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PubMed2002

Multiple sclerosis presenting as ataxic hemiparesis.

Multiple sclerosis (MS) can present with many clinical pictures, but only rarely as a lacunar syndrome. The following case presentation is of multiple sclerosis with initial presentation as ataxic hemiparesis (AH), indistinguishable from the vascular syndrome. This case serves to illustrate that even classic lacunar syndromes can actually be the initial manifestation of multiple sclerosis and that other etiologies besides ischemic stroke need to remain in the differential diagnosis until a definitive has been concluded.

Adult↗
PubMed2003

Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis.

Autoimmune diseases such as multiple sclerosis are characterized by complex genetic traits and pathomechanisms that translate into clinical heterogeneity. This wide heterogeneity of multiple sclerosis as well as different biological responses to immunomodulatory drugs can be expected to contribute to differential treatment responses. Strategies that dissect the relationship between the treatment response and the biological characteristics in individual patients are valuable not only as a clinical tool, but also in leading to a better understanding of the disease. Here we address the in vitro and ex vivo RNA expression profile under one approved therapy of multiple sclerosis, interferon-beta (IFN-beta, Betaseron), by cDNA microarrays and demonstrate that non-responder and responder phenotypes to IFN-beta as assessed by longitudinal gadolinium-enhanced MRI scans and clinical disease activity differ in their ex vivo gene expression profile. These findings will help to better elucidate the mechanism of action of IFN-beta in relation to different disease patterns and eventually lead to optimized therapy.

Follow-Up Studies↗
PubMed1986

Glutathione redox cycle enzyme activities in erythrocytes of multiple sclerosis patients.

The erythrocytes of multiple sclerosis patients with elevated superoxide dismutase levels were tested for the activities of glutathione redox cycle enzymes. No differences were observed between multiple sclerosis and normal control erythrocytes when the activities were referred to either hemoglobin concentration or lactate dehydrogenase content. Our results indicate that no adaptative changes occur in the activities of glutathione redox cycle enzymes in erythrocytes of multiple sclerosis subjects as a consequence of an elevated superoxide dismutase level.

Adult↗
PubMed1980

Depression as a major symptom of multiple sclerosis.

Thirty patients suffering from multiple sclerosis have been compared with 30 patients suffering from other chronic neurological diseases. The degree of disability was similar in these two groups. The patients with multiple sclerosis had experienced more episodes of severe depression both before and after the onset of neurological symptoms. The possible reasons for these episodes are discussed and it is concluded that in some patients serious affective disorder may be a presenting or complicating feature of multiple sclerosis.

Adult↗
PubMed1975

Racial predilection in multiple sclerosis.

Comparisons between the geographic distribution of multiple sclerosis and the habitats of various racial groups showed that racial factors alone could not explain the increase in prevalence of the disease with latitude. Racially similar groups living in different areas had different frequencies of multiple sclerosis. Conversely, racially different groups, living in the same area, had similar prevalence rates of multiple sclerosis. Moreover, migrants moving from one environment to another at a young age (before adolescence) appeared "to acquire" the risk of multiple sclerosis of the new environment. These observations suggest than an environmental factor independent of race influenced the risk of acquiring multiple sclerosis. Nonetheless, some genetic factors associated with race may also be implicated, for example, HL-A tissue antigens (perhaps by virtue of a common association with the immune response (Ir) gene), the Gm and Inv immunoglobulin characteristics and skin pigmentary characteristics (perhaps through interactions between pigmentation and calcium metabolism). The specific environmental factors determining risk of multiple sclerosis and the mechanism whereby the racial (genetic) factors may influence risk remain to be elucidated.

Africa↗
PubMed1975

Bitemporal visual field defects in presumed multiple sclerosis.

