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PubMedDate not supplied

Experimental therapies for multiple sclerosis: current status.

Multiple sclerosis is the most common cause of nontraumatic disability affecting young adults in the United States. Its etiology remains unclear, but evidence points to alteration of normal immune system function in the pathogenesis of this illness. This article reviews the results of clinical trials of experimental therapeutic agents in multiple sclerosis. The background and action of each treatment are described, and the clinical experience with each agent is reviewed. Obstacles to evaluating the effectiveness of treatment methods in MS and challenges to the design of future clinical trials and the interpretation of trial outcomes are discussed.

Azathioprine↗
PubMed2004

The influence of immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis.

OBJECTIVES: In multiple sclerosis (MS), several neuroimmunomodulatory effectors are known, including melatonin. They are able to influence disease-related neurophysiogical changes (disability or impaired vision) as well as neuropsychological performance (e.g. cognition and depression). In this study we assessed the relationship between immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis. METHODS: We evaluated 26 young female patients with benign MS treated with/without immunomodulating therapies with regard to their physical disabilities (Expanded Disability Status Scale, EDSS), their visually evoked potentials (VEP), their plasma melatonin concentrations as well as their performance regarding emotional and cognitive tests and compared them with healthy matched controls. RESULTS: Patients with MS showed deficits in cognitive and emotional functions compared to healthy controls, which were in accordance with their increase in EDSS over time. However, in contrast to untreated patients, patients receiving immunotherapy showed significantly increased dysfunction with respect to actual mood (p = 0.02) and a tendency to increased depression scores (p = 0.072). However, neither treatment subgroup had cognitive deficits. In untreated patients, melatonin levels correlated with reduced scores in the cognitive tests (p = 0.045) but not with depression or VEP latencies. Patients with long-standing MS (>10 years) showed a significant correlation (p = 0.01) to their increased depression scores and their melatonin levels, but no correlation with VEP or cognitive dysfunction, compared to patients with shorter disease duration (< or =10 years). CONCLUSION: These results indicate that in MS all aspects of the psycho-neuroimmunological network can be affected. Despite the potential influence of immunomodulation on depression, no connection with melatonin representing the retinohypothalamic tract/pineal gland circuits could be detected. However, visual perception as well as visuoconstructive abilities were affected in MS patients. Neuropsychological tests in MS should concentrate on cognitive variables, which reflect the clinical status more accurately and may be used to monitor disease-modifying therapies.

Adult↗
PubMedDate not supplied

Changes in neurotransmitters in multiple sclerosis.

Patients with multiple sclerosis were found to have increased cerebrospinal fluid, noradrenaline, and excitatory amino acid (glutamate and aspartate) levels, with increased blood glutamine, asparagine, and glycine levels. An association was found between these biochemical parameters and the nature and severity of neurological symptoms, as well as with the course of the disease. Neurotransmitters are proposed to have a role in the pathogenesis of multiple sclerosis, particularly in the biochemical mechanisms of the relationship between the nervous and immune systems, as well as in the neurochemical mechanisms underlying the development of neurological deficit.

Adolescent↗
PubMed1978

Cranial CT appearance of acute multiple sclerosis.

In acute multiple sclerosis, cranial computerized tomography (CT) may show periventricular and deep white matter contrast-enhanced lesions that are easier to see using 8 mm rather than 13 mm cranial CT sections. Follow-up studies show that the lesions evolve either to areas of density similar to the surrounding white matter or to low-density lesions. We presume they represent foci of active demyelination with extravasation of iodine through an altered blood-brain barrier. Enhanced cranial CT studies may be helpful in diagnosing acute multiple sclerosis and in following the course of the white matter lesions.

Acute Disease↗
PubMedDate not supplied

[Clinical features of relapsing remitting-multiple sclerosis. Prognostic factors].

Multiple sclerosis is the most frequent chronic neurological disease in young adults of the white population in developed countries. The diagnosis has been notably improved by the use of universal diagnostic criteria and by the extraordinary help of the paraclinical methods of laboratory studies, evocated potentials and particularly magnetic resonance imaging. Nowadays there are consensus criteria for the classification of the different clinical subtypes. Relapsing remitting multiple sclerosis is the most frequent subtype and eventually evolves to a secondary progressive form. Ultimately there have been notably advances in the knowledge of the natural history and of the pathogenetic mechanisms of the disease, which has permitted a more precocious therapeutic intervention, that ideally will provide a more benign prognosis for this disease.

Age of Onset↗
PubMed1998

[Endogenous retroviral sequences analogous to that of the new retrovirus MSRV associated with multiple sclerosis (part 1)].

Multiple sclerosis (MS) is still of unknown origin and may involve autoimmune, genetic and viral components in a pathogenic sequence whose relative importance is yet to be determined. A peptide, isolated from the cerebrospinal fluid of MS patients, is similar to a fragment of the pol protein reverse transcriptase (RT) of the newly reported MSRV retrovirus. The 700 amino acid sequence of MSRV-RT is closely related to a novel human retroviral-like sequences. We also identified a gag-like sequence upstream of this human genomic RT-like sequence, which allowed us to identify altogether 4,000 nucleotides, possibly coding for an endogenous retroviruses. Homologous sequences found in other locations in the human genome seem to characterize a new family of retroviral endogenous sequences, which may be of relevance to multiple sclerosis.

