Multiple Sclerosis References 2003; Authors: H-J
(71 References)
Haase, C. G., M. Tinnefeld, et al. (2003). "Depression and cognitive impairment in disability-free early multiple sclerosis." Behav Neurol 14(1-2): 39-45.
Cognitive and emotional capabilities were evaluated in 73 female patients with stable relapsing-remitting definite, and/or laboratory-supported multiple sclerosis (MS) and were compared with 32 matched healthy controls. Patients were categorized according to their score in the expanded disability status scale (EDSS) to either no (EDSS 0, n = 33) or few clinical signs (EDSS 1-2, n = 40) of MS without physical disability. Patients with EDSS > 0 were characterized by significantly (p < 0.001) higher scores on "von Zerssen's" depression scale, compared to controls. Patients with higher EDSS scores (1-2) showed significantly decreased performance with respect to the total score of Kimura's Recurring-Figures-Test (p < 0.001), in addition. Regarding visuo-constructive functioning, patients with EDSS=0 performed to a significantly lower level (p < 0.001), compared to controls. These results indicate that depression may present as an early sign in MS followed by cognitive impairment, in particular visuo-spatial short-term memory, before physical disability appears. Neuropsychological tests as mentioned here could serve as early diagnostic tools to detect subtle disease progression and to initiate and monitor disease modifying therapies.
Haegert, D. G. (2003). "The initiation of multiple sclerosis: a new infectious hypothesis." Med Hypotheses 60(2): 165-70.
Both genetic and environmental factors cause multiple sclerosis (MS). Few genes have been identified, however, and environmental factors remain elusive. Some postulate an infectious cause, but no pathogens are reproducibly demonstrable in CNS lesions. I postulate that the CNS is not the infectious target in MS, but propose a two-hit infectious hypothesis focusing on nai;ve CD4 T-cells that initiate demyelination: (1) Various common viruses infect the thymus during childhood (first hit) and enhance nai;ve CD4 T-cell reactivity to CNS autoantigens; (2) Heterogeneous pathogens fully activate these T-cells during adulthood (second hit) to initiate myelin injury. The novel concept of thymic infection provides insight into the nature of some susceptibility genes, helps explain the high discordance rates in genetically susceptible individuals, and suggests it is futile to search for pathogens in MS lesions. Pathogen heterogeneity, i.e., the lack of a single infectious cause, implies there can be no simple therapies to prevent or treat MS.
Hakansson, N., P. Gustavsson, et al. (2003). "Neurodegenerative diseases in welders and other workers exposed to high levels of magnetic fields." Epidemiology 14(4): 420-6; discussion 427-8.
BACKGROUND: Previous work has suggested an increase in risk of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease among workers exposed to extremely low-frequency magnetic fields (ELF-MF). We evaluated the relation between ELF-MF from occupational exposures and mortality from neurodegenerative diseases. METHODS: The study was based on a cohort of Swedish engineering industry workers, comprising 537,692 men and 180,529 women. The cohort was matched against the 3 most recent censuses and The Causes of Death Registry. Levels of ELF-MF exposure were obtained by linking occupation according to the censuses to a job exposure matrix. We used 4 levels of exposure and considered both the primary and contributing causes of death, 1985-96. RESULTS: The risk of Alzheimer's disease as primary or contributing cause of death increased with increasing exposure to ELF-MF among both men and women, with a relative risk (RR) of 4.0 and a 95% confidence interval (95% CI) of 1.4-11.7 in the highest exposure group for both sexes combined. There was a RR of 2.2 (95% CI: 1.0-4.7) for ALS in the highest exposure group with the suggestion of an exposure-response relationship. No evidence of increased risk was seen for Parkinson's disease or multiple sclerosis. CONCLUSIONS: The findings support previous observations of an increased risk of Alzheimer's disease and ALS among employees occupationally exposed to ELF-MF. Further studies based on morbidity data are warranted.
Halfpenny, C. A. and N. J. Scolding (2003). "Immune-modifying agents do not impair the survival, migration or proliferation of oligodendrocyte progenitors (CG-4) in vitro." J Neuroimmunol 139(1-2): 9-16.
Limited intrinsic myelin repair occurs in multiple sclerosis (MS), mediated by oligodendrocyte progenitors that divide and migrate into demyelinated lesions. Experimental remyelination suggests that this repair restores function and may protect axons from subsequent degeneration. Immunomodulatory drugs such as corticosteroids, interferon-beta and azathioprine are widely used in MS. However, their influence on disease progression is modest, for reasons that are not fully explained. The direct effects of these drugs on remyelination biology remain relatively unexplored. We have investigated the effect of these MS therapies on oligodendrocyte progenitors to identify whether drug treatment might directly compromise repair, either therapeutic or spontaneous. None of these drugs affected CG-4 survival, migration or proliferation.
Hallal, D. E., A. S. Farias, et al. (2003). "Costimulatory molecule expression on leukocytes from mice with experimental autoimmune encephalomyelitis treated with IFN-beta." J Interferon Cytokine Res 23(6): 293-8.
Interferon-beta (IFN-beta) is of benefit in the treatment of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), but the mechanisms by which it exerts this beneficial effect remain uncertain. The present data demonstrate that IFN-beta therapy impairs the proliferative response to concanavalin A (ConA) and myelin basic protein (MBP), decreases expression of the CD80 molecule on leukocytes of treated mice, and may thereby impede the Th1 cell activation-promoting anergy in EAE. Moreover, IFN-beta therapy increases expression of the CTLA4 molecule, which induces a counterregulatory Th2 response. The reduction of CD80 expression with concomitant increase of CTLA4 expression alters the course of EAE and may be useful as a monitor in therapy with IFN-beta.
Halper, J., P. Kennedy, et al. (2003). "Rethinking cognitive function in multiple sclerosis: a nursing perspective." J Neurosci Nurs 35(2): 70-81.
Cognitive impairment is a common problem in multiple sclerosis (MS); up to 65% of patients exhibit some neuropsychological dysfunction during the course of their disease. It is a major contributing factor to unemployment, accidents, impairment of daily functioning, and loss of social activity in those affected by MS. The areas of cognition typically impaired are memory, attention, information processing, executive functions, and visuospatial skills. Cognitive dysfunction is independent of disease duration and level of disability; cognitive decline may begin in the earliest stages of MS before patients become even mildly disabled. Structural brain imaging studies show a positive correlation between the extent of brain atrophy and cognitive dysfunction. Despite its prevalence in MS, cognitive dysfunction often goes undiagnosed or is misdiagnosed as depression, stress, stubbornness, lack of intelligence, or psychosis. Because nurses play such an important role in the care of patients with MS, they are in a position to identify patients with cognitive dysfunction, educate patients and their families on ways to cope with cognitive deficits, and counsel patients on available treatment options. Practical guidelines help nurses identify and care for cognitively impaired MS patients.
Hand, J. L. and R. S. Rogers, 3rd (2003). "Oral manifestations of genodermatoses." Dermatol Clin 21(1): 183-94.
Many genodermatoses have distinct oral features that may help identify or confirm a genetic diagnosis. Oral features of the disorders described here are summarized in Table 1. These conditions provide clear examples of rapid progress in the field of genetic technology relevant to patient care. Less than a decade ago, the exact genetic locus of most of these disorders was unknown. Today, for many of these disorders, the exact location of the disease-causing mutation is known and clinical genetic testing is available for patients. This information has impact not only for genetic counseling and anticipatory medical care, but also provides insight into the mechanisms of disease. How this rapid progress will impact care, and ultimately treatment of patients, remains to be seen.
Hansen, F. (2003). "Rising above despair. Finding hope beyond MS." J Christ Nurs 20(1): 14-5.
Harney, S. M., J. L. Newton, et al. (2003). "Molecular genetics of rheumatoid arthritis." Curr Opin Pharmacol 3(3): 280-5.
Following the successful determination of the molecular genetics of single-gene disorders, attention has not surprisingly turned to complex genetic disorders. However, preliminary experience suggests that unravelling the genetic component of common inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus, might be a harder nut to crack.
Hartelius, L., D. Theodoros, et al. (2003). "Comparability of perceptual analysis of speech characteristics in Australian and Swedish speakers with multiple sclerosis." Folia Phoniatr Logop 55(4): 177-88.
The aims of the present study were to compare the perceptual assessments of deviant speech signs (dysarthria) exhibited by Australian and Swedish speakers with multiple sclerosis (MS) and to explore whether judgements of dysarthria differed depending on whether the speakers and the judges spoke the same or different languages. Ten Australian and 10 Swedish individuals with MS (matched as closely as possible for age, gender, progression type and severity of dysarthria) were assessed by 2 Australian and 2 Swedish clinically experienced judges using a protocol including 33 speech parameters. Results show that the following perceptual dimensions were identified by both pairs of judges in both groups of speakers to a just noticeable or moderate degree: imprecise consonants, inappropriate pitch level, reduced general rate, and glottal fry. The reliability (Spearman rank-order correlation) of the consensus ratings from the Australian and the Swedish judges was high, with a mean rho of 85.7 for the Australian speakers and mean rho of 84.3 for the Swedish speakers. The most difficult perceptual parameters to assess (i.e. to agree on) included harshness, level of pitch and loudness, precision of consonants and general stress pattern. The study indicated that perceptual assessments of speech characteristics in individuals with MS are informative and can be achieved with high inter-judge reliability irrespective of the judge's knowledge of the speaker's language.
