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Results for “Multiple Sclerosis, Chronic Progressive”

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PubMed1995

A longitudinal study of the T cell activation marker CD26 in chronic progressive multiple sclerosis.

Activated T cells are implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Serial measurements of T cell activation molecules and T cell subpopulations were performed over 12 months in patients with chronic progressive multiple sclerosis and healthy controls, and correlated with clinical indices of disease progression measured by standardized disability scores. Of the markers studied, the activation molecule CD26 appeared to exhibit a more consistent pattern and to be elevated in MS patients; therefore we concentrated our attention on this marker, especially in view of recent evidence of its role in T cell activation. In this small patient group, the elevation of CD26 in the MS patients did not reach statistical significance, when compared to the level in the controls. Interestingly, the percentage of CD26 but not CD25 or HLA-DR correlated with the MS patients' disability scores. However, the clinical significance of this observation as an indication of disease activity in chronic progressive MS remains to be demonstrated in studies of larger patient populations.

Adult↗

PubMed1997

Treatment with electromagnetic fields reverses the long-term clinical course of a patient with chronic progressive multiple sclerosis.

It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious onset of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. To date no therapeutic modality has proven effective in reversing the clinical course of CP MS although there are indications that prolonged treatment with picotesla electromagnetic fields (EMFs) alters the clinical course of patients with CP MS. A 40 year-old woman presented in December of 1992 with CP MS with symptoms of spastic paraplegia, loss of trunk control, marked weakness of the upper limbs with loss of fine and gross motor hand functions, severe fatigue, cognitive deficits, mental depression, and autonomic dysfunction with neurogenic bladder and bowel incontinence. Her symptoms began at the age of 18 with weakness of the right leg and fatigue with long distance walking and over the ensuing years she experienced steady deterioration of functions. In 1985 she became wheelchair dependent and it was anticipated that within 1-2 years she would become functionally quadriplegic. In December of 1992 she began experimental treatment with EMFs. While receiving regularly weekly transcortical treatments with AC pulsed EMFs in the picotesla range intensity she experienced during the first year improvement in mental functions, return of strength in the upper extremities, and recovery of trunk control. During the second year she experienced the return of more hip functions and recovery of motor functions began in her legs. For the first time in years she can now initiate dorsiflexion of her ankles and actively extend her knees voluntarily. Over the past year she started to show signs of redevelopment of reciprocal gait. Presently, with enough function restored in her legs, she is learning to walk with a walker and is able to stand unassisted and maintain her balance for a few minutes. She also regained about 80% of functions in the upper limbs and hands. Most remarkably, there was no further progression of the disease during the 4 years course of magnetic therapy. This patient's clinical recovery cannot be explained on the basis of a spontaneous remission. It is suggested that pulsed applications of picotesla EMFs affect the neurobiological and immunological mechanisms underlying the pathogenesis of CP MS.

Adult↗

PubMed1988

Natural killer (NK) cells in chronic progressive multiple sclerosis patients treated with lymphoblastoid interferon.

Natural killer (NK) cell functional activity, as defined by the lysis of 51Cr-labelled K-562 cells, and number, defined phenotypically by anti-Leu-11, are significantly decreased in chronic progressive multiple sclerosis (MS) when compared to normal controls. When age- and sex-matched populations are compared, NK cell functional activity is again significantly reduced in MS compared to controls but not when compared to a control group of other medical disease (OMD). The MS group could be differentiated from the OMD group, however, when results of NK cell functional activity are combined with NK cell phenotype. With the administration of lymphoblastoid interferon daily for 6 months, NK cell activity increased significantly at 48 h and at 1 week. By 1 month, activity decreased to a level slightly above placebo treatment values. The results likely reflect interferon's enhancement of mature NK cell activity combined with a variable effect on recruitment of pre-NK cells.

Adult↗

PubMed1995

Meta-analysis of clinical studies of the efficacy of plasma exchange in the treatment of chronic progressive multiple sclerosis.

