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PubMed1995

Does hemispheric dominance influence brain lesion distribution in multiple sclerosis?

To evaluate whether hemispheric lesion distribution in multiple sclerosis is related to the uneven interhemispheric localisation of cerebral function, a 10 item self administered questionnaire evaluating hand preference and supratentorial brain MRI was obtained in 23 patients with clinically definite multiple sclerosis. The mean degree of hand preference was +74 (range -86 to +100). The median lesion volumes were 7275 (range 1045-22,440) mm3 for the left hemisphere and 5385 (range 1010-19,490) mm3 for the right hemisphere. The degree of hand preference correlated with the index of interhemispheric lesion distribution (P = 0.02). The data suggest that local events, possibly related to specialisation of hemispheric function, might be responsible for the increased vulnerability of the dominant hemisphere to the pathological process of multiple sclerosis.

Adolescent↗
PubMed1985

[Metabolic aspects of multiple sclerosis].

According to the present opinion multiple sclerosis (MS) is caused by a concurreance of various factors. This predisposing factor seem to be related to a disturbance of the lipid- and fatty acid metabolism, characterized by decreased concentrations of polyunsaturated fatty acids (PUFA) and essential fatty acids (EFA) in the plasma, the blood cells, the cerebrospinal fluid (CSF) and white matter of the brain in patients with MS. A disturbed absorption of EFA could be excluded. Now the question arises whether there is a disturbed utilisation of EFA with the consequence of biochemical changes in myelin and blood cells. According to lipid-chemical and lipolytic enzymological studies a disturbance of the fatty acid elongation system as well as primary increased activation of the phospholipase A1 is conceivable. According to the demonstrated results the conception of a metabolic immunological caused generalised defect of the biological membranes - especially those of the myelin sheath and platelets - as predisposing factor for the increased platelet aggregation is possible. Even though these ideas do not yet allow a concrete pathogenetic conclusion, the prostaglandins (PG) might be of importance because their precursors are fatty acids and influence the immune mechanisms. Possibly, new approaches follow from the synopsis of present working hypotheses for an extended biochemical-immunological model of multiple sclerosis. Further immunological and laboratory methods should concentrate on differentiating MS from other diseases of the central nervous system and on diagnosing the disease in its early stage. The results of this work are fully discussed in other publications. Separate prints can be requested from the author.

Fatty Acids, Essential↗
PubMed1991

Evidence for early lower urinary tract dysfunction in clinically silent multiple sclerosis.

The occurrence of micturition complaints as late sequelae of multiple sclerosis is well studied and documented. However, no reports exist on urologically asymptomatic patients with a relatively short disease duration. In a prospective study of 40 patients with definite multiple sclerosis (mean disease duration 5 years), urodynamic investigations (cystometry and pressure-flow study) were combined with neuro-urophysiological measurements (cortical evoked potentials and sacral reflex latencies). Patients with (13) and without (27) micturition complaints were investigated. Neurourodynamic abnormalities were seen in 35 of 40 patients (88%). The lower urinary tract proved to be afflicted by multiple sclerosis at an early stage of the disease. Early neurourodynamic investigations had clinical implications. All of the complaining and half of the noncomplaining patients showed urodynamic abnormalities upon which the need for further followup and eventual therapeutic intervention was based. We conclude that neurourodynamic testing of a urinary functional system can be worthwhile as part of the initial diagnostic evaluation in patients with proved multiple sclerosis.

Adult↗
PubMed2001

Immunologic therapy for relapsing-remitting multiple sclerosis.

The treatment of relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis, has been revolutionized in recent years. In addition to effective treatment of acute relapses, therapies are now available to prevent relapses, reduce the burden of disease as seen on magnetic resonance imaging, and possibly even slow the course of disease. There are now several agents either approved, awaiting approval, or in various stages of development in many countries. Evidence suggests that early intervention with these agents will yield the best results in the long run. The current approach to treatment of RRMS is the focus of this discussion.

