Lack of blindness procedures in Alzheimer's study.
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Adult↗
Biomedical subjects
I Prohovnik
Publications and source records attributed to I Prohovnik.
Abnormal cranial magnetic resonance imaging scans in sickle-cell disease. Neurological correlates and clinical implications.
OBJECTIVE: Eight asymptomatic patients with sickle-cell disease (SCD) with magnetic resonance imaging (MRI) abnormalities consistent with cerebral infarcts (group 1) and eight asymptomatic patients with SCD with normal MRI scans (group 2) were followed up to assess the neurological correlates and the clinical outcome. DESIGN: Patients in the two cohorts underwent clinical evaluations and xenon 133 regional cerebral blood flow (rCBF) studies within 1 month of the entry MRI. This study sequence was repeated up to 5 years later. Neuropsychological studies also were performed in six group 1 patients and eight group 2 patients at the end of the study. SETTING: The patients were recruited from the Comprehensive Sickle Cell Center at Columbia University, New York, NY. PATIENTS: All patients had SCD, hemoglobin SS, and normal findings on clinical evaluation at entry. The group 1 cohort had clinically silent MRI abnormalities consistent with cerebral infarction. The group 2 cohort was age matched to group 1 and had normal MRI studies. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The natural history of MRI abnormalities and the neurological correlates were assessed to determine the predictive value of subclinical MRI lesions as a risk factor for clinically apparent stroke. RESULTS: The mean duration of MRI follow-up was 3.7 years. In group 1, four patients (50%) demonstrated progressive MRI abnormalities and three patients (38%) became clinically symptomatic. In group 2, findings for all patients remained normal on clinical and radiological examination. Both groups had markedly elevated rCBF values. Individual rCBF differences correlated with the specific MRI abnormalities. The psychometric study results were similar in the two cohorts. Eighty-three percent of group 1 and 88% of group 2 patients had defective scores in one or more areas of cognitive functioning. Three patients met cognitive criteria for dementia. CONCLUSIONS: Cranial MRI abnormalities have important prognostic implications even when detected in clinically asymptomatic patients. Cognitive abnormalities exist in patients with SCD even in the absence of MRI abnormalities or clinical stroke.
Adolescent↗
Alzheimer-type neuropathology in elderly schizophrenia patients.
Traditionally, schizophrenia has been studied in early adulthood. Its course and outcome during senescence are largely unknown and subject to controversy. We reviewed the consecutive neuropathologic records of 1,046 patients who were chronically hospitalized in New York State mental institutions, and we selected for analysis all 802 patients who died after age 50 with a clinical antemortem diagnosis, as recorded in the autopsy notes, of schizophrenia (n = 544) or dementia (n = 258). The prevalence of neuropathologic diagnoses consistent with Alzheimer's disease (AD) was 51 percent in the dementia group and 28 percent in the schizophrenia sample. This prevalence rate in the schizophrenia sample (mean age = 77) was considerably higher than that estimated for the general population. When evaluated against age of death, AD findings in demented patients were age invariant, whereas the rate of such findings in schizophrenia patients rose monotonously from under 5 percent below age 60 to 50 percent at age 90 and over. The age-relative rate of AD diagnosis in schizophrenia patients was similar to a curve postulated for first-degree relatives of familial AD patients and was markedly higher than population estimates. These findings as a basis for comparison with other retrospective studies of pathological records are presented. Our own study, as well as others, suffers from three intrinsic limitations. The clinical diagnoses are taken from death notes and have no formal verification. Likewise, neuropathologic diagnoses were based upon informal criteria in use at the time; since that time, formal diagnostic criteria have been evolving, and new staining methods have become available. Finally, it is not possible to determine from this material whether these patients are representative of all elderly schizophrenia patients or even of those who are institutionalized. Therefore, despite the large sample size on which our current findings are based, a new study has begun to address these weaknesses by complete review and rediagnosis of medical records and neuropathological material, using current methods, standardized criteria, and quantitative measures of degenerative changes. Specifically, the new ongoing study examines whether autopsied patients are representative by performing detailed diagnostic reviews of a control sample of nonautopsied patients from the same institutions. These results, if confirmed in the new study, demonstrate substantially greater vulnerability of chronic schizophrenia patients to the development of AD (or, at least, to histological changes typical of this disease). Possible association with chronic neuroleptic treatment and pathophysiological mechanisms remains to be elucidated.