OBJECTIVE: To examine the hypothesis that addition of therapeutic plasma exchange (TPEX) to an immunosuppressive drug regimen increases that regimen's efficacy to halt the progression of chronic progressive multiple sclerosis (CPMS). METHODS: The literature was searched for prospective controlled clinical trials evaluating the efficacy of TPEX in CPMS. Six studies were eligible for meta-analysis. Their results were combined, using Cochran's and Peto's methods. Three outcome measures were studied: 1) the change in Kurtzke's disability status scale (DSS) scores, 2) the relative odds of neurologic decline by 1 or more DSS grades, and 3) the relative odds of neurologic improvement by 1 or more DSS grades, in the treatment versus the comparison group of patients. Reported results of neurologic evaluations at 6, 12, 24, and 36 months of follow-up were analyzed separately. RESULTS: TPEX significantly (P < .05) reduced the proportion of patients who experienced neurologic decline (by 1 or more DSS grades) at 12 months of follow-up (relative odds of decline = 0.441, 95% confidence interval = 0.210-0.929). CONCLUSIONS: There is a need for further clinical research into the possibility of a beneficial effect of TPEX in patients with CPMS likely to experience neurologic decline over the ensuring 12 months. Targeting treatment to a particular subgroup of CPMS patients may be necessary for TPEX to prove effective.

Chronic Disease↗

PubMed1990

Decrease of CD4+CD45+ T-cells in chronic-progressive multiple sclerosis.

Circulating lymphocyte subpopulations defined by anti-CD45 and other more common T-cell-specific monoclonal antibodies were analysed in 77 patients with multiple sclerosis and 38 healthy controls. A selective decrease of CD4+CD45+ cell percentages and absolute numbers in chronic-progressive patients was found; in 13 out of 26 patients this subpopulation was less than 11% CD4+CD45+ cells. Similarly, the whole CD45+ cell subset, as well as CD45+ cells expressed as percentages of CD4+ cells, were significantly reduced in chronic-progressive multiple sclerosis. CD4+CD45+ cells, commonly termed "inducer of suppression" T-lymphocytes, did not correlate with percentages or numbers of CD8+ cells. It is concluded that suppressor inducer T-cells act on the CD8+ subset function rather than reducing CD8+ cell numbers. Since CD4+CD45+ cells represent an early stage of lymphocyte maturation (naive T-cells), an under-representation of this subpopulation in active multiple sclerosis might reflect an increased conversion of naive cells into memory cells. This concept may be relevant for a better understanding of the disease pathogenesis.

Adult↗

PubMed1996

Treatment with electromagnetic field alters the clinical course of chronic progressive multiple sclerosis--a case report.

It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. No therapeutic modality has shown specific efficacy in the treatment of patients with CP MS and there are no data to indicate that any pharmacologic or other modality alters the clinical course of CP MS. Treatment with picotesla electromagnetic fields (EMFs) is a highly effective modality for the symptomatic management of MS including the chronic progressive form. In addition, this treatment also appears to alter the natural course of the disease in CP patients. A 36 year-old man experienced, at the age of 31, insidious weakness in the legs and several months later developed difficulties with balance with ataxia of gait. His gait abnormality progressed slowly over the following years and at the age of 35 he was severely disabled with spastic paraparesis and ataxia using a rolling walker for ambulation and a scooter for longer distances. In particular, his disability had progressed rapidly over the six months preceding the initiation of treatment with EMFs. He as classified have CP MS and his prognosis was considered extremely unfavorable due to the degree of cerebellar and pyramidal tract involvement and the rapid course of deterioration. In July 1995 the patient began experimental treatment with EMFs. While receiving three treatment sessions a week over 12 months he experienced improvement in cerebellar functions such as gait, balance and tremor as well as bowel and bladder functions, mood, sleep and cognitive function and resolution of diplopia, blurring of vision, dysarthria, paresthesias in the hands, and fatigue. Most remarkably, there was no further progression of the disease during the course of magnetic therapy. This case illustrated that treatment with EMFs, in addition to producing symptomatic improvement, also reverses the clinical course of CP MS.

