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Biomedical subjects

M Alter

Publications and source records attributed to M Alter.

32 records · Page 2Linked to original sources

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

Amyotrophic lateral sclerosis: a population study.

A country-wide study of the frequency of amyotrophic lateral sclerosis (ALS) was undertaken in Israel for the period 1960-1970. Israel was chosen for this study because of its excellent medical facilities and detailed demographic information. Moreover, the population includes representative groups from all parts of the world for comparison of frequency. A wide variety of motor system disease was screened in all hospitals, clinics, and chronic care facilities in the country, death certificates were reviewed and physicians with a neurological practice were contacted to derive a tentative list of cases. Only those who fit strict clinical diagnostic criteria or had autopsy confirmation were included in estimates of prevalence and incidence. On January 1, 1965, the mid-point of the study, 62 patients with ALS were living in Israel. The age-adjusted prevalence of ALS on that date was 3 per 100,000 population. The average annual age-adjusted incidence for the period 1960-1970 was 0.78 per 100000 population )0.86 in males, 0.46 in females; ratio 1.9:1). There was no appreciable change in trend of incidence over the study interval. Age-specific incidence rates were similar in native-born inhabitants of Israel, immigrants from Europe and immigrants from Afro-Asian countries. The range in age-adjusted incidence among subgroups of immigrants to Israel from various countries was 0.25 to 1.20 per 100000 population but small numbers precluded testing the statistical significance of these rather narrow differences. Mean age at onset was 55.4 years for males and 52.4 years for females. The mean age at death was 60.2 for males and 58.0 for females. The average annual mortality from ALS was 0.58 per 100000 population. There were no familial aggregates of ALS in Israel and autopsy data showed no neurofibrillary changes, granulovacuolar or inclusion bodies. There are only a few other population studies of ALS in different regions of the world. The average annual incidence in these other studies ranged from 0.4 to 1.4 per 100000 population. Thus, the incidence in Israel falls within this narrow range. The present study lends further support to the impression that ALS has a remarkably uniform geographic distribution with Guam and the Kii peninsula of Japan being the only known areas with significantly high rates. If an environmental factor contributes to the pathogenesis of ALS, the factor must also have a uniform geographic distribution.

Adult

A family with amyotrophic lateral sclerosis and Parkinsonism.

Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) are known to occur simultaneously among some Chamorro inhabitants of Guam and other Mariana Islands (Stanhope et al., 1972). Outside of the Western Pacific Islands, the concurrence of ALS and PD seems to be rare. However, it has been observed to occur with sufficient frequency to suggest some causal association. The following is a report of a patient suffering from ALS whose family history included PD in several of the immediate relatives.

Amyotrophic Lateral Sclerosis

Is multiple sclerosis an age-dependent host response to measles?

Several lines of evidence support the possibility that multiple sclerosis (M.S.) may be an age-dependent host response to measles. In animals, measles evokes different responses depending upon age at inoculation. In man, measles is already known to produce at least two age-dependent responses: risk of subacute sclerosing panencephalitis is increased among those who have had measles before 2 years of age and risk of measles encephalitis increases with age, at least during adolescence. Studies of immigrant populations indicate that an event at or before adolescence but not infancy affects risk of M.S. In the tropics where M.S. is rare, measles tends to be acquired very early in life, usually before the age of 3, whereas in temperate areas, measles tends to be acquired later, after the age of 5. A retrospective study has shown that M.S. patients tend to have had measles later than controls. Mechanisms which might underlie an age-dependent host response to measles include maturation of an immune system (k.g., number of available B cells) or change in the metabolic state of a target cell (e.g., oligocytes which change from laying down myelin to maintaining it). If the hypothesis that M.S. is a host response to later measles infection is valid, then mass measles vaccination programmes should produce a decline in the rate of M.S., but the effect may not be discernible before 1980.

Adolescent

Hereditary Amyotrophic Lateral Sclerosis. A report of two families.

An aggregation of 14 cases of amyotrophic lateral sclerosis (ALS) was encountered in two families in Minnesota. Although the classical clinical features of ALS predominated, some members of one family showed, in addition, extrapyramidal signs, peripheral sensory impairment in the upper and lower limbs and mild mental fallout. Autosomal dominant inheritance with incomplete penetrance was the most likely mode of transmission. Pathological changes were the same as those seen in sporadic ALS although one patient also showed degeneration of the substantia nigra. These two families were compared to others in the literature and an effort was made to refine the classification of familial ALS.

Adult

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

Multiple sclerosis and childhood infections.

There is evidence that some event in childhood may determine risk of multiple sclerosis: Elevated titers to measles and other childhood infections suggest a childhood infection. Therefore, childhood infections reported by 30 patients with multiple sclerosis and matched controls were compared. Patients reported a childhood infection between 5 and 9 years (not simply exposure to an infection) more often than controls. The mean age of measles peaked somewhat later (age 7) in patients than in controls (age 4); this differnce approached statistical significance (p less than 0.1). Evidence that host response to measles is age-dependent was reviewed. It was proposed that age of measles (rather than the fact of injection) may influence the risk of developing multiple sclerosis.

Adolescent

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

Subacute sclerosing panencephalitis: incidence among ethic groups in Israel.

During the period 1968-73, 46 patients with subacute sclerosing panencephalitis (SSPE), a fatal childhood disease related to rubeola, were encountered in Israel. The incidence per million population was 3.4 for Sephardic Jews, 3.2 for Arabs and only 0.5 for Ashkenazic Jews. An environmental factor which sharply demarcated Arabs and Sephardic Jews from Ashkenazic Jews, and which might account for the differences in incidence of SSPE, was family size: 42.3% of Arab families and 21.5% of the families of Sephardic Jews but only 1.1% of Ashkenazic Jewish families had five or more children. It is postulated that older siblings in large families might constitute vectors which introduce rubeola to the younger siblings at a time when they are at unusual risk of developing SSPE (i.e. before two years of age), whereas in small families, rubeola tends to be acquired later in childhood when the risk of SSPE is reduced.

Adolescent

Effect of cyclandelate on dementia.

Cyclandelate, a vasodilator, was administered to 24 patients with dementia. The dementia in these patients was presumed to be due to cerebral ischemia caused by atherosclerosis in cerebral vessels after other possible causes were ruled out. In a double-blind, cross-over study, patients received 200 mg of cyclandelate four times daily for six weeks and a placebo for six weeks. Six psychological tests, which reflect various aspects of higher cortical ability, were used to evaluate the effect of cyclandelate on the dementia. Cyclandelate was found to be no more effective than placebo in improving higher cortical function in these demented patients.

Aged