Uri Leibowitz

Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation.

The frequency of multiple sclerosis has been found to increase with increasing latitude. This peculiar geographical distribution has given rise to various hypotheses implicating an environmental factor in the aetiology of the disease (Dean, 1949; Westlund and Kurland, 1953; Kurland and Westlund, 1954; Kurland, Mulder, and Westlund, 1955; Acheson, Bachrach, and Wright, 1960; Mutlu, 1960; Alter, Halpern, Kurland, Bornstein, Leibowitz, and Silberstein, 1962; Kurland and Reed, 1964). Recently, Poskanzer, Schapira, and Miller (1963) have discussed the possibility of an infectious aetiology and have suggested that multiple sclerosis may be an occasional manifestation of a widespread subclinical infection. They think that an enteric infection should be considered because of many similarities in the epidemiological pattern of poliomyelitis and multiple sclerosis. They postulate further that the prevalence of clinically apparent multiple sclerosis might be correlated with the level of sanitation, a situation analogous to that observed in poliomyelitis. Thus, in areas where the sanitary level is high, infection may be acquired later in life, when the individual is more susceptible to the process which produces multiple sclerosis. Conversely, where sanitation is poor, infection may be acquired early when the individual is less susceptible. Although supporting evidence is meagre, these postulates are attractive because they are compatible with the known geographical distribution of the disease. In temperate areas where sanitation is generally on a high level, multiple sclerosis is common; in tropical regions the sanitary level is generally poorer and multiple sclerosis is rare. There are some clinical observations suggesting that the central nervous system of older individuals may be less resistant to the pathological process of

Cerebral multiple sclerosis.

AMONG THE MOST DIFFICULT FORMS of multiple sclerosis (MS) to diagnose are those that include cerebral signs and symptoms such as hemiparesis, hemianopia, psychosis, and convulsions. Although the latter signs are welldocumented manifestations of MS,I their occurrence in a given case may raise doubts about the diagnosis unless the signs occur together with other disseminated neurological signs and a history of remissions and exacerbations is elicited. In the present study, the frequency with which cerebral signs occurred in a nationwide series of MS patients ascertained in Israel is reported. In addition, certain clinical factors were examined to determine if they were associated with increased risk of the cerebral form of MS.

Epidemiological study of multiple sclerosis in Israel Part III Multiple sclerosis and socio-economic status

The frequency of multiple sclerosis increases with latitude both in the northern and southern hemisphere (Dean, 1949; Kurland, Mulder, and Westlund, 1955; Acheson, Bachrach, and Wright, 1960; Sutherland, Tyrer, and Eadie, 1962). This peculiar distribution suggests that an environmental factor (or factors) whose distribution is also correlated with latitude plays a role in the aetiology of the disease. The nature of the environmental factor remains obscure, although a wide variety of factors, including climatic variables, e.g., sunlight, temperature, and cultural factors, e.g., diet, have been considered over the years. In view of the apparent difficulty in determining the nature of the aetiological agent in multiple sclerosis, attempts to narrow the range of possibilities have merit. In this regard, the observations of Miller, Ridley, and Schapira (1960) that multiple sclerosis is more common among individuals in the higher socio-economic classes deserves attention. It is generally true that the socio-economic level of populations in temperate zones where multiple sclerosis is common tends to be higher than in tropical regions where the disease is rare. Therefore, a relation between socio-economic level and the distribution of multiple sclerosis seems feasible and the aetiological agent could conceivably be some condition related to socio-economic status. Data collected in Israel afforded an opportunity to evaluate the suggestion of Miller et al. (1960) that there was a relation between socio-economic status and risk of multiple sclerosis, and Israel offers a number of advantages for studies of socio-economic factors in relation to chronic illnesses like multiple sclerosis. The country is small and its population is ofa size permitting collection of data from the nation as a whole. Bias introduced by studying one region or another may thus be avoided in Israel. Moreover,

Clinical studies of multiple sclerosis in Israel: III, Clinical course and prognosis related to age at onset