Adjuvants, Immunologic↗
PubMed1999

Estimating the prevalence of multiple sclerosis in the United Kingdom by using capture-recapture methodology.

The geographic distribution of multiple sclerosis is nonrandom, as the disease is more prevalent in temperate than in tropical regions. Surveys conducted between 1970 and 1996 suggest that multiple sclerosis is more prevalent in the northern part of the United Kingdom than in the southern part. This north-south gradient ("the latitudinal gradient") might be a methodological artifact, because high prevalence figures from serial surveys of the northern part of the United Kingdom might have been the result of better ascertainment. By using capture-recapture methods, the authors found that case ascertainment was similar in the northern and southern parts of the United Kingdom. When prevalence figures for multiple sclerosis in the southern United Kingdom were increased to account for the number of unobserved cases, the difference persisted: The prevalence of multiple sclerosis in the northern part of the United Kingdom appeared to be at least 180 cases per 100,000 persons, whereas the maximum prevalence in the southern part of the United Kingdom was less than 160 cases per 100,000 persons. The distribution of multiple sclerosis in the United Kingdom is not uniform and is consistent with the hypothesis that populations with a high prevalence of multiple sclerosis may be genetically predisposed to the disease.

Adult↗
PubMed2003

Intermediate uveitis in childhood preceding the diagnosis of multiple sclerosis: a 13-year follow-up.

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.

Azathioprine↗
PubMed1998

High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition.

OBJECTIVE: To determine the incidence and prevalence of multiple sclerosis in the Lothian and Border Health Board Regions of south east Scotland. METHODS: Incidence study: all patients were identified in whom a diagnosis of Poser category probable or definite multiple sclerosis was made by a neurologist between 1992 and 1995. Prevalence study: all patients known to have multiple sclerosis who were alive and resident in the study area on 15 March 1995 were recorded. RESULTS: The crude annual incidence rates of probable or definite multiple sclerosis per 100000 population were the highest ever reported: 12.2 (95% confidence interval (95% CI) 10.8-13.7) in the Lothian Region and 10.1 (95% CI 6.6-13.6) in the Border Region. A total of 1613 patients with multiple sclerosis were resident in the study area, giving standardised prevalence rates per 100000 population of 203 (95% CI 192-214) in the Lothian Region and 219 (95% CI 191-251) in the Border Region. Prevalent cases were more likely than expected to have a Scottish surname (risk ratio 1.24, 95% CI 1.14-1.34). CONCLUSION: Orkney and Shetland were previously thought to have by far the highest prevalence of multiple sclerosis in the world: about double that found in England and Wales. However, the prevalence in south east Scotland is equally high, suggesting that the Scottish population as a whole has a genetic susceptibility to the disease, and undermining the hypothesis that patterns of infection specific to small sparsely populated island communities are important in the causation of multiple sclerosis.

Adolescent↗
PubMed1975

Quantitative estimation of cerebrospinal fluid globulins in multiple sclerosis. A comparison of electrophoretic and immunologic methods.

CSF samples were obtained from 44 multiple sclerosis patients during exacerbation and from 50 age and sex-matched non-multiple sclerosis controls. In an attempt ot select the most suitable test for diagnosis of multiple sclerosis, each sample was analyzed by three methods: (1) electrophoresis, (2) electroimmunodiffusion, and (3) radial immunodiffusion (RID). Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded positive results in 50, 55, and 59 percent of the multiple sclerosis patients respectively. Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded 10, 12, and 8 percent false positives (beyond mean +/- 1 S.D.) respectively. Thus the three tests did not differ much with regard to yield of true or false positive results. When factors such as simplicity, time and equipment involved, and the interval between the test and results are taken into account, radial immunodiffusion appears to be most suitable for an avverage CSF diagnostic laboratory. For a laboratory with special interest in multiple sclerosis, agarose gel-electrophoresis of concentrated CSF appears to be the test of choice.

Adult↗
PubMed1985

[Role of neuroallergy in the pathogenesis of multiple sclerosis].