Hartelius, L. and M. Lillvik (2003). "Lip and tongue function differently affected in individuals with multiple sclerosis." Folia Phoniatr Logop 55(1): 1-9.
Clinical dysarthria test scores on lip function and tongue function were compared for 77 dysarthric as well as non-dysarthric subjects with multiple sclerosis (MS) and 15 control subjects. Results show that tongue function was significantly more severely affected than lip function in individuals with MS. Furthermore, tongue function, but not lip function, was significantly more severely affected in the MS individuals with no dysarthria compared to the control group. Test items requiring increased rate of movement (oral and verbal diadochokinesis) were significantly more severely affected than the items requiring range and force of movement, but only in the dysarthric MS subgroup. Moderate correlations were found between tongue and lip function and neurological deficit scores, number of years in disease progression, and perceptually perceived consonant and vowel precision. Consequently, tongue dysfunction can be detected clinically and subclinically using a dysarthria test procedure, and as an early sign of articulatory dysfunction it should be an early target in therapeutic interventions.
Harting, I., J. Sellner, et al. (2003). "[Multiple sclerosis: imaging, diagnostic criteria and differential diagnosis]." Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 175(5): 613-22.
Multiple sclerosis (MS) is the most common demyelinating inflammatory disease of the central nervous system (CNS), presenting with multifocal, disseminated inflammatory lesions referred to as plaques. Magnetic resonance imaging (MRI) typically depicts multiple, round to oval, circumscript lesions predominantly involving periventricular and subcortical white matter, brainstem and cerebellum. More recent investigations have demonstrated that the macroscopically visible plaques only present the tip of the iceberg: Already early in its course, MS causes neuroaxonal damage and diffusely involves the entire brain parenchyma including normal appearing white matter. These changes are reflected by strongly T 1 w hypointense lesions and atrophy of early onset, by reduction of the neuronal Marker N-acetylaspartate (NAA) on spectroscopy, by a decrease of the magnetization transfer ratio (MTR), by an increased in diffusibility and decreased anisotropy on diffusion-weighted imaging (DWI). MRI imaging is an important tool in the diagnosis of MS by revealing the characteristic spatial and temporal dissemination of the cerebral and spinal manifestations of this disease. Diagnostic criteria increase the diagnostic specificity and allow better differentiation from other diseases with multifocal white matter abnormalities.
Hartrich, L., B. Weinstock-Guttman, et al. (2003). "Dynamics of immune cell trafficking in interferon-beta treated multiple sclerosis patients." J Neuroimmunol 139(1-2): 84-92.
PURPOSE: To investigate the effects of interferon-beta-1a (IFN-beta-1a) on the trafficking of cell populations in peripheral blood cells of multiple sclerosis (MS) patients. METHODS: In this open-label pharmacodynamic study, peripheral blood was obtained from 10 relapsing-remitting (RR) MS patients just prior to and at 1, 2, 4, 8, 24, 48, 120, and 168 h after intramuscular injection of 30-microg IFN-beta-1a. Timed samples were also obtained from five controls at 0, 8, 24, 48 and 168 h. The blood cells were analyzed using four-color flow cytometry with antibody conjugates directed against cell surface proteins specific for T cells, B cells, NK cells, and the activation marker, CD69. RESULTS: IFN-beta-1a treatment resulted in selective, time-dependent effects on many cell populations in peripheral blood. The trafficking of T-helper and T-suppressor/cytotoxic subsets of T cells were qualitatively different. The most prominent effects were on the trafficking of natural killer cells, the levels of which decreased to 23.5% of pretreatment values at 8 h after treatment. The levels of CD69-positive NK cells increased to a peak value of 606% of pretreatment levels at the 24-h time point. In untreated controls, these characteristic trafficking effects were not observed. There was inter-patient heterogeneity in the levels of activated NK cells at the 6-month time point that may potentially be relevant for individualizing IFN-beta therapy. CONCLUSIONS: IFN-beta treatment can induce specific, selective, and time-dependent trafficking of cells and its effects on different subsets of a given cell type are not qualitatively similar. The dynamics indicate that the activation of NK cells by IFN-beta is possibly dependent on the trafficking of NK cells. The activated NK cell levels after prolonged therapy may potentially provide a surrogate marker for IFN-beta exposure.
Hartrumpf, M., J. M. Albes, et al. (2003). "The hemodynamic performance of standard bileaflet valves is impaired by a tilted implantation position." Eur J Cardiothorac Surg 23(3): 283-91.
OBJECTIVES: Severe sclerosis of the native aortic annulus can result in a tilted implantation position of mechanical prostheses. In this study, the effects of tilting and rotation on the hemodynamic performance of standard bileaflet valves were assessed in an extracorporeal mock circulatory system. METHODS: A pulsatile mock circulation driven by a Berlin Heart system was developed. Main physiological components of the human circulation were mimicked. SJM-AHPJ prostheses (21, 23, 25 mm) were mounted in an artificial aortic root containing physiologically oriented coronary ostia. All experiments were performed under constant conditions (stroke volume 60 ml, heart rate 70 bpm, systolic pressure 130 mmHg). Hydrostatic pressures were measured via fluid-filled catheters, transvalvular flow by ultrasonic probes. Data were digitally recorded at 50 Hz. Multiple pressure, volume, energy, and dimension parameters were derived off-line. Each valve was tested in a 0 degrees (untilted) versus 20 degrees (tilted) position at three axial rotation angles (0 degrees, 45 degrees, 90 degrees ). Tilting was performed independent of rotation by elevation of the prosthesis in the non-coronary sinus. RESULTS: In all valves and all rotation angles, tilting resulted in a size-dependent significant increase of mean pressure gradient (range, 28-35% [21 mm valve], 59-96% [23 mm valve], 124-220% [25 mm valve]), valvular resistance (39-51, 84-121, 177-332%), regurgitation volume (84-148, 32-131, 93-118%), and systolic energy loss (113-146, 30-132, 69-213%), as well as a decrease of total stroke volume (2-5, 0-11, 3-10%), effective stroke volume (6-11, 9-14, 14-22%), cardiac output (6-11, 8-14, 13-22%), and effective opening area (16-24, 32-37, 47-57%). The strongest impairment of hemodynamic performance was seen at 90 degrees rotation with reference to total and effective stroke volume, cardiac output, mean pressure gradient, and regurgitation fraction. CONCLUSIONS: Tilting of bileaflet valves resulted in a significant impairment of systolic and diastolic hemodynamics. Superiority of larger valves diminished in the tilted position. The strongest tilting effect was seen at 90 degrees rotation. Such a position should therefore be avoided or surgically corrected by rotating the valve.
Harzheim, M., M. Altenschmidt, et al. (2003). "IFN-beta1a (Rebif((R))) Modifies the Expression of Microfilament-Associated Cell-Cell Contacts in C6 Glioma Cells." J Interferon Cytokine Res 23(2): 83-9.
Multiple sclerosis (MS) is a chronic inflammatory disease characterized by multifocal demyelination and axonal damage in the central nervous system (CNS). The disruption of the endothelial blood-brain barrier (BBB) with consecutive transmigration of inflammatory cells into the brain parenchyma is of critical importance in the pathogenesis of MS. The integrity of the BBB and the adjacent network of glial cells partially depends on the assembly of intercellular contacts between astrocytes. We demonstrate that recombinant interferon-gamma (rIFN-gamma), a proinflammatory cytokine critically involved in the disruption of the BBB, downregulates the expression of the cell adhesion molecules N-cadherin and vinculin in astrocytic C6 cells using Western blot and immunofluorescence microscopy. By contrast, IFN-beta1a, an established treatment for relapsing-remitting MS, increases the expression of N-cadherin and vinculin and partly inhibits the downregulation of these adhesion molecules by phytohemagglutinin (PHA)-stimulated IFN-gamma-secreting human T lymphocytes in coculture experiments. In summary, we demonstrate that IFN-beta1a modifies the assembly of N-cadherin- and vinculin-mediated intercellular contacts between astrocytic C6 cells in vitro. This effect may also contribute to the therapeutic action of IFN-beta1a in MS.
Haufschild, T., H. J. Kaiser, et al. (2003). "Influence of red wine on visual function and endothelin-1 plasma level in a patient with optic neuritis." Ann Neurol 53(6): 825-6.
Haupts, M., G. Elias, et al. (2003). "[Quality of life in patients with remitting-relapsing multiple sclerosis in Germany]." Nervenarzt 74(2): 144-50.
The concept of health-related quality of life (QoL) includes physical, psychological,and social aspects.This pertains to consequences of chronic diseases and their therapies beyond biological or pharmacological relations. A considerable amount of literature concerning QoL has been published with regard to neurological and non-neurological entities.This study summarizes data from a study in 717 persons with remitting-relapsing multiple sclerosis (MS).Of them,576 could be reevaluated longitudinally after 1 year of treatment with interferon-beta 1a (44 microg subcutaneous Rebif once weekly). Compared to populations of healthy controls or other patients, considerable reductions in the eight subscales and both physical and emotional sum scales of the German version of the short form of the Rand Health Questionnaire (SF-36) questionnaire were assessed. These reductions were even more pronounced in persons with gait impairments. Most SF-36 scales only modestly correlated to physical disability.This indicates that QoL as reported by patients does not depend solely on the physical symptoms of MS.Most findings remained stable for the study population as a whole during 1 year of therapy, while statistically significant improvements were found in clinical responders as defined in this study (relapse-free, physically stable, stable or improved in physician's judgement). Side effects of therapy were not reflected in lower QoL scale values. Implications of findings for future concepts in MS therapy are discussed.
