Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia.

BACKGROUND: Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. METHODS: Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. RESULTS: Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11-1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07-1.21; RRobese: 1.10, 95% CI 1.02-1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98-1.22; RRnormal to obese: 1.28, 95% CI 1.10-1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05-1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. CONCLUSIONS: We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

Measurement of regional substrate utilization rates by emission tomography.

Emission tomography can be used to monitor, in vivo and regionally, the utilization of metabolic substrates labeled with positron-emitting radioisotopes produced by a cyclotron. The concept was validated by measuring brain glucose utilization with carbon--11-labeled glucose in rhesus monkeys.

Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans.

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100 g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.

Cerebral oxygen metabolism after aneurysmal subarachnoid hemorrhage.

Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure the regional cerebral metabolic rate for oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood flow (rCBF) 16 times in 11 patients with aneurysmal SAH. All studies were performed preoperatively; no patient had hydrocephalus or intracerebral hematoma on brain CT. Eight patients with no arteriographic vasospasm who were studied on days 1-4 post-SAH had a significant 25% reduction in global CMRO2 compared to age-matched controls, and no significant change in global OEF, suggesting a primary reduction in CMRO2 caused by SAH. Four patients studied seven times during arteriographic vasospasm had significantly increased rOEF with unchanged CMRO2 in arterial territories affected by arteriographic vasospasm compared to territories without vasospasm, indicative of cerebral ischemia without infarction. No brain regions studied with PET were infarcted on follow-up CT. We conclude that the initial aneurysm rupture produces a primary reduction in CMRO2, and that subsequent vasospasm causes ischemia.

Autoregulatory vasodilation of parenchymal vessels is impaired during cerebral vasospasm.

Impaired CBF autoregulation during vasospasm after aneurysmal subarachnoid hemorrhage (SAH) could reflect impaired capacity of distal vessels to dilate in response to reduced local perfusion pressure or simply indicate that the perfusion pressure distal to large arteries in spasm is so low that vessels are already maximally dilated. Autoregulatory vasodilation can be detected in vivo as an increase in the parenchymal cerebral blood volume (CBV). Regional CBV, CBF, and oxygen extraction fraction in regions with and without angiographic vasospasm obtained from 29 positron emission tomography studies performed after intracranial aneurysm rupture were compared with data from 19 normal volunteers and five patients with carotid artery occlusion. Regional CBF was reduced compared to normal in regions from SAH patients with and without vasospasm as well as with ipsilateral carotid occlusion (P < .0001). Regional oxygen extraction fraction was higher during vasospasm and distal to carotid occlusion than both normal and SAH without vasospasm (P < .0001). Regional CBV was reduced compared to normal in regions with and without spasm, whereas it was increased ipsilateral to carotid occlusion (P < .0001). These findings of reduced parenchymal CBV during vasospasm under similar conditions of tissue hypoxia that produce increased CBV in patients with carotid occlusion provide evidence that parenchymal vessels distal to arteries with angiographic spasm after SAH do not show normal autoregulatory vasodilation.

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.

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man.

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.

Muteness of cerebellar origin.

Acute bilateral damage to large areas of both cerebellar hemispheres including the dentate nuclei led to temporary loss of speech in six children. In each case muteness was unassociated with motor paralysis, loss of higher cognitive functions, or cranial nerve dysfunction. Muteness lasted one to three months. All patients were severely dysarthric during recovery. We conclude that transient muteness may result from acute bilateral cerebellar injury.

Cavernous hemangioma of the spinal cord: report of 2 unusual cases.

We present 2 cases of spinal cord intramedullary cavernous hemangioma; 1 patient is the 1st reported case of multiple spinal cord lesions. Diagnosis is greatly enhanced by the use of MRI.

Cerebral hemodynamic impairment: methods of measurement and association with stroke risk.

