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PubMed2004

Trends in survival and cause of death in Danish patients with multiple sclerosis.

The Danish Multiple Sclerosis Registry contains information about all Danish patients in whom multiple sclerosis has been diagnosed since 1948. The purpose of this study was to analyse trends in survival and causes of death of these patients and to compare them with those of the general population. The study comprised all patients with onset in the period 1949-1996. All case records were validated and classified according to standardized diagnostic criteria. Data on emigration and death were obtained by record linkage to official registers. The end of follow-up was 1 January 2000 for emigration and death, and 1 January 1999 for cause-specific deaths. Standardized mortality ratios and excess death rates were calculated for various causes of death and periods after multiple sclerosis onset, and time trends in survival probability were analysed by Cox regression. The study comprised 9881 patients, of whom 4254 had died before end of follow-up. The median survival time from onset was approximately 10 years shorter for multiple sclerosis patients than for the age-matched general population, and multiple sclerosis was associated with an almost threefold increase in the risk for death. According to death certificates, more than half (56.4%) of the patients had died from multiple sclerosis. They also had excess mortality rates from other diseases, except cancer, and from accidents and suicide. The probability for survival improved significantly during the observation period. Thus, the 10-year excess mortality was almost halved in comparison with that in the middle of the 1900s.

Adult↗

PubMed2001

Immunopathogenesis of the multiple sclerosis lesion.

Multiple sclerosis (MS) is thought to be an autoimmune disease with a chronic inflammatory response directed against central nervous system (CNS) myelin antigens. Immunologic studies indicate that autoreactive CD4+ lymphocytes migrate into the CNS causing blood brain barrier (BBB) disruption, an initial event in the evolution of the MS lesion. Subsequent antigen recognition within the CNS initiates inflammatory responses that, through the multiple effector mechanisms, lead to demyelination. Magnetic resonance imaging (MRI) studies provide new insights into the evolution of the MS lesion, revealing an active and continuous pathologic process that is not only localized to focal lesions, but also diffusely affects normal appearing white matter (NAWM). Standard T2-weighted images are exquisitely sensitive, showing changes due to inflammation, edema, demyelination, and axonal loss, but because of the lack of pathologic specificity, they only moderately correlate with the clinical parameters. New MRI techniques, including magnetic resonance spectroscopy, magnetization transfer, and diffusion imaging, provide a better measure of axonal loss and demyelination, the most clinically relevant components of MS lesions. Hopefully, they will enable us to more accurately monitor disease activity and evaluate the effects of new therapies on the progression of the disease.

Antigen Presentation↗

PubMed2004

Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis.

In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a "detour" circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.

Animals↗

PubMed1985

[Contribution to proton nuclear magnetic resonance imaging in multiple sclerosis. Contribution of a multiple spin echo sequence].

Single or multiple parenchymatous anomalies were detected in 48 of 49 patients with multiple sclerosis by proton magnetic resonance imaging (MRI) combined with a spin-echo sequence in the 4 planes of the section passing through the ventricular bodies. Lesions were identified in the frontal, orbital and particularly juxta-ventricular white substance, and were of variable appearance, the most common being spots in the parenchyma and juxta-ventricular bands. A limited number of sections is sufficient for the MRI study of anomalies in clinically defined multiple sclerosis, the diagnostic value of this examination suggested by these findings requiring confirmation by prospective studies.

Adolescent↗

PubMed1993

Update on multiple sclerosis therapy.

Multiple sclerosis is a demyelinating disorder of the central nervous system characterized by exacerbations and remissions of symptoms. This article deals with symptomatic therapy involving treatment of spasticity, fatigue, neurobehavioral disorders, paroxysmal disorders, pain, bladder dysfunction, and cerebellar dysfunction. This article also reviews immunosuppressive therapies including treatment of acute exacerbations or overall progression of the disorder with resultant accumulation of disability.

Amantadine↗

PubMed2003

The role of illness severity and illness representations in adjusting to multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is an incurable, chronic and unpredictable disease of the central nervous system. The purpose of this study was to investigate whether MS patients' illness representations impact on their adjustment to this debilitating illness even when controlling for the severity of their condition. METHODS: One hundred and sixty-eight MS patients completed a questionnaire booklet comprised of the Illness Perceptions Questionnaire-Revised and a range of adjustment variables including the Sickness Impact Profile, the Fatigue Scale, the Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem Scale. The severity of patients' MS was measured by the type of MS, length of illness, remission status and ambulatory ability. RESULTS: Hierarchical multiple regression analyses demonstrated that illness severity accounted for the majority of the variance in physical and role dysfunction, while patients' illness representations were the most significant predictors of levels of social dysfunction, fatigue, anxiety, depression and self-esteem. CONCLUSIONS: Patients' illness representations play a significant role in adjustment to MS. These results suggest that a psychological intervention, which addresses patients' illness representations, may assist in their adjustment to MS.

