Joseph A. Resch

A family with hereditary ataxia: HLA typing

In a previously unreported family with olivopontocerebellar atrophy, the kindred contained over 600 individuals in five generations. Of 83 offspring of affected individuals who are over 38.8 years of age (the mean age of the onset of disease in this family), 47 had ataxia; there was autosomal dominant transmission. Clinical findings included lower bulbar palsies, hyperreflexia, ataxia, incoordination, scanning and explosive speech, and, in some, slow motor-nerve conduction velocities. There was cortical and cerebellar atrophy of pontine nuclei, inferior olives, and XII nuclei, and loss of Purkinje cells in the cerebellum. Seventy-three individuals of the III and IV generations were typed for HLA histocompatibility antigens. A maximum lod score of 1.97 was found at male recombination fraction 0.18 and female recombination fraction 0.36. When the lod score values reported in other studies were combined with the values in this family, the maximum lod score was found to be 4.681 at a recombination frequency of 0.22.

Hypertension and Cerebral Atherosclerosis

This study consisted of an analysis of autopsy material from 3,824 persons who were 30 years of age or older in whom the arterial circle of Willis was scored for the severity and extent of atherosclerosis. Several criteria were used for hypertension. These consisted of the heart weight, the clinical diagnosis of hypertension, and the blood pressure. Regardless of which criterion was used, a definite increase in the severity of atherosclerosis of the circle of Willis was noted in the presence of hypertension. The increase was most pronounced when clinical criteria were used.

Respiratory rate and pattern disturbances in acute brain stem infarction.

Respiratory rates and patterns were studied in 23 patients with acute brain stem infarction using impedance pneumography. Autopsy was obtained in six of eight fatal cases. Pontine lesions were present in all patients, with coexistent infarction of midbrain in four and of medulla in nine. Respiratory rate and pattern abnormalities observed included Cheyne-Stokes respiration, Cheyne- Stokes variant pattern and tachypnea. Abnormalities of respiratory rate and pattern of varying duration were observed at some time in all patients. All patients in whom prominent Cheyne-Stokes respiration or tachypnea were observed had extensive bilateral pontine lesions involving both basal and tegmental portions. However, not all patients with large pontine infarcts had Cheyne-Stokes respiration or tachypnea. Cheyne-Stokes respiration was prominent in four patients (two fatal, two nonfatal). Cheyne-Stokes variant pattern was present frequently in four patients (one fatal, three nonfatal). Sustained tachypnea developed in five patients, four of whom died. In ten patients (one fatal, nine nonfatal), normal respiratory rate and pattern predominated with only rare or occasional appearance of Cheyne-Stokes respiration or Cheyne-Stokes variant pattern, especially during sleep. The types of respiratory rate and pattern abnormalities in acute brain stem infarction were not specifically related to the level of lesions, but rather to the size and bilaterality of the lesions. Respiratory alkalosis was present in varying degrees in most patients with either tachypnea or prominent CSR.

Cerebrovascular Disease: Frequency and Population Selectivity in an Upper Midwestern Community