The neurotropic effects of sera were determined in patients with multiple sclerosis and in animals with experimental allergic encephalomyelitis (EAE) using some newly devised methods. When multiple sclerosis and EAE were at the stage of exacerbation, the kallikrein-kinin system was activated and immune complexes content in the blood serum increased. The authors conclude that neuroallergy plays the major role in the development of multiple sclerosis exacerbations and that the devised methods are valuable for the laboratory confirmation of multiple sclerosis diagnosis.

Animals↗
PubMedDate not supplied

Expression of Fas antigen on T cell subpopulations in peripheral blood of patients with relapsing-remitting multiple sclerosis.

BACKGROUND: During the relapse of multiple sclerosis, the activation of T cells, autoreactive to myelin antigens in blood, enhanced and maintained as a result of anomalous mechanisms of their earlier elimination, leads on para- and autocrine basis to the activation of antigen- non-specific cells of immune system. In consequence, activated cells secrete a range of proinflammatory cytokines and display activation antigen expression on their surface, which results in blood-brain barrier damage. The differentiation of lymphocytes into effector cells in blood during MS relapse is to increase the number of cells supporting inflammatory reactions and simultaneously to reduce the number of cells which play a role of suppressors. Fas antigen is present among activation antigens found on T cells. Once this antigen has been combined with the ligand, it transmits apoptic signal to the cell. The presence of Fas antigen on activated peripheral blood T cells may enable us to estimate their activation and it may also indicate a potential to eliminate those cells from blood. The aim of the study was to provide a quantitative assessment of the subpopulations of CD3, CD4 and CD8 lymphocytes in peripheral blood and to investigate Fas antigen expression on these subsets in patients with relapsing-remitting multiple sclerosis, in relation to clinical activation of the disease. MATERIAL AND METHODS: Thirty-five patients participated in the study, including 14 patients finding themselves in clinical relapse of the disease and 21 patients in the state of remission. Additionally, 21 healthy subjects were included. Quantitative assessment of individual subpopulations and Fas co-expression was carried out with the use of monoclonal antibodies anti CD3, CD4 and CD8 as well as anti CD95 antibodies, and flow cytometer Pas/Dako Galaxy. RESULTS: The differences in the percentage of particular lymphocytes between 3 groups proved insignificant. Patients in the relapse of the disease showed significantly greater Fas expression on subpopulations CD3 and CD4 when compared to the results obtained from remission patients and control subjects. This difference was not observed for Fas expression on subset CD8. CONCLUSIONS: The investigation of Fas receptor expression may be useful in order to monitor clinical course of the disease, which is characterised by the periods of exacerbation and remission.

Adult↗
PubMed1999

Clinical and MRI study of brain stem and cerebellar involvement in Japanese patients with multiple sclerosis.

OBJECTIVES: To investigate the clinical and MRI features of brain stem and cerebellar lesions in Japanese patients with multiple sclerosis. METHODS: A retrospective study of 66 consecutive Japanese patients with multiple sclerosis (42 women and 24 men) was done by reviewing the medical records and MRI films. Forty nine patients were diagnosed as having clinically definite multiple sclerosis and 17 patients as having clinically probable multiple sclerosis according to Poser's criteria. Prevalence rates of each brain stem and cerebellar manifestation and frequency and distribution of MRI lesions in these patients were studied. RESULTS: Forty three patients (65%) had one or more infratentorial manifestations. Cranial nerves were clinically involved in 28 patients (42%), and most of the lesions were identified by MRI. Among them, manifestations of facial, trigeminal, and abducens nerves were relatively common. Cerebellar ataxia was found in 20 patients (30%). The MRI study showed that the lesions responsible for ataxia in these patients were mainly found in the cerebellar peduncles, but cerebellar hemispheric lesions were detected in only four patients (6.4%). CONCLUSION: The low frequency (6.4%) of the cerebellar MRI lesions in these patients is in sharp contrast with the figures reported for white patients with multiple sclerosis (50%-90%). Racial and genetic differences may have an influence on the susceptibility of each part of the CNS to demyelination in multiple sclerosis.