Adaptation, Psychological↗

PubMed1983

Reaction time deficit in multiple sclerosis.

50 multiple sclerosis (MS) patients were evaluated, according to an objective weighting scale measuring neurologic deficit, and investigated with continuous reaction time (CRT). Compared to a group of 105 controls, the reaction times of the MS patients were significantly delayed. The CRT method could correctly classify 80% of the controls and 72% of the patients. The CRT was especially sensitive for patients in the progressive phase of the disease and independent of dyscoordination.

Adult↗

PubMed2002

[Cause of familial multiple sclerosis].

The multiple sclerosis was described in 3 persons of a family, in the mother and her two adult sons. In the report the necessity of MRI examination was emphasized when the neurological signs and symptoms appeared in the family of MS victim. The initiation of the immunomodulatory therapy in the early stage of the disease is an important step to influence the natural unfavourable course of the disease.

Adjuvants, Immunologic↗

PubMed2005

Relapsing-remitting tumefactive multiple sclerosis.

Tumefactive multiple sclerosis (MS) is a rare form of demyelinating disease. The natural course of the disease has been characterized as presenting with a mass-like demyelinating lesion converting to typical relapsing-remitting disease with future exacerbations. Herein we describe a case of a patient whom over a six-year period developed relapsing-remitting tumefactive MS. The natural course, pathophysiology, prognosis and diagnosis are briefly discussed.

Demyelinating Diseases↗

PubMed1998

Restricted use of VH4 germline segments in an acute multiple sclerosis brain.

Multiple sclerosis (MS) cerebrospinal fluid and brain contain increased IgG and oligoclonal bands. Whether this oligoclonal and polyclonal IgG is directed against a disease-relevant antigen remains unknown. To distinguish between random activation versus a targeted B-cell response, we analyzed the IgG heavy chain variable region (VH) repertoire expressed in different lesions of an acute MS brain. To obtain a representative sample of the VH repertoire, we constructed directional complementary DNA libraries from plaque-periplaque messenger RNA and amplified VH regions from the library by nested polymerase chain reaction. When MS VH sequences were aligned to germline segments, about 60% of different VH sequences in the acute MS brain were VH4 germline segments, significantly greater than the known approximately 20% VH4 germline prevalence. Specific VH sequences were overrepresented and expressed at multiple plaque sites. Within some overexpressed populations, there were distinct sequence differences (clonal variants) indicative of clonal expansion. Alignment of VH sequences to their closest germline counterparts revealed extensive somatic mutation and the preferential accumulation of amino acid replacement mutations in complementarity determining regions. These observations suggest the limited B-cell response found in this acute MS brain was antigen driven.

Amino Acid Sequence↗

PubMed1980

Double-blind, controlled trial of immunosuppression in treatment of multiple sclerosis.

30 multiple sclerosis patients in a double-blind, controlled trial were given immunosuppressive treatment consisting of antilymphocyte globulin, prednisolone, and azathioprine, or placebo. After 15 months of treatment the immunosuppressed group had a reduction in the number of relapses and some retardation of the clinical course of the disease (p < 0.06). The beneficial effect was seen only in females.

Antilymphocyte Serum↗

PubMed2003

Genomic and proteomic analysis of multiple sclerosis. Opinion.

Multiple sclerosis (MS) and other autoimmune diseases result from the dysregulation of genetic and proteomic programs. In MS, the loss of immune homeostasis leads to aberrant targeting and destruction of the myelin sheath, which manifests as the clinical syndrome of MS. The advent of technologies to perform large-scale analysis of mRNA transcript and protein expression will transform our understanding of the mechanisms underlying the initiation and progression of MS, and will yield new targets for therapeutic intervention.

Animals↗

PubMed2005

[Multiple sclerosis--update].

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. The inflammation causes focal demyelination and loss of axons, neurons and glial cells. Typical symptoms and signs are monocular blurred vision, double vision, sensory symptoms and motor weakness, and eventually also cognitive deficits and a disturbed micturition. In younger patients the neurological deficits tend to be present for a limited time and then to improve and disappear, only to be followed by new and different deficits later on. Each relapse may leave neurological deficits which in a later course tend to progress slowly, uninterrupted by remissions. When older patients present for the first time with MS, they tend to present with primary progressive spasticity. Important ancillary tests and findings to confirm the diagnosis are multiple focal lesions on MR images, oligoclonal bands in the cerebrospinal fluid, and slowed evoked potentials. Relapses are treated with corticosteroids. Immunomodulation with beta-interferons or glatiramer acetate reduce the number and severity of relapses and long-term disability. Very active forms can be treated with immunosuppression using mitoxantrone. Individual manifestations such as urinary tract infections or paroxysmal phenomena should be treated accordingly with medication.

