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PubMed1978

[HLA-DRW antigens and multiple sclerosis].

Previous studies of multiple sclerosis patients showed the existence of a positive association between multiple sclerosis and HLA-A3 and B7, as well as a negative association with B12, These observations have been confirmed. In addition, a more marked association has been observed with two recently identified B-cell antigens, DRW2 and DRW3, closely related to HLA-D locus. The presence of cold lymphocytotoxic antibodies was found to bear no relationship with those two specificities. These results suggest that two genes of the HLA-DR region may play a role in the pathogenesis of multiple sclerosis.

Adolescent↗

PubMed1975

Racial predilection in multiple sclerosis.

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

Africa↗

PubMed1975

Pathology of the early lesion in multiple sclerosis.

Ideas concerning the nature of multiple sclerosis continue to be strongly influenced by the unusual morphology of the disease. A review of classic histology studies, however, reveals that there is less agreement than might be supposed concerning several important histiological features of the early lesion. Electron microscopy of brain biopsies, of immersion fixed autopsy tissue and of autopsy tissue fixed by early in situ brain perfusion suggests that the mechanism of demyelination in multiple sclerosis may be an unusual one that involves a progressive reduction in the number of myelin lamellae around nerve fibers in the vicinity of cells of uncertain origin that contain filamentous and multilamellated cytoplasmic inclusions unlike the usual pleomorphic inclusions seen in myelin phagocytes. Lymphocytes are not directly involved in this process but are observed to contact the inclusion material following its delivery to the Virchow-Robin spaces. The putative neurogenic or viral antigen in multiple sclerosis may be contained in this material. The occurrence of filamentous nuclei in early lesions fixed by immersion is an unrelated phenomenon, which may be an autolytic or drug induced artifact although this has not yet been established.

Antigens↗

PubMedDate not supplied

[Dantrium in the treatment of increased muscle tonus in patients with multiple sclerosis].

In 19 patients with multiple sclerosis and 1 with subacute sclerosing panencephalitis the mean increase in muscle tonus was found to be 3.1 (range 1--4 according to Burke-Ashwort). In 10 controls with multiple sclerosis the mean spasticity was 2.4. Dantrium was given in doses up to 800 mg for 14--16 days and it caused a greater reduction of spasticity than placebo (p less than 0.05). In 12 patients (60%) varying degrees of muscle tonus reduction was observed. In 11 patients the efect of Dantrium was compared with that of other drugs (Clonazepam, Tetradiazepam, Carisoprodol and Lyoresal). In 6 cases Dantrium was a more effective drug than other muscle relaxants and in 5 cases no difference was observed or other drugs were superior to Dantrium.

Adult↗

PubMed1975

The significance of perivascular infiltrations in multiple sclerosis.

143 autopsy cases of multiple sclerosis (19 acute and 124 chronic cases) were analysed histologically for the extent of active demyelination and the degree of infiltration within and outside the demyelinating lesions and in the leptomeninges. The results were compared with the duration of the illness. Infiltrations were found in 60% of all cases but more often (74%) in those with active demyelination. Inflammatory lesions outside demyelinating foci were observed in 27% of the total, and in 80% of them active demyelination was present. Inflammatory lesions in the meninges were present in 41% of the total and in 80% of these were accompanied by active demyelination. The duration of illness correlated with decreasing severity of active demyelination and of perivascular infiltration. Patients treated with cortico-steroids and/or immunosuppressive substances showed no or only moderate inflammatory lesions. The duration of illness in both these groups was significantly longer than the average of untreated patients. The significance of these pathological findings for the CSF cytology in multiple sclerosis is discussed.

Adrenal Cortex Hormones↗

PubMed1976

Optic neuritis in relation to multiple sclerosis.

Available estimates of the frequency with which a patient with optic neuritis develops multiple sclerosis range from as low as 13% to as high as 87%. In an effort to obtain a better estimate, a nation-wide study of optic neuritis was carried out in Israel. Patients who fulfilled strict diagnostic criteria of optic neuritis were identified and examined periodically. Between 1955 and 1964, 105 patients were found and on the basis of these, the average annual age-adjusted incidence of optic neuritis in Israel was 0.56 per 10(5) population compared to 1.2 per 10(5) cases of multiple sclerosis per year, i.e. optic neuritis was about half as frequent as multiple sclerosis each year. As with multiple sclerosis, optic neuritis was more common in European immigrants to Israel than Afro-Asian immigrants. During a follow-up interval which ranged from 3.3 to 15.6 years (mean 9.5 years), at least 27 of the 105 patients developed multiple sclerosis (28%). A life-table analysis showed that after 10 years 32.3 +/- 5.6% of patients with optic neuritis would develop multiple sclerosis and, after 14 years, about half would develop multiple sclerosis. Risk of dissemination was highest in those who were youngest when optic neuritis developed. Neither sex nor ethnic background influenced risk significantly. Results of the present study support earlier work using life-table methods carried out in Hawaii which also showed that between 29 and 39% of patients with optic neuritis will develop multiple sclerosis within 10 years of onset. The life-table method is a better predictor of prognosis than newer laboratory techniques such as spinal fluid studies of IgG, kappa-lambda light chain ratios and serum/CSF IgG ratios.

