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PubMed2002

Current concepts in multiple sclerosis: Part I.

Multiple sclerosis (MS) is a complex and challenging autoimmune disease of the central nervous system, affecting approximately 0.1% of the US population. Evidence to date suggests that viral infection triggers autoimmune attack against nerve cells in genetically-susceptible individuals. Neurologic deficits then appear, typically with a variable course and episodes of remission. Partial treatment success has been obtained with immunomodulating agents, such as interferon-beta and intravenous immunoglobulins. Current research is directed at elucidating potential viral causes of MS, as well as the interaction of host genes with the immunopathogenic mechanisms involved in MS. In the future, it may be possible to vaccinate susceptible individuals against MS, as well as refine immunomodulation therapy for the treatment of MS.

Humans↗
PubMed1990

Effect of low saturated fat diet in early and late cases of multiple sclerosis.

144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.

Activities of Daily Living↗
PubMed1983

Depressive episodes in patients with multiple sclerosis.

Thirty multiple sclerosis patients were assessed: 15 with predominantly cerebral involvement of their demyelinating disease and 15 with predominantly spinal cord and cerebellar involvement. The groups were matched with regard to age, duration of illness, and Kurtzke disability scores. Assessment included neuropsychological testing, the Beck Depression Inventory, and a psychiatric interview patterned after the Schedule for Affective Disorders and Schizophrenia. A group of normal volunteers served as controls for the neuropsychological testing. There were significantly more major depressive episodes in the cerebral group, as assessed by the patients' histories and by interview, and there was a trend toward more depressive symptoms in this group, as measured by the Beck inventory.

Adult↗
PubMed2003

[Glatiramer acetate (Copaxone) influence on different stages of multiple sclerosis pathogenesis].

Multiple sclerosis (MS)--autoimmune disease of CNS, characterized by myelin destruction and axonal damage. The action of drugs recommended for its treatment [symbol: see text] aimy[symbol: see text] at the reduction of the autoimmune responses. These responses lead to the neurological damage. One of immunoregulators is glatiramer acetate--Copaxone. Copaxone acts at different phases of MS pathogenesis and probably has a neuroprotective action. Copaxone reduces the rate of relapses and leads to clinical stabilisation in cases of relapsing-remmiting MS. Its efficacy and safety has been confirmed in long-term clinical and MRI-trials. Copaxone has few side-effects that are non-significant.

Adjuvants, Immunologic↗
PubMed1982

Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients.

Multiple sclerosis (MS) and matched control sera had similar antibody titers to coronaviruses OC43 and 229E when tested by a radioimmunoassay method. In contrast, cerebrospinal fluid from MS patients contained coronavirus antibodies more frequently and in higher titers than matched controls. Intrathecal antibody synthesis to OC43 and 229E viruses was detected in 41% (9/22) and 26% (7/27) of MS patients, respectively, but was not found in any of the neurologic control patients. This intrathecal antibody synthesis may mean that coronaviruses play an etiologic or pathogenic role in MS. Alternatively, intrathecal synthesis of coronavirus antibodies may be but part of a generalized and variable intrathecal antibody synthesis that is typical for MS patients.

Antibodies, Viral↗
PubMed2000

Partial synergy of bisindolylmaleimide with apoptotic stimulus in antigen-specific T cells--implications for multiple sclerosis.

In multiple sclerosis (MS), induction of T cell apoptosis constitutes a promising therapeutic strategy. Recently, bisindolylmaleimide has been shown to be an effective treatment of experimental autoimmune encephalomyelitis, presumably due to enhancement of CD95-mediated T cell apoptosis. Therefore, we studied the effects of bisindolylmaleimide on human (auto)antigen-specific T cells. We observed a synergistic effect of bisindolylmaleimide with apoptotic stimulus assessed via caspase activity and annexin V-binding, but no potentiation of DNA fragmentation or cell death. Thus, bisindolylmaleimide might be useful for modulating T cell apoptosis, yet more potent substances have to be generated re-establishing immunological control over auto-reactive T cells.

Annexin A5↗
PubMedDate not supplied

Diagnostic techniques in multiple sclerosis.

Although multiple sclerosis (MS) has been an area of great interest and effort in numerous scientific disciplines, its etiology, pathogenesis and therapy remain mysterious. Perhaps the most significant advances have resulted from the ability to be more precise in establishing the diagnosis of MS. Among the most important of the new diagnostic tools are electrophysiological techniques for examination of the visual and oculomotor systems. Tests such as the visually evoked potential (VEP) can confirm the existence of clinically suspected lesions and document the presence of asymptomatic ones. Various electrophysiological techniques for detection and evaluation of MS, as well as CSF analysis, psychological and neuroradiological procedures, and immunological observations are described. The relationship between optic neuritis and MS is reviewed, as are therapeutic regimens in use and under study.

