Biomedical subjects

C M Filley

Publications and source records attributed to C M Filley.

At least 37 records · Page 2Linked to original sources

PubMed1999

Frontal lobe lesions and executive dysfunction in children.

OBJECTIVE: To investigate the relationship of frontal lobe lesions and neuropsychologic performance in school-aged children to determine whether damage to frontal regions results in specific cognitive sequelae. BACKGROUND: The role of the frontal lobes in executive function remains incompletely understood, particularly in children. METHOD: This retrospective study included children aged 8 to 17 with brain lesions of various etiology (n = 63) or diverse psychiatric disorders (n = 48). All were evaluated for details of neurologic and medical history and for scores on the Wechsler Intelligence Scale for Children (WISC-III) and the Wisconsin Card Sorting Test, and all but the psychiatric patients had neuroimaging scans. Five groups were analyzed--dorsolateral frontal, medial-orbital frontal, focal nonfrontal, diffuse, and psychiatric--and neuropsychologic test results were compared using a Kruskal-Wallis nonparametric analysis of variance. RESULTS: Children with damage to dorsolateral frontal regions were more impaired on the Wisconsin Card Sorting Test than those in all other groups. Comparable performance on the Wechsler scale was found in all groups, suggesting that intellectual functioning did not account for this difference. CONCLUSIONS: These data provide evidence for a prominent role of the dorsolateral frontal regions in the mediation of executive function in children. They also support the use of the Wisconsin Card Sorting Test in children as a measure of dorsolateral frontal integrity.

Adolescent↗

PubMed1999

Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls.

OBJECTIVE: To examine neuropsychologic functions in patients with chronic obstructive pulmonary disease (COPD) and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. BACKGROUND: Cognitive deficits have been documented in patients with COPD, but few studies have compared the neuropsychologic status of these patients with that of other neurologic groups. METHOD: Cognitive test results from 32 patients with COPD and mild hypoxemia (mean age, 70.3 years; mean education, 13.2 years; mean partial arterial oxygen pressure, 68.8 mm Hg) who had no neurologic symptoms were compared with 31 subjects with mild Alzheimer disease (AD) and 31 normal controls similar in age, education, and sex. Seventy-three percent of the patients with COPD were receiving supplementary oxygen. RESULTS: Significant group differences across 11 cognitive scores were found using analysis of variance, and post hoc analyses indicated that patients with mild AD performed significantly worse than normal controls and patients with COPD on most tests. The group with COPD and the group with AD demonstrated lower letter fluency compared with controls. Although the patients with COPD performed significantly worse than controls on verbal fluency tasks, they were not in the clinically impaired range, and, overall, the group with COPD was similar to the controls on most cognitive tests. CONCLUSIONS: These findings suggest that many patients with COPD and mild hypoxemia who don't have neuropsychiatric histories may perform normally on cognitive measures. Oxygen therapy may partially account for preservation of cognitive function in these patients. Results also suggest that patients with COPD and normal controls can be readily distinguished from patients with mild AD based on levels and patterns of neuropsychologic test results. Any significant cognitive deficits in patients with mildly hypoxemic COPD may warrant continued neurologic evaluation.

Aged↗

PubMed1998

Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review.

A woman developed the delusional syndrome of erotomania 4 years after subarachnoid hemorrhage from a ruptured basilar artery aneurysm. The authors review the literature on erotomania in association with neurologic and medical conditions. Although no cause-and-effect relationship can be established between the neurologic event and erotomania in this patient, the possible neuropsychiatric correlates of this syndrome highlight the need for careful attention to neurologic and medical factors in future cases. Available information suggests that diffuse brain dysfunction may contribute to erotomania, perhaps by interfering with the operations of cerebral regions subserving complex emotional function.

Aneurysm, Ruptured↗

PubMed1998

The behavioral neurology of cerebral white matter.

