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At least 19 recordsLinked to original sources
PubMed2000

Anti-spasticity agents for multiple sclerosis.

BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.

Anti-Dyskinesia Agents↗
PubMed2000

Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).

BACKGROUND: Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis (ALS) in some countries but not others. Questions persist about its clinical utility because of high cost, modest efficacy and concern over adverse effects. OBJECTIVES: To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Group Register for randomized trials and enquiry from authors of trials and other experts in the field. The most recent search was conducted in June 1999. SELECTION CRITERIA: Types of studies: randomized trials TYPES OF PARTICIPANTS: adults with a diagnosis of ALS Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: per cent mortality at 12 months with riluzole 100 mg Secondary: per cent mortality as a function of time with 100 mg and with all doses of riluzole, scales of neurologic function, quality of life, muscle strength and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomized trials. Each reviewer graded them for methodological quality. Data extraction was performed by a single reviewer and checked by the other two. We obtained some missing data from investigators. We performed meta-analyses with RevMan software using a fixed effects model. MAIN RESULTS: The two eligible trials included a total of 794 riluzole treated patients and 320 placebo treated patients. The methodological quality was acceptable and the trials were easily comparable. There were significant differences between the riluzole and placebo groups of both trials, in terms of the primary outcome measure, which was per cent mortality at 12 months with the 100 mg dose of riluzole. The odds ratio for the combined studies was 0.57 (95%CI 0.41 to 0.80) at 12 months. In the secondary outcome measures, there was a survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months. Pooled data from the 50, 100 and 200mg dose groups in the larger trial showed a lower per cent mortality with riluzole compared to placebo only at 12 months (odds ratio (OR) 0.64, 95% CI 0.47 to 0.88). There was no beneficial effect on bulbar function, or muscle strength. There were scant data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients (weighted mean difference (WMD) 35.5 days, 95% CI 5.9 to 65. 0). A threefold increase in serum alanine transferase was more frequent in riluzole treated patients than controls (WMD 2.65, 95% CI 1.51 to 4.65). REVIEWER'S CONCLUSIONS: Riluzole 100 mg per day appears to be modestly effective in prolonging survival for patients with ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Multiple sclerosis-associated virus-related pol sequences found both in multiple sclerosis and healthy donors are more frequently expressed in multiple sclerosis patients.

In the etiopathogenesis of multiple sclerosis (MS), both genetic and environmental factors play an important role. Among environmental factors, viral infections are most likely connected with the etiology of MS. There are many evidence suggesting possible involvement of retroviruses in the development of autoimmune diseases including MS. Multiple sclerosis-associated retrovirus (MSRV) seems to be the important candidate for viral etiology of MS. The aim of the study was to analyze MSRV pol sequences in patients with MS. As control, groups of myasthenia gravis, Parkinson's disease, and migraine patients, and healthy individuals have been studied. The MSRV pol sequences have been analyzed in RNA isolated from the serum and in DNA and RNA of peripheral blood lymphocytes from untreated MS patients and control groups. The MSRV pol sequences have been detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and PCR technique, using specific oligonucleotide primers. In the serum RNA (cDNA), MSRV pol sequences have been identified in 31/32 MS patients. MSRV pol sequences were detected in serum cDNA of 9/17 myasthenia gravis patients, 7/16 Parkinson's disease patients, 10/21 migraine patients, and 13/27 healthy individuals. MSRV pol sequences were observed also in RNA from lymphocytes of all MS patients, 12/17 myasthenia gravis patients, 9/16 Parkinson's disease patients, 14/21 migraine patients, and 18/27 healthy donors. In the DNA from peripheral blood lymphocytes of all studied patients and healthy individuals, MSRV pol sequences have been found. The observed pattern of fiber-fluorescence in situ hybridization (FISH) signals suggests the presence of multiple copies of MSRV pol sequences, most likely tandemly dispersed in the genome. It can be concluded that MSRV pol sequences are endogenous, widespread in lymphocytes DNA, and transcribed into RNA of MS patients as well as of other studied patients and healthy individuals. However, more frequent expression of MSRV sequences detected in lymphocytes RNA (cDNA), as well as their presence in higher frequency in the serum of MS patients, may suggest the involvement of MSRV in the etiopathogenesis on MS.

Adult↗
PubMed2006

Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society.

Besides immunomodulation and immunosuppression, the specific treatment of symptoms is an essential component of the overall management of multiple sclerosis (MS). Symptomatic treatment is aimed at the elimination or reduction of symptoms impairing the functional abilities and quality of life of the affected patients. Moreover, with symptomatic treatment the development of a secondary physical impairment due to an existing one may be avoided. Many therapeutic techniques as well as different drugs are used for the treatment of MS symptoms, but only a few of them have been investigated, especially in MS patients, and are approved by the national health authorities. Despite an overwhelming number of publications, only a few evidence-based studies exist and consensus reports are very rare, too. Therefore, it seemed necessary to develop a consensus statement on symptomatic treatment of MS comprising existing evidence-based literature as well as therapeutic experience of neurologists who have dealt with these problems over a long time. This consensus paper contains proposals for the treatment of the most common MS symptoms: disorders of motor function and coordination, of cranial nerve function, of autonomic, cognitive, and psychological functions as well as MS-related pain syndromes and epileptic seizures.