Three patients with presumed multiple sclerosis had bitemporal hemianopia mimicking that caused by parasellar tumors; the visual loss was probably due to a plaque within the chiasm. The diagnosis of multiple sclerosis was made on the basis of a history of relapse and remission, signs and symptoms indicating involvement of different levels of the central nervous system, and normal neuroradiological studies. Extensive neuroradiological studies may be delayed or omitted in patients with established multiple sclerosis and nonprogressive bitemporal visual field defects if central visual acuity is not greatly reduced.

Adolescent↗
PubMedDate not supplied

The role of spouse responses to disability and family environment in multiple sclerosis.

Research in the area of family issues and multiple sclerosis has mainly focused on the impact of multiple sclerosis on the spouse. The aim of the current study was to examine the relationship between patients' ratings of their spouses' responses to multiple sclerosis patient disability behaviors and the impact on patient psychological and physical functioning. Multiple sclerosis patients were interviewed over the telephone using standardized questionnaires to assess patient physical and psychological functioning, spouse responses to patient disability and well behaviors (i.e., how does the spouse respond when you're having difficulties related to multiple sclerosis?), and family environment factors. The study was set in a large university-based Multiple Sclerosis Clinical Center. Forty-four of 64 patients approached with definite multiple sclerosis participated in the study. Physical functioning was assessed by the Kurtzke-EDSS, SIP, SF-36, and psychological functioning was assessed by the CES-D and SF-36. Scores on the SF-36 were generally lower compared with a normative sample of individuals with major medical problems; however, mean Kurtzke scores of 5.60 reflected moderate to severe impairment. Exploring spouse responses to disability, correlation analyses revealed that solicitous spouse responses to patient disability behaviors were significantly associated with greater multiple sclerosis-related physical disability. This relationship was stronger for patients who were more depressed. Spouse negative responses to patient disability behaviors were associated with poorer mental health, whereas spouses' encouragement of patient well behaviors was associated with lower emotional distress. Poorer psychological functioning was found in patients with families who were reported to have higher conflict and/or who were more controlling. Higher levels of independence in families were associated with better psychological and physical functioning in the patients. These preliminary findings suggest that patients' perceptions of their families' responses to disability and family environment factors may be important areas for further research. The findings may also provide potential targets for clinical intervention in the future.

Activities of Daily Living↗
PubMed1987

The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis.

In 125 patients with multiple sclerosis, intrathecally synthesized antibodies against measles, rubella and zoster viruses were determined with an ELISA. 70% of patients with chronic progressive disease synthesized measles antibodies in comparison to 50% with a relapsing course. Women suffering from chronic progressive multiple sclerosis exhibited zoster antibodies 3 times as frequent as the other patients. These data indicate that relapsing and chronic progressive forms of multiple sclerosis exhibit different antiviral responses within the central nervous system which remain stable during the course of the disease.

Adolescent↗
PubMed2003

A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501 positive multiple sclerosis patients.

The association of multiple sclerosis with alleles/haplotypes from the HLA region on chromosome 6p21 is well established although the remainder of the genome remains relatively unexplored. We have completed a genome-wide screen for linkage disequilibrium in a cohort of Australian multiple sclerosis patients positive for HLA-DRB1*1501. A total of 4346 microsatellite markers provided through the "Genetic Analysis of Multiple sclerosis in EuropeanS" (GAMES) collaborative were analysed in DNA separately pooled from cases (n=217) and controls (n=187). Associations were found in four genomic regions (12q15, 16p13, 18p11 and 19q13) previously identified in linkage genome screens. Three additional regions of novel association were also identified (11q12, 11q23 and 14q21). Further analysis of these regions is required to establish whether the associations observed are due to epistatic interaction with the HLA locus.

Adult↗
PubMed1995

Severe occlusive retinal periphlebitis with vitreous hemorrhage in multiple sclerosis.