Behavioral neurology has primarily focused on brain-behavior relations as revealed by disorders of the cerebral cortex and subcortical gray matter. Disorders of cerebral white matter have received less attention. This article considers the contribution of cerebral white matter to normal behavioral function and the effects of white matter disorders on behavior. Diffuse dysfunction is more common than focal impairment, and the term white matter dementia has been proposed as a clinical entity. Conventional neuroimaging has enabled more accurate identification of white matter regions participating in neurobehavioral operations, and newer imaging techniques may define white matter connectivity within and between the hemispheres. As an essential component of neural networks, cerebral white matter contributes to cognitive and emotional functions, and lesions of white matter disconnect these networks to produce neurobehavioral syndromes.

Behavior↗

PubMed1997

Alzheimer's disease in women.

The progressive and irreversible dementia of Alzheimer's disease affects both men and women, but women constitute the majority of persons with the disease. Women may also have relatively more language impairment and a tendency for greater psychiatric involvement. Diagnosis is founded on the recognition of clinical features and exclusion of other causes of dementia. The etiology of the disease remains unknown. Although a variety of genetic factors is increasingly suspected, no diagnostic genetic test is currently recommended. Recent basic science and clinical data suggest the possibility that estrogen may be helpful both in preventing and in treating Alzheimer's disease, and these potential effects may encourage the use of estrogen in postmenopausal women. Standard treatment for Alzheimer's disease involves counseling and support, as well as consideration of tacrine, a cholinergic agent that may stabilize the course in some patients. Until the cause of the disease is elucidated, however, the development of curative treatment is unlikely.

Alzheimer Disease↗

PubMed1997

Neurobehavioral outcome in pediatric craniopharyngioma.

Neurobehavioral dysfunction occurs in children with craniopharyngioma, both before and after treatment, and its impact on outcome may not be fully appreciated. Also unclear is whether neurobehavioral outcome relates more to tumor location or surgical factors. We reviewed the records of 20 children with craniopharyngioma who were seen between 1983 and 1995. All children had subfrontal craniotomy and either partial (14 children) or gross total (6 children) resection of their tumors. In addition to traditional neuropsychological testing, we assessed social behavior and school performance using standardized ratings based on family interviews and school records. Over a mean follow-up period of 38 months, only 3 of 20 children had a good outcome in all three categories, and 12 of 20 had moderate or severe impairment in at least one category. Outcome did not differ between those who had partial and those with gross total resection. We conclude that neurobehavioral disorders are common and cause important morbidity in children after treatment for craniopharyngioma. To evaluate these impairments in future outcome studies, standard neuropsychological testing should be supplemented by specific behavioral assessments to capture the full range of neurobehavioral disability. In this series, partial versus gross total resection did not influence outcome, implying that tumor location in diencephalic and limbic regions is a more important factor.

Achievement↗

PubMed1997

Education and cognitive function in Alzheimer's disease.

In normal aging, an association exists between level of education and verbal abilities. Clinical experience suggests that this relationship may also hold true in Alzheimer's disease (AD). In this study, we examined performance on selected verbal and nonverbal neuropsychological tests in a series of 51 patients with probable AD. Performance on two verbal measures-the National Adult Reading Test-Revised (NART-R) and the Vocabulary subtest from the Wechsler Adult Intelligence Scale-Revised (WAIS-R)-showed strong correlations with level of education. Scores on three nonverbal tests-WAIS-R Block Design, WAIS-R Digit Symbol, and Boston Diagnostic Aphasia Examination clock drawings-were unrelated to education. Consistent with our hypothesis, AD patients with higher premorbid education showed better performance on certain measures of verbal competence. These results indicate that, as in normal aging, education is associated with verbal abilities in AD.

Aged↗

PubMed1996

Premorbid intelligence estimation and level of dementia in Alzheimer's disease.