Hawke, C. G., D. M. Painter, et al. (2003). "Mycobacteria, an environmental enhancer of lupus nephritis in a mouse model of systemic lupus erythematosus." Immunology 108(1): 70-8.
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of antibodies directed against self antigens. Immune complex glomerulonephritis (GN) is one of the most serious complications of this disorder and can lead to potentially fatal renal failure. The aetiology of SLE is complex and multifactorial, characterized by interacting environmental and genetic factors. Here we examine the nature of the renal pathology in mycobacteria-treated non-obese diabetic (NOD) mice, in order to assess its suitability as a model for studying the aetiopathogenesis of, and possible treatment options for, lupus nephritis (LN) in humans. Both global and segmental proliferative lesions, characterized by increased mesangial matrix and cellularity, were demonstrated on light microscopy, and lesions varied in severity from very mild mesangiopathic GN through to obliteration of capillary lumina and glomerular sclerosis. Mixed isotype immune complexes (IC) consisting of immunoglobulin G (IgG), IgM, IgA and complement C3c were detected using direct immunofluorescence. They were deposited in multiple sites within the glomeruli, as confirmed by electron microscopy. The GN seen in mycobacteria-treated NOD mice therefore strongly resembles the pathology seen in human LN, including mesangiopathic, mesangiocapillary and membranous subclasses of LN. The development of spontaneous mixed isotype IC in the glomeruli of some senescent NOD mice suggests that mycobacterial exposure is accelerating, rather than inducing, the development of GN in this model.
Heesen, C., J. Kolbeck, et al. (2003). "Delivering the diagnosis of MS results of a survey among patients and neurologists." Acta Neurol Scand 107(5): 363-8.
OBJECTIVES : The need for an early disclosure of the diagnosis of multiple sclerosis (MS) has become more pressing with the publication of two recent randomized trials which have indicated that very early treatment may favourably alter the disease course. We assessed the current status of diagnostic and therapeutic information on MS from the point of view of patients and neurologists. METHODS : A standardized questionnaire was sent out through the patients' self-help organization in Hamburg, Germany and to all neurologists. RESULTS : A total of 434 of 1300 patients and 80 of 250 neurologists replied. Neurologists gave 90% of the diagnoses but only 50% of patients reported them as the major aid helping to understand the disease. Fifty per cent of patients were not informed about any form of therapy at the time of diagnosis regardless of whether their MS diagnosis was disclosed within the last 5 years or earlier. In contrast to physicians, patients voted for information about a possible MS even if the diagnosis may not yet be clear. CONCLUSION : From the patients' perspective, information about the diagnosis of MS should be more straightforward, and more information about therapies should be provided.
Heesen, C., M. Bruegmann, et al. (2003). "Therapy-related acute myelogenous leukaemia (t-AML) in a patient with multiple sclerosis treated with mitoxantrone." Mult Scler 9(2): 213-4.
Heinrich, P. C., I. Behrmann, et al. (2003). "Principles of IL-6-type cytokine signalling and its regulation." Biochem J Pt.
The IL-6-type cytokines IL-6, IL-11, LIF, OSM, CNTF, CT-1 and CLC are an important family of mediators involved in the regulation of the acute phase-response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in hematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signaling contributes to the onset and maintenance of several diseases such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e. g. multiple myeloma and prostate cancer). IL-6 type cytokines exert their action via the signal transducers gp130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT and MAPK cascades.This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signaling pathway mediated by tyrosine phosphatases, the SOCS feedback inhibitors and PIAS proteins. Also the cross-talk between the JAK/STAT pathway with other signaling cascades is dicussed.
Helms, G. (2003). "T2-based segmentation of periventricular paragraph sign volumes for quantification of proton magnetic paragraph sign resonance spectra of multiple sclerosis lesions." Magma 16(1): 10-6.
Partial volume averaging of signal from multiple sclerosis lesions influences biexponential fitting of the water T2 relaxation as used for tissue/CSF segmentation of spectroscopic volumes. Periventricular volumes-of-interest comprising CSF, lesion and normal-appearing white matter in varying proportion were studied. The relaxation of the localized water signal was measured at 12 echo times (STEAM, geometric spacing from 30 ms to 2000 ms, least-squares fit). Magnetization transfer (MT) was applied to identify contributions of tissue signal to the CSF component. The T2 of the longlived component (T2(long)=433-1782 ms) and its prolongation after MT were inversely correlated to the MT ratio. Hence, short T2(long) is associated with overestimation of CSF partial volume, and thus metabolite concentrations. A T2-correction for the CSF partial volume was suggested and applied to the quantification of MR spectra of large MS lesions. The T2 of bulk CSF (2280+/-87 ms) and the influence of the TE sampling scheme were also studied.
Hemmer, B., B. Kieseier, et al. (2003). "New immunopathologic insights into multiple sclerosis." Curr Neurol Neurosci Rep 3(3): 246-55.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. Although the immune system seems to play an important role in the pathogenesis of disease, target antigens are still uncertain and pathways leading to tissue destruction have not been fully elucidated. Recent studies have significantly contributed to a better understanding of the disease process and broadened our view on possible scenarios of disease initiation and progression. We review the role of the immune system for the manifestation and evolution of MS and discuss different pathogenetic concepts. We conclude with an outlook on future strategies to identify the cause of MS.
Hempling, S. (2003). "Multiple sclerosis. Interview by Harriet Gaze." Bmj 326(7402): 1323-4.
Hendriks, J. J., H. E. de Vries, et al. (2003). "Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study." Biochem Pharmacol 65(5): 877-85.
Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.
Henkel, G. (2003). "Successful management of multiple sclerosis and persistent vegetative state requires frequent reassessment." J Am Med Dir Assoc 4(4 Suppl): H23-4.
Hennemann, A. (2003). "[Selective adhesion molecule inhibitors. Natalizumab in multiple sclerosis and Crohn's disease]." Med Monatsschr Pharm 26(5): 146-8.
Hennig, H., N. Osterrieder, et al. (2003). "Detection of Marek's disease virus DNA in chicken but not in human plasma." J Clin Microbiol 41(6): 2428-32.
Marek's disease virus (MDV) causes a common lymphomatous and neuropathic disease in domestic chickens and, less commonly, turkeys and quail. It is a member of the alpha-herpesviruses and until now was considered to be strongly cell associated. In 1991, MDV was suggested to be the causative infectious agent of multiple sclerosis (MS) in humans. In a previous study, we investigated the leukocytes of 107 well-defined MS patients for the presence of MDV DNA but were unable to confirm a role for MDV in the pathogenesis of MS. A recent report (S. Laurent, E. Esnault, G. Dambrine, A. Goudeau, D. Choudat, and D. Rasschaert, J. Gen. Virol. 82:233-240, 2001) described the detection of MDV DNA in 20% of 202 human serum samples, regardless of whether the individuals were exposed to poultry. The detection of MDV DNA in chicken serum samples was reported as well. The aim of the present study was to investigate whether we can confirm the presence of MDV DNA in chickens and humans if we use plasma as the source for nucleic acid isolation. Leukocytes and plasma specimens from 16 chickens experimentally infected with MDV serotype 1 and plasma specimens from 300 volunteer blood donors were tested for MDV DNA by two different TaqMan PCR assays. MDV DNA was repeatedly found in the leukocytes as well as in the plasma specimens of all 16 animals. All human samples analyzed, however, tested negative by both assays. Accordingly, Marek's disease in chickens can be diagnosed by detection of MDV DNA in plasma as well as in leukocytes. Once again, we found no evidence for the spread of MDV to humans.
Hensel, M., C. Fiehn, et al. (2003). "[Stem cell transplantation in primary systemic vasculitis]." Med Klin 98(1): 13-8.
BACKGROUND: Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. THERAPY: Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. PATIENTS: Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. RESULTS AND CONCLUSION: Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.
Herrera, B. M. and G. C. Ebers (2003). "Progress in deciphering the genetics of multiple sclerosis." Curr Opin Neurol 16(3): 253-8.
PURPOSE OF REVIEW: Multiple sclerosis is the most common neurological disease affecting young adults. The aetiology is unknown, although many clues point to an autoimmune inflammatory nature. Family studies of multiple sclerosis have shown familial aggregation, and therefore suggest that the disease entails a genetic component that has been widely studied. Some of the studies from the extensive literature in the field of multiple sclerosis genetics published in the past year are discussed here. RECENT FINDINGS: A number of the recent publications considered in this review have reconfirmed the well-known association with the major histocompatibility complex as well as identifying that there are at least two important loci within this region. These findings add further complexity to the role of the major histocompatibility complex in multiple sclerosis. Links to other diseases have been few for multiple sclerosis, but the association with diabetes in the Sardinian population and, perhaps, a 'protective' effect of Down's syndrome can now be added. Numerous candidate genes for susceptibility and disease-modifying effect have also been studied in the literature, but with few replications. Associations with components of the endocrine and the neuro-endocrine system have also been considered in this review along with the potential value of microarray analysis. SUMMARY: Multiple sclerosis is a complex trait that is associated with the major histocompatibility complex, although the form of this association may not be as straightforward as previously thought. Recent findings raise the possibility of an association with haplotype blocks rather than with single alleles. The finding of allelic heterogeneity within the major histocompatibility complex, as with the Sardinians, adds an additional layer of complexity. Genome scans for this and other autoimmune diseases have often been notably disappointing despite many claims for linkages. The reasons for the difficulty may encompass locus heterogeneity, small effects and phenocopies, among others. A variety of attempts to study more restricted populations are in progress, including rare individual pedigrees with high recurrence risk.
