And by some unknown mechanism possibly an increase of cosmic particles may account for an increase in the prevalence of MS. This hypothesis is being tested further.

A long-term cooperative project continues on the effect of change of climate after MS has occurred. To date, little evidence indicates an improvement in a patient from a move to a warmer climate. The National Institute of Neurological Diseases and Blindness, the National Research Council Followup Agency, and the Veterans Administration are cooperating in this research.

Amyotrophic lateral sclerosis (ALS)

ALS is prevalent in the Mariana Islands, including Guam. On Guam, ALS causes about 10 percent of the deaths, or more than 100 times that of other populations. Scientists believe most Guam cases are carried through the genes of inheritance, and suggest the theory that a similar cause of ALS is responsible elsewhere.

Treatment of ALS is related to the international picture. Because of the high incidence of ALS in Guam, a large-scale study was possible there to test two drugs recommended from a study in the United States. Unfortunately, these drugs were found to be ineffective. Nevertheless, the epidemiological discovery of numerous cases in Guam has provided a known location for testing future potential

cures.

Age-adjusted mortality rates of ALS for the United States, Canada, Australia, Japan, and six European countries are suprisingly uniform. No geographic variation in ALS deaths is found in continental United States. Official rates are higher for the white population than for Negroes, but further data and interpretation are needed. (Sources: "Multiple Sclerosis and Amyotrophic Lateral Sclerosis-Etiologic Significance of Recent Epidemiologic and Genetic Studies," Leonard T. Kurland, Donald W. Mulder, Knut B. Westlund; reprinted from the New England Journal of Medicine, 252: 649-702 (April 21 and 28), 1955. (2) "Epidemiologic Investigations of Amyotrophic Lateral Sclerosis," Leonard T. Kurland and Donald W. Mulder; reprinted from Neurology, Minneapolis, May-June 1954, vol. 4, No. 5-6.) Parkinson's disease

Parkinson's disease was formerly known as the "shaking palsy," and by the medical term, "paralysis agitans." It has been estimated that as many as a million Americans have this ailment.

While death is rarely due to Parkinson's as a primary cause, the long-term crippling it may produce makes it a leading concern in neurological research.

An epidemiologist of the National Institute of Neurological Diseases and Blindness has completed some studies on the geographic distribution of Parkinsonism, and is making further investigations. The reported death rates for Parkinsonism in Canada were similar to those in the United States, with more males than females reported as dying of the disease.

Parkinsonism is prevalent in the population of the Mariana Islands. A series of genetic analyses on Parkinsonism in Guam is being completed, with results anticipated during 1959.

Sporadic cases of Parkinsonism are still being seen which resemble the many cases which followed the 1918 epidemic of influenza and encephalitis and various later encephalitis epidemics. The nature of

the virus, if one is responsible, has not yet been determined. The study of encephalitis offers some hope of clarification of this confused situation. A worldwide investigation of encephalitis might help to solve its connection with Parkinsonism.

A careful study in Denmark revealed that a significant number of Parkinson patients had relatives with Parkinson symptoms. This also has been noted in America where records have been compiled of families where a number of members in several generations have been affected. To determine whether this was due to hereditary influence, or similarity of environment, further investigation must be made.

(Source: Unpublished data, Epidemiology Branch, NINDB, 1959.) Neurological disorders of childhood

Several European reports have offered data indicating that some congenital abnormalities of the central nervous system may occur more commonly in some population groups than in others. Other studies have indicated that some brain damage may occur more commonly among infants born in winter than in summer months. Certain studies in the United States have suggested that expectant mothers may tend to choose a protein-deficient diet during the warmer summer months. But these suggestions are yet to be proven.

Now that increased emphasis is being placed on congenital abnormalities in this country, it would be most unfortunate if advantage were not taken of this work to project certain phases on an international basis. With a little more effort and a relatively small expenditure of money, it is possible that certain causes of brain damage might be uncovered through an international approach which might not be found in this country.

An international approach would afford a chance to compare rates of cerebral palsy and other neurological disorders of childhood in the United States with those of other countries. Some of the factors which could provide the basis for comparison might be the difference in procedures of delivery and handling of the newborn, variations in the practice of using X-ray, and the diverse factors related to nutrition. and infections during pregnancy.

Hereditary muscular and neuromuscular disorders

There are several useful national and international population reports available of muscular dystrophy, myotonic dystrophy, myotonia congenita (Thomsen's disease), infantile progressive muscular atrophy (Werdnig-Hoffmann's disease), and peroneal muscular atrophy (Charcot-Marie-Tooth). This is one of the areas of great need, and perhaps untapped sources of new scientific information could be gained from further epidemiological investigations on an international basis.