Simple sight-word reading tasks have demonstrated utility in the estimation of premorbid intelligence, although the effects of progressive dementia on such tasks has not been thoroughly examined. The present investigation sought to examine estimated IQ scores from the National Adult Reading Test-Revised (NART-R; Blair & Spreen, 1989) in relation to a WAIS-R-based (Wechsler, 1981) estimate of IQ in a series of patients with probable Alzheimer's disease across varying levels of dementia. Results suggest that while NART-R scores do show a decrement with dementia severity, this decline is mild, in contrast to traditionally based IQ scores and other measures of cognitive function, which show more marked declines. Similarly, compared with other tasks, the NART-R showed the strongest correlation with education across the sample as a whole, while the other indices were more related to level of dementia. These findings support the use of measures such as the NART-R in estimating premorbid intellectual functioning in patients at various levels of dementia severity, including those with more advanced cognitive deterioration.

Aged↗

PubMed1996

Ethical concerns in the use of palliative drug treatment for Alzheimer's Disease.

The cases of 3 patients with Alzheimer's disease (AD) who had varied outcomes from treatment with tacrine or other palliative drugs illustrate the need to consider the benefits of such agents for each case on an individual basis. In the absence of a cure, the most important factor in the care of AD patients may be the physician's attitude that irreversibility does not imply untreatability.

Alzheimer Disease↗

PubMed1995

Acute arcuate fiber demyelinating encephalopathy following Epstein-Barr virus infection.

We describe a patient who presented with an acute monophasic illness characterized by behavioral abnormalities, visual illusions, and a seizure, who had magnetic resonance- and brain biopsy-documented evidence of multifocal central nervous system demyelination. Serological studies were diagnostic of recent Epstein-Barr virus infection and included evidence of intrathecal synthesis of Epstein-Barr virus-specific IgG antibodies against the viral capsid antigen. Viral DNA could not be amplified from cerebrospinal fluid by polymerase chain reaction, and viral antigen and genome were not detected in the brain biopsy specimen. The patient's clinical course, diagnostic studies, and neuropathological findings all support the diagnosis of a postinfectious Epstein-Barr virus-mediated demyelinating encephalopathy.

Acute Disease↗

PubMed1995

Neuropsychiatric features of Lewy body disease.

Although traditionally associated with Parkinson's disease, the eosinophilic intracytoplasmic neuronal inclusion known as the Lewy body has recently been regarded as the primary neuropathologic finding in a variety of conditions affecting the aging brain. The term Lewy Body Disease (LBD) will be used in this review to refer to a spectrum of clinical states varying from those due to incidental or mildly symptomatic histopathologic changes to progressive dementia and psychosis. Many unanswered questions remain about the neurobehavioral and neuropathological implications of Lewy bodies, but it is useful to consider the LBD spectrum in terms of the variable effects on neuropsychiatric function that can be observed clinically.

Age of Onset↗

PubMed1995

Episodic memory function in advanced aging and early Alzheimer's disease.

Despite some well-documented differences, normal aging and Alzheimer's disease (AD) share a number of common neuropathological and neuropsychological features. Many of the reported differences are largely quantitative in nature and there is often overlap between the respective distributions of these populations. To assess the issue of overlap and distinguishing features in memory functions between these groups, and to minimize aging effects per se, samples of older individuals in good health (ages 75-95 yr) and younger patients in the early stages of AD (age < 75 yr) were selected to be similar in global cognitive functioning. Despite comparable language and visuospatial scores, these preliminary results suggest important qualitative differences in episodic memory functions between these conditions, even when "low-functioning" or "at-risk" controls are compared with early AD patients. These findings furthermore highlight some of the challenges in defining "normality" among the oldest segment of our population.

Aged↗

PubMed1995

Alzheimer's disease: it's irreversible but not untreatable.

Alzheimer's disease (AD) poses a major clinical challenge because of its high prevalence in the aging population, its prolonged course, and the absence of curative treatment. Important advances have recently been made, however, in the diagnosis of the disease and the elucidation of its neuroscientific basis. Genetic research has identified an allele of apolipoprotein E that may confer a higher risk of developing AD. In addition, new possibilities for treatment are being investigated. One drug therapy--tacrine--has been approved, although uncertainty lingers about its efficacy and safety. In the absence of effective medical treatment, AD is a difficult problem for patients and their families. However, the physician can help by providing emotional support, symptom management, and informed counseling.