Severe ocular complications in multiple sclerosis are rare. A 43-year-old patient had a history of diplopia episodes and optic neuritis in the right eye between 1979 and 1980. In 1984, multiple sclerosis had been diagnosed. The patient presented with visual deterioration in the right eye in 1992. Ophthalmoscopy and fluorescein angiography showed severe occlusive retinal periphlebitis with diffuse retinal hemorrhages and large areas of nonperfusion. At the time of presentation the patient was in general good health and presented no neurological sign. Examinations for other causes of periphlebitis were negative. Although treatment with laser therapy and corticosteroids was initiated, the patient developed recurrent vitreous hemorrhages that required pars plana vitrectomy. In 1993 the patient suffered from a general deterioration of the disease course and was treated with systemic immunosuppressive medication. Vitreous hemorrhage is a rare complication of multiple sclerosis.

Adult↗
PubMed2000

The protective role of Langerhans' cells and sunlight in multiple sclerosis.

The low prevalence of multiple sclerosis in equatorial areas may be the consequence of a physiological immunosuppression induced by ultraviolet radiation on the epidermal Langerhans' cells, which are the antigen-presenting cells. Multiple sclerosis appears to be the consequence of an immune response to an environmental antigen during childhood in the absence of two protective factors: a genetic factor conferred by the HLA haplotypes of Langerhans' cells, and an environmental factor conferred by ultraviolet radiation in sunlight. In the presence of these two factors, T lymphocytes are physiologically immunosuppressed. Their association may play a key role in protection against multiple sclerosis. The varying combinations of these two factors may provide an explanation for the differences in incidence and prevalence of the disease noted within a single region or from one region to another throughout the globe. The hypothetical pathogenic mechanism developed in this article opens up new fields of research, particularly those concerning its therapeutic applications.

Humans↗
PubMed2006

The contribution of demyelination to axonal loss in multiple sclerosis.

The traditional notion that multiple sclerosis is a primary demyelinating disease has led to a plaque-centred view of both aetiology and the pathogenesis of disease progression. The presence of axonal loss has received increasing recognition. However, the relative roles of demyelination and axonal loss have not been fully clarified in multiple sclerosis nor have their possible interrelationships been elucidated. Post-mortem material from the cerebrum, brainstem and spinal cord of 55 multiple sclerosis patients (29 males) with an age range of 25-83 years (mean = 57.5 years) and length of disease history ranging from 2 to 43 years (mean = 17.1 years) was stained for myelin. Plaque load was calculated by summing the relative proportion of plaque area compared with total white matter area of the corticospinal and sensory tracts at each level. This was related to estimates of axonal density and of total axon number in these tracts in the spinal cord. Our results indicate that plaque load did not correlate with brain weight. Unexpectedly, after adjusting for sex, age and duration of disease, correlations between total plaque load and axonal loss in both the corticospinal tract and sensory tracts were weak or absent at each level investigated. Since there was little correlation between plaque load and axonal loss, the possibility that demyelination is not the primary determinant of spinal cord axonal loss warrants consideration.

Adult↗
PubMed1986

An epidemiological description of physical, social and psychological problems in multiple sclerosis.

Chronic disorders such as multiple sclerosis have important behavioural consequences on the lives of patients. The purpose of this study was to describe the frequency distribution of psychosocial disability among a referral clinic population of multiple sclerosis patients and to identify associated factors. A cross-sectional survey was conducted of 301 patients using four health indexes to assess quality of life. An 82% response rate was obtained. In the results are presented the frequencies of behavioural problems compared with the general population and a family practice group. While physical function was found to be closely associated with disease severity, psychosocial disability bore little relationship to the underlying disease or to sociodemographic variables including social class. Eighty percent of psychosocial disability remained unexplained. The physical aspects of multiple sclerosis were not predictive of emotional or social morbidity. The major implication of these findings is that the impact of disease on patients, as distinct from the disease itself, should be dealt with as health problems in their own right.

Activities of Daily Living↗
PubMed1998

Current immunotherapy in multiple sclerosis.