Adult↗

PubMed1991

Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic progressive multiple sclerosis: expected lack of clinical utility.

We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-alpha and IL-1 beta, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients.

Chronic Disease↗

PubMed1989

Chronic progressive multiple sclerosis: changes in phenotype and function of T helper subsets.

We have measured pokeweed mitogen-induced IgG secretion by peripheral blood mononuclear cells obtained from two different groups of progressive multiple sclerosis (MS) patients. MS patients with chronic progressive active disease (CPMS-A) have higher IgG secretion than stable (burnt-out) patients (CPMS-S). We have also measured suppressor cell function and phenotyped the T helper cells of some CPMS-A patients. This group differed from CPMS-S and from controls: they had high IgG secretion, low suppression and their T helper phenotypes showed a high ratio of T helper/inducers over T suppressor/inducers.

Chronic Disease↗

PubMed1991

Serum cytokine levels in chronic progressive multiple sclerosis: interleukin-2 levels parallel tumor necrosis factor-alpha levels.

Serum levels of the cytokines interleukin-1 alpha (IL-I alpha), IL-1 beta, IL-2, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha) and the soluble IL-2 receptor were measured in chronic progressive multiple sclerosis patients (CPMS) and normal, inflammatory, and noninflammatory disease controls. Serum IL-2 levels displayed the most consistent abnormalities in the group of tests for the CPMS group, and were the only cytokine levels to achieve significance in statistical group analyses. However, several patients with CPMS had normal serum IL-2 levels. An incidental finding was a statistical correlation between serum IL-2 and TNF-alpha levels among all groups tested. This finding was supported on analysis of serial serum samples from CPMS patients. These results suggest a linkage of IL-2 and TNF-alpha production, especially in pathological conditions.

Cytokines↗

PubMed1991

Systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis. II. Immunologic evaluation.

Immunologic functions are studied in conjunction with a placebo-controlled trial of lymphoblastoid interferon (IFN) in patients with chronic progressive (CP) multiple sclerosis. Prior to treatment, CD4+ cells are significantly increased and CD8+ cells decreased in the blood of MS patients. Both CD5+ and CD4+ cells increase significantly with IFN therapy early during the treatment phase of the trial, while the number of CD8+ cells decreases steadily, becoming significant at 6 months. CNS IgG synthesis rates increase with IFN treatment and maximize at 3 months. Serum antiviral activity also increases with IFN treatment. In the IFN-treated group, a trend toward improvement, determined clinically and by MRI, likely reflects the influence of a subpopulation of 10 patients. This subpopulation is now further characterized by an early increase in CNS IgG synthesis and numbers of CD5+ cells in the blood. Although these immune functions may identify a number of CP MS patients who might benefit from IFN, it is unlikely that these mechanisms actually mediate the potentially beneficial effects of this cytokine.

Adult↗

PubMed2000

Treatment of chronic progressive multiple sclerosis with intravenous immunoglobulins--interim results on drug safety of an ongoing study. IVIG study group.

In a blinded administrative look we analyzed the safety profile of intravenous immunoglobulin (IVIG) treatment in an ongoing randomized, placebo controlled double blind study on the treatment of multiple sclerosis (MS) patients with primary or secondary chronic progressive MS. Up to October 1999 131 patients were included in the study. Collectively, these patients received approximately 1,200 infusions either with IVIG (400 mg/kg bodyweight every 4 weeks) or with placebo; approximately 600 IVIG infusions were administered. All reported serious adverse events (SAE), including reports on adverse events submitted directly to the drug safety department of the sponsor, were closely analyzed A total of 25 SAE's (in 25 patients) have been reported up until 15th October 1999, whereby the main criterion for 'serious' in all of these cases was hospitalization. None of these 25 SAE were regarded as drug related. No side effects relating to liver functions, kidney functions or rheological problems have been reported. Since the mean score on the EDSS-scale of the patients at the point of inclusion in the study was 5.6 (median EDSS: 6.0) we conclude that IVIG treatment, at a dose of 400 mg/kg bodyweight every 4 weeks, is a relatively safe therapy even for severely disabled multiple sclerosis patients.

