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Antibodies to vaccinia and measles viruses in multiple sclerosis patients.

A virologic comparison was made of 144 patients with multiple sclerosis, 34 of their healthy siblings, and 40 patients with other neurologic diseases (OND). Antibodies in serum and cerebrospinal fluid (CSF) to vaccinia and measles viruses were measured, and these were correlated in the multiple sclerosis patients with the clinical characteristics of their disease. The CSF antibody to vaccinia virus was more frequent and at a higher titer in multiple sclerosis patients than in either control group. Moreover, a statistically significant increase was found in both frequency and titer of CSF vaccinia antibody in patients with the progressive form of the disease as compared with those classified as relapsing-remitting. Statistically significant differences between multiple sclerosis patients and their siblings were not observed for CSF or serum measles virus antibody, although both groups had significantly higher serum antibody titers than patients with OND.

Adult↗

Choreoathetosis in multiple sclerosis.

Extrapyramidal symptoms are extremely rare in multiple sclerosis. We examined a patient with a ten year history of multiple sclerosis, who developed choreoathetoid movements of both upper extremities. To our knowledge this is the second case report of this association.

Adult↗

[Multiple Sclerosis Functional Composite Measure (MSFC) standardized in the Brazilian population].

The Multiple Sclerosis Functional Composite Measure (MSFC) is an outcome measure in multiple sclerosis developed by USA National Multiple Sclerosis Society (1994), a three-part composite clinical measure--9-Hole Peg Test, Timed 25-Foot Walk and PASAT. It should be multidimensional in order to reflect the principal ways MS affects an individual. The MSFC was applied in 91 Brazilian subjects and standardized to be use in MS centers.

Adult↗

Decrease of suppressor inducer (CD4+2H4+) T cells in multiple sclerosis cerebrospinal fluid.

T-lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis are predominantly CD4+ (inducer) as opposed to CD8+ (suppressor/cytotoxic) T cells. The CD4+ lymphocytes can be subdivided into populations that express high densities of the CDw29 (4B4) determinant and have helper inducer function or express high densities of CD45R (2H4) determinant and have suppressor inducer function. In the present study, we characterized the nature of these CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis by performing flow cytometric analysis on paired samples of blood and cerebrospinal fluid. There were significantly lower percentages of CD4+2H4+ T cells in the cerebrospinal fluid than in the peripheral blood (p = 0.001, paired t test). In contrast, there were increased percentages of helper inducer (CD4+4B4+) T cells in the cerebrospinal fluid (p = 0.001, paired t test), compared with the peripheral blood. Analysis of subjects with other inflammatory disorders of the central nervous system did not show significant decreases in CD4+2H4+ T cells in cerebrospinal fluid, though in some, decreases were also observed. These results indicate that the CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis are predominantly helper inducer, as opposed to suppressor inducer T cells, and that the relative decrease of suppressor inducer cells in the peripheral blood of multiple sclerosis patients is not due to their migration to the cerebrospinal fluid. Furthermore, the increased numbers of helper inducer cells in the cerebrospinal fluid may contribute to local autoimmune processes in the central nervous system compartment of multiple sclerosis patients.

Humans↗

Hypertrophic neuropathy and multiple sclerosis.

In a 62-year-old man with multiple sclerosis, postmortem examination disclosed clinically unsuspected findings of hypertrophic neuropathy. The brain and spinal cord contained many typical plaques of multiple sclerosis. Most spinal roots were thickened, and microscopic examination showed onion-bulb changes characteristic of hypertrophic neuropathy. This is the eleventh reported case of a sporadic hypertrophic neuropathy in a patient with multiple sclerosis.

Central Nervous System Diseases↗

Evaluation of three different ways of assessing tremor in multiple sclerosis.

OBJECTIVES: To examine the comparative reliability and validity of three simple ways of rating upper limb tremor in patients with multiple sclerosis. METHODS: Three examiners independently rated severity of upper limb tremor in patients with multiple sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples. The correlations of the tremor severity scores with scores from arm dexterity tests and a tremor related disability scale were also assessed. RESULTS: Rating tremor on posture had a good intrarater and interrater reliability. However, these reliabilities decreased when kinetic tremor was assessed, in part because dysmetria was a confounding factor. The intrarater reliabilities of rating tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate. Tremor severity scored by all three methods correlated highly with scores obtained from the nine hole peg test, finger tapping test, and a tremor related activities of daily living (ADL) questionnaire, indicating that all three methods were valid ways of assessing tremor in multiple sclerosis. CONCLUSION: Multiple sclerosis tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner. However, scoring kinetic tremor was less reliable. In addition, the nine hole peg and finger tapping tests provide useful objective assessments of upper limb function in tremulous patients with multiple sclerosis.