Information concerning the genetic characteristics of population groups may also have a number of practical applications related to estimation of gene frequencies and mutation rates. For example, in the case of childhood progressive muscular dystrophy, which is inherited in a sex-linked recessive manner, it is important to know the rate at which these genes mutate in the population if their control or elimination rate is to be made effective. Cases of one form of muscular dystrophy develop in the population as a result of spontaneous mutation from normal parents. Investigators studying this disease ex

tensively in Utah estimated a mutation rate of 1 per 10,000 male births.

Muscular dystrophy, which appears to be comparatively common in parts of Utah, has been traced back to an early pioneer, born in England in 1775, who settled in the Salt Lake area in the early 19th century and reared a large family.

It was estimated that the minimal prevalence rate for muscular dystrophy in North Carolina was about 4 cases per 100,000 population. In surveys in Northumberland and Durham Counties in England, 84 cases were found in a population of about 2,262,000 (also a prevalence of about 4 cases per 100,000 population). Fifty-eight cases of one of the three described clinical types have been reported to have occurred in 1,249 individuals in a single kindred.

Surveys of myotonic dystrophy in England reveal a prevalence rate of almost 1 per 100,000 population. No adequate mortality statistics are available for this disorder. Population studies and prevalence figures of the other muscular disorders mentioned above have been reported for England, Canada, Denmark, and Guam. Some mortality statistics are available in these areas. However, in view of the confusion in diagnosis of amyotonia congenita and infantile progressive muscular atrophy, for example, it is uncertain how valid mortality statistics would be. (Source: "Descriptive Epidemiology of Selected Neurologic and Myopathic Disorders With Particular Reference to a Survey in Rochester, Minn.," L. T. Kurland, Journal of Chronic Diseases, St. Louis, Vol. 8, No. 4, pp. 378-418, October 1958.)

In areas such as these, where a need for research definitely exists, international epidemiological studies would contribute toward greater unification in methods of identification, classification, and diagnosis of these hereditary muscular and neuromuscular disorders.

The first approach to these disorders in this country has been a neuropathological one-the anatomical study of nerve and muscle tissue in normal and diseased states. Careful studies of infants suffering from muscle weakness have indicated that this disorder is comprised of several different diseases which have often been confused as a single entity.

Further, it is now clearly evident that there is an abnormal protein content in dystrophic muscle. Through an international epidemiological approach and with continued research in this country, it may be possible to determine with accuracy the actual abnormal molecules in the diseased muscle, and hopefully to determine ways in which these elements can be modified.

Kuru

Epidemiological studies have led to the discovery and documentation of kuru in New Guinea. This rapidly fatal disease of the nervous system has been discovered in an isolated population living in the inland plateaus. It bears many resemblances to certain disorders of the nervous system known in the civilized world, but has certain distinctive features.

Within the isolated valley where this disorder exists, the investigators have ferreted out and recorded most of the cases. The disorder has an extremely high incidence, affecting approximately 2 percent of the population each year, and probably accounts for over 50 percent of all deaths. For each examined case, detailed history has been

recorded. (Source: "Kuru: Clinical Study of a New Syndrome Resembling Paralysis Agitans in Natives of the Eastern Highlands of Australian New Guinea," V. Zigas and D. C. Gajdusek, The Medical Journal of Australia, November 23, 1957.)

The successful acceptance of the research team among this primitive tribe has made possible the conduct of over 30 autopsies, and a number of brains have been forwarded to several neuropathologists for special examination. A thorough report of the pathology of kuru has been published.

In searching for the cause of kuru, the geographical characteristics of the region were mapped and the distribution of the disease was charted. Its distribution corresponds closely to an isolated ethnic group called the Fore Tribe. This lends strong support to a genetic origin.

A number of laboratory studies have been completed. Examination of blood serological specimens from patients and nonpatients both in affected and nonaffected areas has demonstrated the existence of an abnormality of the protein fraction, but the relationship of this to kuru has not been defined.

Abnormalities of adrenal hormone compounds also have been demonstrated, and these have been associated with abnormalities of sodium and potassium levels in the blood serum, strongly suggesting the existence of some endocrine imbalance in this disease. The existence of some hormone imbalance is further suggested by a preponderance of the disease in small children and in women.

In a further effort to establish a genetic relationship, blood grouping in this population is also being conducted, and over 2,000 specimens of blood serum have been obtained for this purpose. This serum is also being subjected to antibody studies in order to obtain information on the virus exposure and experience of this previously untouched population.

În the kuru study and in the other investigations mentioned above, the expanding medical-statistical discipline of epidemiology has become a significant part of research programs. It is being used to study incidence, geographic distribution, and population selectivity in a way which may stimulate and support clinical and laboratory research efforts toward etiology and control of the noninfectious neurological diseases.