Adult↗

PubMed2001

Low-dose oral methotrexate treatment in chronic progressive multiple sclerosis.

We aimed to further assess the safety and efficacy of low-dose oral methotrexate (LDOM) treatment for chronic progressive MS (CPMS). We studied 20 CPMS patients, including 16 with secondary progressive MS who had shown disease progression in the previous year. The mean follow-up was 23 months. The mean EDSS score was 6.3+/-1.1 before treatment and 6.4+/-1.1 after one year of treatment. At one year, 15 of 20 patients were still being treated, and 10 were stable. Twelve patients have completed 18 months of treatment, and eight are stable. Two patients stopped treatment because of side effects, two more because they did not perceive benefit, and one was lost to follow-up. Six patients had mild, transient increases in liver enzymes not requiring treatment interruption, and two had localized herpes zoster. Magnetic resonance imaging (MRI) performed before treatment and at one year remained unchanged in responders. We confirm that LDOM is safe in carefully selected and monitored CPMS patients. MTX is inexpensive and, given its anti-inflammatory and immunomodulatory properties, may be used as add-on therapy in non-responders to interferon beta, although hepatic toxicity may be a problem in long-term treatment.

Adult↗

PubMed1997

Tolerance induction to myelin basic protein by intravenous synthetic peptides containing epitope P85 VVHFFKNIVTP96 in chronic progressive multiple sclerosis.

Peptide-based tolerance induction may be useful for antigen-specific immunotherapy of human autoimmune diseases. Induction of tolerance to myelin basic protein (MBP) was examined in a Phase I clinical trial in multiple sclerosis (MS) patients with chronic progressive disease using a peptide that is immunodominant for MBP specific T cells and B cells. Tolerance induction was monitored by quantification of MBP specific autoantibodies in cerebrospinal fluid (CSF). The route of peptide administration was important since only intravenous but not intrathecal or subcutaneous injection induced tolerance to MBP. Following a single intravenous injection of a peptide containing epitope P85VVHFFKNIVTP96, MBP autoantibodies were undetectable for three to four months. Tolerance was more prolonged following a second injection since autoantibodies were low or undetectable after one year in the majority of patients. Duration of tolerance to MBP depended on MHC class II haplotypes of patients; tolerance was long-lived in all patients with disease associated HLA-DR2. No neurological or systemic side effects were observed, regardless of the route of peptide administration. These data demonstrate that intravenous administration of a soluble peptide can result in long-lasting tolerance to an autoantigen in humans.

Autoantibodies↗

PubMed2000

Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31.

The hereditary leukodystrophies represent a group of neurological disorders, in which complete or partial dysmyelination occurs in either the central nervous system (CNS) and/or the peripheral nervous system. Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive, neurological disorder characterized by symmetrical widespread myelin loss in the CNS, and the phenotype is similar to that of chronic progressive multiple sclerosis. We report clinical, neuroradiological and neuropathological data from the originally reported ADLD family. Furthermore, we have localized the gene that causes ADLD to a 4 cM region on chromosome 5q31. Linkage analysis of this family yielded a LOD score of 5.72 at theta = 0.0 with the microsatellite marker D5S804. Genetic localization will lead to cloning and characterization of the ADLD gene and may yield new insights into myelin biology and demyelinating diseases.

Brain↗

PubMed1989

Effective treatment of chronically progressive multiple sclerosis with low-dose cyclophosphamide with minor side-effects.