IT HAS BEEN ESTIMATED that in 60 to 70% O f patients with multiple sclerosis the disease begins between the ages of 20 and 40 years.l-G Consequently, onset of symptoms earlier or later in life may give rise to doubts about the correctness of the diagnosis. This doubt is justified if patients with disease of early and late onset indeed are different clinically from those with onset in the more “typical” age period. On the other hand, if only incidence differs, the age criterion in diagnosis deserves less emphasis. The literature provides some information relating age at onset to the clinical picture, but many of the published case series are based on selected patients attending a particular hospital or clinic. Such patients may not be representative of patients in the general population since, as a rule, only the more severe or doubtful cases are referred. Nonrepresentative series should not be used to provide information on clinical characteristics of multiple sclerosis at different ages of onset. The present study is based on a countrywide survey of multiple sclerosis completed in Israel in 1961.? The broad scope of the Israeli study permits the assumption that bias in selection of cases was minimal, and, therefore, a comparison of clinical manifestations and course of multiple sclerosis in groups with different age of onset was considered to be of value.

Bell's palsy—two disease entities?

THERE IS A WIDELY HELD IMPRESSION that peripheral facial paralysis may be the result of exposure to cold or wind. Indeed, one author1 states that “there is not the slightest doubt that exposure to drought may produce a Bell’s palsy.” One should, therefore, expect to find a higher frequency of Bell’s palsy in autumn and winter than in spring and summer. But this is not the case. Many authors who studied the distribution of new cases of Bell’s palsy did not find the frequency of this disease to be higher in the cold season of the year.1-6 However, all the published reports gave analyses of the total patient series, disregarding the age distribution of the patients. Such analyses may conceal seasonal variations which might be present in specific age groups. In the present report, analysis of a large series of cases by age as well as by season is presented. Evidence of seasonal incidence in Bell’s palsy may be of importance in etiologic considerations.

Clinical factors associated with increased disability in multiple sclerosis.

The course and clinical mainfestations of multiple sclerosis ( R S ) are so variable that each patient presents a diffcrent clinical picture. Due to this variability, it is impossible to prcdict the prognosis in the initial stages of the disease in the individual case. Howevcr, by studying groups of patients, it should be possible to find thc frequency with which certain clinical factors are associated with greater or lcsscr disability. Such evaluations may dircct the attention of clinicians and investigators to conditions which contribute to he development of disability and may perhaps provide insights into pathogenetic and etiologic mechanisms. One approach to this problem used by many investigators involves analysis of thc clinical characteristics of a large series of paticnts with MS. However, in order to be useful for revealing prognostic indicators, a clinical analysis requires that the series of cases should be unsclcctcd insofar as possiblc. Many of the published series of RIS cases were not representative of thc cntire population of paticnts, c.g. series limited to the experienc of a particular hospital or clinic (Miillr 1949, Mc.4lpinr & Compston 1952) , autopsied caws (Friadman & Davidson 1945, Sanitsky & RangelZ 1950, Carter et al. 19501, remitting cases only (ilZacLean & Berkson 1951), and male patients (Rurtrke 1056). Other studies included populations only from northern countries (Allison & Millar 1954, Sutherland 1956, Hyl les fed 1961) . In Israel, it was possible to identify all patients with RIS in the country and an analysis of clinical variables associated with poor prognosis in such a case series might provide insights of special value in predicting outcome.