Activities of Daily Living↗

Prevalence of multiple sclerosis in the L'Aquila district, central Italy.

OBJECTIVE: To estimate the prevalence of multiple sclerosis in the L'Aquila district, central Italy. METHODS: All available case sources were screened. Definite and probable cases of multiple sclerosis, classified according to the Poser criteria, were considered as prevalent cases. RESULTS: On the prevalence day, 31 December 1996, 158 patients (105 women and 53 men; ratio 2:1) affected by definite (n=131) or probable (n=27) multiple sclerosis were alive and resident in the L'Aquila district. Mean (SD) age was 38.4 (11.9) years (38.9 (11.7) years for women and 38.5 (12.3) years for men, p=0.9). The overall crude prevalence was 53.0/100 000 (95% confidence interval (95% CI)=45.4-62.0); 68.4/100 000 (95% CI=56. 5-82.8) in women, and 36.7/100 000 (95% CI=28.1-48.0) in men. The prevalence was similar (55.9/100 000) when standardised to the 1996 European population. Mean (SD) age at onset of multiple sclerosis was 29.4 (9.6) years and mean (SD) duration of the disease was 9.4 (7.4) years, without any significant difference between sexes. Mean age at onset was significantly higher in patients with the primary progressive than in those with the relapsing-remitting course (p=0. 0002, Scheffé's test). CONCLUSIONS: The prevalence found in the L'Aquila district gives support to the consideration of Italy as an area in which multiple sclerosis has been shown to have high prevalence at least in the populations that were surveyed recently.

Adolescent↗

Assessment of memory in multiple sclerosis patients using the Memory Assessment Scale.

Previous assessment of memory function in multiple sclerosis patients has yielded mixed findings regarding the type and severity of memory deficits, which may be due to (1) differential selection of scales for memory assessment; (2) limited, inconsistent or weak reliability and validity data for the memory scales employed; (3) poor standardization techniques; (4) lack of theoretical foundation for the measure; and (5) limited control of confounding variables, e.g., education, age and the use of nonverbal memory tests. The purpose of the present study was to assess memory function in multiple sclerosis subjects using the verbal subtests of the Memory Assessment Scale, a relatively new measure designed to overcome many of the aforementioned problems. Participants included 57 patients diagnosed as relapsing-remitting, 47 diagnosed as chronic progressive (two generally recognized types of multiple sclerosis), and 132 control participants. A multivariate analysis controlling for age and verbal IQ was significant (Wilks = 5.64, p < .001). One way follow-up tests showed both groups with multiple sclerosis had significantly diminished performance across all memory variables when compared with controls, with the exception of List Clustering Acquisition. This indicated that the patients used clustering (mentally grouping similar words together) as often as controls did. These findings provide support for the presence of significant and consistent verbal memory impairment in multiple sclerosis patients and the particular importance of using psychometrically sound measures in the assessment of this population.

Adolescent↗

Transmission of multiple sclerosis by blood transfusion?

A survey of 14,000 multiple sclerosis patients revealed 289 blood donors; 65 of them had already shown clinical manifestations at the time of blood donation. In view of current immunological and virological hypotheses on multiple sclerosis, such patients should not be accepted as blood donors. An effort is being made to determine whether multiple sclerosis has been transmitted to the recipients of this blood.

Blood Donors↗

[Results of international multiple sclerosis research].

The present state of international multiple sclerosis research is summarized in a diagram on the pathogenesis of multiple sclerosis (MS). Recent epidemiological findings are reviewed, stressing regional increases in the frequency and the lower prevalence rates but more serious manifestation in the far east. Findings on HLA-antigens point to a genetic component. The frequency of DR2/DW2 correlates with the proximity to the disease susceptibility gene on chromosome 6. Diagnostic progress includes the measurement of visual evoked potentials, the results of computer tomography and most recently the nuclear magnetic resonance (NMR) method, which makes it possible to visualize foci earlier and in greater number. The new diagnostic possibilities by analysis of the humoral and cellular response are briefly described. With respect to the therapy of MS it is stressed, that cause-related treatment comprises only a small part of the wide range of therapeutic possibilities. The immunosuppressive treatment with azathioprine, cyclophosphamide and cyclosporin A is discussed, also therapy with interferon and interferon-inductors. Finally, current experiments with hyperbaric oxygenation are mentioned. The essential necessity of systematic research on the pathogenesis of MS as the prerequisite of effective causal therapy is stressed.

Antibody Formation↗

British Isles survey of multiple sclerosis in twins: MRI.