Amino Acid Sequence↗
PubMed1994

Histopathology and the blood-cerebrospinal fluid barrier in multiple sclerosis.

Histopathology of multiple sclerosis is defined by a chronic inflammatory process and the presence of large confluent plaques of demyelination. Ongoing disease activity is due to an active inflammatory process, mainly mediated by T lymphocytes and macrophages, and is associated with blood-brain-barrier damage. B lymphocytes and plasma cells are present especially in the lesions that occur during the late chronic stage of the disease. Although all plaques are characterized by demyelination, the patterns of oligodendroglia destruction and of damage to other tissue elements, such as axons and astrocytes, are variable in different cases. Oligodendrocytes are less affected by plaques that develop during the first bouts of the disease than by those plaques arising after several years of disease duration. Our data indicate that mechanisms of plaque formation may vary in different multiple sclerosis patients and in different stages of the disease process.

Acute Disease↗
PubMed1996

Analysis of polymorphisms of the 2',3'-cyclic nucleotide-3'-phosphodiesterase gene in patients with multiple sclerosis.

Susceptibility to multiple sclerosis (MS) is widely held to have a genetic component. Possible candidate genes conferring this susceptibility include those coding for proteins specific to central nervous system (CNS) myelin. 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) is an enzyme found at high concentrations in CNS myelin, however its function is unknown. The amino acid sequence of CNPase shows a C-terminal motif characteristic of proteins involved in signal transduction pathways, suggesting a key role in myelin function. We have analysed the entire expressed sequence of the human CNPase gene in patients with multiple sclerosis and in healthy controls using single strand conformation polymorphism (SSCP) analysis. Nine previously undescribed mutations were detected, most of these occurred with equal frequency in both groups. However, a T-->C transition at nucleotide position 4306 in the region of the gene coding for the 3' untranslated region of the mature mRNA was found in a homozygous form in two out of 54 patients but in none of 100 controls. While the significance of this is unclear, it would appear unlikely that mutations in the expressed regions of the human CPNase gene contribute to genetic susceptibility to MS in the majority of sufferers.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

Multiple sclerosis--Indian experience.

Multiple sclerosis (MS) does occur in India but it is rare. No epidemiological studies have been done. The calculations based on the hospital data suggest an approximate prevalence rate of 0.17 to 1.33 per 100,000 of population in different parts of India. One hundred and five patients with clinically definite MS (2 proven at autopsy) and 14 patients with neuromyelitis optica were seen in the Bombay region from 1957 to 1983. The mean age of onset for MS patients was 27.7 years. There were 60 female and 45 male patients. The clinical data in this larger series confirm the conclusions reached earlier, namely that the Indian MS patients are more akin to those reported from Japan and other Asian countries as compared to the West. The relative incidence of neuromyelitis optica was high (6%). The optico-spinal form of MS was the commonest (71.4%). In patients with clinically definite MS there was a high incidence of optic nerve involvement, both at the onset and during the course of the disease; sensory level occurred in a large number of patients and cerebellar involvement was less frequent. Multiple sclerosis in this series affected patients of all communities and different dietary habits. MS was more common in the higher socioeconomic group whereas neuromyelitis optica was mainly seen in patients in the low socioeconomic group.

Cerebrospinal Fluid Proteins↗
PubMedDate not supplied

[Effect of short-term administration of sunflower oil on the blood serum level of linoleic and arachidonic acids and lipids in multiple sclerosis].

Patients with multiple sclerosis had an oral load of sunflower seed oil in daily doses of 40 g during five days. This daily doses contained 27 g of linoleic acid (LA). Prior and after diet supplementation with sunflower seed oil the levels of linoleic and arachidonic acids were determined in the serum of patients. The values were expressed as relative percentages of total fatty acids. Before addition of sunflower oil to the diet the serum levels of linoleic acid (LA) and arachidonic acid (AA) were in these patients significantly lower than in controls amounting to 17.0% and 1.05% (p less than 0.001). After addition of sunflower oil the levels of LA and AA rose to 32.7% and 3.02%. The concentration of total lipids and non-esterified fatty acids in the serum increased also significantly after addition of sunflower oil. Determinations of LA and AA 10 days after withdrawal of sunflower oil showed that their levels were 23.7% and 1.95% respectively. In 2 patients addition of sunflower oil only slightly changed the very low serum LA level. These results indicate that LA and AA deficiency in patients with multiple sclerosis has the character of a non-specific dietary deficiency mainly, although the role of genetic factors controlling the levels of polyunsaturated fatty acids cannot be ruled out.

Adult↗
PubMed2006

Allelic variation investigation of the estrogen receptor within an Australian multiple sclerosis population.

UNLABELLED: Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. OBJECTIVES: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

Alleles↗
PubMed2003

Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study.