Asian People↗
PubMed1986

The mystery of the origin of multiple sclerosis.

Our present understanding of the aetiology and pathogenesis of multiple sclerosis is discussed in relation to the views of Sir William Gowers. He perceived that both environmental and genetic factors might be implicated in the aetiology of the disease. Evidence for the former was first reported in 1903, but has become convincing only in the past 20 years; the nature of the environmental factor remains obscure. Evidence for a genetic influence on susceptibility has accumulated since the 1930s, the most compelling coming from the recent Canadian twin study. The number and mode of operation of the genetic factors is still uncertain, but there is evidence for the implication of genetically controlled cellular immune mechanisms in the pathogenesis of the disease. The precise relationship between transient changes in immunological status and the development of new lesions has yet to be defined; magnetic resonance imaging (MRI) promises to play a significant role in this analysis because of its sensitivity in detecting abnormalities in multiple sclerosis. MRI is not in itself specific; it is probable that the similar appearances in multiple sclerosis and cerebral vascular disease both derive at least in part from the influence of astrocytic gliosis on proton content and distribution. The significance of the gliosis is uncertain. Gowers believed that the primary defect in multiple sclerosis lay in the astrocyte. Recent observations on the immunological functions of this cell in vitro suggest that it could be involved early in the pathogenesis of the lesion.

Brain↗
PubMed2000

[Multiple sclerosis and new imaging methods].

UNLABELLED: BACKGROUND OF PROBLEM: The recognition of the power of MRI and CT to show the involvement of the central nervous system in multiple sclerosis, as well as in other neuropathological phenomena, stimulate considerably their use in the assessment of diagnosis. Much experience gained during the development and clinical application of imaging on the basis of magnetic resonance (MRI) justify the use of this method also in verification of the diagnosis of multiple sclerosis. The development and clinical application of specific pulse sequences and unconventional techniques as e.g. "magnetisation transfer imaging", and other new methods with greater resolution are used in applied research. Routine clinical examinations of the brain and spinal cord are performed especially by use of "dual echo spin images". Flair sequences are not always more significantly sensitive, however, they can provide surprisingly remarkable facts. SUBJECTIVES: The aim of this study is to support the firm or tentative clinical diagnosis of multiple sclerosis. METHODS AND MATERIAL: 131 patients with multiple sclerosis were hospitalized at our clinic and examined by use of computerised tomography (CT) and magnetic resonance (MRI). The results of these examinations confirmed firmly the diagnosis of multiple sclerosis in 98 patients. The tentative diagnosis assessed in 33 patients was not supported by MRI. The findings gained by brain examination were evaluated according to the conditions assessed by Fazekasz and American Multiple Sclerosis Association. Examinations were performed by Signa Contour 0.5 Tesla magnetic resonance on transverse planes, and on sagital planes in T1 VO and T2 VO. RESULTS: During the initial period (1995-1996), CT examination of the brain was performed in 16 patients with firm diagnosis of multiple sclerosis, out of whom only 24% had the pathological periventricular finding within the white matter. Therefore, a majority of patients were subdued to MRI. In these patients, the characteristic finding of hyperintensive lesions were found within T2 VO. They were situated within periventricular white matter as well as in cerebellum, and in 24 patients they were located within the cervical part of the spinal cord. The patients forming the latter group had severe neurologic findings, and ranged 4-9 of the Kurtzke scale. MRI enabled to assess the diagnosis of multiple sclerosis in all patients. Out of the group of 33 patients, only 2 were subdued to CT of the brain. Their findings did not yield any changes in shape of brain tissue structures. MRI findings in these patients did not verify the diagnosis of multiple sclerosis sufficiently. The neurological findings were not pronounced, achieving the 1-3 degree of Kurtzke scale. CONCLUSION: Current techniques of CNS imaging, either by use of computerised tomography of MRI do not enable the assessment of the firm diagnosis of multiple sclerosis to full extent. MRI is capable only of supporting it. (Ref. 7.)

