cases, whereas involvement of the motor cortex is variable.

Aged↗
PubMed2006

The multiple sclerosis trait and the development of multiple sclerosis: genetic vulnerability and environmental effect.

The remarkably low rate of concordance of multiple sclerosis (MS) in monozygotic twins has never been fully explained but it implies the possibility of a systemic condition called the multiple sclerosis trait (MST), which is quite different from asymptomatic MS. It results from the action of an antigenic challenge on the immune system of a genetically vulnerable person that does not cause damage to the nervous parenchyma; it may never evolve into the disease MS. A subsequent environmental viral-antigenic event in some MST-carriers can change the trait into the disease. This event could be an infection, which need not be symptomatic, or a vaccination. The MS may become symptomatic, remain asymptomatic, or manifested only by lesions visible by MRI. It is likely that the development of the MST, called activation, occurs early in life, while the transition from MST to MS, called acquisition, takes place at puberty in most patients. Differences in prevalence between pre-puberal migrants, and the locally born children of migrants, and their population of origin may also be explained by the MST.

Environment↗