Heystek, H. C., B. den Drijver, et al. (2003). "Type I IFNs differentially modulate IL-12p70 production by human dendritic cells depending on the maturation status of the cells and counteract IFN-gamma-mediated signaling." Clin Immunol 107(3): 170-7.
Type I IFNs (IFNalpha/beta) are approved for the treatment of a variety of diseases, including the autoimmune disease multiple sclerosis (MS). The proinflammatory cytokines IL-12 and IFN-gamma have been proposed to contribute to the pathogenesis of MS. Since dendritic cells (DCs) are recognized as major producers of IL-12p70 and promote the development of IFN-gamma-producing Th1 cells, we investigated the direct effect of IFNalpha/beta on monocyte-derived DCs at different stages of development. We demonstrate that IFNalpha/beta enhance IL-12p70 production by immature DCs but inhibit IL-12p70 production by mature DCs. Importantly, IFNalpha/beta strongly counteracted the IL-12-enhancing effect of IFN-gamma on DCs irrespective of their maturation status. Exposure of DCs to IFNalpha/beta during maturation does not affect their maturation or cytokine profile upon CD40 ligation. The differential modulatory effect of IFNalpha/beta on the IL-12-producing capacity of DCs and their cross-regulatory effect on IFN-gamma may reduce inflammatory processes and therefore be therapeutically effective in MS.
Hisahara, S., H. Okano, et al. (2003). "Caspase-mediated oligodendrocyte cell death in the pathogenesis of autoimmune demyelination." Neurosci Res 46(4): 387-97.
Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas of demyelination. MS is believed to be an autoimmune disorder mediated by activated immune cells such as T- and B-lymphocytes and macrophages/microglia. Lymphocytes are primed in the peripheral tissues by antigens, and clonally expanded cells infiltrate the CNS. They produce large amounts of inflammatory and cytokines that lead to demyelination and axonal degeneration. Although several studies have shown that oligodendrocytes (OLGs), the myelin-forming glial cells in the CNS, are sensitive to cell death stimuli, such as cytotoxic cytokines, anti-myelin antibodies, nitric oxide, and oxidative stress, in vitro, the mechanisms underlying injury to the OLGs in MS/EAE remain unclear. Transgenic mice that express the anti-apoptotic protein specifically in OLGs and caspase-11-deficient mice are significantly resistant to EAE induction. Histopathological analyses show that the number of caspase-activated OLGs and dead OLGs are reduced in the CNS of these mice. The numbers of infiltrating immune cells and the amounts of cytokines are also markedly reduced in EAE lesions. Therefore, caspase-mediated OLG death leads to the exacerbation of demyelination and the deterioration of neurological manifestations by inducing local inflammatory events.
Hobart, J. C., A. Riazi, et al. (2003). "Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12)." Neurology 60(1): 31-6.
OBJECTIVE: To develop a patient-based measure of walking ability in MS. METHODS: Twelve items describing the impact of MS on walking (12-Item MS Walking Scale [MSWS-12]) were generated from 30 patient interviews, expert opinion, and literature review. Preliminary psychometric evaluation (data quality, scaling assumptions, acceptability, reliability, validity) was undertaken in the data generated by 602 people from the MS Society membership database. Further psychometric evaluation (including comprehensive validity assessment, responsiveness, and relative efficiency) was conducted in two hospital-based samples: people with primary progressive MS (PPMS; n = 78) and people with relapses admitted for IV steroid treatment (n = 54). RESULTS: In all samples, missing data were low (< or =3.8%), item test-retest reproducibility was high (> or =0.78), scaling assumptions were satisfied, and reliability was high (> or =0.94). Correlations between the MSWS-12 and other scales were consistent with a priori hypotheses. The MSWS-12 (relative efficiency = 1.0) was more responsive than the Functional Assessment of Multiple Sclerosis mobility scale (0.72), the 36-Item Short Form Health Survey physical functioning scale (0.33), the Expanded Disability Status Scale (0.03), the 25-ft Timed Walk Test (0.44), and Guy's Neurologic Disability Scale lower limb disability item (0.10). CONCLUSIONS: The MSWS-12 satisfies standard criteria as a reliable and valid patient-based measure of the impact of MS on walking. In these samples, the MSWS-12 was more responsive than other walking-based scales.
Hoffmann, V., S. Schimrigk, et al. (2003). "Efficacy and safety of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients." J Neurol Sci 211(1-2): 81-4.
Available immunomodulatory and conventional steroid treatment options for patients with progressive multiple sclerosis (MS) only provide limited symptomatic benefit. We performed an open trial on the short-term and long-term efficacy and safety of repeated intrathecal application of the sustained release steroid triamcinolone acetonide (TCA) in 36 progressive MS patients. Six TCA administrations, performed every third day, reduced the EDSS score (initial: 5.6+/-0.93 [mean+/-S.D.]; end: 4.9+/-1.0; p<0.001) and increased the walking distance (WD) (initial: 294+/-314 m; end: 604+/-540 m; p<0.001). Twenty MS patients continued intrathecal TCA treatment with one TCA injection performed with a variable frequency ranging from 6 to 12 weeks. Both EDSS and walking distance remained stable in these patients until the end of the follow-up investigation period. No serious side effects occurred. We conclude that repeated intrathecal TCA injection provides substantial benefit for progressive MS patients with predominantly spinal symptoms.
Holick, M. F. (2003). "Vitamin D: A millenium perspective." J Cell Biochem 88(2): 296-307.
Vitamin D is one of the oldest hormones that have been made in the earliest life forms for over 750 million years. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. Vitamin D is metabolized in the liver and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. 1,25(OH)(2)D receptors (VDR) are present not only in the intestine and bone, but in a wide variety of other tissues, including the brain, heart, stomach, pancreas, activated T and B lymphocytes, skin, gonads, etc. 1,25(OH)(2)D is one of the most potent substances to inhibit proliferation of both normal and hyperproliferative cells and induce them to mature. It is also recognized that a wide variety of tissues, including colon, prostate, breast, and skin have the enzymatic machinery to produce 1,25(OH)(2)D. 1,25(OH)(2)D and its analogs have been developed for treating the hyperproliferative disease psoriasis. Vitamin D deficiency is a major unrecognized health problem. Not only does it cause rickets in children, osteomalacia and osteoporosis in adults, but may have long lasting effects. Chronic vitamin D deficiency may have serious adverse consequences, including increased risk of hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes. There needs to be a better appreciation of the importance of vitamin D for overall health and well being. J. Cell. Biochem. 88: 296-307, 2003.
Hollsberg, P., H. J. Hansen, et al. (2003). "Altered CD8+ T cell responses to selected Epstein-Barr virus immunodominant epitopes in patients with multiple sclerosis." Clin Exp Immunol 132(1): 137-43.
An increased frequency of antiviral CD8+ T cells is seen in chronic viral infections. During herpes virus infections the expanded CD8+ T cells are thought to control the reactivation of the latent infection. Because multiple sclerosis (MS), a presumed autoimmune disease of the central nervous system, has been associated with a late Epstein-Barr virus (EBV) infection, we wished to examine whether the CD8+ T cell response to EBV epitopes differed between MS patients and healthy controls. Here we report an increased frequency of CD8+ T cells responding to EBV epitopes from nuclear antigen 3 A (HLA-A2/CLG) and latent membrane protein 2 (HLA-B7/RPP) in MS patients. Noticeably, the altered CD8+ T cell response occurred to some but not all EBV epitopes and did not reach the high level seen during acute infection. The responses towards two immunodominant epitopes from human cytomegalovirus (HCMV) were similar in MS patients and normal controls. Together, our data demonstrate the presence of an increased frequency of CD8+ T cells reacting with two epitopes from EBV in patients with MS. The altered response to only two of the tested EBV epitopes would be consistent with the presence of cross-reactive epitopes.
Holmoy, T., B. Vandvik, et al. (2003). "T cells from multiple sclerosis patients recognize immunoglobulin G from cerebrospinal fluid." Mult Scler 9(3): 228-34.
Idiotopic sequences are created after V, D and J recombinations and by somatic mutations during affinity maturation of immunoglobulin (Ig) molecules, and may therefore be potential immunogenic epitopes. Idiotope-specific T cells are able to activate and sustain the B cells producing such idiotopes. It is therefore possible that idiotope-specific intrathecal T cells could help maintain the persisting intrathecal synthesis of oligoclonal IgG observed in patients with multiple sclerosis (MS). This study was undertaken to examine T-cell responses to cerebrospinal fluid (CSF) IgG. Peripheral blood mononuclear cells (PBMC) from 14 of 21 MS patients and four of 17 control patients with other neurological diseases proliferated upon stimulation with autologous CSF IgG, while five and three, respectively, responded to serum IgG. By comparison, responses to myelin basic protein were recorded in only four MS and three control patients. Data from a limited number of patients indicate that the CSF IgG responsive cells were CD4+ and human leucocyte antigen DR restricted, that PBMC also respond to CSF IgG from other MS patients and that the CSF may contain T cells responding to autologous CSF IgG. This suggests that CSF IgG, or substances bound to this IgG, may represent T-cell immunogens, which could contribute to the intrathecal immune response in MS.
