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Biomedical subjects

C M Filley

Publications and source records attributed to C M Filley.

At least 19 recordsLinked to original sources

Central nervous system angiocentric, angiodestructive T-cell lymphoma (lymphomatoid granulomatosis).

Most neurosurgeons and neurologists still consider lymphomatoid granulomatosis (LG) as a type of central nervous system (CNS) vasculitis. However, new insights, primarily from the hematologic literature, have cast doubt on the benign character of this disorder. In this article we (1) report a case of an 18-year-old woman with diffuse CNS disease and no mass lesion who developed multiple small cortical infarcts and dementia secondary to multifocal angiocentric, angiodestructive lymphoma; we (2) review other cases of LG with predominant CNS involvement; we (3) summarize the current understanding of LG, which is now considered to be a premalignant or overt angiocentric, angiodestructive T-cell lymphoma rather than a non-neoplastic vasculitis: the importance to neurologic surgeons and neurologists is that while pulmonary involvement in LG is generally the most prominent finding, patients may present with early or dramatic CNS disease; and we (4) note that although dementia is uncommon in young adults, this report adds yet another rare condition to the long differential list of dementia in this age group.

Adult

Concussion in sports. Guidelines for the prevention of catastrophic outcome.

Concussion (defined as a traumatically induced alteration in mental status, not necessarily with loss of consciousness) is a common form of sports-related injury too often dismissed as trivial by physicians, athletic trainers, coaches, sports reporters, and athletes themselves. While head injuries can occur in virtually any form of athletic activity, they occur most frequently in contact sports, such as football, boxing, and martial arts competition, or from high-velocity collisions or falls in basketball, soccer, and ice hockey. The pathophysiology of concussion is less well understood than that of severe head injury, and it has received less attention as a result. We describe a high school football player who died of diffuse brain swelling after repeated concussions without loss of consciousness. Guidelines have been developed to reduce the risk of such serious catastrophic outcomes after concussion in sports.

Adolescent

Lack of efficacy of hydergine in patients with Alzheimer's disease.

BACKGROUND: There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease. METHODS AND RESULTS: Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument). CONCLUSIONS: Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.

Aged

White matter dementia in chronic toluene abuse.

We studied 14 chronic toluene abusers with a comprehensive neuropsychological evaluation and cerebral magnetic resonance imaging (MRI). There were 10 men and 4 women, and the mean age was 29 years. Using a blinded global assessment of neuropsychological functioning, we found 3 patients to be normal, 3 in a borderline range, and 8 impaired. Independent analyses of white matter changes on MRI disclosed that the degree of white matter abnormality was strongly correlated (p less than 0.01) with neuropsychological impairment. Dementia in toluene abuse appears to be related to severity of cerebral white matter involvement.

Adult

Cytochrome oxidase deficiency in Alzheimer's disease.

We assayed cytochrome oxidase and other electron transport chain activities in platelet mitochondria isolated from patients with Alzheimer's disease (AD). Five of 6 patients had striking reductions of platelet cytochrome oxidase activity (patient mean, 83.72 +/- 82.99 nmol/min/mg; control mean, 167.14 +/- 36.21 nmol/min/mg; n = 8). Other electron transport chain catalytic activities were not significantly different than control values. AD may be a systemic illness, a primary defect in cytochrome oxidase may be pathogenically important in its production, and the mitochondrial genes encoding cytochrome oxidase subunits may be important in producing the defect.

Aged

A comparison of dementia in Alzheimer's disease and multiple sclerosis.

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.

Aged

Cognitive loss in multiple sclerosis. Case reports and review of the literature.

Neuropsychological and neuroradiologic evidence of cerebral lesions is described for 12 patients with multiple sclerosis in whom cognitive disability was far greater than any other neurologic disability. Cognitive dysfunction resulted in significant functional impairment at work or home in three fourths (9 of 12) of the patients described here, despite mild physical disability (mean Kurtzke Expanded Disability Status Scale score, 3.2). A unique feature of the neurologic examination in these patients was the presence of prominent frontal release signs (gait apraxia and placing response) in the lower extremities. Two new scales, a Cognitive Function Scale and a Frontal Release Scale, were adapted for the investigation of these patients. The extensive literature relating to cognitive dysfunction in multiple sclerosis is reviewed and discussed with regard to its clinical relevance.

Adult

Toluene abuse causes diffuse central nervous system white matter changes.

We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2-weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill-defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene-induced metabolic changes in myelin.

Brain

Diffuse Lewy body disease and progressive dementia.

Thirty cases of diffuse Lewy body disease (DLBD) have been reported, primarily by neuropathologists, but an associated clinical syndrome has not been clearly defined. Four recent cases have led us to examine the clinicopathologic correlations. Patients are usually elderly, with symptoms lasting from 1 to 20 years. Progressive dementia or psychosis is typically the first and most prominent feature. Parkinsonian signs, initially mild or absent, become common eventually, and rigidity is usually severe. Involuntary movements, myoclonus, quadriparesis in flexion, orthostatic hypotension, and dysphagia have also been noted. Classic, concentric Lewy bodies are found profusely in the brainstem, basal forebrain, and hypothalamic nuclei, while less well defined "Lewy-like" bodies occur in limbic structures and in deep neocortical layers. In addition, focal spongiform changes in the mesial temporal lobe were found in two of our cases. We suggest that DLBD may be another specific cause of progressive dementia.

