Cerebral Blood Flow Deficits Research Articles

Regional Cerebral Blood Flow and Cognitive Deficits in Chronic Lyme Disease

Regional Cerebral Blood Flow and Cognitive Deficits in Chronic Lyme Disease

Aspirin or amiloride for cerebral perfusion defects in cocaine dependence

Cocaine dependent (CD) patients have regional cerebral blood flow (rCBF) deficits that may be related to occlusion of blood vessels by vasoconstriction and abnormal platelet aggregation. This study determined whether aspirin, which reverses platelet aggregation, or amiloride, a vasodilator, significantly reversed this rCBF hypoperfusion. This 1-month randomized trial compared clusters of voxels with significant hypoperfusion in recently abstinent CD patients after aspirin (325 mg daily), amiloride (10 mg daily) or placebo treatment. Forty-nine primary CD patients and 18 non-drug abusing controls were compared using single photon emission computed tomography (SPECT) neuroimaging with 99mTc-hexamethyl-propyleneamine-oxime and statistical parametric mapping (SPM). Platelet aggregation to adenosine diphosphate (ADP) was examined after treatment to determine whether rCBF improvement was related to decreased platelet aggregation. Following treatment, areas of hypoperfusion were improved with amiloride, unchanged with aspirin, and worsened with placebo in comparison to baseline levels. Platelet aggregation after ADP showed no significant change during the month, but reduced rCBF significantly improved after 1-month treatment with amiloride compared with placebo and cocaine abstinence alone.

EEG deficits in chronic marijuana abusers during monitored abstinence: preliminary findings.

Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence. A three-minute period of EEG was recorded during resting eyes-closed conditions from eight electrodes (F(3), C(3), P(3), O(1), F(4), C(4), P(4), and O(2)). The artifacted EEG was converted to six frequency bands (delta, theta, alpha(1), alpha(2), beta(1), and beta(2)) using a fast Fourier transform. During early abstinence, absolute power was significantly lower (p < 0.05) for the marijuana abusers than for the control subjects for the theta and alpha(1) bands. These reductions in theta and alpha(1) power persisted for 28 days of monitored abstinence. These EEG changes, together with cerebral blood flow deficits, might underlie the cognitive alterations observed in marijuana abusers. Additional research is needed to determine how long these deficits persist during abstinence and if treatment with neuroprotective agents may reverse them.

Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis.

Regional cerebral blood flow (CBF), a good indirect index of cerebral pathologic changes in Alzheimer disease (AD), is more severely reduced in patients with higher educational attainment and IQ when controlling for clinical severity. This has been interpreted as suggesting that cognitive reserve allows these patients to cope better with the pathologic changes in AD. To evaluate whether premorbid engagement in various activities may also provide cognitive reserve. We evaluated intellectual, social, and physical activities in 9 patients with early AD and 16 healthy elderly controls who underwent brain H(2)(15)O positron emission tomography. In voxelwise multiple regression analyses that controlled for age and clinical severity, we investigated the association between education, estimated premorbid IQ, and activities, and CBF. In accordance with previous findings, we replicated an inverse association between education and CBF and IQ and CBF in patients with AD. In addition, there was a negative correlation between previous reported activity score and CBF in patients with AD. When both education and IQ were added as covariates in the same model, a higher activity score was still associated with more prominent CBF deficits. No significant associations were detected in the controls. At any given level of clinical disease severity, there is a greater degree of brain pathologic involvement in patients with AD who have more engagement in activities, even when education and IQ are taken into account. This may suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between brain damage and the clinical manifestation of AD.

Neurosis of acquired helplessness and role of hypoxia in the formation of this disorder in rats.

Acquisition of instrumental defense response with pain reinforcement uncertainty (25% reinforcement) induced the development of acquired helplessness in 50% rats. Acquired helplessness is characterized by the absence of responses to conditioned (light) and unconditioned stimuli (pain), minor response of plasma corticosterone to learning, gas markers of circulatory cerebral hypoxia (Delta A/V pO2 carotid artery/jugular vein), low sensitivity to severe hypobaric conditions, and high resistance of Purkinje cells in the cerebellum. Piracetam improved learning and prevented the development of acquired helplessness. Local changes in cerebral blood flow and energy deficit in neurons responsible for emotional stress during acquired helplessness impair adaptive capacity, but reduce energy consumption and protect neuronal structures.

Isradipine enhancement of cerebral blood flow in abstinent cocaine abusers with and without chronic perfusion deficits.

Nine cocaine abusers with cerebral blood flow (CBF) deficits (hypo-perfused areas) on HMPAO SPECT scans were compared to six without these deficits after six doses of isradipine (5 mg TID). When comparing the scan before isradipine to that after using SPM analysis, the ratio of hypo- to hyper-fusion showed a 16% increase in the maximum Z scores and 30% fewer areas of hypo-perfusion among those cocaine abusers with deficits. These deficits may represent segmental cerebral vasospasm that was reversed by this vasodilating agent in cocaine abusers with areas of hypo-perfusion (deficits) as baseline.

Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study

Background: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. Methods: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. Results: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. Conclusions: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder.

Statistical maps of cerebral blood flow deficits in Alzheimer's disease.

Images of cerebral blood flow or metabolism are useful as adjunct to the differential diagnosis of cortical dementia. The aim of this study was to create statistical objective voxel maps of significant differences in regional cerebral blood flow between patients with Alzheimer's disease and age-matched healthy volunteers. Maps of significantly reduced cerebral blood flow were created based on a spatially normalized distribution of cerebral blood flow, measured with O-15-water and positron emission tomography in 16 Alzheimer's patients, compared to 16 healthy age-matched volunteers. After spatial normalization of voxel counts, the t-statistic of the cerebral blood flow deficit was determined from the local voxel-SDs. In the patients, significant reduction (P < 0.05) of the flow distribution was present in regions near the hippocampus, extending rostrally to the temporo-parietal region in both hemispheres, including the medial parietal cortex plus smaller frontal areas. The maximum reduction occurred in the left tapetum/hippocampus (53%, P = 0.061). In conclusion, statistical maps of cerebral blood flow deficits objectively reveal the location of deficits, identifying areas that are difficult to identify by subjective visual inspection of conventional sections of cerebral blood flow maps. This is particularly well illustrated by the pronounced flow reduction of the medial parietal cortices.

Tau protein in cerebrospinal fluid is significantly increased at the earliest clinical stage of Alzheimer disease.

The concentration of tau protein in cerebrospinal fluid (CSF) was determined in 40 patients with clinically diagnosed probable Alzheimer disease (AD) and in 36 cognitively healthy controls. A significant increase of CSF tau was found in the AD patients, even in 19 subjects with very mild dementia as defined by a Mini-Mental State Examination score of 25 and above. Using a cutoff value of 260 pg/mL the sensitivity of elevated tau was 0.89, the specificity was 0.97, and the proportion of correctly allocated cases was 95%. In the AD groups there were no significant associations between CSF tau level and age, age at onset, duration of illness, apolipoprotein E genotype, severity of cognitive impairment, or deficit in regional cerebral blood flow as measured using 99Tm-ethyl cystein dimer single photon emission computed tomography. The findings demonstrate that CSF tau is significantly increased at the earliest clinical stage of AD and shows only minimal overlap with age-matched cognitively healthy controls. This finding suggests that CSF tau could be a biological marker of AD even before dementia has developed.

Relationship between Cerebral Blood Flow and Neurological Deficit Resolution in Acute Ischemic Stroke

Relationship between Cerebral Blood Flow and Neurological Deficit Resolution in Acute Ischemic Stroke

Relation between cerebral blood flow and neurologic deficit resolution in acute ischemic stroke.

Early intervention remains the key to acute ischemic stroke therapy. Many patients whose deficits would later resolve without intervention are exposed to the risks of stroke treatment without benefit. The purpose of this study was to determine whether patients with transient deficits could be distinguished from patients with evolving strokes on the basis of acute cerebral blood flow (CBF) measurements before any clinical distinction could be made. Fifty-three patients who presented with acute hemispheric stroke symptoms and who underwent xenon-enhanced CT (XeCT) CBF studies within 8 hours of onset of symptoms (and before any clinical improvement) were studied. Eight patients (15%) had a complete resolution of their symptoms within 24 hours (not related to treatment). All eight patients with deficits that resolved had normal CBF in the symptomatic vascular territories (mean time to XeCT = 3 hours, 51 min). Mean CBF in the regions of interest of the symptomatic vascular territories of patients who had deficits that resolved was 35.4 +/- 8.1 mL x 100 g(-1) x min(-1) compared with 17.3 +/- 9.3 mL x 100 g(-1) x min(-1) of patients with evolving strokes (p = 0.00058). Patients with ischemic neurologic deficits that will later resolve can be acutely distinguished from patients with evolving cortical infarctions using XeCT CBF measurements. CBF measurements may assist in the triage of patients for acute stroke therapy by selecting patients with a favorable prognosis and may not benefit from therapy but would still be exposed to the potential risks and expense of treatment.

A technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography study in adolescent patients with major depressive disorder.

