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Results for “Multiple Sclerosis, Chronic Progressive”

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At least 865 records · Page 48Linked to original sources
PubMed1996

Development of cladribine treatment in multiple sclerosis.

Cladribine is a new type of drug with properties of selective lymphocyte suppression that appear to favorably alter the clinical course of progressive multiple sclerosis (MS). The history of the development of cladribine treatment in chronic progressive MS is discussed, and the application of cladribine treatment to progressive multiple sclerosis in a double-blind, placebo crossover study is reviewed. Cladribine selectively targets both resting and dividing lymphocytes and may be able to destroy the activated lymphocytes that induce CNS demyelination, thus producing stabilization or improvement in chronic MS. Although the role of cladribine has not yet been fully defined, additional studies are underway to evaluate the efficacy and safety of cladribine in both progressive MS and relapsing-remitting MS.

Cladribine↗
PubMed1988

Clinical experience with azathioprine: the pros.

We performed a randomized, placebo-controlled, double-blind, comparative clinical trial of 36 weeks of methylprednisolone and 3 years of azathioprine in 98 patients in the chronic progression phase of multiple sclerosis (MS). We demonstrated a trend in favor of the combination therapy for limiting progression. The relapse rate in the azathioprine recipients was half that of the control group, and visual evoked potential latencies were stabilized in those who received the combination. We think that a therapeutic trial of continuous use of the combination of adrenal steroids with azathioprine would be worthwhile if administered early in the course of the disease.

Azathioprine↗
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↗
PubMed2002

Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P=.02).

Adolescent↗
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↗
PubMed2003

CD24 is a genetic modifier for risk and progression of multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We found that the CD24v/v renders a >2-fold increase in the relative risk of MS in the general population (P = 0.023). Among familial MS, the CD24v allele is preferentially transmitted into affected individuals (P = 0.017). Furthermore, 50% of CD24v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA demonstrated that the CD24v allele can be expressed at higher efficiency than the CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.

Alanine↗
PubMed1992

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients.

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-I infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Deltaretrovirus Antibodies↗
PubMed2006

Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines.

Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells.

Age Factors↗
PubMed1985

Multiple sclerosis. Current concepts in management.

Multiple sclerosis is a chronic, often progressive disease of the central nervous system which can produce visual, sensory, motor, and genitourinary dysfunction. Although there is no cure, many disabling symptoms can be ameliorated. Baclofen is the treatment of choice for spasticity and is usually given in doses of 30 to 80 mg/day, although higher doses may be used. Bladder symptoms in multiple sclerosis generally fall into the categories of failure to store, failure to empty, and mixed types. Most patients can be managed after obtaining a urine culture and sensitivity and post-voiding residual. A variety of anticholinergic agents plus intermittent self-catheterisation is usually the most effective treatment for bladder dysfunction. Prevention of infection is accomplished by urinary acidifiers or low-dose antibiotics. There is no evidence that long term use of corticosteroids has a beneficial effect on the outcome of multiple sclerosis, although they appear to be useful in hastening the recovery time from an acute exacerbation. There are a number of experimental therapeutic agents which are used to modulate the immune response, which may prove to be of use in slowing or arresting the progression of multiple sclerosis.

Adrenal Cortex Hormones↗
PubMed1978

T and B lymphocytes in the cerebrospinal fluid of various neurological diseases.

Cerebrospinal fluids (CSF) from 66 patients with a variety of neurological disorders were studied for total protein content, absolute amount of albumin, IgA, IgG and IgM, as well as their quotients (fraction to total protein ratio), cell numbers and B cell and T cell levels. In addition, the percentage of B cells and T cells in the blood was determined in 34 patients and serum immunoglobulin levels were estimated in 51 patients. In noninflammatory diseases of the CNS, the percentage of B cells was slightly higher and T cell levels were lower in the CSF in comparison to corresponding blood values. The B cell to T cell ratio in viral meningitis was altered in the CSF. An apparent increase in the T cell level led to a decrease of B cell values. Similar changes were also found in optic neuritis. The percentage of T cells was higher in relapsing multiple sclerosis than in the chronic progressive form. There were less striking changes in the B cell to T cell ratios in the CSF of other inflammatory diseases of the CNS.