Humans↗
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↗
PubMed1999

The natural history of multiple sclerosis: a geographically based study. 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation.

Classifications of multiple sclerosis subtypes have been largely based on clinical phenomenology. Nevertheless, definitions of relapse, remission and progression have been imprecise. Recently an international consensus group, as part of a reclassification of disease subtypes, recommended dropping the term 'relapsing-progressive' (RP) and retaining the term 'progressive-relapsing' (PR) multiple sclerosis. The term 'RP' multiple sclerosis had been applied when the early course combined both relapses and progression and was believed to identify some patients with a worse than average outcome. The PR group consisted of patients with primary progressive disease who later in their course developed relapses. Since the terminology has been largely arbitrary, we have evaluated the validity of the terms 'RP' and 'PR' multiple sclerosis in the context of long-term outcome within a large population-based cohort of progressive multiple sclerosis patients seen at the London Multiple Sclerosis Clinic (Canada) between 1972 and 1984. Mean follow-up of the entire cohort was 25 years. Designation of RP multiple sclerosis did identify a more rapidly progressive subgroup. To realign these natural history data with consensus recommendations, these patients were reassigned to secondary progressive (SP) or to primary progressive (PP) multiple sclerosis, with progression defined as at least 1 year of progressive deterioration. PP multiple sclerosis patients with relapses after a year were designated as having PR multiple sclerosis. Relapses in primary progressive multiple sclerosis occurred in 27.8% of patients at some point even two to three decades after onset. In general these relapses were mild and remitting, but served to blur the distinction between progressive and relapsing-remitting disease. The long-term outcomes of time to Kurtzke disability scores (DSS) of 3, 6, 8 and 10 were compared among the progressive subtypes. Times to these disability end-points and to death were not different between PR and PP multiple sclerosis. Survival curves for progressive patients have been amended to incorporate the reassignment of PR multiple sclerosis patients into the PP group and the RP multiple sclerosis patients into the PP and SP subgroups. The time to reach DDS 3, 6, 8 and 10 for a population-based cohort of primary and secondary progressive patients resulting from the elimination of the categories of RP multiple sclerosis and PR multiple sclerosis has been established. These results provide justification for retaining only PP and SP multiple sclerosis as the subgroups of progressive disease.

Adult↗
PubMed1999

The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis.

We report a natural history study of 216 patients with primary progressive (PP)- multiple sclerosis defined by at least 1 year of exacerbation-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-multiple sclerosis patients had a mean age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0. The rate of deterioration from disease onset was substantially more rapid than for relapsing-remitting multiple sclerosis, with a median time to disability status score (DSS) 6 and DSS 8 of 8 and 18 years, respectively. Forty-nine percent of patients were followed through to death. Examination of the early disease course revealed two groups with adverse prognostic profiles. Firstly, a shorter time to reach DSS 3 from onset of PP-multiple sclerosis significantly adversely influenced time to DSS 8. Second, involvement of three or more neurological systems at onset resulted in a median time to DSS 10 of 13.5 years in contrast to PP-multiple sclerosis patients with one system involved at onset where median time to death from multiple sclerosis was 33.2 years. However, age, gender and type of neurological system involved at onset appeared to have little influence on prognosis. Life expectancy, cause of mortality and familial history profile were similar in PP-multiple sclerosis and non-PP-multiple sclerosis (all other multiple sclerosis patients from the total population). From clinical onset, rate of progression was faster in the PP-multiple sclerosis group than in the secondary progressive (SP)-multiple sclerosis group. When the rates of progression from onset of the progressive phase to DSS 6, 8 and 10 were compared, SP-multiple sclerosis had a more rapid progressive phase. A substantial minority (28%) of the PP-multiple sclerosis cohort had a distinct relapse even decades after onset of progressive deterioration. These studies establish natural history outcomes for the subgroup of multiple sclerosis patients with primary progressive disease.

Adult↗
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↗
PubMed1976

[Chronic pernicious course in multiple sclerosis with involvement of the optic nerves and total spinal sclerosis (diffuse spinal sclerosis) (author's transl)].

Four cases with the clinical diagnosis of chronic MS are presented, which, histologically, show large solitary demyelinated and gliotic areas involving almost the entire spinal cord over 12-25 segments as well as the optic chiasm. The abortive form of the neuromyelitis optical syndrome in MS is discussed. The additional involvement of the cerebral hemispheres suggests that the clinical and histological picture described is related to Schilder's disease.

Adult↗
PubMed1996

Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis.

Standardization of terminology used to describe the pattern and course of MS is essential for mutual understanding between clinicians and investigators. It is particularly important in design of, and recruitment for, clinical trials statistically powered for expected outcomes for given patient populations with narrowly defined entry criteria. For agents that prove safe and effective for MS, knowledge of the patient populations in definitive clinical trials assists clinicians in determining who may ultimately benefit from use of the medication. An international survey of clinicians involved with MS revealed areas of consensus about some terms classically used to describe types of the disease and other areas for which there was lack of consensus. In this report, we provide a summary of the survey results and propose standardized definitions for the most common clinical courses of patients with MS.

Disease Progression↗