Adolescent↗

PubMed1977

Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis.

Fifty-nine multiple sclerosis patients were investigated with regard to blood-brain barrier function by determining the CSF-protein and the CSF/S albumin ratio. Abnormal values were found in 19% and 32% respectively. The occurrence of CSF-IgG elevation due to synthesis within the CNS was analysed by determining the CSF IgG/protein and CSF IgG/albumin ratios and the IgG-index = (CSF/S IgG ratio)/(CSF/S albumin ratio). Increased values were found in 75%, 80% and 86%, respectively. Oligoclonal IgG was found in CSF by agarose gel electrophoresis in 88% of the patients. The IgG-index is the parameter recommended for the demonstration of an IgG elevation in CSF due to synthesis within the CNS.

Adult↗

PubMed1977

A possible association between house pets and multiple sclerosis.

29 patients with multiple sclerosis (M.S.) from families in New Jersey believed to have more than 1 member with this disease and 29 controls matched for age, sex, neighbourhood, and socio-economic status were questioned about their ownership of pets. No difference in ownership of cats or dogs was found. Exposure to small indoor pets (cats or dogs), however, was significantly higher in the M.S. group (P less than 0-001). Exposure to small indoor pets was particularly striking during the ten years before onset of initial symptoms of M.S. when the M.S. group was compared to the control group (P less than 0.01). 33 of 49 M.S. patients in these families had a cat or dog in the house within one year before onset of the first neurological symptom. 3 families had more than 1 member in whom initial symptoms of M.S. developed in the same year despite wide age ranges. These results suggest that exposure to house pets may sometimes be associated with subsequent M.S. Our findings should be interpreted with caution until they are confirmed by others.

Adult↗

PubMedDate not supplied

[Visual somatosensory and auditory evoked potentials in multiple sclerosis].

In a group of 15 patients with multiple sclerosis and in a control group of 20 healthy subjects visual evoked potentials produced with flashes or checkerboard pattern, auditory evoked potentials after stimulation with three different tones, and somatosensory evoked potentials after stimulation of the left, right or both median nerves, and reactions to stroboscopic stimulation at seven different frequencies were investigated. Recording was done with unipolar leads from frontal, central, occipital and temporal regions on the left and right side. In patients with multiple sclerosis the cortical responses to all these stimuli had lower amplitude than in healthy subjects, and the reponses to stroboscopic stimulation were also abnormal in the group of patients. Different clinical signs related to various defects of sensory functions showed a high correlation with electrophysiological anomalies. Non-linear discrimination analysis was carried out using 13 variants (the amplitudes were calculated from peak to peak and correlation coefficients were calculated between identical regions on the left and right side) comparing the group of patients with the control group. Using this method it was possible to establish the correct diagnosis in all cases of multiple sclerosis and 85% of healthy subjects could have been included into the asymptomatic group. Since the methods used in these investigations are easy and can be easily automated the authors think that they could be very useful in the clinical diagnosis of multiple sclerosis.

Acoustic Stimulation↗

PubMed1979

Pes cavus and claw toes deformity in patients with spinal cord injury and multiple sclerosis.

Patients with spinal cord injury or multiple sclerosis were surveyed for the presence of extreme foot deformities and spasticity. Pes cavus and claw toes were found in eight of 80 spastic spinal cord injury and two of 20 multiple sclerosis patients. Pes cavus and claw toes were not found in 29 flaccid spinal cord injury patients. Pes cavus and claw toes were associated with flexor reflexes which could be elicited by pin prick proximal to the knee, suggesting extreme spasticity--and by low excitatory thresholds for the anterior tibialis as indicated electromyographically. Complications of severe spasticity associated with spinal cord injury and multiple sclerosis include pes cavus and claw toes, mediated in part by spasms of the anterior tibialis.

Adult↗

PubMed2025

Entertainment activities and the risk of multiple sclerosis: A Mendelian randomization analysis.

Modifying environmental and lifestyle factors may have the potential to prevent and ameliorate multiple sclerosis. Further elucidating the etiology of multiple sclerosis and proposing actionable prevention measures are of significant importance, but establishing causality in epidemiological data can be challenging. This study employed a two-sample Mendelian randomization analysis to evaluate the causal effect of entertainment activity factors on the risk of multiple sclerosis. Publicly accessible summary statistics derived from genome-wide association studies were utilized to assess 14 modifiable forms of entertainment activities. The inverse variance weighted random effects method was used as the primary analytical approach to estimate causal effects. Additionally, MR-Egger, weighted median, and weighted mode methods were applied to assess robustness. Systematic sensitivity analyses and heterogeneity tests were conducted to verify the reliability of our findings. We found that spending time outdoors in the summer may prevent the development of multiple sclerosis (odds ratio = 0.995; 95% confidence interval 0.991-0.999; P = .010). In contrast, the other entertainment activities studied showed no significant causal relationship with multiple sclerosis. Our results suggest that spending time outdoors in the summer may protect against the development of multiple sclerosis, providing implications for preventive measures against the disease.