Adolescent↗
PubMed1992

CSF and serum ganglioside antibody patterns in MS.

The authors determined CSF and serum IgG and IgM antibodies to seven gangliosides in 48 patients with multiple sclerosis. Differing ganglioside antibody patterns in CSF but not serum allowed to reclassify 93% of MS patients correctly when compared to patients with Guillain-Barré syndrome or neuroborreliosis. This suggest that the antibody patterns are neither random nor alike in inflammatory diseases of the nervous system. CSF ganglioside antibody titres were found to be different for patients with relapsing remitting (RRMS; n = 35) and chronic progressive (CPMS; n = 13) multiple sclerosis. Our study reveals characteristic ganglioside antibody patterns in MS and confirms previous evidence of disturbed immunoregulation in MS.

Adult↗
PubMed2005

[Primary progressive multiple sclerosis as a differential diagnosis of ALS: a case report].

A 44-year-old man was admitted to our hospital because of a five year history of chronic progressive gait disturbance. Neurological examination revealed mild weakness and atrophy of the upper extremities, but severe of the lower ones, and without sphincter disturbance or apparent sensory impairment. Hyperreflexia and positive pathological reflexes of the lower extremities were apparent. EMG showed a reinnervation pattern and decreased number of motor units in the extremities, suggesting ALS. However, multiple plaques on the head and spinal MRI, a prolonged central conduction time of MEP and SEP, a delayed P100 latency of VEP, and a increased IgG index in the CSF indicated primary progressive type multiple sclerosis. After receiving steroid pulse therapy, the weakness of the lower extremities showed slight improvement. Diffuse inflammation in the spinal cord involving not only the pyramidal tract but also the anterior horn cells/intramedullary ventral roots explained the ALS-like clinical picture.

Adult↗
PubMed2004

Predicting the course of relapsing-remitting MS using longitudinal disability curves.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic, progressive disease of the central nervous system that generally occurs in adults under the age of 40 years and ultimately leads to severe neurological disability. Following the progression of MS by monitoring changes in disability levels can facilitate treatment decisions taken by physicians. The aim of this review is to present longitudinal disability curves enabling the assessment of disease progression in patients with relapsing-remitting (RR)MS. METHODS: Patients with a definite diagnosis of MS and an RR disease course were identified using the Multiple Sclerosis Center computerised database. Patients were stratified into major percentile groups based on their Expanded Disability Status Scale (EDSS) score 1 year after disease onset. Model disability curves for each percentile were constructed using mean consecutive EDSS scores for 10 years after disease onset. Model curves were generated by smoothing (parametric and non-parametric regression) and curve approximation (linear regression and moving averages). The predictive ability of model curves was validated by superimposing data from a separate group of patients with RRMS. RESULTS: Disability curves were constructed using data from 1001 patients. A significant difference between the initial percentile assignment and disability progression was indicated by the log-rank test (p < 0.001). Kaplan-Meier and life table analyses demonstrated the validity of the model in predicting disease progression. The probability of experiencing more severe disability than predicted (i. e. deviating from the initial percentile to a higher percentile over time) ranged from 6.5 % (50th percentile) to 15.4 % (75th percentile), while the probability of experiencing less severe disability than predicted (i. e. deviating from the initially assigned percentile to a lower percentile over time) ranged from 6.9% (50th percentile) to 1.6 % (75th percentile). Both suggest reasonable predictive validity. CONCLUSION: In MS, longitudinal disability curves can help to assess individual patient disability, map the effects of immunomodulatory treatments over time, and generally build on the overall clinical impression of disease progression. Such models can act as a tool to aid and support the clinical decision-making process. This review is based on the study published in Multiple Sclerosis (2003) 9:486-491.

