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Childhood infections in multiple sclerosis: a study of North African-born patients who migrated to France. The French Collaborative Group on Multiple Sclerosis.

We conducted a study on 152 patients with multiple sclerosis (MS) who were born in North Africa and migrated to France. Information was obtained from patients on common childhood infections. We found that, in most cases, common childhood illnesses occurred before migration, but these infections occurred at later ages when the patients were in France: the mean differences were equal to 3 years for measles, 2.1 years for chickenpox, and 4.5 years for mumps. In comparison with data available for the general populations of Algeria and France, the mean ages of childhood infections, and particularly measles, were higher in MS patients. Data confirm that, wherever they live, MS patients tend to have childhood infections at a relatively late age and suggest that migration delays the age of viral infections. This might be one of the possible explanations for the effect of migration on the risk of MS.

Africa, Northern↗

Clinical presentation of primary progressive multiple sclerosis 10 years after the incidental finding of typical magnetic resonance imaging brain lesions: the subclinical stage of primary progressive multiple sclerosis may last 10 years.

BACKGROUND: Subclinical multiple sclerosis (MS) has been identified incidentally at autopsy; apparently unaffected individuals with an affected twin have demonstrated magnetic resonance imaging (MRI) changes consistent with MS, and 'MRI relapses' are several times more common than clinical relapses. CASE DESCRIPTION: A 39-year-old, right-handed man underwent MRI and PET scanning in 1986 as a 'normal' control in a Parkinson's disease study, where his father was the proband. MRI indicated multiple areas of abnormal signal intensity in a periventricular and grey-white matter junction distribution. Repeated clinical evaluations over the next 10 years were unchanged until 1996, when he complained of progressive weakness of the right foot and clumsiness in the right hand. MRI now indicated a further area of high signal intensity in the right posterior cord at the level of C5/C6. There was mild pyramidal distribution weakness in the right leg with an extensor plantar response on the same side. Over the next five years there has been mild progression in weakness and fatigue and intermittent Lhermitte's phenomenon. At no stage has there been a history of relapse, cerebrospinal fluid examination was normal and evoked responses (visual and somatosensory) are normal. CONCLUSION: This case demonstrates the phenomenon of subclinical MS, unusually supported by prolonged clinical and MRI follow-up. The patient eventually became symptomatic nine years after MRI diagnosis and is following a primary progressive course. Although MRI is known to be sensitive in identifying subclinical 'attacks', the pattern illustrated here may actually be quite typical of primary progressive MS and is compatible with the later onset seen in this subgroup of patients.

Adult↗

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external sphincterotomy followed by condom catheter drainage is recommended. However, if external urethral sphincterotomy fails to reduce residual urine and detrusor pressure, urinary diversion or bladder reconstruction may be necessary.

Body Temperature↗

Ocular manifestations of multiple sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis is an autoimmune demyelinating disorder of the nervous system that is commonly manifested by visual system involvement and that may initially present with ophthalmologic symptoms. This paper reviews recent findings regarding the ocular manifestations in multiple sclerosis. RECENT FINDINGS: Manifestations of multiple sclerosis in the eye include both the afferent and efferent visual pathways. Optic neuritis, the most common ocular manifestation of multiple sclerosis, may be the initial clinical disease manifestation. Recent long-term follow-up data show that most patients with demyelinating optic neuritis have an excellent prognosis for recovery of central visual acuity. Evidence is emerging, however, for significant and broad reduction in both contrast sensitivity and color perception in multiple sclerosis patients despite near-normal visual acuities. Ocular motor deficits in multiple sclerosis include internuclear ophthalmoplegia and nystagmus, resulting in diplopia, oscillopsia, blurred visual, loss of stereopsis, and reading fatigue. Multiple sclerosis also may be associated with ocular inflammatory diseases, in particular pars planitis and retinal periphlebitis. SUMMARY: Ocular findings may be initial manifestations of multiple sclerosis and may predict additional demyelinating events. Recognizing these syndromes and signs will help clinicians to properly evaluate the patient, formulate an appropriate differential diagnosis, be able to discuss the prognosis with the patient, and help develop an effective therapeutic plan.

Eye Diseases↗

[Acute cerebral multiple sclerosis: importance of a multiple diagnostic approach. Clinical case].

The Authors report a case of acute, apoplectiform, multiple sclerosis, with right hemiparesis and severe motor dysphasia. The way undertaken to arrive to the diagnosis of demyelinating disease is discussed, with special attention to the importance of a multiple diagnostic approach, analysing the sensitivity and the limits of the instrumental methods actually available.

Acute Disease↗

Multiple sclerosis and pregnancy.