Holtmannspotter, M., M. Inglese, et al. (2003). "A diffusion tensor MRI study of basal ganglia from patients with ADEM." J Neurol Sci 206(1): 27-30.
Using diffusion tensor (DT) MRI and histogram analysis, we measured mean diffusivity ((-)D) of basal ganglia grey matter (GM) from eight patients with acute disseminated encephalomyelitis (ADEM), 10 patients with multiple sclerosis (MS), and 10 healthy controls. Patients with ADEM had higher average (-)D (p=0.02) and lower (-)D histogram peak height (p=0.008) of the basal ganglia GM than patients with MS. Microscopic tissue damage occurs in the basal ganglia of ADEM patients, but not in MS patients with a similar burden of MRI-visible brain lesions.
Hoogervorst, E. L., M. J. Eikelenboom, et al. (2003). "One year changes in disability in multiple sclerosis: neurological examination compared with patient self report." J Neurol Neurosurg Psychiatry 74(4): 439-42.
OBJECTIVE: To characterise prospectively the relation between one year changes in neurologist rating of neurological exam abnormalities as measured by the Expanded Disability Status Scale (EDSS) and changes in patient perceived disability as measured by the Guy's Neurological Disability Scale (GNDS) in patients with multiple sclerosis. METHODS: Two hundred and fifty patients with MS were recruited at an outpatient clinic. Disability at baseline and one year follow-up was assessed using the EDSS and GNDS. Correlations between change in EDSS, GNDS-sum score, Functional Systems and GNDS subcategories were studied as well as the significance of changes in EDSS associated with changes in perceived disability. RESULTS: The correlation between one year changes in EDSS versus GNDS was substantially lower (0.19) than cross-sectional correlations between EDSS and GNDS either at baseline (0.62) or at follow-up (0.77). Notably, changes in functional system scores that are based on neurological examination are poorly or not at all correlated with changes in disability as perceived by the patient. Analysing the impact of a significant worsening in EDSS-score, a commonly applied outcome criterion in clinical trials, we found that this was associated with significant worsening, insignificant change, and significant improvement in the patients' perceived disability in 45%, 39% and 15% of patients, respectively. CONCLUSION: Patients' perception of change in disability differs not only quantitatively but also qualitatively from that of an examining physician. This seems to be due both to the fact that there are true differences in change as perceived by the patient and that measured by the physician and to the fact that changes in many dimensions of disability that are relevant to the patient have no measurable impact on the EDSS.
Hoogervorst, E. L., P. de Jonge, et al. (2003). "The INTERMED: a screening instrument to identify multiple sclerosis patients in need of multidisciplinary treatment." J Neurol Neurosurg Psychiatry 74(1): 20-4.
OBJECTIVE: To analyse the value of the INTERMED, a screening instrument to assess case complexity, compared with the Expanded Disability Status Scale (EDSS) and the Guy's Neurological Disability Scale (GNDS) to identify multiple sclerosis (MS) patients in need of multidisciplinary treatment. METHODS: One hundred MS patients underwent INTERMED, EDSS, and GNDS examinations. Patient care needs were assessed by a multidisciplinary team and a goal oriented treatment plan was defined. Correlations between INTERMED, individual INTERMED domains, EDSS, GNDS sum score, and total number of proposed disciplines involved in the treatment plan were studied. RESULTS: Mean (SD) age was 40.6 (10.1) years. Median scores were 14.0 for the INTERMED, 4.0 for the EDSS, and 13.5 for the GNDS sum score. Moderate correlations were found between the INTERMED sum score and EDSS (r=0.59) and GNDS sum score (r=0.60). The number of disciplines as proposed by the multidisciplinary team showed the highest statistically significant correlation with the INTERMED sum score (r=0.41) compared with EDSS (r=0.32) and GNDS sum score (r=0.34). No significant or only weak correlations were found between the psychological domain of the INTERMED and EDSS or GNDS. CONCLUSION: The findings in this study show that there is an additional value of the INTERMED compared with the EDSS and GNDS in identifying MS patients in need of multidisciplinary treatment. The INTERMED domains show the area of the patient's vulnerability and care needs: especially the INTERMED's psychological and social domains may guide the clinician to deal with specific problems that complicate healthcare delivery.
Hooper, J. and I. R. Whittle (2003). "Costs of thalamic deep brain stimulation for movement disorders in patients with multiple sclerosis." Br J Neurosurg 17(1): 40-5.
Several studies have shown that thalamic deep brain stimulation (DBS) reduces tremor and improves hand performance in patients with multiple sclerosis (MS). The purpose of this paper is to describe the cost implications of DBS in MS patients and to highlight postoperative medical requirements that can be associated with this therapy. In a prospective study of thalamic DBS in MS patients the mean equipment costs were pounds 4769 (median pounds 7010, Medtronic, 1998 prices); mean neurosurgical inpatient costs per operated patient (n = 15) were pounds 4848 (range pounds 1982-8920, median pounds 5110); and mean in-patient postoperative rehabilitation cost pounds 4602 (range pounds 0-32,225, median pounds 1783). In addition there were transport and follow up costs. Mean neurosurgical inpatient stay following stereotactic DBS implantation was 15 days (median 12 days); and mean inpatient, postoperative rehabilitation stay 54 days (median 25 days). Although there were significant improvements in hand function and tremor reduction at 12 months postoperation, the level of patient performance in activities of daily living, their perception of their handicap and ipse facto the amount of home support required were unchanged from preoperative levels. This study has highlighted significant unforeseen medical requirements and costs that can occur in MS patients who have thalamic DBS surgery.
Horsfield, M. A., G. J. Barker, et al. (2003). "Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis." J Magn Reson Imaging 17(4): 389-97.
Quantitative evaluation of brain magnetic resonance imaging (MRI) scans is now an accepted part of the trial of new putative treatments for multiple sclerosis (MS). However, conventional MRI is not pathologically specific, and it does not reveal the details of the pathological processes that underlie the progression of the disease. Magnetization transfer (MT) imaging is a relatively new quantitative technique that appears to offer some pathological specificity, and can be used to monitor the changes over time in both individual lesions and the central nervous system as a whole. This paper considers the case for incorporating MT imaging into new clinical trials, so that the utility of MT for monitoring the modification of MS progression by treatment can be assessed. Specific guidelines for implementing MT imaging as part of a large multicenter clinical trial are given, and practical considerations when planning such a trial are detailed. It is anticipated that MT imaging will be incorporated into many new trials in the near future. J. Magn. Reson. Imaging 2003;17:389-397.
Hosokawa, M., A. Klegeris, et al. (2003). "Expression of complement messenger RNAs and proteins by human oligodendroglial cells." Glia 42(4): 417-23.
Neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing most, if not all, of the complement proteins. Little is known, however, about the capacity of oligodendroglial cells to generate complement components. This study evaluated expression of complement mRNAs and their protein products by human oligodendrocytes. Cells were isolated and cultured from white matter of seven adult cases that had undergone surgical temporal lobe resection for epilepsy. Oligodendroglial cultures were characterized by the expression of such cell type-specific mRNAs as myelin proteolipid protein (PLP), oligodendrocyte-specific protein (OSP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and were further characterized by immunostaining for such differentiation markers as myelin basic protein (MBP), PLP, CNPase, and O4. RT-PCR analysis showed that the oligodendroglial cells expressed detectable levels of complement mRNAs for the C1q B-chain, C1r, C1s, C2, C3, C4, C5, C6, C7, C8 gamma subunit, and C9. Immunostaining was positive for C1q, C1s, C2, C3, C4, C5, C6, C7, C8, and C9. Double immunostaining for the oligodendrocyte marker O4 and the complement protein C3 demonstrated that all O4-positive cells were also positive for C3, indicating constitutive C3 expression. These results indicate that oligodendroglial cells may be a source of complement proteins in human brain and thus could contribute to the pathogenesis of several neurodegenerative and inflammatory diseases of the CNS, such as Alzheimer's disease, multiple sclerosis, and progressive supranuclear palsy, where complement-activated oligodendrocytes are abundant. GLIA 42:417-423, 2003. Copyright 2003 Wiley-Liss, Inc.
Houzen, H., M. Niino, et al. (2003). "The prevalence and clinical characteristics of MS in northern Japan." J Neurol Sci 211(1-2): 49-53.
In Japan, there is a low prevalence rate (PR) of multiple sclerosis (MS; 0.8-4.0/100,000) but a relatively high frequency of "optic-spinal form" MS (OS-MS). There have been no intensive epidemiologic frequency studies, however, in over 30 years. We performed a province-wide prevalence study of MS in the Tokachi province of Hokkaido, the northernmost island of Japan, and compared the observed clinical features with other populations in Japan and Western countries. Prevalence was determined on March 31, 2001. The primary sources for the case ascertainment were 13 hospitals that treated patients with neurologic diseases including MS in Tokachi. Patients were classified according to Poser's criteria. The prevalence rate of clinically definite or laboratory-supported definite MS (LSDMS) was 8.57 per 100,000 [31/361,726; male/female ratio=1:2.9, and age at onset=29.1+/-14.2 (mean+/-SD) years]. Out of the 31 patients, 5 (16%) were classified as OS-MS. The prevalence rate of MS in the Tokachi province was the highest reported in Orientals to date, although still low in comparison with Western communities at a similar latitude. In contrast to the previous reports in Japan, there was a relatively low frequency of OS-MS in Hokkaido.