Adjuvants, Immunologic↗

PubMed1999

Is it MS? Presenting symptoms and diagnosis of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic neurological disease in our community. OBJECTIVE: To discuss the presenting symptoms that suggest the diagnosis of MS and consider how to confirm the diagnosis and evaluate the differential diagnosis. DISCUSSION: There are protean presenting symptoms of MS but because of the distribution of pathology predominantly in the peri-ventricular region of the brain, certain symptom complexes are more common. With the recent availability of treatment for MS which has been demonstrated to slow the progress of the disease, the need for early diagnosis has become even more important.

Diagnosis, Differential↗

PubMed2006

[Contribution of ecological evaluation of executive disorders in multiple sclerosis].

INTRODUCTION: Multiple sclerosis (MS) is a major cause of neurological disability among young adults. The cognitive disorders are the second cause of alteration of quality of life after physical handicap and are often responsible for loss of social-occupational adaptability. The prevalence of cognitive disorders is 40 to 65%. The alteration of executive functions predominates whereas instrumental functions are generally preserved. The assessment of these disorders is often underestimated by the usual battery of neuropsychological tests. However, the link between psychometric results and executive difficulties of daily life is uncertain. OBJECTIVES: To evaluate the sensitivity of an ecological test compared to standard psychometric tests in assessment of executive disorders in MS. METHODS: Twenty subjects with clinically definite MS were matched for age, sex and pre-morbid intellectual level with control subjects. A battery of neuropsychological and ecological tests was applied to all subjects. The performances on these tests formed a global score of executive function (SFE). The "paper and pencil" multiple errands test was used as the ecological test to examine planning and goal-oriented behavior. We also assessed fatigue and depression with the Fatigue Severity Scale and the Beck Depression Inventory. RESULTS: There was no significant differences between MS patients and controls in neuropsychological executive tests, except for verbal fluencies (p=0.01). The performances were significantly decreased in the MS group for the multiple errands test (p=0.01). 75% of MS subjects have a pathological score for this test. There was a significant link between the performances with this test and SFE (p=0.009). CONCLUSIONS: Executive disorders are underestimated in MS. However, we suggest that an ecological approach is more reliable than standard neuropsychological tests to estimate the cognitive difficulties in daily life in MS subjects. The results of our study favor further research to ascertain the usefulness of ecological assessment in MS.

Adult↗

PubMedDate not supplied

[Some aspects of histopathology in multiple sclerosis].

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Inflammation, demyelination and a variable degree of oligodendrocyte loss belong to the key features of this disorder. DEVELOPMENT: In MS plaques, different stages of demyelinating activity can be distinguished based on the presence of myelin proteins within the cytoplasm of macrophages, the degree of remyelination and the expression of macrophage activation antigens. Additionally, different patterns of oligodendrocyte loss and preservation can be found indicating a heterogenous pathogenesis of demyelination in MS. In the present report, we present criteria for classification of demyelinating activity as well as patterns of oligodendrocyte pathology.

Antigens↗

PubMedDate not supplied

Multiple sclerosis update.

Multiple sclerosis (MS) is the most common central nervous system disease among young adults and the third leading cause of disability in the United States. It is estimated that 400,000 Americans have this disorder of the brain and spinal cord, which causes disruption in the smooth flow of electrical messages from the brain to nerves throughout the body. The clinical manifestations vary more in MS than any other neurologic disease. Because of the complexity of MS, a collaborative approach to care of these clients and their family is ideal. This article provides an update on the diagnosis, pharmacologic management, and collaborative care for patients and families.

Activities of Daily Living↗

PubMed1998

Serum amyloid A protein is elevated in relapsing-remitting multiple sclerosis.

In multiple sclerosis (MS), the signs of inflammation that can be detected in the central nervous system are not mirrored by unequivocal markers of activation of the immune system in the periphery. We performed a serial monitoring of serum amyloid A protein (SAA), a major acute phase reactant, in peripheral blood of patients with relapsing-remitting MS over a 3-month period. Patients were monitored in parallel with gadolinium-enhanced magnetic resonance imaging (Gd-MRI) of the brain. The results show that signs of ongoing peripheral inflammation, reflected by elevations of SAA levels, can be detected in MS patients.

Adult↗