Multiple sclerosis causes disability in young adults and, like most autoimmune diseases, affects women more commonly than men. The disease can therefore present at a time when many have, or are considering, starting a family. The effect of pregnancy on the outcome of multiple sclerosis is reviewed and the management of pregnant women who have multiple sclerosis is discussed.

Adult↗

Neuroimaging in multiple sclerosis.

Neuroimaging in multiple sclerosis is now dominated by MR imaging. This article will focus primarily on conventional MR imaging studies in multiple sclerosis, but will also discuss briefly some of the more recent advances related to MR imaging. Fast spin-echo imaging, fluid attenuated inversion recovery MR studies, three-dimensional volumetric studies, magnetization transfer, and magnetic resonance spectroscopy as it applies to multiple sclerosis are examined.

Brain↗

Biochemical findings in multiple sclerosis. III. Immunoglobulins of restricted heterogeneity and light chain distribution in cerebrospinal fluid of patients with multiple sclerosis.

Several biochemical parameters, the most important of which are total IgG, kappa and lambda light chain distribution and thin layer isoelectric focusing, were determined in the cerebrospinal fluid of 36 multiple sclerosis patients. Their ages and the evolution period of their disease are widely spread and no sex differentiation was made.

Adult↗

Multiple sclerosis: immunogenetic analyses of sib-pair double case families. II. Studies on the association of multiple sclerosis with C2, C4, BF, C3, C6, and GLO polymorphisms.

The complement component polymorphisms of C2, C4, BF, C3, C6, and the enzyme polymorphism GLO were studied in 13 sib-pair double case families with multiple sclerosis. A significant association was seen between MS patients and the C4 haplotype A4,B2 as compared with their healthy siblings. This finding seems to parallel reports on C2 hypocomplementemia in MS patients since C4 A4,B2 in normal individuals was also seen to be in linkage disequilibrium with the C2 deficiency allele (C2QO) by other investigators.

Complement C2↗

Natural history of multiple sclerosis: a unifying concept.

Multiple sclerosis can follow very different patterns of evolution and variable rates of disability accumulation. This raises the issue whether it represents one or several distinct diseases. We assessed demographic and clinical characteristics in 1844 patients with multiple sclerosis that we categorized according to the classification of Lublin and Reingold (1996) into 1066 (58%) relapsing-remitting, 496 (27%) secondary progressive, 109 (6%) progressive relapsing and 173 (9%) primary progressive cases of multiple sclerosis. Relapsing-remitting and secondary progressive cases shared similar age at disease onset (median = 28.7 versus 29.5 years; P = 0.21), initial symptoms of the relapsing-remitting phase, degree of recovery from the first neurological episode, and time from the first to the second episode. By contrast, disease duration was twice as long in secondary progressive than in relapsing-remitting cases (mean +/- SD = 17.6 +/- 9.6 versus 8.7 +/- 8.6 years; P < 0.001). Progressive relapsing and primary progressive cases were essentially similar in their clinical characteristics. In patients experiencing a progressive course, median age at onset of progressive phase was similar in secondary progressive cases and in cases who were progressive from onset (39.1 versus 40.1 years; P = 0.47). The proportion of cases with superimposed relapses during progression was approximately 40% in both categories. Finally, the 1562 patients with an exacerbating-remitting initial course and the 282 patients with a progressive initial course of the disease were essentially similar with respect to the time course of disability accumulation from assignment to a given disability score, and the age at assignment of disability landmarks. These observational data suggest that the clinical phenotype and course of multiple sclerosis are age dependent. Relapsing-remitting disease can be regarded as multiple sclerosis in which insufficient time has elapsed for the conversion to secondary progression; secondary progressive forms as relapsing-remitting multiple sclerosis that has 'grown older'; and progressive from onset cases as multiple sclerosis 'amputated' from the usual preceding relapsing-remitting phase. Times to reach disability milestones, and ages at which these landmarks are reached, follow a predefined schedule not obviously influenced by relapses, whenever they may occur, or by the initial course of the disease, whatever its phenotype. This leads to a unifying concept of the disease in which primary and secondary progression might be regarded as essentially similar. From the clinical and statistical positions, multiple sclerosis might be considered as one disease with different clinical phenotypes rather than an entity encompassing several distinct diseases-the position of complexity rather than true heterogeneity.

Adult↗

[Deafness and tinnitus in flare-ups in 10 cases of multiple sclerosis].