Humans↗

PubMed1975

Early sterile autopsy in etiological studies on multiple sclerosis.

The clinical findings and course in the first 2 cases of multiple sclerosis are described, in whom it was possible to isolate a virus from brain tissue by early sterile autopsy and fusion technique. It is noteworthy that in one of these cases multiple sclerosis probably occurred in female members of the family through three consecutive generations. A report is made on an additional case, in which no virus could be isolated, but in which electron microscopic studies showed two types of virus particles: nucleocapsid-like structures and particles identical in form and size with papova virus. Electron microscopic findings and attempts to cultivate a virus in multiple sclerosis published by other authors are discussed. It is pointed out, that the results described provide as yet no proof for the viral etiology of multiple sclerosis. They support the hypothesis, however, that a virus may play an essential role in the etiology and/or pathogenesis of this disease. Problems in relation to brain autopsy in multiple sclerosis are discussed. Early sterile autopsy is considered the most practicable possibility for obtaining tissue material for culturing and for ultrastructural studies in multiple sclerosis.

Adult↗

PubMed1978

Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies.

Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.

Antibodies, Viral↗

PubMed1976

Genetic association of multiple sclerosis and HL-A determinants.

Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.

Epitopes↗

PubMed1975

Cerebrospinal fluid proteins in multiple sclerosis.

Various CSF proteins were studied in 255 definite multiple sclerosis patients at various disease stages and compared with corresponding values obtained from 174 controls. The CSF changes in acute multiple sclerosis patients included a significant increase of total proteins and of gamma globulin, IgG, IgA, IgM, alpha-2 ceruloplasmin, 7S-gamma-1, and cytotoxic index for nerve cells in tissue culture, and significant decreases of pre-albumin, alpha-1, and alpha-2 and of the beta/gamma globulin ratio. The CSF levels of IgG, IgA, and IgM remained significantly higher in steroid-treated multiple sclerosis patients than in controls, but the levels often were significantly reduced while patients were on treatment or in remission. During remission or treatment with ACTH and/or steroids, the alpha-2 ceruloplasmin, 7S-gamma-1, and cytotoxic index were significantly reduced and the pre-albumin, alpha-1, and alpha-2 globulin classes and the beta/gamma ratio showed a tendency to return to normal.

Adolescent↗

PubMed1979

Dorsal spinal cord stimulation in the treatment of multiple sclerosis.

Previously published work indicated significant improvement in the symptoms of multiple sclerosis with dorsal spinal cord stimulation. In this study 23 patients with multiple sclerosis documented by history, examination, laboratory studies, and clinical course were treated with dorsal spinal cord stimulation and followed for 19 to 45 months (mean, 32 months). Pre- and postoperative clinical assessment was carried out using the Kurtzke Scale. Walking velocity, upper limb coordination, sphincter function, and sensory function were also evaluated quantitatively. No statistically significant objective improvement in any of these measures was demonstrated. Fifty per cent of the patients initially reported subjective symptomatic improvement, but this declined to 30% at last follow-up. Fifteen of 23 patients experienced complications related mainly to the hardware used and required a total of 21 subsequent operative procedures for correction of these complications. These results do not support the continued clinical use of dorsal spinal cord stimulation in the symptomatic treatment of multiple sclerosis.

Electric Stimulation Therapy↗

PubMed1979

[Immunoreactions of the delayed type in patients with multiple sclerosis (author's transl)].

Skin tests were performed in 34 multiple sclerosis patients. The incidence of positive reactions was reduced in these patients compared with healthy controls, with regard to different recall antigens with the exception of varidase, as well as the PHA and DNCB. No definite differences in reaction between patients who had been suffering from multiple sclerosis for a long time or for a short time, could be established. However, there was a certain dependence on the stage of the disease in so far as positive reactions were less frequent during the acute episode--more pronounced during the subsiding attack than at the onset of the episode--, than during the interval between two attacks. These results suggest that multiple sclerosis is primarily characterised by a weakness of cell-mediated immunity and that this weakness becomes more pronounced during the acute episode. The differences between the skin test reactions performed during the individual phases of the disease are too slight to assist in defining the acute episodes. It may be possible to identify changes in the reaction level via long-term studies.

Humans↗

PubMed1976

[Gustatory disturbances in multiple sclerosis].

90 patients with advanced multiple sclerosis were examined electrogustometrically and with taste solutions. In 4 cases only the bitter sensation was diminished all over the tongue. 4 other patients showed a prolonged latency. Besides a unilateral dissociated hypogenusia in 4 patients there were no further serious taste disturbances. One man showed a taste and sensory hyperpathia on one side of the body.

Adult↗