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At least 1,243 records · Page 69Linked to original sources
PubMed1984

Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia.

We evaluated 16 Guamanian Chamorros with amyotrophic lateral sclerosis and 33 patients with parkinsonism-dementia for disturbances of calcium and vitamin D metabolism. The serum immunoreactive parathyroid hormone level was mildly elevated in 6 patients with amyotrophic lateral sclerosis and in 5 patients with parkinsonism-dementia. There were significant positive correlations between serum immunoreactive parathyroid levels and duration of illness in male patients with motor neuron disease, but not in female patients or in patients with parkinsonism-dementia. Intestinal absorption of calcium, as assessed by serum and urinary activity of calcium 47 following oral administration, was decreased in 2 patients with amyotrophic lateral sclerosis and in 4 patients with parkinsonism-dementia, all of whom had low levels of serum 1,25-dihydroxyvitamin D. Reductions in cortical bone mass were striking in patients with motor neuron disease. A significant negative correlation was found between the percentage of cortical area of the second metacarpal bone and muscle atrophy and weakness, and significant positive correlations were found between degree of immobility and ratio of urinary hydroxyproline to creatinine in patients with amyotrophic lateral sclerosis and parkinsonism-dementia. In general, abnormalities in calcium metabolism were subtle. Thus, if the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.

Adult↗
PubMed1986

Absence of antibody to HTLV I and III in sera of Canadian patients with multiple sclerosis and chronic myelopathy.

Recently, elevated titers of antibody to HTLV I have been demonstrated in patients with tropical spastic paraparesis and multiple sclerosis. We evaluated the possible role of human retroviruses HTLV I and III in Canadian patients with multiple sclerosis and chronic idiopathic myelopathy. Using sensitive enzyme immunoassays, we were unable to find antibody to either HTLV I or III in 201 patients with multiple sclerosis, 29 patients with chronic myelopathy, 51 patients with other neurological disorders, or 29 normal subjects. These data do not support a role for these viruses in the cause of sporadic multiple sclerosis and chronic myelopathy in a regionally based Canadian population, but do not exclude a role for other antigenically distinct retroviruses.

Antibodies, Viral↗
PubMed1987

Multiple sclerosis disease activity correlates with gadolinium-enhanced magnetic resonance imaging.

Magnetic resonance imaging provides a method of visualizing multiple sclerosis plaques, but the age and activity of these plaques cannot be determined with routine magnetic resonance images. Gadolinium DTPA is a paramagnetic contrast agent that does not cross an intact blood-brain barrier. We studied 16 patients with multiple sclerosis, using magnetic resonance imaging, gadolinium-enhanced magnetic resonance imaging, and computed tomographic scans. Gadolinium enhancement of multiple sclerosis plaques correlated with the clinical activity of the disease and corresponded anatomically with the symptoms and signs. We conclude that gadolinium enhancement of magnetic resonance images is a promising tool in the investigation of multiple sclerosis lesions and that it may provide a method for objective follow-up in clinical trails.

Adult↗
PubMed1987

Myelin-associated glycoprotein in multiple sclerosis lesions: a quantitative and qualitative analysis.

Myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and proteolipid protein (PLP) were quantitated by immunoassays in nine plaque, inner periplaque, outer periplaque, and normal-appearing white matter regions from brains of five multiple sclerosis patients and compared with the levels found in white matter samples of control subjects matched for age, postmortem time, and brain region. In plaque and inner periplaque regions, all three proteins were substantially reduced due to extensive myelin loss. In outer periplaque regions, MBP and PLP were close to control levels, but MAG was significantly reduced to a mean of 57% of control. All three proteins were close to control levels in the normal-appearing white matter samples. MAG in the various regions was qualitatively examined on Western blots by binding of lectins and by immunostaining with polyclonal and monoclonal antibodies against carbohydrate and protein epitopes of MAG. Densitometric scanning of these blots did not reveal any qualitative differences in the oligosaccharide or polypeptide moieties of MAG between samples from control subjects and those from multiple sclerosis patients. However, a high proportion of the MAG in the multiple sclerosis samples was often in the form of dMAG, a proteolytic derivative of MAG that is formed by a myelin-associated, Ca2+-activated, neutral protease. The preferential loss of MAG at the periphery of multiple sclerosis plaques may be initiated by its proteolytic conversion to dMAG.