Adult↗
Pressure autoregulation is intact after arteriovenous malformation resection.
The loss of autoregulatory control of cerebral perfusion to changes in perfusion pressure in tissue remote from an arteriovenous malformation (AVM) has been proposed as the mechanism underlying "normal perfusion pressure breakthrough." This study is the first direct test of this mechanism. Studies were performed during the resection of moderate to large AVMs in 25 patients undergoing 28 procedures under isoflurane anesthesia. Cerebral blood flow (CBF) was measured (xenon-133 method) in the hemisphere adjacent to the nidus before resection after dural exposure (pre), after AVM removal before dural closure at spontaneous systemic blood pressure (post), and, finally, with the mean arterial pressure increased by 20 mm Hg, using phenylephrine (post-BP). AVM resection resulted in a significant enhancement of perfusion in the adjacent hemisphere (30 +/- 2 vs. 25 +/- 1 ml/100g/min, P < 0.01), but no further increase of CBF occurred during increased perfusion pressure (30 +/- 2 ml/100g/min). One patient suffered a postoperative hemorrhage and another developed intraoperative brain swelling during the course of the resection that necessitated staging the procedure. These two patients had the highest increases in CBF, but intact pressure autoregulation. Preserved autoregulation to increased mean arterial pressure after resection does not support a hemodynamic mechanism for the observed increase in CBF from before the resection to after the resection. Pathological events, however, do appear to be related to increases in hemispheric perfusion.
Adolescent↗
Regional cerebral blood flow in mood disorders. II. Comparison of major depression and Alzheimer's disease.
We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression, 30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and Alzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subprofile Model, developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning.
Aged↗
Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease.
A higher prevalence of dementia in individuals with fewer years of education has suggested that education may protect against Alzheimer's disease (AD). We tested whether individuals with more years of education have a more advanced AD before it is clinically evident. As a measure of pathophysiological severity, we quantified regional cerebral blood flow (rCBF), by the 133Xenon inhalation technique; a specific pattern of flow reduction in the parietotemporal cortex corresponds to AD pathology. In 3 groups of patients with probable AD, matched for clinical measures of dementia severity but with varying levels of education, whole-cortex mean flows were comparable. However, the parietotemporal perfusion deficit was significantly greater in the group with the highest level of education, indicating that AD was more advanced in this group. We conclude that education or its covariates or both may provide a reserve that compensates for the neuropathological changes of AD and delays the onset of its clinical manifestations.
Alzheimer Disease↗
Structural brain imaging abnormalities associated with schizophrenia and partial trisomy of chromosome 5.
Chromosomal abnormalities occurring in association with mental illness provide a unique opportunity to study the interaction of genetic abnormalities and the brain in mental illness. Four individuals from a family in which schizophrenia was found to cosegregate with a partial trisomy of chromosome 5 were studied with computed tomography and magnetic resonance imaging. Temporal lobe atrophy was found in the two trisomic males and in the asymptomatic balanced translocation female. In addition, a large cavum septum pellucidum and a cavum vergae were found in the older trisomic individual. Scans from the normal male were free of abnormalities. These results suggest that molecular studies of the translocation breakpoints in this chromosomal abnormality may be of interest, and encourage further studies of brain structure in other chromosomal abnormalities associated with psychosis.
Adult↗
Caudate hemorrhage with moyamoya-like vasculopathy from atherosclerotic disease.