64/105 subjects who have a twin with multiple sclerosis included in a study of clinical concordance also underwent MRI of the brain. 8/23 monozygotic and 1/41 dizygotic co-twins from this subgroup were clinically concordant of whom 8/9 had MRI appearances typical of multiple sclerosis. Of the 48 clinically discordant twins aged less than 60, abnormalities on MRI were detected in 6/15 (40%) monozygotic and 13/33 (39%) dizygotic twins compared with 7/37 (19%) healthy age-matched controls. Abnormalities on MRI typical of multiple sclerosis (defined by the Fazekas criteria) were, however, present in only 2/15 (13%) monozygotic and 3/33 (9%) dizygotic twins and 0/37 controls. These results suggest that about 10% of monozygotic and dizygotic twins have "subclinical multiple sclerosis". It is likely that most of the MRI abnormalities seen in clinically discordant twins, however, represent incidental pathology.

Adolescent↗

Multiple sclerosis in island populations: prevalence in the Bailiwicks of Guernsey and Jersey.

The aim of this study was to establish for the first time the prevalence of multiple sclerosis in the Bailiwicks of Guernsey and Jersey, as representing the most southerly part of the British Isles. All patients with multiple sclerosis in the Channel Islands resident on prevalence day were identified by contacting all medical practices, Multiple Sclerosis, and Action Research for Multiple Sclerosis societies by letter and visits. The crude overall prevalence rates were 113/100,000 (95% confidence interval (95% CI) 90.3-135.7) and 86.7/100,000 (95% CI 63.3-110.0) for the Bailiwicks of Jersey and Guernsey respectively. When standardised to the age and sex structure of a previously reported Northern Ireland population the standardised prevalence ratios were 120.2/100,000 (95% CI 96.0-144.3) for Jersey and 95.6/100,000 (95% CI 69.9-121.3) for the Bailiwick of Guernsey. When compared with recent studies in the northern United Kingdom the prevalence rates for multiple sclerosis in the Channel Islands lend some support to the proposed latitudinal gradient in the British Isles although the standardised prevalence ratio in the Bailiwick of Jersey is similar to those found in recent studies of southern Britain. The standardised prevalence rates of probable and definite multiple sclerosis for the male populations were 37.3/100,000 (95% CI 17.9-56.7) for the Bailiwick of Guernsey and 45.5/100,000 (95% CI 26.3-64.7) for the Bailiwick of Jersey whereas the standardised prevalence rates for the female populations were 97.5/100,000 (95% CI 73.9-143.5) and 139.5/100,000 (95% CI 112.6-181.2) respectively. Thus there is a striking and unexplained 43% higher prevalence of probable and definite multiple sclerosis in the female population of Jersey compared with that of the Bailiwick of Guernsey. This seems to be due to an unusually low prevalence of the disease among the female population of the Bailiwick of Guernsey compared with that of the United Kingdom mainland.

Adolescent↗

Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord.

Lesions appearing in the CNS of patients in the chronic phase of the inflammatory, demyelinating disease multiple sclerosis often fail to repair, resulting in neurological dysfunction. This failure of remyelination appears, in many cases, to be due not to the destruction of the local oligodendrocyte precursor population, a source for new myelin-forming cells, but to the failure of the precursor cells to proliferate and differentiate, at least in brain lesions. The spinal cord is also a prominent site for lesions in multiple sclerosis, but nothing is known about the fate of the oligodendrocyte precursor population in this area. The present study has therefore analysed spinal cord samples with demyelination from 16 subjects with longstanding multiple sclerosis for the presence of oligodendrocyte precursor cells. Immunolabellings of 10 microm thick sections with the O4/anti-galactocerebroside (GalC) antibody combination, to visualize O4-positive, GalC-negative oligodendrocyte precursor cells, revealed that such cells were prevalent in many spinal cord lesions, with densities of up to 35 cells/mm(2). Six of the spinal cord lesions contained < or =3 O4-positive, GalC-negative cells/mm(2), but such cells were widespread in brain lesions from these multiple sclerosis cases that were available for study (8-26 cells/mm(2)). The density of the O4-positive, GalC-negative oligodendrocyte precursor cells in all spinal cord and brain lesions studied thus far (n = 41) decreased significantly with declining numbers of debris-laden macrophages. In addition, lesions lacking macrophages tended to be derived from the older patients and there was a negative correlation between the density of the oligodendrocyte precursor cells and clinical age of the multiple sclerosis subject at death, and disease duration. The analysis further revealed that lesions from subjects with primary progressive and secondary progressive multiple sclerosis contained, on average, similar numbers of oligodendrocyte precursor cells/mm(2) and that immature oligodendrocytes were only present in significant numbers in lesions with high precursor densities. Taken together, the present data suggest that there is a gradual reduction in the size of the O4-positive, GalC- negative oligodendrocyte precursor population with increasing age of the lesion, that the generation of new oligodendrocytes becomes increasingly more impaired and that lesions are not repopulated to a significant extent by migratory oligodendrocyte precursor cells present in the adjacent unaffected tissue. Hence, strategies intended to promote endogenous remyelination in multiple sclerosis patients should focus on both enhancing the long-term survival of oligodendrocyte precursor cells and on stimulating these cells to proliferate and differentiate into remyelinating oligodendrocytes.