Disability Evaluation↗
PubMed1996

Providing a neuropsychology service for people with multiple sclerosis in an interdisciplinary rehabilitation unit.

Multiple sclerosis (MS) is a chronic progressive disease with symptoms that are often difficult to interpret and distinguish from other neurological disorders. These symptoms are discussed together with psychological interventions, physical management and occupational therapies. A review of studies is presented as well as concepts for service provision for MS patients in the NHS. Finally, current practice in an interdisciplinary rehabilitation unit is discussed, and some recent advances in MS treatment are noted.

Brain↗
PubMed1990

Some clinical and pathologic observations on chronic myelopathy: a variant of multiple sclerosis.

Four patients with progressive demyelinating myelopathy with symptoms spanning six to 25 years are described. There was no clinical evidence of dissemination of lesions in the central nervous system. Radiological evidence of dissemination was present in two cases; in one this was absent at the time of presentation and was only demonstrated after six years of progressive unifocal disease. In one case, pathological examination revealed a solitary area of chronic demyelination. In all cases but one, oligoclonal bands were detected on cerebrospinal fluid (CSF) electrophoresis. Some cases of chronically progressive myelopathy result from focal demyelination in the absence of a second lesion demonstrable by clinical, radiographic or necropsy examination.

Aged↗
PubMed1994

A putative new retrovirus associated with multiple sclerosis and the possible involvement of Epstein-Barr virus in this disease.

Since tropical spastic paraparesis in 1985 was found to be associated with HTLV-I infection, it has been suggested that a retrovirus might be involved in multiple sclerosis (MS). Our group has studied long-term cultures of cerebrospinal fluid cells and peripheral blood mononuclear cells from MS patients and controls with the purpose of elucidating the possible involvement of a retrovirus in MS. For an extended period electron microscopical analysis (EM) of T-cell lines, derived from MS patients and controls and cultured for 4 weeks was performed. In two cultures obtained 8 months apart from a patient with progressive MS, retrovirus-like particles were observed in 1-2% of the cells examined. Recently a B-lymphoblastoid cell line (LCL) producing retrovirus-like particles and EBV was established from a 30-year-old male patient with a chronic progressive myelopathy, clinically resembling multiple sclerosis. Similar cell lines have now been established from two MS patients. The retrovirus-like particles produced by the LCL have been purified by gradient ultracentrifugation. In the purified material reverse transcriptase assays are clearly positive in the gradients where EM shows retrovirus-like particles. Antigen characterization, nucleic acid sequence analysis and antibody studies are now being performed. The retrovirus found is definitively different from other known human retroviruses. It has previously been found that 100% of patients with MS have antibodies against EBV, in contrast to controls where only 86-95% have antibodies against this virus. Previous epidemiological studies have pointed toward a post-pubertal primary EBV infection as an important event in the induction of MS disease. These studies have now been substantiated by our group. Though it is still unknown whether EBV infection is a prerequisite for development of MS or whether the 100% EBV seropositivity is a consequence of the MS disease, we have put forward the hypothesis that the etiological agent for development of MS and MS-like diseases is a new hitherto uncharacterized retrovirus, whereas development of neurologic disease is related to or even dependent on a delayed infection with a virus from the herpes group, most likely EBV. This dual infection hypothesis has been analyzed and was found to be in accordance with the most consistent epidemiological characteristics of MS. We have previously, also from epidemiological data, negated retroviruses, behaving as the known human retroviruses, as an independent cause of MS.

Adult↗
PubMed1989

Love, self-esteem, and multiple sclerosis.

Multiple sclerosis (MS) is a progressive chronic disease which generally appears in early adulthood. The debilitating symptoms of MS can have adverse effects on the sufferer's self-esteem, a vital coping resource for sufferers of chronic diseases. This study explores the effects of positive affect and social isolation--conceived broadly together as love--on self-esteem. We found that love was the most powerful predictor of self-esteem, followed by attitude stage, number of years since diagnosis, social class, and physical restriction.

Activities of Daily Living↗
PubMed1989

A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

Adolescent↗