Howard, A. K., D. K. Li, et al. (2003). "MRI contributes to the differentiation between MS and HTLV-I associated myelopathy in British Columbian coastal natives." Can J Neurol Sci 30(1): 41-8.
BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in British Columbian Coastal Natives has, to date, been a clinical and laboratory diagnosis. However, magnetic resonance imaging (MRI) abnormalities have been well-described in other populations in which HAM/TSP is endemic. METHODS: In order to assess the usefulness of MRI as a diagnostic tool in this population, we compared scans of HAM/TSP patients with those of HTLV-I positive non-HAM/TSP British Columbian Coastal Natives (carriers) and multiple sclerosis patients presenting with progressive paraparesis. Results: The typical nonspecific findings of thoracic cord atrophy and increased signal in the periventricular and subcortical white matter on T2-weighted images were confirmed in the HAM/TSP patients. Despite a lack of specificity of the MRI findings between HAM/TSP patients and HTLV-I carriers, criteria that could effectively differentiate HAM/TSP patients from multiple sclerosis patients with similar clinical presentations were determined. CONCLUSIONS: Clinical and radiological correlations suggest that longitudinal MRI investigations charting the course of HAM/TSP may reveal the clinical significance of these lesions and further define the role of MRI in the diagnosis of this entity. Magnetic resonance imaging is an important supplement to immunological and clinical data in differentiating multiple sclerosis from HAM/TSP.
Hug, A., M. Korporal, et al. (2003). "Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis." J Immunol 171(1): 432-7.
Multiple sclerosis (MS) is an inflammatory and possibly autoimmune mediated demyelinating disease of the CNS. Autoimmunity within the CNS may be triggered by dysfunction of peripheral immune tolerance mechanisms via changes in the homeostatic composition of peripheral T cells. We have assessed the release of naive T lymphocytes from the thymus in patients with relapsing remitting MS (RRMS) to identify alterations in the equilibrium of the peripheral T cell compartment. Thymic T cell production was estimated by measuring TCR excision circles (TRECs) as a traceable molecular marker in recent thymic emigrants. A total of 46 treatment-naive patients with active RRMS and 49 gender- and age-matched healthy persons were included in the study. The levels of TREC-expressing CD4(+) and CD8(+) T lymphocytes were significantly decreased in MS patients, and TREC quantities overall matched those of 30 years older healthy individuals. The average concentrations of TRECs/10(6) CD4(+) and CD8(+) T lymphocytes derived from MS patients and healthy donors were 26 x 10(3)/10(6) and 28 x 10(3)/10(6) vs 217 x 10(3)/10(6) and 169 x 10(3)/10(6), respectively. To account for any influence of T cell proliferation on TREC levels, we assayed T lymphocytes from additional patients with MS and normal individuals for telomere length (n = 20) and telomerase activity (8 MS patients, 16 controls), respectively. There were no significant differences between CD4(+) and CD8(+) T cells from MS patients and controls. Altogether, our findings suggest that an impaired thymic export function and, as a consequence, altered ability to maintain T cell homeostasis and immune tolerance may play an important pathogenic role in RRMS.
Hughes, G. R. (2003). "Migraine, memory loss, and "multiple sclerosis ". Neurological features of the antiphospholipid (Hughes') syndrome." Postgrad Med J 79(928): 81-3.
The antiphospholipid syndrome (APS, Hughes' syndrome), first described in 1983, is a prothrombotic disease in which neurological events feature prominently. Strokes, transient ischaemic attacks, and headaches (including migraine) are important complications. However, it is clear that other neurological symptoms, including diplopia, memory loss, ataxia, and "multiple sclerosis-like" features are common. A notable feature of Hughes' syndrome is the clinical response to anticoagulants; features such as headache and memory loss often improving dramatically with appropriate warfarin dosage. APS may well become recognised as an important (and potentially treatable) cause of neurological disease.
Hughes, R. A. (2003). "Interferon beta 1a for secondary progressive multiple sclerosis." J Neurol Sci 206(2): 199-202.
This non-systematic review identified four randomised trials that have tested the efficacy of interferon beta in secondary progressive multiple sclerosis (SPMS). Two were trials of interferon beta 1a (IFNb1a) and two of interferon beta 1b (IFNb1b). All have shown significant reductions in relapse rates and accumulation of new magnetic resonance imaging (MRI) lesions, but only one trial (of IFNb1b) showed significant slowing of disability progression. Post hoc analyses of these trials suggest that the differences in outcomes might be partly explained by the differences between the trials in the proportions of patients with relapsing disease. In one of the trials of IFNb1a (the SPECTRIMS trial), the hazard ratio for progression in the treated relapsing patients with relapses in the two pre-study years was 0.74 compared to placebo patients with pre-study relapses and 1.01 in the treated patients compared to the placebo patients without pre-study relapses. In the same trial, the treatment effects on MRI parameters were more marked in the patients who had recent pre-study relapses compared with those who had not. These observations have led to the recommendation in national guidelines that prescribing of IFNb in SPMS be limited to those patients who have had disabling relapses in the last 2 years. These conclusions should be reviewed when the full results of all four trials have been published.
Huitinga, I., Z. A. Erkut, et al. (2003). "The hypothalamo-pituitary-adrenal axis in multiple sclerosis." Ann N Y Acad Sci 992: 118-28.
During multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), activation of the hypothalamo-pituitary-adrenal (HPA) axis is considered to modulate the immune system in such a way that the probability of recovery from a relapse is increased. In a series of postmortem studies we observed a significant activation of corticotropin releasing hormone (CRH) neurons and increased cortisol in the cerebrospinal fluid (CSF) of MS patients, indicating activation of the HPA axis in this disease. On the other hand, sepsis, while elevating cortisol in control subjects, did not associate with a further increase of cortisol in MS patients. Thus, the activated HPA-system in MS does not respond to an acute inflammatory stimulus. In order to investigate the role of chronic inflammation in the CNS in the activation of the HPA axis in MS, MS lesions in the hypothalamus were quantified and interleukin (IL)-6 levels in the CSF were determined. There was no difference in IL-6 levels between MS and control patients. A positive correlation was found between cortisol and IL-6 in control subjects with sepsis, but not in MS patients with sepsis or MS and control groups without sepsis. Thus, IL-6 in the CSF of MS patients is not the cause of the activation of the HPA system in MS. We found a remarkably high incidence (95% of the patients) of MS lesions in the hypothalamus, of which the majority (60%) were active. The more active lesions were present in the hypothalamus, the shorter the disease duration to the moment of death, indicative of a worse disease course. Preliminary data show suppression of the activation of CRH neurons by active hypothalamic MS lesions. We propose that this suppression of CRH neurons by active hypothalamic MS lesions causes the concomitant unfavorable disease course via an inadequate cortisol response during relapses of MS.
Ilyas, A. A., Z. W. Chen, et al. (2003). "Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis." J Neuroimmunol 139(1-2): 76-80.
The identity of target antigen(s) in multiple sclerosis (MS) remains elusive despite much effort to identify it. We analyzed cerebrospinal fluid (CSF) from patients with MS, other neurological diseases (OND), other diseases (OD) and healthy controls for antibodies against purified sulfatide, a major glycosphingolipid of human myelin, by an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-immunostaining technique. Elevated anti-sulfatide antibodies were significantly higher in MS patients as compared with the OND group (p<0.05) and all controls combined (P<0.025). Binding of high titer antibodies to sulfatide was confirmed with TLC-immunostaining. Anti-sulfatide antibodies were detected in all subtypes of MS although the frequency was higher in patients with secondary progressive MS (SPMS) than in patients with primary progressive (PPMS) and relapsing-remitting MS (RRMS). The data demonstrate a humoral response to sulfatide in the CSF of patients with MS.
Inglese, M., B. S. Li, et al. (2003). "Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis." Magn Reson Med 50(1): 190-5.
It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy.
Issa, Y., D. C. Watts, et al. (2003). "Mercuric chloride: toxicity and apoptosis in a human oligodendroglial cell line MO3.13." Biomaterials 24(6): 981-7.
A human-human oligodendroglial cell line MO3.13 was chosen in this study to model the loss of oligodendrocytes that occurs during episodes of multiple sclerosis. The influence of mercuric chloride (HgCl(2)) upon cell viability specifically the mode of cell death, whether by an active apoptotic mechanism or passive necrosis was determined by morphological and biochemical analysis. Mitochondrial dehydrogenase activity MTT assay showed that HgCl(2) had toxic effects on MO3.13 cells at levels of (5-25 microM) with approximately 50% cell death observed at 58 microM. Death of cells was dependent on both time and concentrations of HgCl(2). Differentiated MO3.13 cells exposed to low concentrations (25 microM) of HgCl(2) exhibited features of apoptotic cell death, including cell shrinkage and chromatin condensation. High doses of HgCl(2) (>100 microM) induced death with characteristics of necrosis. Biochemical analysis showed that HgCl(2) activated the caspase family of proteases. This was measured directly by cleavage of fluorescent substrates and by immunoblotting assay of caspase substrate proteins; alpha-fodrin, lamin B and poly (ADP-ribose) polymerase (PARP). These results indicate that HgCl(2) is toxic at low concentrations for oligodendroglial cells and that the MO3.13 cell line dies in an apoptotic manner when exposed to low concentrations of HgCl(2). However, blood mercury concentrations in vivo in a normal population with amalgam restorations are lower by a factor of some 500 times than those causing toxicity in vitro suggesting a good safety margin in respect of environmental uptake.
