Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Report of a case simulating psychiatric disease and normal pressure hydrocephalus.
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Biomedical subjects
Publications and source records attributed to A Heyman.
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We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.
We studied 18 families with Alzheimer's disease in family members, under the assumption that the disease is due to a single gene with an autosomal dominant form of inheritance. There was no evidence of linkage of Alzheimer's disease with any of 27 phenotypic gene markers analyzed, but close linkage for the Rh and MNS blood group loci was excluded.
Brain computed tomographic scans of 60 patients with early-onset Alzheimer's disease (mean age, 60.7 years) were compared with those of age- and sex-matched control subjects. Computed tomographic analysis included standard ventricular measurements as well as subjective ratings of ventricular and sulcal size. These indices were correlated with the results of a battery of neuropsychological tests and electroencephalographic findings. Linear measurements of ventricular size were significantly greater in the patients with Alzheimer's disease than in the age-matched control group (p less than 0.0005). Using subjective appraisal of ventricular and sulcal size, the neuroradiologist noted abnormalities significantly more often in patients than in controls (p less than 0.0005). Linear measurements of ventricular size correlated significantly (p less than 0.05) with the severity of aphasia and dementia and the presence of electroencephalographic abnormalities. There was, however, no correlation between the subjective judgment of cortical atrophy and the degree of impairment as measured by neuropsychological tests. The findings in this study demonstrate the usefulness of computed tomographic imaging in Alzheimer's disease of early onset.
We compared the clinical associations, arteriographic findings, and long-term outcome of 93 patients with amaurosis fugax and 212 patients with focal cerebral ischemia (transient ischemic attacks [TIAs]). The group of patients with cerebral TIAs included a significantly larger proportion of blacks and had a higher prevalence of hypertension than the group with amaurosis. Operable atherosclerotic lesions of the carotid arteries were more often associated with amaurosis (66%) than with cerebral TIAs (51%). The seven-year cumulative rate of cerebral infarction, however, was less in patients with amaurosis (14%) than in those with cerebral TIAs (27%; p less than 0.02). This difference in outcome persisted after adjustment for race, hypertension, and type of therapy. There were no significant differences, however, in the cumulative rates either of recurrent TIAs or of myocardial infarction or sudden death in the two groups of patients.
A case-control study was performed to determine the possible roles of various environmental factors, prior illnesses, drug use, and personal habits in the development of Alzheimer's disease. Such information was collected from 40 patients with onset of dementia prior to age 70 and from 80 community control subjects matched for age, sex, and race. No significant differences were found between patients and control subjects in toxic environmental exposures, animal contacts, smoking, drinking, or unusual dietary habits. A significantly higher frequency of prior thyroid disease was found in women patients than in women control subjects (25.0% and 7.1%, respectively). A history of severe head injury was also obtained significantly more often among the patients than among the controls (15.0% and 3.8%, respectively). Aside from these differences, which may prove to be important associative factors in this illness, there appeared to be no major premorbid demographic or clinical factors associated with this form of dementia. There was evidence, however, of a genetic factor that was manifested in an excess of dementia and mental retardation (including Down's syndrome) in families of patients with Alzheimer's disease.
A prospective study was made of the morbidity and mortality from ischemic heart disease in 390 patients with focal TIA caused by atherosclerotic vascular disease. The 5-year cumulative rate of myocardial infarction or sudden death in these patients was 21.0%, a rate only slightly less than that of fatal or nonfatal cerebral infarction (22.7%). Risk factors including diabetes, angina, and ECG abnormalities were associated with an increase in morbidity and mortality from ischemic heart disease. A major factor associated with these cardiac events was the presence of atherosclerotic obstructive or ulcerative lesions in the carotid arteries. These observations indicate that focal TIA caused by carotid atherosclerosis is a predictor not only of cerebral infarction, but also of serious cardiac disease and death.
Arsenic-induced deaths have been known to occur from accidental poisoning, as a result of medical therapy, and from intentional poisonings in homicide and suicide. Twenty-eight arsenic deaths in North Carolina from 1972 to 1982 included 14 homicides and seven suicides. In addition, 56 hospitalized victims of arsenic poisoning were identified at Duke Medical Center from 1970 to 1980. We present four case histories of arsenic poisoning in North Carolina and discuss the clinical manifestations.
Ten patients with either the familial or sporadic form of Alzheimer disease (AD) were studied cytogenetically to confirm reports of aneuploidy and "long acentric fragments" associated with the disease. Findings in leukocytes of patients were compared with those in eight unaffected relatives and seven persons of similar age. Observations from encoded slides involving 3,800 conventionally stained and 1,396 G-banded metaphases (one patient) showed no significant increase in aneuploidy. The frequency of cells with hypermodal counts, a reliable measure of aneuploidy, was 4.2% and 1.1%, respectively, in women and men with familial AD and 4.0% and 2.3%, respectively, in women and men with the sporadic form of the illness. Similar frequencies of hypermodal cells occurred in female (2.6%) and in male (2.0%) control subjects. In contrast to the lack of aneuploidy, a small but significant number of false "long acentric fragments" was found in cells of women with AD (P less than .05). These aberrations are thought to represent premature centromere division (PCD) in intact chromosomes, primarily supernumerary Xs. Often in multiple copies, PCD occurred in 2.8% of their cells and in 0.6% of cells from control women. PCD occurred in 3.6% of cells of women with the familial form and in 1.7% of cells of women with the sporadic type of dementia. Among unaffected relatives PCD increased with age. The rarity of PCD in G-banded metaphases from an affected female (3/1,396) suggests that metaphase spreading techniques also may affect observable frequency. Thus PCDs occur more frequently in, but are not unique to, AD and may represent an epiphenomenon of aging, a process also characterized by the occurrence of neurofibrillary tangles and senile plaques in the cerebral cortex.