Tumors of the nervous system: Incidence and population selectivity☆☆☆

Abstract The frequency and population selectivity of primary tumors of the nervous system was determined for the entire population of Israel. A national tumor registry in the Ministry of Health included information on patients discharged from all hospitals in the country as well as data from autopsies and death certificates. During the 5-yr period 1961–1965, 1,354 cases were identified. The average annual incidence was 12.8 per 100,000 population. Histological verification of tumor was available for 69 per cent of the cases included in this study. Glioma was the most commonly verified tumor (27 per cent) and, in decreasing frequency, verified tumors included meningioma (17 per cent), neurofibroma (12 per cent), pituitary adenoma (5 per cent), neuroblastoma (3 per cent), hemangioma (2 per cent), craniopharyngioma (1per cent) and dermoid (1 per cent). The distribution of tumors by type within the nervous system was calculated: 3 out of 4 involved the brain and, of these, 50 per cent were in the cerebrum. Seven per cent occurred in the spinal cord and 12 per cent affected peripheral nerves. Most of the tumors were more common in males, with the exception of meningioma which showed a female preponderance. When ethnic groups in Israel were compared as regards frequency of primary nervous system tumors, the African born immigrants had the lowest average annual incidence (7.3 per 100,000 population) and European immigrants had the highest (15.6 per 100,000 population). The immigrants born in Asian countries had an intermediate rate closer to the African, whereas the Israeliborn had rates closer to the Europeans. The differences in incidence among the ethnic groups could not be attributed to an unusual predilection to tumor at a given site in the nervous system. Five-year survival rates were calculated and, in order of decreasing survival, the tumors were: craniopharyngioma and dermoid (100 per cent), pituitary adenoma (89 per cent),hemangioma (73 per cent), meningioma (62 per cent), medullloblastoma (58 per cent), neurofibroma (52 per cent), neuroblastoma (25 per cent) and glioma (21 per cent). Age distribution data were also calculated. Direct comparisons between the Israeli series and others in the literature were difficult because of differences in method of case collection and classification of tumors. However, studies in Rochester Minnesota, and in Sweden, which used a simliar method to that employed in Israel gave an average incidence close to that observed in Israel. Literature on ethnic and racial differences in tumor incidence was reviewed and the relatively constant frequency of various nervous system tumors over the last several decades was noted. The implications of epidemiologic information about nervous system tumors were discussed with reference to etiologic considerations.

Does pregnancy increase the risk of multiple sclerosis

The association of pregnancy and onset or relapse of multiple sclerosis is well known to every clinician and raises practical problems in clinical work. The problem of the relationship between multiple sclerosis and pregnancy and childbirth had been the subject of several investigations. Early investigators (Beck, 1913) considered pregnancy so detrimental to patients with multiple sclerosis that therapeutic abortion was recommended. However, termination of pregnancy did not guarantee remission (von Hoesslin, 1934). Millar, Allison, Cheeseman, and Merrett (1959), in a careful analysis of the subject, concluded that the exacerbation rate of multiple sclerosis among women who had been pregnant was increased as compared with women who had not been pregnant, and Schapira, Poskanzer, Newell, and Miller (1966) also found that the frequency of relapse among women with multiple sclerosis who had been pregnant was somewhat higher than in non-pregnant patients. In contrast to the above studies, there are others which purport to have found no detrimental effect of pregnancy upon the course of the disease (Muller, 1949; Tillman, 1950; McAlpine and Compston, 1952). Kurland (1952) pointed out that the childbearing period corresponds to the ages during which multiple sclerosis is active, namely, 15 to 45. If a woman were pregnant only three times then she would spend about 36 months in a pregnant or post-partum state and chance association with the onset or exacerbation of multiple sclerosis of about the extent reported would be possible. If pregnancy and delivery had an aetiological role in the pathogenesis of multiple sclerosis, then a comparison of the obstetrical histories of patients with multiple sclerosis and controls before the onset of illness might be of interest. The present study uses this approach, comparing the obstetrical history of

Slowly progressive and acute visual impairment in multiple sclerosis.

Acute deterioration of vision at onset or during the course of multiple sclerosis (MS) is a well-recognized manifestation of the disease. However, in M S , vision may also show progressive deterioration or optic nerve involvement may be insidious without associated visual symptoms. In this paper we report the incidence of slowly progressive, acute optic nerve involvement and visual impairment in a large series of MS patients followed for many years.

EFFECT OF BRAIN STEM TRANSECTIONS ON VASOMOTOR RESPONSES TO NERVE STIMULATION

Abstract1. Stimulation of the rabbits sciatic nerve produces blood pressure rises. Transections through the brain stem convert most of these pressor reactions into biphasic or depressor responses.2. the level of transection at which reversal takes place, depends on the frequency of stimulation. the critical plane is located more rostrally for low rates of sciatic stimulation and more caudally for high rates of stimulation. the level also varies from one animal to the other and, in the same animal, it differs for stimulation of the sciatic nerve or of its two major branches.3. When the full effect of transection has been established, injection of pentobarbitone does not cause any further change. Similarly, after repeated doses of pentobarbitone, when no further qualitative change of vasomotor responses can be produced by additional applications of the anesthetic, brain stem transections are also ineffective.4. the variability of the effect of brain stem transections is ascribed to the heterogeneous nature...