Aged

Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis.

Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35, p less than 0.01). However, we did not find a significant correlation between the Kurtzke Expanded Disability Status Scale and any MRI or NSB summary measures. Compared with the Mini-Mental State Exam (MMSE), the NSB cognitive summary score yielded a prevalence estimate for cognitive impairment that is more consistent with previous findings in chronic/progressive MS. The NSB is a useful screening test for cognitive dysfunction in chronic/progressive MS because of its relationship to cerebral lesions on MRI and its greater sensitivity than the frequently used MMSE.

Adult

Neurobehavioral outcome after closed head injury in childhood and adolescence.

Hospital records of 53 children and adolescents, aged 18 years or less, with closed head injury were reviewed for information on long-term outcome. Computed tomographic scans were used to divide the patients into clinicopathologic groups. Within these groups, duration of coma was the major index of severity. Outcome was assessed using the Glasgow Outcome Scale and by evaluating social behavior, school performance, and vocational functioning. Patients with diffuse injury plus focal lesions fared worse than those with diffuse injury only. Coma lasting more than one month led to a poorer outcome in both groups. Many individuals had limiting emotional disturbances, which may have resulted from disruption of frontal systems modulating arousal and social behavior.

Adolescent

Wechsler Intelligence Scale profiles, the cholinergic system, and Alzheimer's disease.

Forty-one patients with putative Alzheimer's Disease (AD) were evaluated to determine the diagnostic utility of a profile of Wechsler Adult Intelligence Scale (WAIS) subtests which has been proposed by Fuld (1984) to identify cholinergic dysfunction. Only nine (21.9%) of these patients had positive Wechsler profiles. Half (n = 21) of the AD patients had been given the WAIS, and the other half (n = 20) the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Positive profiles occurred more often in the AD subgroup given the WAIS-R, but this difference was not statistically significant. Specificity of the formula was evaluated using Wechsler results of 42 older normals and 30 patients who were being evaluated for dementia but who did not have AD. One of the 42 normals (2.4%) and five of the patient controls (16.7%) showed a positive Wechsler profile. Because of the Fuld formula's low sensitivity, a negative Wechsler profile cannot be used to help rule out AD. Although specificity of the formula is high, the diagnostic value of a positive Wechsler profile is modest even under the most favorable AD baserate conditions.

Aged

Delayed reduplicative paramnesia.

A 25-year-old man with a remote history of closed head injury and left hemiparesis developed the false belief that his hospital was located in another city, close to his home. This delusion appeared more than 3 years after his injury, from which he had made a good recovery. No previous delusional or other psychotic thinking had occurred. Clinical and neuropsychological data supported the existence of right hemisphere and bifrontal pathology. This case illustrates that a specific delusional belief may arise in a patient with appropriate cerebral pathology years after the initial event.

Adult

Acquired aphasia in childhood: clinical and CT investigations.

We studied eight children with acquired aphasia. All had left hemisphere lesions. In most, the correlation between the CT lesion site and the resulting aphasic syndrome duplicated an anatomic-clinical correlation described in adults. Rapid recovery of language fluency distinguished the children from reported adults. Late follow-up indicated poor scholastic achievements, reflecting an acquired handicap in new learning. Anatomic-clinical correlates and recovery patterns suggest that brain organization for language is similar but not identical in children and adults.

Adolescent

Neuropsychologic features of early- and late-onset Alzheimer's disease.

Forty-one patients with clinically diagnosed Alzheimer's disease were divided into two groups for comparison of neuropsychologic features in those with early- and late-onset disease. Handedness was also assessed in all patients. Twenty-three patients with onset before age 65 had significantly more language impairment, whereas 18 patients with onset at age 65 or older had more difficulty with visuoconstructional function. Memory was severely impaired in all patients. Only one patient in each group was left-handed, and the same results were obtained when these were excluded. These observations support the notion of left hemisphere vulnerability in early-onset Alzheimer's disease and can be interpreted as demonstrating the clinical variability of the illness rather than the necessity of dividing it into two distinct entities.

Age Factors

Neurologic sequelae of chronic solvent vapor abuse.

Neurologic abnormalities were seen in 13 of 20 patients with a history of chronic solvent vapor (primarily toluene) abuse for 2 or more years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cognitive (60%), pyramidal (50%), cerebellar (45%), and brainstem/cranial nerve (25%) findings. Eight of nine CTs revealed diffuse atrophy of cerebral hemispheres, cerebellum, and brainstem. BAERs were abnormal in three of four patients, and EEG abnormalities were seen in three of seven patients. Chronic exposure to solvent vapor may cause persistent neurologic impairment.

Adolescent

Education provides no protection against Alzheimer's disease.

It has been suggested that educational achievement confers protection against dementia. We examined educational level and age of onset in 28 patients with Alzheimer's disease, and assessed the progression of dementia over a mean period of 28 months using both a measure of neurobehavioral status and an index of functional impairment. No protective effect of education was found in either early- or late-onset dementia.

Alzheimer Disease