Genetic aspects and associated clinical disorders were studied in a consecutive series of 68 men and women in whom Alzheimer's disease appeared at or before age 70. Secondary cases of dementia were found in 17 (25%) of the families, affecting 22 of the probands' siblings and parents. The cumulative incidence of Alzheimer's disease in these relatives was approximately 14% at age 75. An increased frequency of Down's syndrome was observed among relatives of the probands: a rate of 3.6 per 1,000, as compared with an expected rate of 1.3 per 1,000. A history of thyroid disease was established in 9 (19.6%) of the 46 female probands, a frequency greater than that reported in the general population. There was no excess of hematological malignancies among the blood relatives, and parental age at the time of birth of the probands did not differ from the norm. The results of this study indicate that early-onset Alzheimer's disease is associated with a genetic factor manifested in a substantial familial aggregation of dementia, a probable excess of Down's syndrome in the probands' relatives, and a possible association with thyroid dysfunction in women with this form of dementia.
The present report describes the distribution of histocompatibility antigens in 52 patients with Alzheimer's disease. No significant associations were observed between this illness and particular HLA types before or after statistical correction for multiple comparisons. These findings are discussed in terms of the difficulties inherent in the clinical diagnosis of Alzheimer's disease and with regard to the choice of suitable control populations.
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A survey of the rural community in Evans County, Georgia, revealed cervical arterial bruits in 72 (4.4 per cent) of 1620 persons 45 years of age of older without previous stroke, transient ischemic attacks, or overt ischemic heart disease. The prevalence of such asymptomatic bruits increased with age and was greater in women and persons with hypertension. We estimated the risk of stroke associated with cervical bruits during a six-year follow-up period, taking age and blood pressure into account. The presence of asymptomatic bruits was associated with a significantly higher risk of stroke in men but not in women, with odds ratios of 7.5 and 1.6, respectively. Despite the high risk of stroke among men with bruits, the correlation between the location of the bruits and the type of subsequent stroke was poor. Moreover, cervical bruits in men were a risk factor for death from ischemic heart disease. We suggest that asymptomatic cervical bruits are an indication of systemic vascular disease and do not themselves justify invasive diagnostic procedures or surgical correction of underlying extracranial arterial lesions.
A self-administered questionnaire designed to identify people with transient cerebral ischemia (TIA) in large population groups was distributed to approximately 10,000 elderly persons living in public and private retirement facilities in the United States. The population resided in eight cities, and 74% completed the survey. Transient focal neurological symptoms compatible with a diagnosis of TIA within the previous year were reported by 6.4% of the respondents. Uncertain manifestations of TIA, i.e., dizziness, light-headedness, or loss of balance, were noted by an additional 15.4%; the remaining 78.2% had no manifestations of this disorder. A clinical history for TIA was taken by a neurologist in a sample of 1,712 respondents to determine the validity of the questionnaire responses. Thirty (7.1%) of 423 persons presumed by the questionnaire to have TIA met the standard clinical criteria for the diagnosis. An additional 8 cases of TIA were found by the neurologist among the 1,289 interviewed persons presumed by the questionnaire to have uncertain TIA or no evidence of the disorder. The twelve-month period prevalence of TIA was estimated to be 8.2 per 1,000 in the total respondent population and 5.8 per 1,000 among those without a history of prior completed stroke. Despite the high proportion of false-positive neurological symptoms of TIA elicited by the questionnaire, this survey instrument nevertheless screened out for further study the 6% of the population in whom 55% of the TIAs occurred.
A computerized information system has been developed for storing and retrieving the clinical, demographic and laboratory data on 267 patients with transient cerebral ischemia admitted to Duke University Hospital during the past 4 years. The major objective of this computer system is to improve patient care by providing the clinician with immediate information for decision-making and prognostication, based on experience with prior patients with cerebral ischemia similar to those under the clinician's care. The data bank also provides a resource for clinical investigation for transient cerebral ischemia, and represents a repository of detailed information not available in the usual printed sources of medical instruction.
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The results of a retrospective study of patients undergoing carotid endarterectomy for hemispheric and/or nonhemispheric symptoms of transient ischemic attacks are presented. During an approximately 3-year period of follow-up observation, recurrent cerebral ischemia following carotid endarterectomy was two to three times more frequent among patients with nonhemispheric transient ischemia than among those with hemispheric transient ischemia. Patients with symptoms of both hemispheric and nonhemispheric transient ischemia had the highest frequency of transient ischemic attacks and stroke during the follow-up period and also had the greatest surgical morbidity and mortality. The results of this study suggest that carotid endarterectomy has little or no therapeutic value in treating patients with vertebral-basilar ischemia.