Ito, S., T. Hattori, et al. (2003). "Is atopic dermatitis a risk factor for intervertebral disc degeneration? A preliminary clinical and MRI study." J Neurol Sci 206(1): 39-42.
Atopic dermatitis (AD) is a common allergic disease that has recently been reported to be complicated with acute myelitis. To clinically evaluate the occurrence of myelitis in AD, 65 consecutive AD patients were neurologically examined. Of these, 37 underwent cervical MRI scans. Unexpectedly, the neurologic and MRI findings did not suggest myelitis, but rather, in most cases, cervical spondylosis. Therefore, we assessed the relationship between AD and cervical spondylosis. In addition, cervical MRI findings in 26 patients with multiple sclerosis (MS) and in 12 normal controls were also evaluated. The neurologic examinations in the AD patients frequently showed hyperreflexia in the legs, and sensory and motor disturbances were often present in the limbs. Cervical MRI findings suggestive of spondylosis, such as intervertebral disc degeneration and bulging/protrusion, were found more frequently in AD patients than in MS patients, with statistical significance. Posterior spondylolisthesis was observed with higher frequency in AD and MS patients than in normal controls. We concluded that AD might be a risk factor for intervertebral disc degeneration. As far as we know, this is the first paper describing the potential association between disc degeneration and AD.
Iversen, L. (2003). "Cannabis and the brain." Brain 126(Pt 6): 1252-70.
The active compound in herbal cannabis, Delta(9)-tetrahydrocannabinol, exerts all of its known central effects through the CB(1) cannabinoid receptor. Research on cannabinoid mechanisms has been facilitated by the availability of selective antagonists acting at CB(1) receptors and the generation of CB(1) receptor knockout mice. Particularly important classes of neurons that express high levels of CB(1) receptors are GABAergic interneurons in hippocampus, amygdala and cerebral cortex, which also contain the neuropeptides cholecystokinin. Activation of CB(1) receptors leads to inhibition of the release of amino acid and monoamine neurotransmitters. The lipid derivatives anandamide and 2-arachidonylglycerol act as endogenous ligands for CB(1) receptors (endocannabinoids). They may act as retrograde synaptic mediators of the phenomena of depolarization-induced suppression of inhibition or excitation in hippocampus and cerebellum. Central effects of cannabinoids include disruption of psychomotor behaviour, short-term memory impairment, intoxication, stimulation of appetite, antinociceptive actions (particularly against pain of neuropathic origin) and anti-emetic effects. Although there are signs of mild cognitive impairment in chronic cannabis users there is little evidence that such impairments are irreversible, or that they are accompanied by drug-induced neuropathology. A proportion of regular users of cannabis develop tolerance and dependence on the drug. Some studies have linked chronic use of cannabis with an increased risk of psychiatric illness, but there is little evidence for any causal link. The potential medical applications of cannabis in the treatment of painful muscle spasms and other symptoms of multiple sclerosis are currently being tested in clinical trials. Medicines based on drugs that enhance the function of endocannabinoids may offer novel therapeutic approaches in the future.
Izquierdo, G. and J. L. Ruiz Pe a (2003). "[Clinical evaluation of multiple sclerosis: quantification by use of scales]." Rev Neurol 36(2): 145-52.
INTRODUCTION. Clinical evaluation is indispensable in multiple sclerosis (MS) for the quantitative measurement of the extent of the disorder, which is in turn required to find out how the disease is evolving and the influence the different forms of treatment are having on it, both in the experimental phase and in the usual monitoring they are subjected to. METHOD. We review the different scales that are used to evaluate the distinct symptomatic and functional aspects of MS and the repercussions these have on the extent of disability displayed in the patient s social and personal life. Although in recent years, the EDSS has been an essential, irreplaceable scale in MS, other instruments of measurement that complement it have also begun to appear. The fatigue, cognitive function and quality of life scales are being used more and more frequently. The Multiple Sclerosis Functional Composite is an instrument that is used more and more frequently in MS and has proved to be highly sensitive in the evaluation of very important clinical trials. CONCLUSIONS. The lack of correlation between the distinct scales corroborates the fact that they measure complementary aspects of MS.
Jan, M. H. and C. J. Jankosky (2003). "Multiple sclerosis presenting as neurological decompression sickness in a U.S. navy diver." Aviat Space Environ Med 74(2): 184-6.
A case of clinically definite multiple sclerosis presenting as neurological decompression sickness is presented. A 23-yr-old U.S. Navy diver experienced onset of hypesthesia of the left upper trunk approximately 19 h after making two SCUBA dives. She did not seek medical attention until 3 wk later, at which time she was diagnosed with possible neurological decompression sickness. She was treated with hyperbaric oxygen, but demonstrated no improvement. Further evaluation led to the diagnosis of multiple sclerosis. This case underscores the potential similarity in neurological presentation between multiple sclerosis and decompression sickness. The differential diagnosis of neurological decompression sickness, particularly in atypical cases, should include multiple sclerosis. The appropriateness of medically clearing multiple sclerosis patients for diving is discussed.
Janssens, A. C., J. B. de Boer, et al. (2003). "Expectations of wheelchair-dependency in recently diagnosed patients with multiple sclerosis and their partners." Eur J Neurol 10(3): 287-93.
The aim of the present paper was to quantify expectations of wheelchair-dependency in patients recently diagnosed with MS (n = 101) and their partners (n = 78). Expectations focused on the risk and seriousness of becoming wheelchair-dependent in 2 years, 10 years or lifetime. Expectations were compared with natural history data, compared between patients and their partners, and related to clinical characteristics. Our results show that patients overestimated their 2-year and 10-year risks of wheelchair-dependency, but underestimated their lifetime risks. A large number of patients were uncertain about their 2-year risk, even those with no or only minimal disability [Expanded Disability Status Scale (EDSS) <3.0]. One-third of the patients perceived the 10-year and lifetime risk to be 50%, which, as they explained in the interviews, reflected their uncertainty: they did not know what to expect - it might happen or not. Patients with more functional limitations had higher perceptions of risk, but lower perceptions of seriousness. Concordance in perceived risk and seriousness between patients and partners was moderate. The overestimation of the short-term risks and the substantial differences in expectations within couples warrant further research on the impact of expectations on their treatment decisions and psychological well-being.
Jarrett, L., A. Bradford, et al. (2003). "Attitudes to long-term care in multiple sclerosis." Nurs Stand 17(17): 39-43.
At a recent conference workshop, a group of specialist nurses examined their attitudes towards individuals with multiple sclerosis moving into long-term care. This article summarises how the group members examined their attitudes, the literature reviewed and what was learnt by sharing experiences. It also suggests how nurses could promote positive attitudes towards, and ease, the transition of patients into long-term residential care.
Jarus-Dziedzic, K., E. Kasper, et al. (2003). "Incidental stereotactic diagnosis of cerebral insults." Neurol Res 25(2): 173-8.
Among the patients (6854 patients 1990-1999) who underwent computer-assisted stereotactic biopsy most were referred with the presumptive diagnosis of a brain mass lesion. Forty-three cases (0.63%) were found in which the final histopathological diagnosis excluded a neoplastic, infectious or inflammatory lesion but disclosed a cerebral insult. Histologically these could be subdivided into ischemic insults in 38 cases (88%) and hemorrhagic insults in five cases (12%). On the basis of clinical and radiological findings in this group, 35 patients (81%) were sent to our department because of suspected neoplasmatic lesions, two patients (5%) because of multiple sclerosis, two patients (5%) because of inflammatory disease and one patient (2%) because of a suspected infectious parasitic disease. All patients underwent initial CT examinations which showed hypodense lesions of the brain in 38 patients (88%) and hyperdense lesions in five cases (12%). Constant enhancement on CT scans of the mass lesion was found in 12 patients (28%) only. Fourteen lesions (33%) were located in the right hemisphere, five lesions (12%) in the left hemisphere, nine lesions (21%) in the basal ganglia, four lesions (9%) in the midbrain, two lesions (4.5%) in the corpus callosum and one lesion (2%) in a thalamus. Multiple lesions were present in eight cases (19%). The most common initial neurological symptoms upon clinical presentation were hemiparesis (18 patients, 42%), epilepsy (eight patients, 18%), a change in mental status (six patients, 14%). There was no mortality and no operative morbidity associated with the stereotactic biopsy in this group of patients. The most common neurological disorder, cerebrovascular insult, rarely poses diagnostic problems. If there are doubts a serial stereotactic biopsy can safely clarify the situation.
Jean, I. and C. Fressinaud (2003). "Spontaneous central nervous system remyelination is not altered in NFH-lacZ transgenic mice after chemical demyelination." J Neurosci Res 73(1): 54-60.
