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At least 865 records · Page 48Linked to original sources
PubMed2006

Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.

OBJECTIVE: To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis. DATA SOURCES: We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles. STUDY SELECTION: We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort. DATA EXTRACTION: Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis. DATA SYNTHESIS: Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis. CONCLUSIONS: The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.

Adult↗
PubMed2000

Proton magnetic resonance spectroscopy of temporal lobe white matter in patients with histologically proven hippocampal sclerosis.

The purpose of this study was to assess temporal lobe white matter changes accompanying hippocampal sclerosis on magnetic resonance (MR) imaging using single-voxel 1H MR spectroscopy and to strengthen the hypothesis that these white matter changes are caused by myelin alterations. In 11 patients with histologically proven hippocampal sclerosis, preoperative coronal fluid-attenuated inversion recovery images were visually assessed by two experienced neuroradiologists for hippocampal signal increase and size decrease, atrophy of collateral white matter, and temporal lobe gray/white matter demarcation loss. Single-voxel 1H MR spectroscopy of the white matter of each anterior temporal lobe was also performed, excluding the amygdala and hippocampus. The N-acetyl-aspartate (NAA)/choline and NAA/creatine ratios were calculated. In 12 healthy volunteers both temporal lobes were spectroscopically examined. In all patients the excised hippocampi were histologically assessed for the presence of sclerosis, and the excised neocortical temporal lobes were examined for gray and white matter abnormalities. MRI abnormalities were found on the right in six patients, on the left in four, and one scan was normal. Hippocampal signal increase was seen in nine patients, hippocampal size decrease in ten, atrophy of collateral white matter in nine, and gray/white matter demarcation loss in six. A significant decrease in the NAA/choline ratio was found in temporal lobe white matter ipsilateral to the pathologic hippocampus (symptomatic side), compared with the contralateral, asymptomatic side (P < 0.01), and also compared with controls (P < 0.001). The ipsilateral NAA/creatine ratio was also significantly decreased (P < 0.05) compared with the contralateral side and the control subjects (P < 0.001). Histological examination showed hippocampal sclerosis to a different degree in all patients. Neither gliosis nor cortical dysplasia was found in the ipsilateral, symptomatic temporal lobe. Significant decrease in the mean of NAA/choline ratios is found in temporal lobe white matter of patients with histologically confirmed hippocampal sclerosis. As this indicates neuronal loss or dysfunction, the number of axons may be reduced, with associated decrease in myelin density.

Adult↗
PubMed2004

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. REVIEWERS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses.

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.

Adjuvants, Immunologic↗
PubMed2002

Treatment of multiple sclerosis with the pregnancy hormone estriol.

Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8 mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo-controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy.

Adolescent↗
PubMed2005

Is optic neuritis more benign than other first attacks in multiple sclerosis?

Optic neuritis presentations are thought to have a better prognosis. The aim of our study was to compare conversion to multiple sclerosis on the different topographies of CISs. We prospectively evaluated 320 patients with CISs (123 with optic neuritis, 78 with brainstem syndromes, 89 with spinal cord syndromes, and 30 with other topographies) who were observed for a median of 39 months. Patients underwent brain MRI within 3 months of their first attack and again 12 months later. Conversion to multiple sclerosis determined either clinically or by MRI was evaluated according to topography. Baseline MRI was normal in 49.2% of patients with optic neuritis compared with 24% in brainstem syndromes, 24% in spinal cord syndromes, and 18.5% in other syndromes. Optic neuritis behaved differently from the other CISs for lower conversion to clinically definite multiple sclerosis and smaller proportion of patients fulfilling MRI dissemination in space, time, or both. Nevertheless, when only patients with abnormal cranial MRI results at baseline were selected, no differences for clinical or MRI conversion were found. Optic neuritis has a smaller risk for conversion to multiple sclerosis. Nevertheless, MRI at baseline, not CIS topography, appears to be the crucial issue at multiple sclerosis presentation.