Aged↗

PubMed1995

Neurobehavioral presentations of brain neoplasms.

We studied 8 patients with frontal or temporolimbic neoplasms who had psychiatric presentations to clarify diagnostic criteria for distinguishing psychiatric disease from structural brain lesions and to examine brain-behavior relationships associated with cerebral neoplasms using modern neuroimaging techniques. Medical records were retrospectively reviewed for evidence of neurobehavioral and neurologic manifestations, tumor histologic features, and the results of treatment. Clinical presentations were correlated with tumor location as determined by computed tomography and magnetic resonance imaging. Patients with frontal lobe tumors presented with abulia, personality change, or depression, whereas those with temporolimbic tumors had auditory and visual hallucinations, mania, panic attacks, or amnesia. After treatment, neurobehavioral syndromes abated or resolved in 7 of 8 patients. We recommend that any patient 40 years of age or older with a change in mental state, cognitive or emotional, should have neuroimaging of the brain. Any patient with a psychiatric presentation who has specific neurobehavioral or neurologic findings or an unexpectedly poor response to psychopharmacologic treatment should also have brain imaging. These case reports extend and update observations on the importance of frontal and temporolimbic systems in the pathogenesis of neurobehavioral disorders.

Adult↗

PubMed1994

Attention and vigilance functions in normal aging.

Clinical observation and considerable research have documented that a slowing of cognitive processing occurs in many healthy older persons. The neuropsychological characterization of this slowing, however, remains unclear, as does its neuroanatomic basis. In a preliminary attempt to help clarify this issue, we conducted two studies with healthy older individuals to evaluate whether declines in immediate and/or sustained attention appear with advancing age. In Study I, 166 subjects aged 50-69 and 70-90 were given several standard tests of immediate attention. No major differences in simple attentional function emerged. In Study II, 38 subjects in the same age ranges were administered tests of sustained attention. Significant differences between groups were seen on a digit cancellation task, despite similar performances on other measures requiring visual scanning and psychomotor speeded responses. The results of the two studies suggest that whereas simple attention tends to remain stable with aging, sustained attention appears to decline after the age of 70. This factor likely contributes to the general slowing of cognition often reported in the elderly, and may be associated with specific age-related neuroanatomic changes.

Journal Article↗

PubMed1994

Reduced platelet cytochrome c oxidase activity in Alzheimer's disease.

We evaluated a simplified method for preparation and analysis of platelet cytochrome c oxidase activity in Alzheimer's disease (AD) and control patients. Mean cytochrome c oxidase activity in controls (n = 17) was 0.233 sec-1/mg whereas mean cytochrome c oxidase activity in Alzheimer patients (n = 19) was 0.193 sec-1/mg, p = 0.033. Complex III (ubiquinol:cytochrome c oxidoreductase), complex II (succinic dehydrogenase), and citrate synthase were all assayed as internal controls and were not significantly different in controls and Alzheimer patients. There is a relatively specific loss of platelet cytochrome c oxidase activity in Alzheimer disease patients.

Aged↗

PubMed1994

Electron transport chain defects in Alzheimer's disease brain.

Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer's disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (p < 0.001). Concentrations of cytochromes b, c1, and aa3 were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX.

Aged↗

PubMed1993

Neuroleptic medications inhibit complex I of the electron transport chain.

Neuroleptic medications are prescribed to millions of patients, but their use is limited by potentially irreversible extrapyramidal side effects. Haloperidol shows striking structural similarities to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces parkinsonism apparently through inhibition of NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial electron transport chain. We now report that haloperidol, chlorpromazine, and thiothixene inhibit complex I in vitro in rat brain mitochondria. Clozapine, an atypical antipsychotic reported to have little or no extrapyramidal toxicity, also inhibits complex I, but at a significantly higher concentration. Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson's disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.

Adult↗