Adult↗
PubMed1988

Immunotherapy of multiple sclerosis.

Based on the assumption that multiple sclerosis is an autoimmune disease, a number of clinical trials designed to suppress the immune system or to restore immune balance in multiple sclerosis have been attempted. Depending on the disease category, the clinical goals of immunotherapy differ. Therapeutic goals include improving recovery from acute attacks, preventing or decreasing the number of relapses, and halting the disease in its progressive stage. The ultimate goal of multiple sclerosis therapy is the early treatment of patients in an attempt to halt the onset of progression. Specific strategies of immunotherapy include generation of a suppressor influence, removal of helper/inducer cells, manipulation of activated T cells, manipulation of class II major histocompatibility complex-bearing cells, alteration of lymphocyte traffic, extracorporeal removal of serum factors or cells, and manipulation of antigen-specific cells. Present treatment modalities are beginning to show some efficacy of nonspecific immunosuppression, but these treatments are limited by their toxicities. As the immunotherapy of multiple sclerosis moves to the next stage in the coming years, patients at an earlier stage of their disease will have to be treated, nontoxic forms of therapy developed, clinical trials lengthened, and a laboratory monitor of the disease developed. Given the positive effects of immunotherapy seen thus far in the disease, it is possible that appropriate immunotherapeutic intervention may provide effective treatment for the disease in the future.

Autoantibodies↗
PubMed1989

The prevalence of primary Sjögren's syndrome in a multiple sclerosis population.

A central nervous system illness closely resembling multiple sclerosis has been described in patients with primary Sjögren's syndrome. From these reports, the estimated prevalence of this syndrome could be similar to that of multiple sclerosis in a high-frequency area. We evaluated 192 consecutive patients in our multiple sclerosis clinic to determine if such cases had gone unrecognized. We did not find any patients with clinical or serological evidence of primary Sjögren's syndrome. We conclude that it is rare for neurological manifestations of Sjögren's syndrome to mimic multiple sclerosis in our population.

Adult↗
PubMed1989

Galactosylceramide: a reliable serum index of demyelination in multiple sclerosis.

Eight patients with multiple sclerosis were followed for several months to determine if serum levels of galactosylceramide, a major lipid component of myelin, correlate with the clinical evolution of the disease. In the patients with the chronic progressive form of multiple sclerosis, galactosylceramide remained undetectable. In the patients with relapsing-remitting multiple sclerosis, there was a good correlation between the elevation of serum galactosylceramide levels and clinical relapses. This serum assay should prove of value in the follow-up of patients with multiple sclerosis.

Adult↗
PubMed1990

Elevated soluble interleukin-2 receptor levels in patients with active multiple sclerosis.

The level of soluble interleukin-2 receptor (sIL-2R) was quantitated with enzyme-linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL-2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL-2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL-2R level may be useful in evaluating disease activity in patients with multiple sclerosis.

Adult↗
PubMed1991

The predictive value of intrathecal immunoglobulin synthesis and magnetic resonance imaging in acute isolated syndromes for subsequent development of multiple sclerosis.