Adult↗
PubMed1983

Zinc in multiple sclerosis.

Zinc profiles were examined in 68 patients with multiple sclerosis, 62 normal volunteers, and 13 patients with other neurological diseases. Plasma zinc levels were slightly increased in patients with multiple sclerosis and significantly increased in those with other neurological impairments (p less than 0.01), compared with control subjects. Albumin-bound as well as protein-bound zinc levels were normal in all groups tested. The alpha 2 macroglobulin-bound zinc level was significantly lower (p less than 0.01) in patients with multiple sclerosis than in control subjects. Erythrocyte-bound zinc levels were significantly increased (p less than 0.05) in patients with multiple sclerosis when compared with control subjects. Erythrocyte-bound zinc was normal in patients with other neurological impairments. Because erythrocyte-bound zinc levels are relatively independent of daily fluctuations in dietary zinc intake, an increase in these values may suggest alterations in the control mechanisms governing zinc compartmentalization in patients with multiple sclerosis.

Blood Proteins↗
PubMed1985

High-resolution computed tomography in multiple sclerosis.

Eighty-five patients were classified as having definite (n = 34), probable (n = 18), or possible (n = 33) multiple sclerosis using the criteria of Poser. Each patient had an enhanced computed tomographic examination, and most had cerebrospinal fluid and evoked response studies at the same time. Abnormalities including focal decreased brain density, abnormal enhancement, and cerebrospinal fluid space enlargement were found in 62% of patients (85% of those with definite, 39% of those with probable, and 52% of those with possible multiple sclerosis), and abnormal enhancing areas were demonstrated in 29% (44% of those with definite, 17% of those with probable, and 21% of those with possible disease). In the subgroup of patients with definite multiple sclerosis and recent clinical exacerbation (within the prior 8 weeks), abnormal enhancement was present in 89%. There was a strong correlation between clinical exacerbation and abnormal contrast enhancement. Cerebrospinal fluid studies (IgG, white blood cell count, total protein) had no correlation with exacerbation or abnormal enhancement. Maps of low-density and enhancing areas were similar to those previously described in postmortem studies. Computed tomography thus provides an in vivo, objective, and anatomically specific map of the brain parenchyma and the integrity of the blood-brain barrier that is useful in research studies evaluating the treatment of multiple sclerosis. It is also useful in patients in whom the diagnosis of multiple sclerosis is suspected but not certain on the basis of clinical and laboratory evaluation.

Adult↗
PubMed1985

Balo's concentric sclerosis: new observations on lesion development.

A 54-year-old woman with a four-month history of progressive neurological illness was found at postmortem examination to have lesions of Balo's concentric sclerosis. Balo lesions were found in several areas scattered widely throughout the central nervous system, including the spinal cord, a previously unreported location, and were studied by histological and ultrastructural methods. Balo lesions consisted of bands of intact myelin alternating with zones of demyelination. These lesions were centered on a perivascular cuff of inflammatory cells. The center of the lesion was the oldest area with the concentric rings of demyelination decreasing in age with increasing distance from the center. The bands of intact myelin comprised mainly remyelinated fibers, were similar to those seen at the edges of chronic active multiple sclerosis plaques, and may have represented the repaired margins of preceding episodes. The occurrence of small foci of acute demyelination centered on perivascular cuffs and other changes typical of both acute and chronic active multiple sclerosis may indicate that the lesion of Balo's concentric sclerosis represents an intermediate stage in the development of an established multiple sclerosis lesion.

Central Nervous System↗
PubMed1988

Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4+ 2H4+) T cells in multiple sclerosis.

