Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson's disease.

OBJECTIVES: The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare the effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine the relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS. METHODS: We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson's disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS. RESULTS: DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity are related to premotor cortex rCBF changes during V-STN DBS (r=-0.40, p=0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r=-0.43, p=0.02). CONCLUSIONS: DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location.

Cerebral hemodynamics and cognitive impairment: baseline data from the RECON trial.

OBJECTIVE: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.

Reduced uptake of [¹8F]FDOPA PET in asymptomatic welders with occupational manganese exposure.

BACKGROUND: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[(18)F]fluoro-l-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine whether welding exposure is associated with damage to nigrostriatal neurons in asymptomatic workers. METHODS: We imaged 20 asymptomatic welders exposed to Mn fumes, 20 subjects with idiopathic Parkinson disease (IPD), and 20 normal controls using FDOPA PET. All subjects were examined by a movement disorders specialist. Basal ganglia volumes of interest were identified for each subject. The specific uptake of FDOPA, K(i), was generated for each region using graphical analysis method. RESULTS: Repeated measures general linear model (GLM) analysis demonstrated a strong interaction between diagnostic group and region (F(4,112) = 15.36, p < 0.001). Caudate K(i)s were lower in asymptomatic welders (0.0098 + 0.0013 minutes(-1)) compared to control subjects (0.0111 + 0.0012 minutes(-1), p = 0.002). The regional pattern of uptake in welders was most affected in the caudate > anterior putamen > posterior putamen. This uptake pattern was anatomically reversed from the pattern found in subjects with IPD. CONCLUSIONS: Active, asymptomatic welders with Mn exposure demonstrate reduced FDOPA PET uptake indicating dysfunction in the nigrostriatal dopamine system. The caudate K(i) reduction in welders may represent an early (asymptomatic) marker of Mn neurotoxicity and appears to be distinct from the pattern of dysfunction found in symptomatic IPD.

Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): A single-center RCT.

BACKGROUND: Constraint-induced movement therapy (CIMT) is among the most developed training approaches for motor restoration of the upper extremity (UE). METHODS: Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS) was a single-blind phase II trial of CIMT during acute inpatient rehabilitation comparing traditional UE therapy with dose-matched and high-intensity CIMT protocols. Participants were adaptively randomized on rehabilitation admission, and received 2 weeks of study-related treatments. The primary endpoint was the total Action Research Arm Test (ARAT) score on the more affected side at 90 days after stroke onset. A mixed model analysis was performed. RESULTS: A total of 52 participants (mean age 63.9 +/- 14 years) were randomized 9.65 +/- 4.5 days after onset. Mean NIHSS was 5.3 +/- 1.8; mean total ARAT score was 22.5 +/- 15.6; 77% had ischemic stroke. Groups were equivalent at baseline on all randomization variables. As expected, all groups improved with time on the total ARAT score. There was a significant time x group interaction (F = 3.1, p < 0.01), such that the high intensity CIT group had significantly less improvement at day 90. No significant differences were found between the dose-matched CIMT and control groups at day 90. MRI of a subsample showed no evidence of activity-dependent lesion enlargement. CONCLUSION: Constraint-induced movement therapy (CIMT) was equally as effective but not superior to an equal dose of traditional therapy during inpatient stroke rehabilitation. Higher intensity CIMT resulted in less motor improvement at 90 days, indicating an inverse dose-response relationship. Motor intervention trials should control for dose, and higher doses of motor training cannot be assumed to be more beneficial, particularly early after stroke.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Pathophysiology of parkinsonism due to hydrocephalus.

We report a patient with hydrocephalus who developed levodopa responsive parkinsonism and severe bradyphrenia associated with shunt malfunction and revision. Magnetic resonance imaging revealed periaqueductal edema involving medial substantia nigra. [18F]dopa positron emission tomography demonstrated reduced uptake in the caudate and putamen with relative sparing of the posterior putamen. Hydrocephalus associated with shunt malfunction can cause a distinct parkinsonian syndrome with greater dysfunction of projections from the medial substantia nigra to anterior striatum than in idiopathic Parkinson's disease.

Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD.

