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Biomedical subjects

S Gilman

Publications and source records attributed to S Gilman.

At least 55 records · Page 3Linked to original sources
PubMed1998

The significance of family history status in relation to neuropsychological test performance and cerebral glucose metabolism studied with positron emission tomography in older alcoholic patients.

Patients with severe chronic alcoholism have decreased rates of glucose metabolism in the medial frontal lobe and correlated abnormalities of neuropsychological functioning. The potential influence of family history of alcoholism has not been examined in these patients. In a retrospective study, we used neuropsychological tests and neuroimaging employing [18F]fluorodeoxyglucose with positron emission tomography to study 48 older subjects who had histories of severe, chronic alcohol dependence. These patients were divided into two groups: 27 with a first-degree relative with chronic alcoholism and 21 patients without first-degree relative with chronic alcoholism. No differences were found between groups on either neuropsychological or neuroimaging tests. These results suggest that a family history of alcoholism does not moderate the damaging effects of severe chronic alcoholism on the functioning of the medial frontal lobe.

Adult↗
PubMed1997

Positive and negative factors in movement control: a current review of Denny-Brown's hypothesis.

In his extensive writings, Denny-Brown hypothesized that two competitive 'tropisms,' one positive (exploratory) and one negative (withdrawal) act to coordinate normal movements at all levels of the neuraxis. Lesions in particular areas of the central nervous system result in disequilibrium between these tropisms, leading to disorders of posture and movement, including involuntary movements. The tactile manifestations of unbalanced exploratory tropisms are grasping responses, whereas the complementary withdrawal tropisms are avoiding responses. In Denny-Brown's view, at the level of the cerebral cortex, grasping responses result from frontal lobe injury whereas avoiding responses result from parietal lobe lesions. In this report we review Denny-Brown's conceptions of positive and negative tropisms, their anatomical loci, and whether his hypothesis has merit in a contemporary approach to brain function. We find that Denny-Brown's view on the anatomical loci associated with these behaviors is incomplete, but that the idea of conflicting behavioral tendencies is valuable for understanding and managing some neurological and perhaps also psychiatric disorders. For example, his hypothesis offers an important perspective in understanding the paradoxical success of stereotaxic surgery to alleviate the symptoms of Parkinson's disease.

Brain Injuries↗
PubMed1997

Impaired upper limb coordination in alcoholic cerebellar degeneration.

BACKGROUND: Alcoholic cerebellar degeneration (ACD) is a disorder resulting from severe chronic alcoholism and malnutrition and is characterized by cognitive disturbances, ataxia of gait, and truncal instability, with generally preserved coordination of the upper extremities. OBJECTIVES: To determine whether cognitive deficits in patients with ACD are the same as those seen in patients with severe chronic alcoholism without ACD and to determine whether upper limb motor coordination is different in the 2 groups. DESIGN: We examined cognitive function and upper limb coordination in 56 patients with severe chronic alcoholism, 13 with ACD and 43 without ACD, who had comparable levels of total alcohol intake. Neuropsychological and motor function was measured using an expanded Halstead-Reitan Neuropsychological Test Battery, including the Tactual Performance Test and Grooved Pegboard Test. RESULTS: Neither group had impaired coordination of upper limb function on clinical neurological examination. Both groups had impaired performance on neuropsychological tests involving executive function, but the patients with ACD had greater impairment of upper limb coordination than the patients without ACD as measured by the Tactual Performance Test and Grooved Pegboard Test. CONCLUSIONS: The findings suggest that these 2 groups have similar cognitive deficits but that upper extremity motor functions are more significantly impaired in the ACD group and that quantitative tasks of motor function reveal these impairments.

Alcoholism↗
PubMed1997

Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants.