A consistent immunological finding in patients with progressive multiple sclerosis is a loss of functional suppression. We have recently found decreases in suppressor inducer T cells in progressive multiple sclerosis as measured by two-color immunofluorescence using differentiation markers CD4 and 2H4. In the present study, we examined the relationship between functional suppression and circulating CD4+ 2H4+ T cells using a two-stage assay. (1) T cells were stimulated for 7 days with irradiated non-T cells (autologous mixed lymphocyte reaction [AMLR]) and harvested. It has previously been shown that suppressor T cells are generated during the course of the AMLR. (2) The AMLR-generated suppressor T cells were then incubated with mononuclear cells plus pokeweed mitogen, and immunoglobulin (Ig) synthesis was measured. There was less AMLR-induced suppression of IgG synthesis in patients with progressive multiple sclerosis as compared with normal subjects and patients with other neurological diseases. More importantly, there were significant correlations between decreases in circulating CD4+ 2H4+ cells and the AMLR (p = 0.009). Thus, the decreases in functional suppression and the decreases in the AMLR in multiple sclerosis appear tightly linked to CD4+ 2H4+ cells, and their measurement provides a means to monitor suppressor function phenotypically. Decreases in suppressor inducer T cells may in part explain immunoregulatory abnormalities observed in multiple sclerosis.

Biological Assay↗
PubMed1988

Multiple sclerosis: involvement of interferons in lesion pathogenesis.

To investigate a possible role of interferons (IFNs) in lesion pathogenesis, central nervous system tissue from multiple sclerosis patients and control subjects was stained by immunocytochemical techniques in combination with monoclonal antibodies or polyclonal antisera for the demonstration of IFN-alpha, IFN-beta, and IFN-gamma. The results were correlated to lesion activity, to the presence of class I and class II major histocompatibility antigen-positive astrocytes, and to the composition of cellular infiltrates. IFNs were detectable in active but not in inactive chronic multiple sclerosis lesions. In acute multiple sclerosis plaques, all three types of IFN were widely distributed on glial elements and infiltrating cells. In active chronic multiple sclerosis, labeling of cells for IFN-alpha, IFN-beta, and IFN-gamma was most pronounced at the lesion edge and displayed distinct distribution patterns. Overall, IFN-gamma was more common than IFN-alpha and IFN-beta and was predominantly found on astrocytes. IFN-alpha was detectable mainly on macrophages. Distribution of IFN-beta partially overlapped with that of IFN-gamma and IFN-alpha, in that it was present on some astrocytes and on some macrophages. IFNs were rare in normal white matter remote from lesions and in the gliotic lesion center. Ia antigen and human leukocyte antigen ABC on astrocytes were distributed similarly to IFN-gamma and IFN-beta, respectively. These findings indicate that IFN-gamma may play a role in active lesion growth in multiple sclerosis, whereas IFN-alpha and IFN-beta may exert some local immunosuppressive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis.

Thirty untreated patients with clinically definite chronic progressive multiple sclerosis were matched with 10 patients with clinically stable definite multiple sclerosis and 16 patients with other neurological diseases. A group of 12 normal control (NC) volunteers was matched to these groups. All patients with chronic progressive multiple sclerosis and normal control subjects were analyzed for the concanavalin A suppressor assay, mitogen stimulation, and phenotyping of peripheral blood mononuclear cells. In addition, serum was analyzed for interleukin-2 levels. Results of mitogen stimulation studies did not distinguish the groups. Concanavalin A-induced suppression was significantly decreased in the patients with chronic progressive multiple sclerosis (p less than 0.01). Phenotyping of fresh cells showed an elevated CD4: CD8 ratio in the patients with chronic progressive multiple sclerosis. Neither phenotyping nor concanavalin A-induced suppression correlated with or predicted the degree of disability, but the serum levels of interleukin-2 correlated inversely with disability (p less than 0.01) and directly with a poor prognosis after 18 months of observation (p less than 0.05). Serum levels of interleukin-2 decreased as the disease progressed.

Adult↗
PubMed1989

Decrease of suppressor inducer (CD4+2H4+) T cells in multiple sclerosis cerebrospinal fluid.

