Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid.

Energy metabolism was measured in children receiving long-term treatment with valproic acid. In 8 of 10 randomly selected subjects, the resting respiratory quotient was higher than in age- and sex-matched control subjects (0.91 +/- 0.01 vs 0.87 +/- 0.01; p < 0.05). A shift was observed in fuel consumption, and a significant reduction was found in the amount of fats oxidized (0.68 +/- 0.23 vs 1.18 +/- 0.18 gm.kg-1.day-1), which was accompanied by increased utilization of carbohydrates (5.31 +/- 0.79 vs 3.81 +/- 0.39 gm.kg-1.day-1) in comparison with the control subjects. The resting total energy expenditure was not affected by the treatment. The children with an altered energy consumption pattern (n = 8) received carnitine supplementation for a month; the respiratory quotient then decreased (0.87 +/- 0.02), the oxidation of fats increased (1.42 +/- 0.25), and the consumption of carbohydrates decreased (3.87 +/- 0.79), but no changes in resting energy expenditure were observed. We conclude that carnitine depletion, a known adverse effect of valproic acid administration, may result in inhibited fatty acid oxidation, leading to a shift of substrates utilized from fats to carbohydrates.

Flexible sigmoidoscopy screening for asymptomatic colorectal disease in patients with and without inguinal hernia.

Several studies have evaluated the diagnostic value of flexible sigmoidoscopy for screening asymptomatic patients before hernia repair. All have shown a 16% to 28% incidence of neoplastic (malignant or premalignant) lesions. None of these studies compared a similar group of asymptomatic patients without hernia to determine whether the incidence is increased in patients with hernias. We reviewed 87 consecutive cases of male surgical patients without hernia or any anorectal disease who had flexible sigmoidoscopy between June 1986 and December 1989 (group 1) and compared them with a group of hernia patients that we previously reported (group 2). Patients with stool positive for occult blood were excluded from this study. Examinations in both groups were done under the direct supervision of an attending surgeon (W.W., C.S.C., or J.K.). No significant difference was noted between group 1 and group 2 in mean age (mean 65.6 vs 59.7 years), rate of normal findings (68% vs 63%), and incidence of neoplastic lesions (14% vs 22%). All patients tolerated the procedure well, and there were no complications.

Facial- and postural-affect recognition in senile elderly persons.

Sixteen senile geriatric inpatients were tested for visual affect recognition under four conditions. In the first three conditions, they were presented with different sets of happy, sad and angry facial stimuli. In the fourth condition, postural sketches were used to express the three emotions. The subjects were tested by means of verbal prompting, i.e., they were directed to point to either the happy, sad or angry facial and bodily expressions over a series of trials. Significantly more errors were made to the angry expressions than to the happy and sad ones which, in turn, did not differ from one another. In addition, significantly more errors were generated by the facial stimuli than by the postural representations. These findings suggested a mechanism underlying prosopo-affective agnosia.

Facial-affect recognition in normal preschool children and in senile elderly persons.

The performance of senile elderly persons and of young children was compared on an identical facial affect recognition test. The senile persons were disoriented with impaired recent memory. However, their neurological functioning in visual, perceptual, verbal, and motor processing required for the testing was intact. The children were divided into age groups of 3, 3 1/2, 4, 4 1/2, and 5. Pictures of happy, sad, and angry faces were shown and the subjects were tested for their ability to discriminate between the emotions by the use of prompting and oddity procedures. The very young children (ages 3 and 3 1/2) were found to be at a deficit in recognizing facial expressions, particularly with regard to the recognition of sad faces. The children's recognition level improved as a function of age. The senile persons were found to be significantly more impaired than even the youngest group of children, particularly with regard to the recognition of angry faces. While the children attempted to distinguish between the stimuli on the basis of affect, the seniles tended to "feature-detect", because their facial feature recognition ability remained relatively intact. Thus the impairment of facial affect recognition in senility was quite unlike that of younger children. The extensive deterioration of senile patients in facial affect recognition ability is remarkable and has important therapeutic implications. Since these patients still maintain high level of verbal comprehension, clear verbal expression of our feelings toward them is essential.

Quantitative clinicopathologic study of senile dementia.

In a randomized blind study of 69 mental hospital patients over 50 years of age, a highly significant correlation was observed between the clinical symptoms of organic brain disease and the quantity of senile plaques found in the brains at autopsy. A stepwise multiple regression analysis indicated that independent significant predictors of the quantity of plaques were the level or disorientation and the age of the patient. Additional clinical tests for intellectual deterioration, affect lability, and impairment of memory and judgment did not improve the predictive ability. The correlation between incidental pathologic changes unrelated to the senile form of cerebral degeneration and the clinical symptoms was highly significant, though not obvious. Only after removal of the effect of the quantity of plaques on the clinical symptoms (multiple regression analysis) did the effect of other pathologic processes become evident. A significant one-way fixed-effect relationship was noted between increasing quantity of symptoms and increasing quantity of plaques in 48 cases of senile dementia correctly diagnosed by the psychiatry staff. In the control group of 21 patients without senile dementia, the quantity of plaques was correlated with the age of the patients but not with their clinical symptoms.

Quantitative clinicopathologic study of cerebral amyloid angiopathy.