We held an international consensus conference on frontotemporal dementia, behavioral disturbances, and parkinsonism linked to chromosome 17 to determine whether these are homogeneous or heterogeneous disorders, to agree on terminology, and to develop strategies for further research. The group identified 13 kindreds with sufficient evidence for linkage, finding in common to all a critical 2 cM between markers D17S791 and D17S800. There was agreement that (1) despite previous descriptions that have emphasized one or another clinical or neuropathological feature, the kindreds share clinical and neuropathological features; (2) until more specific information about the genetic defects becomes available, this disorder is best termed frontotemporal dementia and parkinsonism linked to chromosome 17; and (3) further research will be enhanced by identifying the gene or genes responsible for this disorder, detecting additional cases within known families and, in new families, correlating mutations with phenotypes and more fully delineating the clinical, neuropsychological, and neuropathological characteristics of this disorder.

Brain↗
PubMed1997

Unilateral striatal lesions in the cat disrupt well-learned motor plans in a GO/NO-GO reaching task.

We examined the changes in learned and spontaneous motor behavior after a unilateral excitotoxin lesion of the neostriatum. Cats were trained to perform a sensory-cued GO/NO-GO reaching task. Success rate, reaction time, movement speed and kinematic patterns were used to characterize motor system properties. In addition, motor properties before and after the lesion were compared by clinical neurological examinations and video tape observations of free-range behavior. We found that in normal animals motor performance in the task was fluent, highly automatic and skillful with consistent patterns from trial to trial and day to day. The striatal lesion resulted in a marked impairment in the animals' ability to perform the automatic response to the sensory cues in the motor task. In contrast, sensorimotor behavior in contexts apart from the task was altered minimally, with changes that were often difficult to detect. The animals recovered their ability to perform the task gradually, although they never reached prelesion performance levels in up to 24 weeks of evaluation. The animals had difficulty making reaching movements in GO trials and, in NO-GO trials failures to withhold movements were more frequent. Failures were due to a specific inability to execute previously well-learned movements in response to cues and not to an inability to recognize and interpret the cues. The lesion effects were restricted to the automatic motor response to the learned cues, as the animals could make reaching movements to the target without obvious impairment in response to novel stimuli. They also made similar spontaneous movements apart from the motor task that appeared to be unimpaired. The unique motor style and strategies that characterized the behavior of individual animals prior to the lesion were still evident after the lesion, even though they were superimposed on lower success rates and slower movement speeds. Our findings suggest that the basal ganglia facilitate the fluent and rapid execution of sequences of well-learned sensorimotor behavior, but the representations of motor plans are not stored in the basal ganglia.

Animals↗
PubMed1997

Utilization of the Denny-Brown collection: differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions.

The Denny-Brown collection of primate lesion material was used to test the hypothesis that there is a difference in the rate of forelimb and hind limb recovery of locomotor movements after major unilateral cerebral ablation (pre/postcentral gyrus, decortication or hemispherectomy). The results indicate that, following major cerebral injury, hind limb recovery precedes that of the forelimb in adolescent and adult primates, but not in infants. This suggests that there is an underlying physiological basis to the widely-held belief that, in humans, lower limb recovery after stroke is generally more complete than that of the upper limb.

Aging↗
PubMed1997

Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism.

Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of lCMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol.

Adult↗
PubMed1996

Characteristics of the dysarthria of multiple system atrophy.

OBJECTIVE: To characterize the dysarthria in patients with multiple system atrophy (MSA). DESIGN: Motor speech examinations, consisting of oral motor, oral agility, and perceptual speech analysis, were performed on 46 patients with MSA. SETTING: University department of neurology referral center. RESULTS: All patients had dysarthria with combinations of hypokinesia, ataxia, or spasticity. Thirty-two patients had all 3 components, 13 had 2 components, and 1 had only 1 component. In most patients the hypokinetic components were the most severe. Hypokinetic components predominated in 22 patients (48%), whereas ataxic components predominated in 16 (35%), and spastic components in 5 (11%). In 1 patient (2%) the hypokinetic and spastic components were equal and greater than the ataxic components, and in 1 patient (2%) the hypokinetic and ataxic components were equal and greater than the spastic components. One patient (2%) had only ataxic dysarthria. The predominant type of dysarthria corresponded well to the subtype of MSA. CONCLUSIONS: The finding of a mixed dysarthria with combinations of hypokinetic, ataxic, and spastic components is consistent with both the overall clinical and the neuropathologic changes in MSA. Motor speech examination can provide helpful information in evaluating patients who might have MSA.