T-lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis are predominantly CD4+ (inducer) as opposed to CD8+ (suppressor/cytotoxic) T cells. The CD4+ lymphocytes can be subdivided into populations that express high densities of the CDw29 (4B4) determinant and have helper inducer function or express high densities of CD45R (2H4) determinant and have suppressor inducer function. In the present study, we characterized the nature of these CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis by performing flow cytometric analysis on paired samples of blood and cerebrospinal fluid. There were significantly lower percentages of CD4+2H4+ T cells in the cerebrospinal fluid than in the peripheral blood (p = 0.001, paired t test). In contrast, there were increased percentages of helper inducer (CD4+4B4+) T cells in the cerebrospinal fluid (p = 0.001, paired t test), compared with the peripheral blood. Analysis of subjects with other inflammatory disorders of the central nervous system did not show significant decreases in CD4+2H4+ T cells in cerebrospinal fluid, though in some, decreases were also observed. These results indicate that the CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis are predominantly helper inducer, as opposed to suppressor inducer T cells, and that the relative decrease of suppressor inducer cells in the peripheral blood of multiple sclerosis patients is not due to their migration to the cerebrospinal fluid. Furthermore, the increased numbers of helper inducer cells in the cerebrospinal fluid may contribute to local autoimmune processes in the central nervous system compartment of multiple sclerosis patients.

Humans↗
PubMed1989

Chronic progressive multiple sclerosis: serial magnetic resonance brain imaging over six months.

Eight patients in the chronic progressive stage of multiple sclerosis were studied prospectively with magnetic resonance imaging of the head and neurological examination every 2 weeks for 6 months. There were no clinical relapses and disability ratings did not change between the start and completion of the study. Despite the clinical inactivity, a total of 86 active events (new, reappearing, or enlarging lesions) were identified by magnetic resonance imaging over the 6 months, with 50 (51%) of 98 follow-up scans showing evidence of one or more active lesions. New and changing lesions were indistinguishable in appearance, distribution, and temporal pattern from those previously seen in patients who had relapsing and remitting multiple sclerosis. However, as noted previously, the patients in the chronic progressive stage had many more confluent lesions than did the group in relapse. These results strongly suggest that the frequently observed clinical evolution of multiple sclerosis into a chronic progressive course is not accompanied by a fundamental change in the disease process. In fact the chronic progressive stage seems associated with more active changes demonstrated by scans than does relapsing and remitting multiple sclerosis. This study also confirms our previous experience that serial magnetic resonance imaging is much more sensitive than clinical examination in detecting disease activity in multiple sclerosis.

Adult↗
PubMed1989

Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis.

We measured levels of alpha-tumor necrosis factor (alpha-TNF) in cerebrospinal fluid and serum samples from 50 drug-free patients with multiple sclerosis, 25 patients with other neurological diseases, 27 patients with non-neurological diseases, and 10 normal subjects. The most elevated levels of alpha-TNF were found in patients with inflammatory or autoimmune diseases. Comparable serum levels of alpha-TNF were detected in normal control subjects, patients with multiple sclerosis, and patients with degenerative neurological diseases. In patients with multiple sclerosis, alpha-TNF levels were also unrelated to time elapsed between the occurrence of clinical exacerbation and the time of sample collection. Only 3 patients with chronic progressive multiple sclerosis had detectable alpha-TNF in the cerebrospinal fluid. Our data do not support a role for elevated levels of circulating alpha-TNF in the maintenance of the disease. However, we cannot rule out the possibility that a transient elevation of alpha-TNF triggers the cellular events leading to demyelination in multiple sclerosis.

Adolescent↗
PubMed1990

Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis.

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.

Adult↗
PubMed1994

Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit.

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis possess immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti-voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore-forming alpha 1 subunit of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel alpha 1 subunit-directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both alpha 1 and beta subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.

Amyotrophic Lateral Sclerosis↗