OBJECTIVE: To assess whether subthalamic nuclei (STN) stimulation's primary mechanism of action is to drive or inhibit output neurons. METHODS: Cerebral blood flow responses to STN stimulation were measured using PET in 13 patients with Parkinson disease. Patients were scanned with stimulators off and on (six scans each condition). Clinical ratings, EMG, and videotaping of movements were obtained at each scan. Scans with observable tremor or movement were eliminated from analysis. Brain regions where STN stimulation significantly altered blood flow were identified. RESULTS: STN stimulation increased blood flow in midbrain (including STN), globus pallidus, and thalamus, primarily on the left side, but reduced blood flow bilaterally in frontal, parietal, and temporal cortex. CONCLUSIONS: These data suggest that STN stimulation increases firing of STN output neurons, which increases inhibition of thalamocortical projections, ultimately decreasing blood flow in cortical targets. STN stimulation appears to drive, rather than inhibit, STN output neurons.

Blood flow responses to deep brain stimulation of thalamus.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) provides remarkable relief of tremor in the limbs contralateral to the side of the brain stimulated. The benefits have been sufficiently dramatic that this is now an accepted clinical treatment of essential as well as other forms of tremor. Despite this clinical benefit, the mechanism of action of DBS remains unknown. In this investigation, we sought to determine the effects of VIM DBS on neuronal function. METHODS: The authors used PET measurements of qualitative regional cerebral blood flow in patients with essential tremor to determine the effects of DBS in the left VIM. Each subject had four to six scans with the arms at rest and DBS turned either on or off during alternate scans. Continuous physiologic monitoring revealed no tremor during any of the scans. The PET images from each subject were aligned, averaged, and coregistered to a standard image oriented in stereotactic space. RESULTS: The authors used subtraction image analysis with statistical parametric mapping methods and a restricted volume search to identify a significantly increased flow response at the site of stimulation in thalamus. An exploratory analysis revealed increased flow in ipsilateral supplementary motor area, a region that receives afferents from VIM. CONCLUSIONS: The increased blood flow at terminal fields of thalamocortical projections suggests that DBS stimulates and does not inactivate projection neurons in VIM thalamus.

Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke.

Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05).

Comparison of PET oxygen extraction fraction methods for the prediction of stroke risk.

UNLABELLED: PET measurement of increased oxygen extraction fraction (OEF) identifies patients at high risk for subsequent stroke. OEF methodology remains controversial. In this study we compare the sensitivity and specificity of absolute OEF measurements with ipsilateral-to-contralateral ratios of absolute OEF and count-based OEF estimates. METHODS: Multivariate analyses of OEF methods were performed using data from patients with symptomatic carotid artery occlusion (n = 68). Outcome and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: All 3 methods were predictive of stroke risk in univariate analysis. Only the count-based method remained significant in multivariate analysis. The area under the ROC curve was greatest for the count-based ratio: 0.815 versus 0.769 (absolute) and 0.737 (ratios of absolute). CONCLUSION: All 3 methods are predictive of stroke risk in patients with unilateral carotid artery occlusion. ROC curve analysis is useful for selecting optimal thresholds for maximal sensitivity and specificity.

Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.

BACKGROUND: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and (15)O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.

Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage.

A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 +/- 7.6 vs. 37.0 +/- 13.9 mL 100 g(-1) min(-1), P = 0.0004; CMRO2: 1.4 +/- 0.5 vs. 2.9 +/- 0.9 mL 100 g(-1) min(-1), P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 +/- 0.15 vs. 0.47 +/- 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 +/- 0.16 vs. 0.51 +/- 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset.

Blood-to-brain glucose transport, cerebral glucose metabolism, and cerebral blood flow are not increased after hypoglycemia.

Recent antecedent hypoglycemia has been found to shift glycemic thresholds for autonomic (including adrenomedullary epinephrine), symptomatic, and other responses to subsequent hypoglycemia to lower plasma glucose concentrations. This change in threshold is the basis of the clinical syndromes of hypoglycemia unawareness and, in part, defective glucose counterregulation and the unifying concept of hypoglycemia-associated autonomic failure in type 1 diabetes. We tested in healthy young adults the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport, a plausible mechanism of this phenomenon. Eight subjects were studied after euglycemia, and nine were studied after approximately 24 h of interprandial hypoglycemia ( approximately 55 mg/dl, approximately 3.0 mmol/l). The latter were shown to have reduced plasma epinephrine (P = 0.009), neurogenic symptoms (P = 0.009), and other responses to subsequent hypoglycemia. Global bihemispheric blood-to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves-the latter determined by positron emission tomography (PET)-after intravenous injection of [1-(11)C]glucose at clamped plasma glucose concentrations of 65 mg/dl (3.6 mmol/l). For these calculations, a model was used that includes a fourth rate constant to account for egress of [(11)C] metabolites. Cerebral blood flow was measured with intravenous [(15)O]water using PET. After euglycemia and after hypoglycemia, rates of blood-to-brain glucose transport (24.6 +/- 2.3 and 22.4 +/- 2.4 micromol. 100 g(-1). min(-1), respectively), cerebral glucose metabolism (16.8 +/- 0.9 and 15.9 +/- 0.9 micromol. 100 g(-1). min(-1), respectively) and cerebral blood flow (56.8 +/- 3.9 and 53.3 +/- 4.4 ml. 100 g(-1). min(-1), respectively) were virtually identical. These data do not support the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport during subsequent hypoglycemia. They do not exclude regional increments in blood-to-brain glucose transport. Alternatively, the fundamental alteration might lie beyond the blood-brain barrier.