We have not encountered any brain single-photon emission tomography (SPET) study performed in adolescent depressed patients in the literature. Therefore, we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) brain SPET in adolescent patients with major depressive disorder (MDD) to examine the possible changes in cerebral perfusion and the possible association between perfusion indices and clinical variables. Fourteen adolescent out-patients (nine females, five males; mean+/-SD age: 13.11+/-1.43 years; range: 11-15 years) fulfilling the DSM-IV criteria for MDD and 11 age-matched healthy control subjects (six females, five males; mean+/-SD age: 13.80+/-1.60 years; range: 12-15 years) were included in the study. 99Tc-HMPAO brain SPET was performed twice in the patient group and once in the control group. The first SPET investigation was performed under non-medicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion index (PI) was calculated as the ratio of regional cortical activity to the whole brain activity. We found significant differences between the PI values of the untreated depressed patients and those of the controls, indicating relatively reduced perfusion in the left anterofrontal and left temporal cortical areas. No significant differences in regional PI values were found between the remitted depressed patients and the controls. Our study suggests that adolescent patients with MDD may have regional cerebral blood flow deficits in frontal regions and a greater anterofrontal right-left perfusion asymmetry compared with normal subjects. The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests that they may be state-dependent markers for adolescent MDD.

Tau protein. A potential biological indicator for early detection of Alzheimer disease

In 40 patients with Alzheimer's disease (AD), in 5 patients with non-AD dementia and in 36 cognitively normal controls the concentration of protein tau was determined in the cerebrospinal fluid (CSF). Of the AD patients, 19 were very mildly demented (MMSE score from 25 to 28). Even in these patients, CSF tau was significantly more elevated than in controls. In the non-AD patients protein tau was less increased. Among the AD patients there was no association between CSF tau and severity of cognitive impairment or deficit in cerebral blood flow, determined by SPECT. Our findings suggest that CSF tau may be elevated even at the predementia stage of AD and be useful as a biological marker for the early recognition of the disease.

Changes in Regional Cerebral Blood Flow following Light Treatment for Seasonal Affective Disorder: Responders versus Nonresponders

Background: Several brain imaging studies of antidepressant pharmacologic treatment utilizing single photon emission computed tomography (SPECT) have reported a normalization of deficits in cerebral blood flow (CBF) associated with recovery; other studies report no change, or a reduction in CBF following successful treatment. There have been no published SPECT studies of seasonal affective disorder (SAD) assessing response to light treatment in relation to changes in regional CBF (rCBF). In this study, we sought to test the hypothesis that increases in rCBF would be observed in SAD patients who responded to light treatment. Methods: Ten depressed patients with SAD underwent functional brain imaging studies with 99mTc-hexamethylpropyleneamine oxime SPECT before and after light treatment. Results: Relative increases in rCBF were observed in all brain regions compared to cerebellum in treatment responders, whereas nonresponders showed no change or decreases in rCBF relative to cerebellum. Significant differences in mean percentage change in rCBF between responders (n = 5) and nonresponders (n = 5) were detected in frontal and cingulate cortex, and thalamus. Conclusions: These findings provide preliminary support for the hypothesis that an increase in rCBF is associated with recovery from depression in SAD.

The functional neuroanatomy of mood disorders

Mood disorders may be associated with global and regional changes in cerebral blood flow and metabolism. The accumulated functional neuroimaging findings in mood disorders were reviewed in order to examine a proposed neuroanatomic model of pathophysiology. Global cerebral blood flow and glucose metabolism appear normal, but may be decreased in late-life depression. Regional cerebral blood flow and glucose metabolism deficits are present, and may be indicators of brain regions participating in neuroanatomic circuits involved in mood disorders. Decreased prefrontal cortex blood flow and metabolism in depressed unipolar and bipolar patients are the most consistently replicated findings, and correlate with severity of illness. Basal ganglia abnormalities have been found in depressed unipolar and bipolar patients, involving decreased blood flow and metabolism. Temporal lobe abnormalities are present in bipolar disorder patients, and perhaps unipolar depression. There is conflicting evidence of abnormalities in other limbic regions. Cognitive impairment may correlate with decreased metabolism in frontal and cerebellar areas. The relationship between functional neuroimaging findings and clinical course, and therefore state and trait characteristics, has not been systematically investigated. Antidepressant medications, but not ECT, seem to reverse some of the identified functional brain changes in the depressed state. The structural, neurotransmitter and neuropathological correlates of these functional abnormalities are yet to be determined. Functional abnormalities in frontal, subcortical and limbic structures appear to be part of the pathophysiology of mood disorders.

Neuropsychological, Psychiatric, and Cerebral Blood Flow Findings in Vascular Dementia and Alzheimer’s Disease

Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer's disease (AD) were examined. A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime. Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients. Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.

SPECT findings on psychosis in Alzheimer's disease.