BACKGROUND AND PURPOSE: Caudate hemorrhage usually results from hypertension, rupture of arteriovenous malformation or aneurysm, or rarely, moyamoya disease. Moyamoya-like changes related to severe atherosclerotic occlusive disease, usually causing ischemic stroke, have been reported. CASE DESCRIPTION: A 51-year-old normotensive patient was admitted with headache due to a left caudate hematoma with ventricular extension. There was a history of smoking, leg claudication, elevated cholesterol, and coronary artery disease. Angiography demonstrated complete extracranial carotid occlusion on the left and atherosclerotic stenosis at the bifurcation on the right, with supraophthalmic occlusion distally. At the base of the brain, bilateral moyamoya-like vessels, presumed to be secondary to atherosclerotic occlusion, were evident, but neither aneurysm nor arteriovenous malformation was present. Cerebral blood flow and transcranial Doppler studies indicated severely impaired cerebral perfusion that improved after bilateral extracranial-to-intracranial bypass surgery. CONCLUSIONS: Atherosclerotic occlusive carotid disease with moyamoya-like changes may be a rare cause of caudate hemorrhage. A decrease in moyamoya vessels with bypass surgery may reduce the risk of recurrent hemorrhage.
Carotid Arteries↗
Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?
We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to "strategic-infarct dementia."
Aged↗
CBF studies with Xenon-133 in arteriovenous malformations: a methodological study.
A new model for the two dimensional rCBF technique using the inhalation of Xenon 133 was tested in patients with arteriovenous malformations. It was hypothetized that, in contrast to the conventional CBF model, it corrects for the artifactual shunt flow through the AVM and thus yields physiological CBF data. Four regions of interest (AVM, contralateral to AVM, ipsilateral hemisphere, contralateral hemisphere) were defined in 17 patients with AVMs and analyzed for differences in grey matter flow (F1). In contrast to the conventional CBF model, the new model shows a decreased flow over the AVM area, corresponding to the results of Xenon CT and SPECT. Furthermore, the blood pool parameter P4 is very sensitive to the location of the AVM. Thus further investigations of the hemodynamics of AVMs with this model are encouraged.
Adult↗
Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats.
The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.
Animals↗
Cerebral blood flow reactivity to changes in carbon dioxide calculated using end-tidal versus arterial tensions.
We retrospectively examined arerial and end-tidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean +/- SD PaCO2 values of 28.2 +/- 5.2 and 38.8 +/- 4.8 mm Hg. The correlation between all PaCO2 and end-tidal PCO2 (PetCO2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between PaCO2 and PetCO2 (y = 0.11x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-1 min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either PaCO2 (1.9 +/- 0.8) or PetCO2 (1.8 +/- 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of PetCO2.
Adult↗
Safety of hypercapnic challenge: cardiovascular and neurologic considerations.
The hemodynamic, cerebrovascular, and neurologic effects of hypercapnia with 4% and 6% CO2 were retrospectively reviewed in 217 patients referred for regional CBF (rCBF) procedures. Inhalation of CO2 significantly increased rCBF, blood pressure, and pulse from baseline. The findings suggest a higher incidence of side effects with 6% CO2 concentration and an equivalent vasoreactivity to 4%. We recommend the use of 4% CO2 for hypercapnic stimulation, and present safety guidelines for its use.
Administration, Inhalation↗
Effect of PaCO2 on cerebral blood flow distribution during halothane compared with isoflurane anaesthesia in the rat.