The number of new strokes diagnosed in the communities of Fargo, North Dakota, and Moorhead, Minnesota, was determined by intensive review of medical records in all hospitals, clinics and nursing homes in the area for the period 1965 to 1966. These two adjacent communities have unusual advantages for such a study because their neurological diagnostic facilities are of excellent quality, the population served is stable, and the communities are isolated from other medical facilities by many miles. Out of a population of 94,000 about one-third of which was over 35 years of age and almost all of which was white, a total of 408 patients were diagnosed as having suffered a new cerebral thrombosis (154 cases), hemorrhage (66 cases), embolus (15 cases), subarachnoid hemorrhage (30 cases) or unspecified CVA (143 cases). The average annual incidence of these strokes was respectively 83, 35, 8, 16 and 76 per 100,000 population. These rates are similar to the rates reported elsewhere in a United States, a Japanese and an English community in which similar case-finding methods were used. The similarity in incidence of various types of stroke suggested by these data is in contrast to the appreciable differences in frequency suggested by mortality data. The possibility exists, therefore, that geographical differences in stroke rates based on mortality may represent an artifact. More valid measures of frequency and population selectivity of cerebrovascular disease may show that this disease, unlike coronary vascular disease, is actually similar in populations differing widely in environmental and racial characteristics. Besides the average annual frequency of strokes, the age-specific frequencies were calculated and revealed a marked increase of all types with age over 40 years except for subarachnoid hemorrhage. The latter showed a bimodal age distribution with peaks in the fifth and after the seventh decade. Seasonal incidence and mortality showed a spring and late fall peak. The sex differences in frequency were very small over a wide age range. Data were also collected on brain stem vascular accidents, ischemic attacks and cerebral arteriosclerosis. An additional 245 patients were listed under these rubrics. These vascular events tend to be underreported and accuracy of diagnosis may be less. Moreover, comparable data from other communities using similar case-ascertainment techniques are lacking. However, if they were included, the average annual incidence of “strokes” would be 347 per 100,000 population. Additional community-wide studies with special attention to ischemic attacks, brain stem vascular accidents and patients labeled vaguely as cerebral arteriosclerosis would probably yield a more accurate estimate of the true frequency of cerebrovascular accidents. Ideally, all such patients should be examined neurologically and classified according to standardized criteria if data are desired which can be compared among different communities.

Respiratory Pattern Disturbances in Ischemic Cerebral Vascular Disease

Impedance pneumography was used to monitor respiratory rates and patterns in 49 patients with acute ischemic cerebral vascular disease. Nine patients had clinical evidence of bilateral ischemic cerebral disease. In one of these, normal respiratory pattern was present at all times; in five, there was intermittent Cheyne-Stokes respiration; in two, there were variants of Cheyne-Stokes pattern, and one patient eventually developed sustained tachypnea with probable hyperpnea. Twenty-eight patients had unilateral cerebral infarct. In five of these, normal respiratory pattern was present at all times; in 15, there was intermittent Cheyne-Stokes respiration; six had a variant of Cheyne-Stokes respiration; two had sustained tachypnea with probable hyperpnea. In 12 patients with brainstem infarcts, Cheyne-Stokes respiration was intermittently present in four, Cheyne-Stokes variant patterns were observed in two, and sustained tachypnea with probable hyperpnea developed in six. Abnormalities of respiratory patterns occurred more frequently during sleep, in the presence of a depressed sensorium, and in patients with severe neurological deficits. Respiratory alkalosis of variable degree was present in all patients with Cheyne-Stokes respiration or sustained tachypnea with probable hyperpnea. Cheyne-Stokes respiration was not always related to bilateral cerebral lesions. Intermittent Cheyne-Stokes respiration was not closely related to immediate prognosis. Sustained tachypnea with respiratory alkalosis was associated with the highest mortality rate among patients with respiratory pattern abnormalities.

The geographic pathology of atherosclerosis: A review of the literature with some personal observations on cerebral atherosclerosis

DEGENERATIVE arterial disease is one of the most important problems in our country today. Despite extensive studies by many investigators, the nature of the etiologic factors involved in this morphologic process remain uncertain. Many of the current concepts regarding human atherosclerosis stem from epidemiologic studies and from consideration of geographic differences in the mortality from coronary disease. These studies have suggested that factors such as climate, geographic location, race, economic status, and social stratum may exert a profound influence on the unknown agents active in the atherosclerotic process. It is difficult, of course, to separate the influence of climate, diet, and hygiene from that of inherited racial characteristics. When clinical data are used, the question of the accuracy of vital statistics and hospital diagnoses as well as the competence of practitioners must be kept in mind. When one considers the many possibilities for error in a comparative study based on the foregoing, it would appear that statistics on the prevalence of atherosclerosis might better be based on autopsy material. Evaluation of the prevalence of atherosclerosis in a population studied by the use of autopsy material is less fraught with variables of judgement than is a purely clinical appraisal. Moreover, non-symptomatic morbid anatomic differences are available for consideration in the final conclusions of a study. It is significant that many of the reports based upon pathologic findings of atherosclerosis indicate that the difference between races and population groups are somewhat less pronounced than those suggested by clinical surveys alone. It is realized, of course, that clinical manifestations, including death from disease, may relate to factors or influences not detectable at autopsy. Recognition also has been given to the fact that there is an inevitable selectivity in autopsy studies. Recent references in the literature by BEADENKOPF et al. [l], MCMAHAN [2], and MAINLAND [3] point out some of the difficulties with hospital studies in general and autopsy studies in particular. Nonetheless, in any area completely devoid of information which is obtainable only by such methods, an autopsy study can provide beginningsof knowledge. We feel that such is the situation with this problem.