Body Temperature↗
PubMed2004

No evidence of pancreatic autoimmunity among patients with multiple sclerosis.

Although multiple sclerosis (MS) usually appears isolated from other autoimmune disorders, an overlap with type 1 diabetes mellitus (T1DM) has been described in Sardinia, where T1DM-associated haplotype HLA-B18-DR3-DQ2 contributes to MS risk. To determine whether in our population MS patients show signs of pancreatic autoimmunity and share this haplotype, sera from 49 MS patients were tested for GAD, IA2, and CPH autoantibodies, and MICA exon 5 polymorphism was genotyped in 30 patients. Pancreatic autoimmune markers were not present among MS patients, nor was any MICA allele associated with MS. Overall, there is no evidence supporting a T1DM/MS overlap in our population.

Adult↗
PubMed2004

IgA antibodies against gliadin and gluten in multiple sclerosis.

BACKGROUND: Multiple changes in antibodies against various antigens are found in multiple sclerosis (MS). OBJECTIVE: We wanted to measure immunoglobulin A (IgA) antibodies to some common food antigens in MS and also IgG against gliadin and gluten. METHODS: The IgA antibodies were measured in serum against gluten, gliadin, lactoglobulin, lactalbumin, casein and ovalbumin in patients with MS and controls using ELISA technique. IgG was likewise measured for gluten and gliadin. RESULTS: Highly significant increases compared with controls were found for IgA and IgG antibodies against gliadin and gluten. IgA antibodies against casein were significantly increased. Anti-endomycium and anti-transglutaminase antibodies were negative. CONCLUSIONS: The data presented indicate that there may be a possible moderately increased uptake of some specific proteins from the gut in MS compared with controls.

Adult↗
PubMed1998

A happy state of mind: a history of mild elation, denial of disability, optimism, and laughing in multiple sclerosis.

Although multiple sclerosis (MS) is often looked on as a disorder of the sensory and motor systems, it can also be associated with changes in emotion and personality. Many patients with MS seem cheerful, optimistic about the future, and strangely unconcerned about their ongoing physical deterioration. In addition, patients with MS have a tendency to break into uncontrollable laughing, even when they have no reason to be happy. This article looks at how these seemingly upbeat affective changes were viewed by early researchers of MS, including Cruveilhier, Charcot, and Moxon during the 19th century and Cottrell, Wilson, and Ombredane in the 1920s. Frequently cited studies on the emotional correlates of MS from the mid-20th century are also presented, and some trends in the more recent literature are identified.

Affect↗
PubMed2005

Imaging the optic nerve in multiple sclerosis.

Although multiple sclerosis (MS) frequently involves the optic nerves, imaging this structure is not yet performed routinely in clinical practice. The recent improvement of magnetic resonance (MR) technology and the development of new MR strategies, capable of providing an, in vivo, overall assessment of MS pathology has allowed objective metrics to be obtained for monitoring disease evolution, essentially in the brain. However, despite this progress, the correlation between brain MR metrics of the disease and clinical disability are still disappointing. An objective and accurate estimate of the presence and extent of optic nerve involvement might help to overcome this clinical/MRI paradox. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of optic nerve damage in MS.

Atrophy↗
PubMed2006

Contribution of peptides to multiple sclerosis research.

Multiple sclerosis (MS) is an autoimmune disease associated with chronic inflammatory demyelination of the central nervous system in genetically susceptible individuals. Because of the disease complexity and heterogeneity, its pathogenesis remains unknown despite extensive research efforts, and specific effective treatments have not yet been developed. Peptide-based research has been important in attempts to unravel particular aspects of this complex disease, including the characterization of the different molecular mechanisms of MS, with the goal of providing useful products for immune-mediated therapies. In fact, in the past decade, peptide-based research has been predominant in research aimed to identify and/or develop target antigens as synthetic probes for specific biomarkers as well as innovative immunomodulating therapies. This review presents an overview of the contributions of peptide science to MS research and discusses future directions of peptide-based investigations.

Animals↗
PubMed2004

Measurement of spinal cord atrophy in multiple sclerosis.