Severe hemodynamic impairment and border zone--region infarction.

PURPOSE: To investigate the relationship between the patterns of cerebral infarction that have been associated with hemodynamic impairment and the presence of severe chronic hemodynamic compromise (increased oxygen extraction fraction) in a large prospectively enrolled group of patients with carotid artery occlusion. MATERIALS AND METHODS: At enrollment in a prospective study of cerebral hemodynamics, 110 patients with carotid occlusion underwent (a) positron emission tomography for the measurement of cerebral oxygen extraction fraction and (b) computed tomographic (CT) or magnetic resonance (MR) examinations of the brain. Infarcts were categorized retrospectively by vascular territory, location, and pattern. The association of these findings with hemodynamic impairment (increased oxygen extraction fraction) was investigated. RESULTS: No border zone-region infarctions were found in 35 asymptomatic patients. In 75 symptomatic patients, cortical border zone-region infarction was found in seven of 36 patients with increased oxygen extraction fraction, and in two of 39 with normal oxygen extraction fraction (P =.08, difference not significant). The pattern of multiple white matter lesions arranged parallel to the lateral ventricle was observed only in symptomatic patients with increased oxygen extraction fraction (eight of 36 patients; P =.002; sensitivity, 22%; specificity, 100%). This finding was more frequent with MR imaging (seven of 14 patients) than with CT (one of 22 patients). CONCLUSION: Multiple white matter infarctions, arranged parallel to the lateral ventricle, are associated with severe hemodynamic impairment. This pattern of infarction is likely due to a hemodynamic mechanism.

Welding-related parkinsonism: clinical features, treatment, and pathophysiology.

OBJECTIVE: To determine whether welding-related parkinsonism differs from idiopathic PD. BACKGROUND: Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder. METHODS: The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations. RESULTS: Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen. CONCLUSIONS: Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.

Absence of selective deep white matter ischemia in chronic carotid disease: a positron emission tomographic study of regional oxygen extraction.

BACKGROUND AND PURPOSE: Deep white matter may be the location of an internal arterial border zone. The purpose of this study was to determine whether the deep white matter was subject to a greater degree of ischemia than was the cortex among patients with chronic carotid occlusion. METHODS: Thirty-six patients with carotid occlusion and structurally normal deep white matter were studied with positron emission tomography. Measurements of oxygen extraction fraction were made in superficial (cortical and subcortical) regions in the middle cerebral artery territory and in deep white matter (internal border zone) regions. The presence of selective ischemia of the deep white matter was assessed by the ratio of deep white matter:superficial oxygen extraction fraction. Ipsilateral hemispheric ratios among patients were assessed as a group as compared with contralateral hemispheric ratios and as compared with normal hemispheric ratios from 15 control volunteers. RESULTS: Mean deep white matter to superficial oxygen extraction fraction ratios (+/-95% confidence limits) were 0.99 (+/-0.07), 1.01 (+/-0.06), and 1.02 (+/-0.08) for ipsilateral, contralateral, and normal hemispheres, respectively. No statistically significant difference was found between ipsilateral and contralateral (P = .691) or normal hemispheres (P = .68), nor was any statistically significant difference found when the analysis was limited to patients with increased superficial oxygen extraction fraction (n = 9). Individual deep white matter:superficial ratios were within the normal range for all patients. CONCLUSION: Normal deep white matter among patients with carotid occlusion is not subject to a greater degree of ischemia than is the overlying cortex. It is unlikely that deep white matter infarctions observed among patients with carotid occlusion are owing to chronic selective hemodynamic compromise occurring at an internal arterial border zone.

The behavioral complications of pallidal stimulation: a case report.