Brain↗
PubMed1979

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis.

We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.

Humans↗
PubMedDate not supplied

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

BACKGROUND: Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. METHODS: Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. FINDINGS: NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. INTERPRETATION: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.

Adult↗
PubMed2003

Multiple paradigm shifts in multiple sclerosis.

PURPOSE OF REVIEW: The present article reviews the currently ongoing scientific debate of our changing views on the pathogenesis of multiple sclerosis and the therapeutic strategies currently available for multiple sclerosis. RECENT FINDINGS: The most important observations include that (a) axonal loss accounts for permanent disability in multiple sclerosis, (b) remyelination should be possible in theory but fails for unknown reasons in the multiple sclerosis lesion, (c) inflammation can be beneficial, (d) treatment should be initiated early, and (e) immunosuppressive strategies exhibit beneficial effects in progressive forms of the disease. SUMMARY: Our current understanding of the immunopathogenesis of multiple sclerosis has changed in the past. Whereas demyelination was originally thought to be relevant for the lasting neurological deficit, it is nowadays commonly accepted that the extent of axonal loss dictates the degree of permanent clinical disability. How axonal damage can be prevented remains elusive. The interaction between the myelinating cell and the neuron gains increasing attention, however the evolving knowledge has not yet yielded new treatment concepts. Hence for the time being, it seems prudent to make optimal use of current approved therapies. Recent trials underlined the need for early initiation of treatment with immunomodulatory drugs. The superiority of one of the interferons is still a matter of debate, and a conclusive answer cannot be given at present. Finally, with mitoxantrone we have a drug at hand which can be used in progressive forms of multiple sclerosis, especially when other disease modifying drugs are not or no longer effective.

Adjuvants, Immunologic↗
PubMed2003

Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.

The correlation between conventional MRI lesion load accumulation and multiple sclerosis clinical evolution is only modest. The assessment of brain parenchymal volume and of its changes over time may provide adjunctive MRI markers reflecting the more disabling aspects of multiple sclerosis pathology. Magnetization transfer (MT) MRI is sensitive to 'occult' multiple sclerosis-related brain damage and might also contribute to overcome the clinical/MRI paradox. In this study, we assessed the value of conventional and MT MRI-derived metrics in predicting the medium-term clinical evolution of patients with different multiple sclerosis phenotypes. We studied 73 patients, with relapsing-remitting multiple sclerosis (n = 34), secondary progressive multiple sclerosis (n = 19) and clinically isolated syndromes suggestive of multiple sclerosis (n = 20), and 16 healthy subjects. Brain dual-echo, T1-weighted (only in patients) and MT MRI scans were obtained at baseline and after 12 months. T2-hyperintense and T1-hypointense lesion volumes, normalized brain volume and average lesion MT ratio (MTR) were measured. MTR histograms from the whole brain tissue were also obtained. Clinical multiple sclerosis evolution and neurological disability were re-assessed in all patients after a median follow-up of 4.5 years. A multivariate analysis was performed to establish which clinical and MRI-derived variables were significant predictors of neurological deterioration at the end of the study period. At the end of follow-up, 34 patients showed significant neurological deterioration. The final multivariable model included average brain MTR percentage change after one year [P = 0.02, odds ratio (OR) = 0.86] and baseline T2-hyperintense lesion volume (P = 0.04, OR=1.04) as independent predictors of medium-term disability accumulation (r2 = 0.23). In this cohort of patients, abnormal values of average brain MTR changes showed a relatively high specificity (76.9%) and positive predictive value (59.1%) for Expanded Disability Status Scale score deterioration in individual cases. In patients with multiple sclerosis, a comprehensive estimation of the short-term changes of both conventional and MT MRI-detectable lesion burden might provide useful prognostic information for the medium-term clinical disease evolution.

Adult↗