Deafness in multiple sclerosis is rare, being reported in less than 1 p. 100 of the cases. Ten cases of deafness associated with tinnitus during acute episodes of multiple sclerosis are presented, the diagnosis being definite in 9 patients and probable, according to McAlpine's criteria, in the tenth case. These were not cases where routine examinations demonstrated a latent hearing defect, but were all patients with sudden, often unilateral, incapacitating deafness during an acute episode of the disease, with regression usually after less than 3 months. Deafness recurred in 3 patients and was the initial symptom in 5 cases. Serial audiometric examinations were performed in most cases together with recordings of various evoked potentials, including early auditory evoked potentials during or after the onset of deafness in all 10 patients. BAEPs abnormalities were noted in 8 and appeared to be correlated more with brain stem demyelinization, as it has been established for a few years, than with the deafness itself. Severe anomalies of auditory evoked potentials regressed after the acute episode in only 1 patient. Lesions of the auditory pathways within the brain stem appear to be the cause of the deafness, as shown by results of auditory tests, which pointed to a central origin. The onset of deafness did not indicate a particular progression of multiple sclerosis.

Adult↗

[Multiple sclerosis and migration].

Multiple sclerosis, original primary demyelination in the central nervous system, is a disease of as yet unknown cause. Epidemiologic research may contribute to the clarification of this problem. Migration studies have proven that susceptibility to multiple sclerosis is associated with ethnic origin and environment, and that the critical age for the disease development is till 15 years. In Croatia, emigrating inhabitants of Gorski Kotar, a region with high exposure to this disease, carry the risk of multiple sclerosis development, provided that have emigrated after adolescence.

Croatia↗

Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group.

Our previously reported multicenter, blinded, randomized, controlled study of two doses of interferon beta-1b (IFNB) in 372 patients demonstrated a reduction in relapse frequency and severity and in MRI activity. We now report the results of the continuation of that study. The median time on study was 46.0 months for the placebo arm, 45.0 months for 1.6 million international units (MIU), and 48.0 months for 8 MIU. IFNB had a persistent beneficial effect on exacerbation rate and MRI burden of disease and was relatively free of long-term side effects. There was a one-third reduction in exacerbation rate in the 8-MIU treatment arm, compared with placebo, in each of 5 years. Serial annual MRI was done in all patients, and 217 of the patients had either a fourth- or fifth-year scan. There was no significant progression of lesion burden in the 8-MIU arm in each successive year compared with baseline (at 4 years, p = 0.917), whereas a highly significant increase in lesion area occurred in the placebo arm (p = 0.0001). Among the 154 noncompleters, there was no systematic bias recognized that favored either treatment arm for the outcome measures of exacerbation rate, disability, or MRI activity. Dropouts in the placebo group had higher exacerbation rates and accumulation of MRI lesion burden than did dropouts in the other treatment arms, which probably reduced the power of the study to demonstrate treatment effects on these measures in the later years of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group.

We studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2-year relapse rate was 1.19 +/- 0.13 for patients receiving copolymer 1 and 1.68 +/- 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two-neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by > or = 1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection-site reaction. Rarely, a transient self-limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

Acute Disease↗

Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis.

Previous studies have shown that zinc levels in erythrocytes are significantly elevated in patients with multiple sclerosis (MS). To examine the correlation between erythrocyte Zn levels and disease activity, we measured erythrocyte Zn levels longitudinally. Levels were dramatically decreased during a clinically documented exacerbation of MS. To determine the localization of increased Zn levels in MS erythrocytes, we employed standard techniques for the isolation of nonhemoglobin erythrocyte membrane ghosts. Patients with MS had three times more Zn in ghost material than did controls. Chloroform-methanol extraction in erythrocyte ghosts followed by determination of Zn levels indicated that most of the membrane-bound Zn was associated with the lipid-soluble fraction. Non-lipid-associated Zn and total membrane protein concentration were similar in MS and control samples. Results suggest that mechanisms which govern cellular availability, compartmentalization of Zn, or the binding of Zn to cell surface membranes may be altered in patients with MS, and that these mechanisms vary with disease activity.

Adult↗

[General practitioners' approach to relapsing multiple sclerosis].

Management of multiple sclerosis depends on close multidisciplinary collaboration but general practitioners play a particularly important role, especially in case of relapse, due to their close relationship with the patient. The purpose of this work was to conduct a survey of general practitioners' knowledge of relapsing multiple sclerosis and ascertain their main difficulties in patient management. One hundred seventy-seven practitioners answered a written questionnaire with two headings, diagnostic criteria for relapse and therapeutic approaches. Analysis of the results showed that this common event is under recognized. While 55.9 p.cent of the general practitioners stated they diagnosed relapse by themselves, only 2.8 p.cent knew its exact definition. Differential diagnosis accounted for a large number of mistakes. Our survey also underlined the use of certain therapeutic options (low-dose oral corticosteroid therapy) for which the effectiveness has not been demonstrated. It would be important to propose specific education on relapsing multiple sclerosis for general practitioners and improve cooperation with specialists. An integrated care network might be useful.

Adrenal Cortex Hormones↗