The intrathecal synthesis of IgM in patients presenting with acute monosymptomatic syndromes may be relevant in predicting eventual progression to multiple sclerosis but has not been previously evaluated. We undertook a prospective 18-month combined clinical, cerebrospinal fluid, and magnetic resonance imaging study of 45 patients who had presented with acute isolated lesions of brainstem and spinal cord to evaluate the predictive value of intrathecal synthesis of IgM and IgG (through the detection of cerebrospinal fluid oligoclonal bands) and magnetic resonance imaging brain lesions at presentation, for the subsequent progression to multiple sclerosis. Results indicate that the highest risk of developing multiple sclerosis is seen in patients who are positive for oligoclonal IgM and IgG bands and who have disseminated cerebral white matter magnetic resonance imaging lesions at the initial presentation. Oligoclonal IgM bands predict progression to multiple sclerosis more frequently than oligoclonal IgG or magnetic resonance imaging alone. Our results confirm and further extend previous reports, and indicate that detection of cerebrospinal fluid oligoclonal IgM bands at presentation is a valuable prognostic indicator in patients presenting with acute isolated brainstem or spinal cord syndromes.

Acute Disease↗
PubMed1992

Multiple sclerosis in children: cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo.

In vivo proton magnetic resonance spectroscopy of 8 children (7-16 years) with established multiple sclerosis revealed distinct alterations in regional cerebral metabolism associated with different aspects of the disease: (1) Localized proton spectra (2 to 4-ml volumes of interest) from multiple sclerosis plaques were generally characterized by a decrease in N-acetylaspartate and creatine, and an increase in cholines and myo-inositol relative to age-matched control subjects, (2) neither chronic nor enhancing plaques (by gadolinium-diethylenetriamine pentaacetic acid) during an acute exacerbation showed elevated levels of lactate or lipids, (3) spectra from adjacent white matter that did not appear suspicious in magnetic resonance images were similar to those of normal control subjects, and (4) cortical gray matter related to neighboring multiple sclerosis lesions showed a notable reduction of N-acetylaspartate. The present results show that functional impairment in multiple sclerosis is linked to gross metabolic disturbances of neuronal cell chemistry. We suggest that focal demyelination is accompanied by increased membrane precursors of proliferative turnover and is associated with secondary neuronal shrinkage or loss, perhaps extending into related cortical gray matter.

Adolescent↗
PubMed1993

Increased levels of circulating intercellular adhesion molecule-1 in multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy.

We evaluated the presence of soluble intercellular adhesion molecule-1 (sICAM-1) antigen in the sera of patients with multiple sclerosis and human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay. Patients with multiple sclerosis in the active phase had higher sICAM serum levels than did control subjects (p < 0.01). In addition, a significantly increased serum level of sICAM-1 was found in patients with HAM (p < 0.001). Furthermore, we found a positive correlation with HAM sICAM-1 and tumor necrosis factor-alpha levels in the sera of patients with multiple sclerosis in the active phase (r = 0.88, p < 0.01) and in those with HAM (r = 0.86, p < 0.01). These results suggest that serum sICAM-1 may be related to clinical activity in patients with multiple sclerosis and the detection of sICAM-1 could be useful as a marker of inflammatory disease.

Adult↗
PubMed1994

Concentric sclerosis (Baló): morphometric and in situ hybridization study of lesions in six patients.

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.

Adult↗
PubMed1994

Establishment and use of multiple sclerosis registers--EDMUS.

EDMUS, the European Database for Multiple Sclerosis, is a clinical database system for multiple sclerosis (MS) that was established on the occasion of the first European Concerted Action for MS, under the auspices of the Commission of the European Communities. Automated functions have been incorporated in the program to preserve consistency between data, generate indexes, provide classifications, and protect a patient's privacy. Retrieval of data, selection of records, and export of selected data to standard software programs are easy. The system is user-friendly, and the user is self-sufficient in all operations. The system has been available since October 1992. By August 31, 1993, it had been implemented in 58 sites. As improvements are made in current operations and new aspects of the disease described, EDMUS is updated. A connection with the North American MS-COSTAR database system for MS is underway, with support of the International Federation of the Multiple Sclerosis Societies. Several international multi-center collaborations are being developed within the framework of a new 3-year European Concerted Action entitled "Establishment and Use of EDMUS as a Database System for Multiple Sclerosis Research in Europe."