We report a case of recurrent manic episodes associated with chronic deep brain stimulation (DBS) targeting globus pallidus (GP) in the treatment of Parkinson's disease (PD). Cardinal PD symptoms and dyskinesia improved with DBS, and neuropsychological testing found improvements in visuospatial measures associated with left DBS and in verbal memory with right DBS when compared to the patient's preoperative baseline. Under conditions of right, left, and bilateral DBS, the patient experienced bouts of mania and hypomania lasting several days at a time. Positron emission tomography (PET) with (15)O-labeled water was performed after his first manic episode under four conditions: no stimulation, right DBS, left DBS, and bilateral DBS. Although no manic switch occurred during the course of the PET study, all three DBS conditions were associated with decreases in regional flow in the left parahippocampus and hippocampus and right mid-cingulate gyrus. Increases in flow in left inferior frontal area, bilateral insula, dorsolateral prefrontal cortex, and cuneus were common to all DBS conditions. GP stimulation in PD may be associated with behavioral and cognitive effects. Distributed blood flow changes observed with pallidal DBS support a role for the pallidum in cognition and affective regulation.

Benign prognosis of never-symptomatic carotid occlusion.

OBJECTIVE: To determine the prognosis of asymptomatic carotid artery occlusion. BACKGROUND: As opposed to symptomatic carotid occlusion, little information is available on the prognosis of asymptomatic carotid occlusion. METHOD: Thirty never-symptomatic and 81 symptomatic patients with carotid occlusion underwent baseline assessment of 15 risk factors together with PET measurements of oxygen extraction fraction (OEF). Every 6-month telephone contact recorded interval medical treatment and subsequent stroke occurrence during an average follow-up of 32 months. Patients, treating physicians, and an end point adjudicator were blinded to PET results. RESULTS: Ischemic stroke occurred in 1 of 30 of never-symptomatic patients (3.3%) and 15 of 81 of symptomatic patients (18.5%; p = 0.03). No strokes in the carotid territory distal to the occluded vessel occurred in the never-symptomatic patients. Multivariate analysis of baseline risk factors for all 111 patients revealed that age, plasma fibrinogen level, and PET findings of high OEF distal to the occluded carotid artery were the only independent predictors of subsequent stroke (p < 0.05). Previous ipsilateral hemispheric or retinal symptoms was not a significant predictive variable. The lower risk of stroke in never-symptomatic patients was associated with a lower incidence of high OEF (4 of 30) as opposed to symptomatic patients (39 of 81; p = 0.002), but there was no significant difference in age or fibrinogen level. CONCLUSIONS: Never-symptomatic carotid occlusion carries a very low risk of subsequent ischemic stroke. This benign prognosis is associated with a low incidence of cerebral hemodynamic compromise in these patients. These data support further the importance of hemodynamic factors in the pathogenesis of ischemic stroke in patients with carotid occlusion.

No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury.

OBJECT: Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs). METHODS: Nine patients were studied a mean of 11.2+/-1.6 hours (range 8-14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6+/-1.8 and their mean age 27+/-9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30+/-2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls. Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59+/-0.44 ml/100 g/minute [p < 0.01] and 0.31+/-0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5+/-8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8+/-0.56 ml/100 g (p < 0.001), OEF rose to 0.45+/-0.13 (p < 0.02), and CvO2 fell to 8.3+/-3 vol% (p < 0.02); CMRO2 remained unchanged. CONCLUSIONS: The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.

Count-based PET method for predicting ischemic stroke in patients with symptomatic carotid arterial occlusion.

PURPOSE: To test the ability of a count-based positron emission tomographic (PET) method, without arterial sampling, for the measurement of regional cerebral oxygen extraction fraction (OEF) to predict ischemic stroke in patients with symptomatic carotid arterial occlusion. MATERIALS AND METHODS: The outcome analysis of a blinded prospective study designed to determine if increased OEF was an independent predictor of stroke in patients with symptoms and with carotid occlusion was repeated by substituting a count-based method of OEF measurement for the original quantitative technique. The performance of the quantitative and count-based methods was assessed by using Kaplan-Meier cumulative survival functions (log-rank, [p < .05]). Receiver operating characteristic (ROC) curves for both methods were generated. RESULTS: Thirteen ipsilateral strokes occurred during a mean follow-up of 3.1 years for 81 patients. All ipsilateral strokes occurred in 50 patients with increased count-based OEF (P = .002, sensitivity 100%, specificity 46%). Sixty-eight patients underwent complete quantitative studies, which allowed comparison of OEF methods. Both the count-based and the quantitative methods were predictive of stroke in this subgroup (P = .005 and .025, respectively). ROC analysis demonstrated a greater area under the curve for the count-based OEF method. CONCLUSION: Count-based PET measurement of OEF without arterial sampling accurately predicts stroke in patients with carotid occlusion.