A rapid screening method is described for detecting amyloid angiopathy (AA) in the meningeal vessels with the use of thioflavin-S and fluorescence microscopy. AA was found most frequently in the brains of patients in whom senile degeneration of the Alzheimer type was complicated by severe arteriosclerosis, vascular hyalinosis and multiple infarcts (73 percent). In 69 randomly drawn mental hospital patients over the age of 55, the degree of AA was significantly correlated with the degree of organic symptomatology (r = .417, p less than .001). Multiple regression analysis, however, revealed that AA as a predictor of clinical symptoms was highly dependent upon another predictor, i.e., the quantity of senile plaques in the brain. In contrast, a highly significant and independent correlation was found between the clinical symptoms and AA in a control sample of 21 patients who had mental illnesses other than senile dementia (r = .683, p less than .001). In these patients the plaque count was very low and arteriosclerosis was prevalent. Among the clinical symptoms, Affect Lability was consistently most highly correlated with AA, whereas Disorientation was most highly correlated with the quantity of plaques.

On the mechanism underlying facial-affective agnosia in senile demented patients.

Two experiments were conducted in which senile demented patients were shown pictures of happy, sad, and angry faces, and tested for their ability to recognize these emotional expressions. Their affect recognition was obviously impaired, as they tended to respond to the line or feature characteristics of the faces, instead of the affective meaning that was suggested by the facial expressions. This impairment was somewhat overcome either by adding verbal cues which created an affective set, or by making feature detection irrelevant to the recognition process. It was shown that if the tendency to detect features is defeated, senile people can extract emotional meaning from facial stimuli. The data suggested that the mechanism underlying facial-affect agnosia is an impairment in the associative connections between the visual impression of facial expression and affective meaning.

Prosopo-affective agnosia and computerized tomography findings in patients with cerebral disorders.

Thirty-nine male patients (median age 61, range 19-92) from a neurologic ward were examined by a test for prosopo-affective agnosia (PAA), i.e., impairment in the recognition of facial affect (emotions) with no impairment in the recognition of facial features (PA, prosopo-agnosia). The scores for patients without hemispheric damage were close to those of normal subjects; the scores for patients with right and left hemispheric disease were lower; and the worst performers were patients with diffuse bilateral disease. The relative independence of PAA from PA was re-affirmed. The neurologic findings on 21 patients were confirmed by computerized tomography (CT). On the PAA test, patients with negative CT results had scores close to those of normal subjects; patients with right or left hemispheric disease had lower scores; and the worst performers were patients with diffuse cortical atrophy. All patients who scored 87.5 percent or lower showed positive results with the CT scan, indicating that the PAA test may have some value in predicting positive CT findings. A significant deterioration in the ability to recognize facial affect was evident in the group of 15 patients aged 65 or older.

Dose reduction and discontinuation of antipsychotic medication.

In 1977 staff members on a 30-bed inpatient ward in a state hospital implemented a program to discontinue the medication of chronic schizophrenic patients who had been hospitalized continuously for five years or more. Six-month follow-up of the 15 patients who met the selection criteria showed that seven were still off medication, and two had improved enough to be discharged. The program was later adopted throughout the hospital; an audit conducted 90 days after its implementation showed that 31 per cent of the patients hospitalized continuously for 90 days or longer were not receiving antipsychotic medication. The authors emphasize the benefits to patients of reducing or discontinuing antipsychotic medication where possible.

Prosopo-affective agnosia as a symptom of cerebral organic disease.

A previously described test for prosopo-affective agnosia (impairment of facial affect recognition) had been applied in 14 disoriented elderly patients with chronic organic brain syndrome, 14 fully oriented elderly patients with non-organic psychiatric disorders, and 14 normal volunteers. In this re-test study of 37 of the 42 subjects, after a six-month interval, the test was found to be reliable (r = .75, p less than .001). The test was also more sensitive in detecting organic disorders than were other frequently applied neuropsychiatric tests. Prosopo-affective agnosia (PAA) appeared unrelated to prosopo-agnosia (PA) (r = .082, ns). Some patients who had the ability to recognize famous faces and faces of ward personnel were severely impaired in the ability to recognize facial affect. The deterioration was more pronounced for the recognition of sadness and anger than for happiness, indicating that patients with this impairment had reverted to an infantile mode of facial-affect recognition. This reversal is another example of the neurologic regression that characterizes dementia.

Prosopo-affective agnosia associated with chronic organic brain syndrome.

Impairment of the ability to recognize facially expressed emotions was studied in 14 chronically disoriented patients with chronic organic brain syndrome (CBS). This impairment was named prosopo-affective agnosia (PAA). A diagnostic requirement was relatively intact neurologic functioning in underlying perceptual-verbal-motor processing. A test was designed for facial-affect recognition in the accurate differentiation of normal persons from chronically disoriented CBS patients. No normal subject made any errors in this test. Despite decades of illness and hospital living, patients with a history of schizophrenia or major affective disorders scored almost at a normal level (95 vs. 100 percent) in this test, and significantly higher (95 vs. 66 percent) than did the disoriented CBS patients. The social and therapeutic implications of the findings are stressed. CBS patients may be impaired with respect to receiving and appreciating elementary aspects of social communications such as recognizing a smile, anger, sadness or disapproval on the faces of people who surround them. This disability requires understanding and a special attitude on the part of the therapeutic team toward such patients.