Europe↗
PubMed1996

Difficulties in distinguishing sporadic from familial amyotrophic lateral sclerosis.

Mutations of the copper/zinc superoxide dismutase (SOD-1) gene are present in around 20% of patients with a family history of amyotrophic lateral sclerosis. The finding of these mutations in patients with sporadic amyotrophic lateral sclerosis is rare. We describe a family with amyotrophic lateral sclerosis associated with the SOD-1 mutation Asp 101 Asn. This mutation was previously described as occurring in a patient with sporadic disease. We discuss the difficulties in defining truly sporadic amyotrophic lateral sclerosis, and the consequent implications on the neurogenetic advice given to other family members.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

A test of the relationship between health locus of control and the course of multiple sclerosis.

This study explored the relationship between health locus of control and the trajectory of multiple sclerosis. A random sample of 100 respondents with multiple sclerosis was selected from the membership list of a state multiple sclerosis support group. The subjects were interviewed in their homes and completed study instruments. Respondents with an internal health locus of control orientation had more knowledge of their disease, practiced more self-care, and had a more benign course of multiple sclerosis than those with an external locus of control. Additional findings included an overall lower divorce rate for the respondents as well as a poor employment outlook.

Activities of Daily Living↗
PubMed1995

Spontaneous and induced remyelination in multiple sclerosis and the Theiler's virus model of central nervous system demyelination.

Remyelination in the central nervous system, originally thought to occur rarely, if ever, is now an established phenomena in multiple sclerosis patients. However, the extent of myelin repair is incomplete and limited. Experimental models of central nervous system demyelination provide an opportunity to study the cellular and molecular events involved in remyelination. These models may provide some clue to why remyelination in multiple sclerosis is incomplete as well as suggest potential methods to stimulate central nervous system repair. In this review we examine the morphological aspects of central nervous system remyelination and discuss both spontaneous and induced remyelination in multiple sclerosis and experimental models of central nervous system demyelination. We give special emphasis to the Theiler's virus model of central nervous system demyelination and its usefulness to identify therapeutic agents to promote remyelination. The role of immunoglobulins in promoting remyelination in both the Theiler's model system and in multiple sclerosis is discussed. Finally, we examine the potential physiological role of demyelination and remyelination and its relationship with clinical manifestations of central nervous system disease.

Animals↗
PubMed1998

A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients.

Magnetization transfer and T2 relaxation data were obtained for five white and six gray matter brain structures from 10 normal volunteers and 9 multiple sclerosis patients. Thirty MS lesions were also analyzed. Magnetization transfer ratios and myelin water percentages were compared. Both techniques showed a significant difference between the average of white and gray matter of the normal volunteers as well as the average of normal-appearing white matter and gray matter of the multiple sclerosis patients. The average magnetization transfer ratio and myelin water percentage for lesions were significantly lower than those of normal-appearing white matter. Myelin water percentages and magnetization transfer ratios were uncorrelated in white and gray matter but showed a small (R = 0.5, P = 0.005) but significant correlation in multiple sclerosis lesions. In summary, the myelin water percentage and the magnetization transfer ratio provide quantifiable but largely independent measures of multiple sclerosis lesion pathology.

Adult↗
PubMed2004

Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients.

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system. Disease mechanisms in multiple sclerosis at the molecular level remain poorly understood and no reliable proteinaceous disease markers are available yet. The goal of the present study is the construction of a protein database of two-dimensional gel electrophoresis (2-DE) separated cerebrospinal fluid (CSF) proteins from multiple sclerosis patients. By means of liquid chromatography tandem mass spectrometry 65 different proteins were identified from 300 spots. Eighteen of these proteins have not been reported previously on 2-DE gels of CSF. Here we report on the identification of these proteins and discuss their potential relation to multiple sclerosis.

Amino Acid Sequence↗