Blood Flow in the Central and Peripheral Nervous System of Dogs Using a Particle Distribution Method

In this study known activities of 85Sr and 169Yb-labeled microspheres were injected sequentially into the left ventricle of anesthetized dogs. Cardiac output was determined before and after each microsphere injection. Blood flow to brain, brain stem, spinal cord, and sciatic nerve was measured from fractional distribution of the microspheres in the tissue samples. Both blood flow and fractional uptake value tended to be higher for brain and brain stem than for spinal cord or sciatic nerve. Increases in arterial PCO2 were positively correlated with increases in blood flow to both central and peripheral nervous tissue. Initial trapping of the labeled microspheres seems to have little effect on subsequent flow to the tissue capillary bed. It appears that the particle distribution technique may provide a reasonable estimate of blood flow in central and peripheral nervous tissue of dogs.

A controlled study comparing trihexyphenidyl hydrochloride plus levodopa with placebo plus levodopa in patients with Parkinson's disease

Patients with Parkinsons disease were treated with trihexyphenidyl hydrochloride plus levodopa or placebo plus levodopa for six to eight months. Worsening of Parkinsons disease followed withdrawal of prior therapy at the beginning of the study. Both groups had recovered to their prestudy status by five weeks, and the improvement was sustained. No differences were noted between the groups in terms of dosage of levodopa required to maintain optimal function, the extent of the beneficial response, and the incidence of adverse reactions. We believe trihexyphenidyl hydrochloride is of no specific value for control of the major features of Parkinsons disease in patients receiving treatment with levodopa.

Cerebral atherosclerosis in selected chronic disease states

Abstract The severity of atherosclerotic involvement of the intracranial cerebral arteries was assessed at autopsy in 3942 adult subjects. The values obtained in groups of subjects at various ages were correlated with the presence or absence of selected chronic disease states. The presence of clinical or pathological evidence of cerebral vascular disease, atherosclerotic heart disease, diabetes mellitus, and, to a lesser degree, chronic renal disease was associated with a relative increase in the severity of cerebral atherosclerosis. In contrast, cerebral atherosclerosis was apparently less severe in groups of subjects with malignant neoplastic disease and peptic ulcer disease. In males with cirrhosis or alcoholism, there was a possible tendency toward less severe cerebral atherosclerosis.

Cerebral atherosclerosis and its relationship to selected diseases in Nigerians: a pathological study.

Factors which are known to be associated with cerebral atherosclerosis were evaluated in Nigerian Africans. Of 465 autopsied adult Nigerians, 62 (13%) had cerebral atherosclerosis. The frequency and severity of atherosclerosis among Nigerians with hypertension, particularly male subjects, were higher than in normotensives. Although there was a similar frequency of hypertension among autopsied Nigerian and Minnesota Caucasian populations, the severity and extent of atherosclerosis were greater in the Minnesota population. The relatively short duration of hypertension in the Nigerian before death might be an important factor which did not permit progressive development of cerebral atherosclerosis. Other factors which predisposed the Nigerian to increased frequency and severity of atherosclerosis included increased heart weight and diabetes mellitus. The relatively low frequency of cerebrovascular disease in the Nigerian may be explained on the basis of a low degree of cerebral atherosclerosis and relatively short duration of hypertension.