Adult↗

The role of myo-inositol in multiple sclerosis.

Myo-inositol was given orally to nine multiple sclerosis patients and nine healthy control subjects. Pattern reversal evoked potential testing was used to assess its effect. The principal positive wave increased in amplitude, duration and area in a dose-dependent manner in the multiple sclerosis group compared with controls. Cerebrospinal fluid concentrations of myo-inositol in multiple sclerosis and controls were similar. The significance of these observations is discussed in relation to recent discoveries in inositol phospholipid function.

Adult↗

Offspring recurrence rates and clinical characteristics of conjugal multiple sclerosis.

BACKGROUND: There has been no previous systematic study of conjugal multiple sclerosis. This study of conjugal pairs with complex traits investigated disease transmissibility and the genetic contribution to frequency and clinical course. METHODS: We studied 45 conjugal pairs concordant for multiple sclerosis from 58 pairs recorded in a national register of familial disease, 86 offspring of the 45 pairs were individually assessed for clinical evidence of neurological disease; those over age 16 underwent cranial magnetic resonance imaging. Clinical features were compared in 33 pairs in whom neither member had symptoms before they met. FINDINGS: Of the 86 offspring, five (6%) had clinically definite multiple sclerosis. A further five children had either characteristic imaging abnormalities or clinical symptoms consistent with demyelination, but did not meet the criteria for clinically definite disease. There was no evidence of clinical concordance, clustering at year of onset, or distortion of the expected pattern of age of onset in the second affected spouse from 33 pairs. The crude recurrence in children of conjugal pairs (1 in 17) is significantly higher than previously reported population-based risk for offspring of single affected parents (1 in 200). INTERPRETATION: Taken with the low prevalence of multiple sclerosis in the spouses of affected individuals, and the lack of concordance for age at onset in these families, the disparity in crude recurrence between children of conjugal pairs and those of single affected parents shows that the recurrence risk in children is determined by genetic factors inherited from both parents.

Adolescent↗

How multiple sclerosis is related to animal illness, stress and diabetes.

At the University of Alberta's multiple sclerosis research clinic 100 patients with multiple sclerosis were matched to control patients for age, sex, race and zone of residence before the age of 15 years. Case and control subjects were interviewed and information was collected by questionnaire on factors that might play a role in the development of multiple sclerosis. The only factors found to be significantly associated with the development of this disorder were a history of leisure time spent in physical activities before the onset of symptoms, exposure to animal illness -- specifically canine distemper -- and a history of severe or prolonged emotional stress. The study also confirmed a familial predisposition to multiple sclerosis and suggested a relation between the disorder and a personal or family history of diabetes mellitus.

Adolescent↗

[Beta-interferon clinical trials using MRI in patients with multiple sclerosis].

Magnetic resonance imaging has revolutionized management of patients with multiple sclerosis. This tool provides information on a dynamic process never visualized before, optimizing diagnostic capacities and formalizing the course of the lesion load. Follow-in clinical assessment and performance testing, MRI constitutes a second line tool for following the course of patients with multiple sclerosis in phase II and III trials. We reviewed the correlations between the radiological and clinical findings and the methodology of published trials on beta interferons in remitting, secondarily progressive and early onset multiple sclerosis.

Brain↗

The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia.

The prevalence of multiple sclerosis in the Australian-born population in five different regions of Australia has a strong correlation with latitude, the disease becoming increasingly prevalent with increasing south latitude. In this study, the prevalence in the migrant population from the UK and Ireland (UKI) in the different regions also showed a significant correlation with latitude, but this relationship was strongly influenced by the high prevalence in Hobart. Except for Hobart, the prevalence in migrants was considerably less than that in their countries of origin. The prevalence of multiple sclerosis among those migrating before the age of 15 years from the high-risk UKI to lower-risk Australia was not significantly different to that among those migrating at or after that age, and this finding was confirmed in a case-control study which demonstrated little association between age at migration and risk of developing multiple sclerosis. These findings suggest that the risk from environmental factors in multiple sclerosis may operate over a period of many years and not only in childhood and early adult life.

Adult↗