This study examined whether psychosis in Alzheimer's disease is associated with cerebral perfusion patterns appreciable by single photon emission computed tomography (SPECT) scans. All cooperative outpatients enrolled in an Alzheimer's disease research center with the diagnosis of probable Alzheimer's disease and a Clinical Dementia Rating of mild or moderate were interviewed with their primary caregivers. Current and past psychiatric functioning was assessed by using the Hamilton Depression Rating Scale, the Structured Clinical Interview for DSM-III-R, and the Behavioral Pathology in Alzheimer's Disease Rating Scale. Patients without premorbid psychosis received SPECT scans, and the scans of the patients with delusions or hallucinations (N = 30) were compared to the scans of patients without these symptoms (N = 16). The patients with delusions (N = 29) had hypoperfusion of the left frontal lobe in relation to the right frontal lobe. The patients with hallucinations (N = 10) had hypoperfusion in the parietal lobe. Psychotic patients with Alzheimer's disease had a pattern of cerebral blood flow deficits significantly different from that of nonpsychotic patients. This suggests that patterns of cerebral dysfunction may be expressed symptomatically as psychosis.

Cardiopulmonary bypass: Perioperative cerebral blood flow and postoperative cognitive deficit

Increased cerebral blood flow occurring during cardiopulmonary bypass as a result of changes in arterial carbon dioxide tension during acid-base regulation is thought to increase postoperative cognitive dysfunction. We studied 70 patients undergoing coronary artery bypass procedures who were randomized to two different acid-base protocols: pH-stat or alpha-stat regulation. Cerebral blood flow, cerebral blood flow velocity, and cerebral oxygen metabolism were measured before bypass, during bypass (hypothermic [28 degrees C] and normothermic phases), and after bypass. Detailed cognitive tests were conducted before operation and 6 weeks after operation. During 28 degrees C bypass, cerebral blood flow was significantly (p < 0.05) higher in the pH-stat group than in the alpha-stat group (41 +/- 2 versus 24 +/- 2 mL.100 g-1.min-1), and cerebral blood flow velocity was significantly increased in the pH-stat group and significantly decreased in the alpha-stat group (152% +/- 10% versus 78% +/- 7%). Cerebral extraction ratio of oxygen demonstrated a relatively greater disruption of autoregulation in the pH-stat group than in the alpha-stat group with relative hyperemia of 0.12 +/- 0.02 versus 0.26 +/- 0.03, respectively, during 28 degrees C bypass. Using the criterion of deterioration in three or more neuropsychologic tests, a significantly higher proportion of patients in the pH-stat group fared less well than in the alpha-stat group (49% +/- 17% versus 20% +/- 13%). Patients in the alpha-stat group experienced less disruption of cerebral autoregulation during hypothermic cardiopulmonary bypass, and this was accompanied by a reduction in postoperative cognitive dysfunction.

Risk factors for cerebral injury and cardiac surgery

Cerebral complications represent the leading cause of morbidity after cardiac operations. With the growing awareness of their social and economic importance, increasing attention is being given to their prevention. In the coronary artery bypass population, advanced age (> or = 75 years) is associated with an 8.9% neurologic deficit rate. Mortality is increased ninefold in the elderly patient with a neurologic deficit. Cardiopulmonary bypass has long been recognized as a cause of neuropsychologic deficits. Emboli are thought to be the causal agent. Retinal microvascular lesions during cardiopulmonary bypass as well as recent demonstration of widespread pathologic subcapillary arteriolar dilatations in the brain after cardiopulmonary bypass have been documented. Despite widespread interest in cerebral blood flow and neurologic deficits, there is no convincing evidence that defines a critically low or dangerously high level of flow. The ascending aorta represents a leading source of embolic neurologic injury. The use of intraoperative ultrasound to identify the diseased aorta may result in alternative operative strategies in an effort to minimize emboli and improve neurologic outcome. Existing literature offers conflicting views on optimal management of carotid artery stenosis in the coronary artery surgical patient. A trend that combined carotid endarterectomy and coronary artery bypass may often be appropriate will need confirmation through a multicenter clinical trial. Open cardiac surgical procedures, particularly in the aged population, carry a significant increased risk of adverse neurologic outcome. Postoperative arrhythmias may result in embolic neurologic deficit. A further understanding of risk factors for cerebral injury will be of value in developing therapeutic approaches to this major clinical problem.

A prospective study comparing SPET with MRI and CT as prognostic indicators following severe closed head injury.

Ten patients were studied prospectively afer severe closed head injury to determine the relationship between long-term clinical outcome and abnormalities detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI obtained within 60 days of injury. The ability of SPET to detect abnormalities not visualized by CT or MRI after cerebral trauma by the results of this study. Changes detected by SPET [global cerebral blood flow (gCBF) and number of regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be more closely correlated with long-term outcome than changes detected by MRI or CT. Templates were used to classify lesions by site and a multivariate analysis was undertaken to establish the importance of defect position in predicting clinical outcome. The results suggest that lesions in the temporal lobes, frontal lobes and basal ganglia are related to poor prognosis, and that SPET yields more useful prognostic data than the other methods.