The underlying pathophysiology of multiple sclerosis is presumed to be autoimmune in nature. Attempts to find an effective treatment for this common disease of the central nervous system have primarily focused on immune-mediated therapies, both immunosuppressive and immunomodulatory. The wide variety of immunological abnormalities detected in multiple sclerosis and its animal model, experimental allergic encephalomyelitis, has prompted the testing of a diverse array of drugs to be used for treatment. Recent successes in the treatment of relapsing-remitting multiple sclerosis with interferon beta and glatiramer acetate have renewed interest in and raised expectations for the effective control of this neurological disorder. Improved methodology in clinical trials, the development of surrogate markers and the availability of novel therapies bode well for more rapid advances.

Animals↗
PubMed1974

Specific laboratory test for diagnosis of multiple sclerosis.

Lymphocytes from patients with multiple sclerosis are much more susceptible to the inhibitory activity of linoleic acid (0.08 mg/ml) when tested for sensitization to thyroid by the macrophage electrophoretic mobility test (91% inhibition) than are those from normal subjects (57% inhibition). Cells from patients with a variety of other neurological diseases give 47% inhibition with linoleic acid. These differences are specific for multiple sclerosis and can be used as an in-vitro diagnostic test for the disease. Nearly 43% of clinically normal near relatives of patients with multiple sclerosis show an "anomalous" figure of about 77%; in the remainder the figure is the same as in the general population (57%). An anomalous result is compatible with lifelong freedom from M.S. Possibly a congenital anomalous handling of unsaturated fatty acids is a constant feature of the disease.

Adult↗
PubMed1996

Multiple sclerosis. Primary health care implications.

Multiple sclerosis is the most common neurologic disease disabling young adults less than 40 years of age in the United States. It is a chronic inflammatory disease of the central nervous system myelin, often viewed as an autoimmune disorder. Due to the difficulty in establishing a diagnosis, several years may pass between first onset of symptoms and an accurate diagnosis. The etiology remains unclear, but current research leans toward an immunologic and viral pathogenesis. The three main goals of treatment are to delay progression of disease, manage chronic symptoms, and treat acute exacerbations. While no cure has been found, copolymer 1 and interferon beta are each generating excitement in possibly delaying progression of multiple sclerosis. As the disease causes a set of highly variable and complex consequences, patients often require care from a multidisciplinary team of health care providers. Therefore, it is essential that primary care providers possess a basic understanding of the etiology, clinical features, prognosis, and treatment of multiple sclerosis.

Adult↗
PubMed2001

Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis.

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are immune-mediated diseases of the CNS. They are characterized by widespread inflammation, demyelination and a variable degree of axonal loss. Recent magnetic resonance spectroscopy studies have indicated that axonal damage and loss are a reliable correlate of permanent clinical disability. Accordingly, neuropathological studies have confirmed the presence and timing of axonal injury in multiple sclerosis lesions. The mechanisms of axonal degeneration, however, are unclear. Since calcium influx may mediate axonal damage, we have studied the distribution of the pore-forming subunit of neuronal (N)-type voltage-gated calcium channels in the lesions of multiple sclerosis and EAE. We found that alpha(1B), the pore-forming subunit of N-type calcium channels, was accumulated within axons and axonal spheroids of actively demyelinating lesions. The axonal staining pattern of alpha(1B) was comparable with that of beta-amyloid precursor protein, which is an early and sensitive marker for disturbance of axonal transport. Importantly, within these injured axons, alpha(1B) was not only accumulated, but also integrated in the axoplasmic membrane, as shown by immune electron microscopy on the EAE material. This ectopic distribution of calcium channels in the axonal membrane may result in increased calcium influx, contributing to axonal degeneration, possibly via the activation of neutral proteases. Our data suggest that calcium influx through voltage-dependent calcium channels is one possible candidate mechanism for axonal degeneration in inflammatory demyelinating disorders.

Adult↗
PubMed1999

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs37.82; P<0.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Adult↗