In order to examine anaesthetic effects on the distribution of cerebral blood flow (CBF) during normo- and hypocapnia, male adult Sprague-Dawley rats were allocated randomly to four groups in a 2 x 2 factorial design, using PaCO2 value and anaesthetic agent as between-group factors. Animals were anesthetized with either 1.38% isoflurane (inspired) or 1.05% halothane (inspired) and the lungs ventilated mechanically at either normocapnia (PaCO2 5.1-5.6 kPa) or hypocapnia (PaCO2 3.1-3.3 kPa) for 1 h. CBF was measured using 14C-iodoantipyrine autoradiography. Local CBF in selected cortical and subcortical regions of interest and area-weighted mean global CBF were calculated. Data were compared by analysis of variance. Normocapnic (mean (SE] CBF for halothane (n = 6) and isoflurane (n = 7) was 120 (8) ml/100 g min-1 (PaCO2 5.6 (0.49) kPa) and 117 (9) ml/100 g min-1 (PaCO2 5.4 (0.5) kPa), respectively. Hypocapnic CBF for halothane (n = 6) and isoflurane (n = 6) was 82 (7) ml/100 g min-1 (PaCO2 3.3 (0.12) kPa) and 82 (6) ml/100 g min-1 (PaCO2 3.2 (0.12) kPa), respectively. Hypocapnia reduced global CBF for both groups by 30% (P less than 0.001), but there was no difference between anaesthetic agents (P greater than 0.8). Hypocapnia decreased CBF in all local structures examined. Although subcortical structures had similar CBF at both normocapnia and hypocapnia, CBF in three cortical samples was greater (P less than 0.05) in both the normocapnic and hypocapnic halothane groups than the corresponding isoflurane groups. The CBF reactivity to changes in PaCO2 was similar for both agents (approximately 2 ml/100 g min-1 mm Hg). (ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗
Thiopental effect on cerebral blood flow during carotid endarterectomy.
To investigate the effect of thiopental on cerebral blood flow (CBF) during carotid endarterectomy, five patients receiving isoflurane-N2O anesthesia were studied. During the period of temporary bypass shunting, a baseline CBF was measured using i.v. Xe washout, and global CBF was calculated from the mean of 10 detectors. Thiopental was given in a dose sufficient (mean 4.5, range 2.6-5.8 mg/kg) to result in burst-suppression on the electroencephalogram (EEG) of approximately 1:1 duration and CBF was measured again. Data were compared using repeated measures analysis of variance. Thiopental significantly reduced mean (+/-SE) CBF (ml/100 g/min) from 37 +/- 6 to 18 +/- 2 (p <0.02). Corresponding PaCO2 (mm Hg) values were 42.8 +/- 1.2 and 41.2 +/- 1.6 and mean systemic blood pressure (mm Hg) was 101 +/- 3 and 100 +/- 6, respectively (NS). Mean % change in CBF was 48 +/- 5 (range 32-62%). There was no relationship between the dose administered and the change in CBF. During steady-state anesthesia, a small dose of thiopental capable of suppressing EEG resulted in a profound reduction in CBF.
Journal Article↗
Middle cerebral artery blood velocity and cerebral blood flow in sickle cell disease.
To understand better the relationship between blood velocity measured by transcranial Doppler and cerebral blood flow measured by the 133Xe inhalation method, we examined 23 patients undergoing evaluation in the Comprehensive Sickle Cell Center at Columbia University. Blood velocity in the middle cerebral artery was directly related to cerebral flow (r = 0.77; p less than 0.05). A multivariate analysis in this sample made it possible to improve this correlation to account for more than 90% of the variability in cerebral blood flow by the use of transcranial Doppler measures of velocity and pulsatility along with the patient's age and hematocrit (r = 0.95; p less than 0.001). It is likely that the combination of Doppler and clinical or demographic variables in other diseases will similarly improve the quantitative estimation of cerebral blood flow.
Adolescent↗
Observations on the physostigmine syndrome in patients with Alzheimer's disease.
The authors present two patients with Alzheimer's disease who each received a single intravenous dose of physostigmine. Subjective complaints and mood changes were disproportional with objectively verified physiological side effects. Such observations may contribute to an understanding of affective disorders and should receive more attention in future studies of cholinesterase inhibitors.
Aged↗
A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy.
The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.
Aged↗