Multiple sclerosis is thought to be an autoimmune, inflammatory, cell-mediated disease. However, there is evidence suggesting that autoantibodies could play a role in the pathogenesis of multiple sclerosis. Many studies have looked for antibodies to candidate antigens such as myelin basic protein or myelin-oligodendrocyte glycoprotein, with inconclusive results. In order to determine whether antibodies to cell surface determinants on oligodendrocyte or neuronal cells were present in multiple sclerosis, we used flow cytometry to detect antibody binding to intact cultured human cell lines, comparing sera from multiple sclerosis patients with sera from patients with other inflammatory CNS diseases. Sera from healthy individuals were used to determine a normal range. Significant surface binding of IgG or IgM antibodies to oligodendrocyte precursor (OPC)-derived cell lines was seen in 50% of multiple sclerosis sera with no significant difference between secondary progressive (SPMS) and relapsing-remitting (RRMS) subgroups. In contrast, binding to a neuronal cell line, SK-N-SH, was seen with 70% of SPMS sera compared with 25% of RRMS sera (P < 0.001). No significant difference in antibody binding between multiple sclerosis sera and control sera was seen when OPCs were differentiated or when the cells were permeabilized to expose intracellular antigens. Results from all nine patients with 'benign' multiple sclerosis were indistinguishable from controls. This study represents a systematic approach to begin to define new antigenic targets in multiple sclerosis and demonstrates that antibodies to accessible antigens on the cell surface of both OPCs and neurons are present in some patients. The results lend support to the possibility that autoantibody-mediated processes are important in a subgroup of multiple sclerosis patients. Identification of the cell surface determinants to which the antibodies bind may shed light on new targets for therapeutic intervention.

Adolescent↗
PubMed1988

Borrelia burgdorferi antibodies in patients with relapsing/remitting form and chronic progressive form of multiple sclerosis.

Sera of 106 multiple sclerosis patients and 103 closely matched controls were examined for Borrelia burgdorferi antibodies. The prevalence rate in multiple sclerosis patients was 14.2%, in controls 25.2%. Overall prevalence was 20.1%. Mean IgG antibody level was insignificantly higher in controls than in multiple sclerosis patients. Patients with a chronic progressive course of multiple sclerosis had an insignificantly higher mean borrelia antibody level, when compared with those suffering from relapsing/remitting form of disease.

Adolescent↗
PubMed1976

Circulating IgE, allergy and multiple sclerosis. Serum levels of IgE, other immunoglobulins and complement (C's) in patients with multiple sclerosis in exacerbation and other neurologic diseases.

Serum levels of IgE, other immunoglobulins and C'3 were measured in 36 MS patients, and the results compared with those of 40 age- and sex-matched patients hospitalized on Neurology Service. Diagnoses among controls included cerebral infarction, cervical spondylosis, nonmigrainous headache, seizure disorders and peripheral neuropathy. Six patients in the MS group and seven in the non-MS group had a past history of allergy to food, drugs, dust or other substances. IgE levels were measured by double-antibody radioimmunoassay. Other immunoglobulins (G, M, D and A) and C'3 were quantitated by Mancini's method. Results indicate that the median IgE and C'3 levels of MS patients were slightly lower than those for non-MS subjects. Concentrations of other immunoglobulins were similar for the two groups. CSF samples from 12 MS and five non-MS patients were studied and none of these contained measureable (greater than 7.5 U/ml) IgE. In view of: 1) recent reports describing mast cells in MS plaques, 2) the suggested role of biogenic amines in the pathogenesis of demyelinating diseases, and 3) because IgE exists in free and cell bound state, it is suggested that tissue surveys of MS plaques for IgE deposits similar to those seen in glomeruli in nephrotic syndromes may provide a clue to the pathogenesis of MS.

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↗
PubMed1979

The contracting cord sign of multiple sclerosis.

A new sign of multiple sclerosis, the contracting cord sign, is described. The myelographic demonstration of a large cord that subsequently decreases in size may suggest multiple sclerosis. Multiple sclerosis must be considered in the differential diagnosis of an enlarged spinal cord. Distinguishing between the collapsing cord and the contracting cord is discussed.

Adult↗
PubMed1980

[Diagnosis and therapy of multiple sclerosis].

The diagnosis of multiple sclerosis is still a clinical one, and depends on the occurrence of neurological symptoms due to lesions at two or more necessarily distinct sites in the white matter of the central nervous system. Up to now there exists no specific laboratory test for the diagnosis of multiple sclerosis. The cerebrospinal fluid-profile strongly supporting the diagnosis of multiple sclerosis consists of: cell count slightly elevated, total protein concentration normal or slightly elevated, in the electrophoresis distinct immunreaction without disturbance of the blood-brain-barrier, i.e. significant increase of gammaglobulins and IgG, oligoclonal pattern of the gammaglobulin subfractions. Newly developed diagnosistic possibilities are based on the determination of myelin basic protein, determination of the different glycerophosphatides and on the measurement of the activity of lipid hydrolyzing enzymes. Disturbances of lipid metabolism play an important role in the course of demyelination. Therapy of multiple sclerosis by steroids and immunsuppression will be discussed.

Adrenal Cortex Hormones↗