Twenty-one multiple sclerosis (MS) patients with a chronically progressive course were treated with a low dose of cyclophosphamide (CY). The control group consisted of 21 MS patients with a chronically progressive course who received the standard treatment (ACTH or cortisone). The control group consisted of patients who preferred the standard therapy because of its beneficial effects. In contrast, the patients of the CY group wanted to try a new therapy because the standard therapy was not effective. Thus before starting the study the progression of the disease was faster in the CY group than in the standard therapy group. As regards age, sex and degree of disability, the two groups were comparable. For 20 of the 21 patients in the CY group the degree of disability (Kurtzke scale) remained stable over 1 year; for 2 of the 20 stable patients there was even an improvement. In the standard therapy group, 7 out of 21 patients were stable over 1 year, while 14 showed progressive disability. A quantitative neurological score at the beginning and 1 year after the therapy showed a nearly identical difference between the CY group and the control group. The changes of the patients' abilities in daily-life activities (which were observed and recorded by the nurses) were similar to the Kurtzke scale data obtained by the physicians. The beneficial effect of CY in chronically progressive MS was thus highly significant (P less than 0.001). The side-effects of low-dose CY were fewer than those of ACTH.

Adult↗

PubMed1996

Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis.

The serum levels of the heterodimeric cytokine IL-12 were measured by solid-phase ELISA in a group of healthy subjects, multiple sclerosis (MS) patients with secondary chronic progressive course of the disease and patients suffering from other neurological diseases (OND). Serum levels of IL-12 higher than 5 pg/ml (limit of sensitivity of the assay) were only found in 2/30 (6.7%) of the healthy subjects and none of the 8 subjects with OND. In contrast, IL-12 was found in the majority of CPMS patients' sera (10/15, 66.7%) with values ranging between 5.5 and 18.6 pg/ml. These results are suggestive for an up-regulated production of IL-12 in CPMS.

Adult↗

PubMed1998

[A case of primary Sjögren's syndrome with CNS disease mimicking chronic progressive multiple sclerosis].

We report a 40-year-old woman with primary Sjögren's syndrome (SjS) with slowly progressive CNS disease. At age 38, she noticed spasticity and very gradual onset of monoparesis in the left leg. She hardly walked by herself at age 40. On admission, neurological examination revealed mild slurred speech, vertical nystagmus, spasticity in the four extremities, spastic monoparesis of the left leg, exaggerated jaw jerk, hyperreflexia in all limbs except right biceps and brachioradialis reflex, and positive bilateral Hoffmann reflexes and Babinski signs. Laboratory examinations disclosed positive anti-nuclear antibody (speckled type) and anti-SS-A/Ro antibody (64x). CSF examination revealed cell count 8/mm3, protein 42 mg/dl, 4 bands of oligoclonal band and the elevation of IgG index. MR-imaging presented multiple plaque-like lesions in white matter of cerebrum and brainstem, which did not show gadolinium enhancement. Additionally she complained of dry eyes. Lacrimal and salivary secretion tests showed hyposecretion of tears and hyposialosis. The biopsied specimen of labial minor salivary gland revealed the destruction of the ducts and periductal lymphocytic infiltrations. The diagnosis of primary SjS was confirmed. We herein report a rare case of primary SjS with CNS disease mimicking chronic progressive multiple sclerosis (MS), and discuss a difficulty in differentiating CNS disease of SjS from MS.

Adult↗

PubMed1993

High-dose methylprednisolone infusions in relapsing and in chronic progressive multiple sclerosis patients. One year follow-up.

Sixty Multiple Sclerosis patients hospitalized either in relapse (28) or in chronic progressive (32) phase of the disease were treated with high-dose methylprednisolone infusions (1 g/daily for 6 days). Clinical examinations, scored by Kurtzke's functional systems (FSs) and expanded disability status scale (EDSS), were performed before treatment, immediately after, and thereafter at 1,3,6 and 12 month intervals. In relapsing cases, 22 patients (78.6%) improved and EDSS mean value decreased by 1.39 points after the treatment; 8 patients had a new bout within one year. In chronic progressive cases, 18 patients (56.2%) improved and EDSS mean value decreased by 0.56 points after the treatment; 13 patients showed a new worsening throughout the follow-up period. The treatment proved to be safe and effective both in relapsing and in chronic progressive patients, determining rapid clinical improvement in most of the cases, and a slowing down of progression in some chronic patients.

Adolescent↗