Aged↗
PubMed1996

Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions.

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological disorder characterized by neuronal degeneration and reactive gliosis in the cerebellum, brainstem, spinocerebellar tracts, and dorsal columns. Multiple system atrophy is a sporadic progressive neurological disorder with degeneration and gliosis in the basal ganglia, cerebellum, brainstem, and spinal autonomic nuclei, and with argyrophilic glial cytoplasmic inclusions. We describe 4 members of a family with the SCA1 mutation and a dominantly inherited progressive ataxia in which autopsy examination of 1 member showed neuropathological changes typical of multiple system atrophy, including glial cytoplasmic inclusions. In this patient, magnetic resonance imaging revealed marked brainstem and cerebellar volume loss and mild supratentorial generalized volume loss. Positron emission tomography with [18F]fluorodeoxyglucose revealed widespread hypometabolism in a pattern found in sporadic multiple system atrophy and not in dominantly inherited olivopontocerebellar atrophy. Positron emission tomography with [11C]flumazenil revealed normal benzodiazepine receptor distribution volumes, similar to those seen in sporadic multiple system atrophy. Two other family members still living had similar changes in the imaging studies. The findings in this family suggest that the SCA1 gene mutation can result in a disorder similar to multiple system atrophy, both clinically and neuropathologically.

Adult↗
PubMed1996

Positron emission tomographic studies of cerebral benzodiazepine-receptor binding in chronic alcoholics.

Positron emission tomography was used with [11C]flumazenil (FMZ) and [18F]fluorodeoxyglucose to study GABA type A/benzodiazepine (GA-BA-A/BDZ) receptors and cerebral metabolic rates for glucose (1CMRg1c) in 17 male patients with severe chronic alcoholism (ALC), 8 with (ACD) and 9 without alcoholic cerebellar degeneration (non-ACD). In comparison with male normal controls of similar ages, the ALC group had significantly reduced FMZ ligand influx (K1), FMZ distribution volume (DV), and 1CMRg1c bilaterally in the medial frontal lobes, including superior frontal gyrus and rostral cingulate gyrus; the ACD group had significant reductions of K1, DV, and 1CMRg1c bilaterally in the same distribution, and also in the superior cerebellar vermis; and the non-ACD group had significant reductions of K1, DV, and 1CMRg1c bilaterally in the same regions of the frontal lobes but not in the superior cerebellar vermis. When compared with the non-ACD group, the ACD group had significant reductions of K1, and DV bilaterally in the superior cerebellar vermis. The results suggest that severe chronic alcoholism damages neurons containing GA-BA-A/BDZ receptors in the superior medial aspects of the frontal lobes, and in patients with clinical signs of ACD, neurons containing GABA-A/BDZ receptors in the superior cerebellar vermis.

Alcoholism↗
PubMed1996

Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.

Adult↗
PubMed1996

Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography.

We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.

Adult↗
PubMed1996

DC60: an example of one of the 450 cases that compose the Denny-Brown collection of primate lesion material.

The Denny-Brown collection consists of films depicting the behavioral responses of approximately 450 monkeys after central nervous system lesions; operative, behavioral, and neuropathologic descriptions; and histologic slides. This collection is available for use by interested investigators. This report describes one case, DC60, to provide an example of the types of material that are available and how these materials might be used better to understand the nervous system. To demonstrate how precisely the actual lesions can be defined and compared with the planned ablations, this report also includes a detailed evaluation of the extent of the lesions made in this case, based on the histologic slides and on photographs of the brain taken before histologic processing.

Animals↗