Harmonious functioning of the nervous system depends on neuron-glia interactions, particularly between the axons and their myelinating cells, i.e., oligodendrocytes (OL) in the central nervous system (CNS). In human demyelinating diseases such as multiple sclerosis (MS), demyelination may be associated with axonal damage, but alterations of the axonal cytoskeleton, which is composed mainly of neurofilaments (NF) and microtubules, are largely unknown, as are the consequences on remyelination. In a model of demyelination induced by lysophosphatidylcholine (LPC), we have shown that demyelination was correlated with a decrease in NF immunolabelling, and that these axonal abnormalities were reduced by platelet-derived growth factor (PDGF)-enhanced remyelination in adult rats. We have analysed the spontaneous remyelination after LPC stereotaxic injection in the CNS of transgenic NFH-lacZ mice, which present axonal atrophy caused by abnormal distribution of NF, associated with hypermyelination in the PNS, and normal myelin thickness in the CNS. Axonal atrophy in the CNS of NFH-lacZ mice was confirmed, but it was not worsened by demyelination. On the contrary, demyelination induced axonal atrophy in wild-type mice, demonstrating that NF are essential for axonal calibre determination. Moreover, an efficient spontaneous remyelination occurred in NFH-lacZ as well as in wild-type mice, indicating that the NF are not necessary for CNS remyelination. These findings point out that NF modifications observed in MS may not be responsible for the lack of remyelination in this disease. Copyright 2003 Wiley-Liss, Inc.
Jellinger, K. A. (2003). "New Frontiers of MR-Based Technique in Multiple Sclerosis." Eur J Neurol 10(4): 467.
Jin, Y. P., J. de Pedro-Cuesta, et al. (2003). "Predicting multiple sclerosis at optic neuritis onset." Mult Scler 9(2): 135-41.
Using multivariate analyses, individual risk of clinically definite multiple sclerosis (CDMS) after monosymptomatic optic neuritis (MON) was quantified in a prospective study with clinical MON onset during 1990-95 in Stockholm, Sweden. During a mean follow-up time of 3.8 years, the presence of MS-like brain magnetic resonance imaging (MRI) lesions and oligoclonal immunoglobulin (Ig) G bands in cerebrospinal fluid (CSF) were strong prognostic markers of CDMS, with relative hazard ratios of 4.68 [95% confidence interval (CI) 2.21-9.91] and 5.39 (95% CI 1.56-18.61), respectively. Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95% CI 1.02-3.04) and 2.21 (95% CI 1.13-3.98), respectively. Based on the above two strong predictors, individual probability of CDMS development after MON was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years. The highest probability, 0.66 (95% CI 0.48-0.80), was obtained for individuals presenting with three or more brain MRI lesions and oligoclonal bands in the CSF, and the lowest, 0.09 (95% CI 0.02-0.32), for those not presenting with these traits. Medium values, 0.29 (95% CI 0.13-0.53) and 0.32 (95% CI 0.07-0.73), were obtained for individuals discordant for the presence of brain MRI lesions and oligoclonal bands in the CSF. These predictions were validated in an external one-quarter sample.
Jin, Y. P., J. De Pedro-Cuesta, et al. (2003). "Birth cohort effects in multiple sclerosis." Ann Epidemiol 13(4): 252-60.
PURPOSE: To identify potential birth cohort effects in multiple sclerosis in Sweden and particularly in Stockholm county.METHODS: Data on multiple causes of death from multiple sclerosis during 1962 to 1995 in Sweden and 1968 to 1995 in Stockholm county were analyzed using age-period-cohort models and curvature.RESULTS: Mortality from multiple sclerosis was higher in Sweden than in Stockholm county, with stable time trends, slight period effects and marked age effects. Cohorts born before or after a central period, from 1910 through 1930, registered lower mortality. A periodic wave-form mortality pattern was identified, following a 5-to-6-year cycle for cohorts born before 1925 both in and outside Stockholm county, and changing to longer or irregular cycles for cohorts born after 1930.CONCLUSIONS: Although methodological constraints inducing the saw-tooth pattern cannot be excluded, these results are consistent with etiologic hypotheses claiming a role for environmental factors in multiple sclerosis.
Jinochova, M., Z. Seidl, et al. (2003). "[Multiple sclerosis and magnetic resonance]." Cas Lek Cesk 142(3): 144-9.
Multiple sclerosis is a demyelinating process presently referred to autoimmune diseases. Its diagnostics is based on clinical examination and paraclinical tests (magnetic resonance, examination of CSF and evoked potentials recording). Magnetic resonance (MR) has the highest significance, both for the diagnostics and for the monitoring of the course of disease and results of treatment. Results of magnetic resonance are not specific for the multiple sclerosis and therefore for the reliable diagnosis the McDonadl's criteria have to be fulfilled. It appears that magnetic resonance is more sensitive to progression of disease than the clinical examination. Monitoring of the course of disease requires new techniques of MR imaging. Automatic, software assisted determination of plaque volumes in T2 and T1 weighted images--so called "lesion load", is checked during the patient's treatment. Assessment of brain volume determines progression of atrophy. The aim of all the new methods of MR imaging is to search for a reliable technique of the disease monitoring and namely for the prediction of disease progression.
Johnson, J. (2003). "On receiving the diagnosis of multiple sclerosis: managing the transition." Mult Scler 9(1): 82-8.
This article reports on one aspect of a wider study into multiple sclerosis (MS) specialist nurse roles in the UK. Insights gained from in-depth patient interviews are discussed in relation to literature regarding the meaning of health-related events, such as diagnosis. The findings of this project indicated that for many people, intense feelings of abandonment and isolation were generated at the time of diagnosis and stayed with the person for many months or years. Differing expectations between patient and neurologist following confirmation of diagnosis could contribute to these findings. It is suggested that imparting a diagnosis of MS should be seen as the start of a transition that needs to be made explicit to the patient and closely linked to the provision of sources of information, advice and ongoing support as people learn to live with and manage the disease.
Jolivalt, C. G., R. B. Howard, et al. (2003). "A novel nitric oxide scavenger in combination with cyclosporine A ameliorates experimental autoimmune encephalomyelitis progression in mice." J Neuroimmunol 138(1-2): 56-64.
Immunotherapy improves experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), while excessive production of nitric oxide (NO) has been implicated in the pathogenesis of this disease. Here, we show that disease progression in SJL/J mice with EAE is improved after treatment with either a subtherapeutic dose of cyclosporine A (CsA) or NOX-100, a nitric oxide scavenger. Importantly, the impact of subtherapeutic doses of CsA in combination with NOX-100 on disease progression in EAE was greater than that attained with either agent alone and led to near total protection. CNS inflammation and gene expression of proinflammatory cytokines and iNOS were also significantly reduced after treatment. These observations point to the potential therapeutic utility of NOX-100 as a dose-reducing agent for CsA in the treatment of MS.
Jones, R. E., D. Bourdette, et al. (2003). "Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis." J Immunol 170(4): 1690-8.
The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.
Jones, S. J. and A. Brusa (2003). "Neurophysiological evidence for long-term repair of MS lesions: implications for axon protection." J Neurol Sci 206(2): 193-8.
After recovery from the acute stage of optic neuritis, a marked prolongation in the latencies of visual evoked potentials (VEPs) is typically observed. We have conducted three studies (one cross-sectional, two prospective), aimed at elucidating the progressive shortening of VEP latency, which frequently ensues over the following months or years. This has been shown to be a progressive process and a prevalent tendency in the patient population, proceeding for more than 2 years in spite of the fact that very little functional improvement in vision occurs after the first few months. We argue that the underlying process of repair is most likely to involve remyelination of demyelinated optic nerve axons. Rather than restoration of visual function (which may be virtually complete after as short a period as 3 months), the main importance of the long-term myelin repair process may consist in protecting demyelinated axons from subsequent, permanent degeneration. In the VEPs of the acutely unaffected fellow eyes followed up over 3 years, we observed an asymptomatic deterioration, possibly due to insidious processes of demyelination and/or axonal degeneration. Even in the relapsing/remitting stage of MS, therefore, there is electrophysiological evidence for involvement of clinically asymptomatic axons, which, in the later stages, may be manifested as progressive functional deterioration.
Jopson, N. M. and R. Moss-Morris (2003). "The role of illness severity and illness representations in adjusting to multiple sclerosis." J Psychosom Res 54(6): 503-11; discussion 513-4.
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.
Jordan, J. F., P. Walter, et al. (2003). "Intermediate uveitis in childhood preceding the diagnosis of multiple sclerosis: a 13-year follow-up." Am J Ophthalmol 135(6): 885-6.
PURPOSE: An association between multiple sclerosis during childhood and uveitis is exceptionally rare. This is a report of a female patient who presented at the age of 8 years with bilateral intermediate uveitis and whose final diagnosis of multiple sclerosis was made at age 21 years. DESIGN: Case report. METHOD: Retrospective chart review of a 13-year follow-up history. RESULTS: Over 10 years our patient was treated systemically and underwent bilateral vitrectomy to reduce permanent side effects. Owing to good visual function and low inflammatory signs, systemic therapy was stopped. Multiple sclerosis was diagnosed at the age of 21, after a 13-year history of uveitis and after 3 years without medication. CONCLUSIONS: In the constellation of uveitis in childhood and later diagnosis of multiple sclerosis, the outlined therapy provided good functional results. Moreover, it may have delayed the manifestation of the underlying disease for 13 years.
Jurewicz, A., M. Matysiak, et al. (2003). "T