In multiple sclerosis (MS), the spinal cord is a common area of involvement, and its dysfunction is likely to be responsible for much of motor disability. It has been reported that atrophy in the cervical spinal cord occurs early and is detectable in patients presenting with a clinically isolated syndrome. This finding has important implications for the early treatment of patients with MS because atrophy is thought to reflect destructive, irreversible pathology and subclinical impairment. Recent clinical trials of disease-modifying agents have included spinal cord imaging and, in particular, the measurement of atrophy as a secondary or exploratory measure of treatment efficacy. This review summarizes the underlying pathology responsible for spinal cord atrophy and the methods available to measure it. The relationships between spinal cord atrophy, other magnetic resonance imaging parameters, and clinical disability are also discussed.

Atrophy↗
PubMed1987

[Immunity and catabolism of nucleic acids: the problem of multiple sclerosis?].

In multiple sclerosis (MS), exogenous or endogenous nucleic acid fragments not (or partially) catabolised inside central nervous system (CNS) could entertain an inflammatory and even demyelinating process, and delay resynthesis of myelin. So, exogenous nucleic acids could act as starting agents for acute phase. Nucleic acid material can be released by the enzymes of nucleic acid catabolism and by the antibodies to nucleic acids possibly synthesized. A preliminary approach of such hypothesis has been made by study of cerebrospinal fluid ribonuclease activity and intrathecal synthesis of antibodies to nucleic acids. These two factors are significantly different in MS and in infectious processes of CNS groups. According to our hypothesis MS could arise from a genetic defect of oligodendrocyte (ODC) acting in genome expression and consequently leading to the persistence of nucleic acid fragments. This defect of ODC might be associated to another immune defect explaining various evolutive forms of the disease.

Antibodies, Antinuclear↗
PubMed2002

Multiple sclerosis update.

Multiple sclerosis (MS) is the most common cause of neurological disability in young European and North American adults. It is defined as dysfunction in different parts of the central nervous system at different points in time. The etiology is likely autoimmune, resulting from environmental and genetic factors. This article summarizes the symptoms, progression, diagnosis, and treatment of MS. MRI and CSF studies have been extremely helpful in identifying individual cases, but the diagnosis remains a clinical diagnosis, and one of exclusion. Methylprednisolone remains the preferred treatment for acute relapses, although plasma exchange has been shown to be helpful in cases when methylprednisolone has failed. Preventive immunomodulatory treatments are the focus of many current research efforts. Although these treatments have been shown to reduce the frequency of MS attacks, the reduction is modest, at 30%. The data that these drugs alter the progression of disability is less compelling.

Adjuvants, Immunologic↗
PubMed2001

T cells, cytokines, and autoantigens in multiple sclerosis.

In multiple sclerosis (MS), inflammatory demyelination in the central nervous system is thought to be initiated by T cells that recognize myelin antigens. T cells are the main regulators of acquired immunity and are involved in the pathogenesis of several organ-specific autoimmune diseases. This review provides an overview of recent studies on the role of T cells in autoimmune demyelination. Because autoreactive T cells are normally present in the mature repertoire of T cells in the blood and lymphoid organs of MS patients, but also in normal controls, particular attention is devoted to the mechanisms of activation and the functional phenotype of such T cells in patients with MS. The role of cytokines as effector molecules and the main candidate antigens are also discussed.

Amino Acid Substitution↗
PubMed2001

Targeting the chemokine system for multiple sclerosis treatment.

Multiple sclerosis (MS) is the most common demyelinating disorder of the human central nervous system (CNS). The typical pathological hallmark of active MS is the presence of inflammatory foci disseminated in the CNS. It is believed that the composition of inflammatory infiltrates is determined in part by the spectrum of chemokines produced in a focus of inflammation. Numerous studies suggest chemokine involvement in MS pathogenesis. Interfering with chemokine-chemokine-receptor interactions may potentially lead to prevention and/or amelioration of CNS inflammatory processes. Initial studies to obtain 'proof-of-principle' used neutralizing antibodies in small animal models of MS. The subsequent generation of chemokine receptor inhibitors were modified chemokine peptides. At present, the development of small molecule antagonists to chemokine receptors is the dominant approach. Current evidence suggests that chemokines and their receptors are promising targets for effective treatment of MS and other CNS inflammatory and autoimmune diseases.

Animals↗
PubMed1989

Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis.

Sixty multiple sclerosis (MS) patients (33 definite, 13 probale and 14 suspected were investigated by computed tomography (CT), magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid (CSF) electrophoresis. MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases. Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brain-stem involvement. All the patients with oligoclonal bands had abnormal MRI and none of the patients with normal MRI had oligoclonal bands in the CSF. The number and the extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability. Our observations stress the importance of the combined use of MRI and EPs in detecting silent CNS lesions in MS patients.

Adult↗