Stenosis or occlusion of the major arteries of the head and neck may cause hemodynamic impairment of the distal cerebral circulation. Hemodynamic factors may play an important role in the pathogenesis of ischemic stroke for patients with cerebrovascular disease. Several neuroimaging methods are currently available for the indirect assessment of the hemodynamic effect of atherosclerotic stenosis or occlusion on the distal cerebrovasculature. Because these methods rely on different underlying physiologic mechanisms, they are not interchangeable. Two basic categories of hemodynamic impairment can be assessed with these techniques: Stage 1, in which autoregulatory vasodilation secondary to reduced perfusion pressure is inferred by the measurement of either increased blood volume or an impaired blood flow response to a vasodilatory stimulus; and Stage 2, in which increased oxygen extraction fraction (OEF) is noninvasively but directly measured. The correlation of different Stage 1 methods with each other and with Stage 2 techniques is quite variable. Clinical studies associating different manifestations of hemodynamic impairment with stroke risk often suffer from methodologic problems. The best evidence to date for such an association is for increased OEF measured in patients with symptomatic carotid occlusion. In the absence of data demonstrating improvement in patient outcome, there is currently no role for the routine use of these tools to guide clinical management in patients with cerebrovascular disease.

Borderzone hemodynamics in cerebrovascular disease.

To investigate the possible existence of chronic selective hemodynamic impairment in the arterial borderzone regions of the brain, we used positron emission tomography (PET) to measure regional mean vascular transit time (rt, equal to the ratio of regional cerebral blood volume to cerebral blood flow) and regional oxygen extraction fraction (rOEF) in 32 patients with either severe internal carotid artery stenosis or occlusion and 11 normal controls. Twenty-four of the patients had had TIAs or amaurosis fugax from 1 to 60 days before PET; all had normal brain CT. We used a stereotactic localization method to locate the anterior and posterior borderzone regions of the middle cerebral artery (MCA) territory. We then calculated ratios of each borderzone to the ipsilateral MCA territory for both rt and rOEF. There was no significant difference from control ratios in any patient subgroup including those with greater than or equal to 75% stenosis or occlusion, those with or without contralateral greater than or equal to 50% stenosis, or those with abnormal hemodynamics in the MCA territory. We therefore found no evidence for selective borderzone hemodynamic impairment in this group of patients with severe carotid artery disease.

Extracranial-intracranial bypass surgery: hemodynamic and metabolic effects.

After superficial temporal artery-middle cerebral artery bypass, cerebral blood flow (CBF) in the operated hemisphere increased in 6 of 17 patients. Preoperatively, the symptomatic hemisphere showed lower CBF in all six, lower oxygen metabolism in five, higher blood volume in four, and higher oxygen extraction in two. With the postoperative increase in hemispheric CBF, there was a decrease in oxygen extraction, but no change in blood volume or oxygen metabolism. In these patients, chronic regional hypoperfusion followed major vascular occlusion. Compensatory responses included dilation of intraparenchymal vessels and increased transport of oxygen from blood to tissue. These changes were partially reversed by cerebral revascularization.

Cerebral blood flow, oxygen utilization, and blood volume in dementia.

Patients with dementia had significant decreases in cerebral blood flow and cerebral oxygen utilization and a mild, but not significant, increase in cerebral blood volume. These studies were not useful in distinguishing patients with cerebral atrophy from patients with normal pressure hydrocephalus, as similar changes in cerebral circulation and metabolism were seen in both groups. Changes in cerebral blood flow after acute decrease in the intracranial pressure also were not helpful differentiating patients with normal pressure hydrocephalus from patients with cerebral atrophy.

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.

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.

Cost-effectiveness analysis of therapy for symptomatic carotid occlusion: PET screening before selective extracranial-to-intracranial bypass versus medical treatment.

UNLABELLED: The St. Louis Carotid Occlusion Study (STLCOS) demonstrated that increased cerebral oxygen extraction fraction (OEF) detected by PET scanning predicted stroke in patients with symptomatic carotid occlusion. Consequently, a trial of extracranial-to-intracranial (EC/IC) arterial bypass for these patients was proposed. The purpose of this study was to examine the cost-effectiveness of using PET in identifying candidates for EC/IC bypass. METHODS: A Markov model was created to estimate the cost-effectiveness of PET screening and treating a cohort of 45 symptomatic patients with carotid occlusion. The primary outcome was incremental cost for PET screening and EC/IC bypass (if OEF was elevated) per incremental quality-adjusted life year (QALY) saved. Rates of stroke and death with surgical and medical treatment were obtained from EC/IC Bypass Trial and STLCOS data. Costs were estimated from the literature. Sensitivity analyses were performed for all assumed variables, including the PET OEF threshold used to select patients for surgery. RESULTS: In the base case, PET screening of the cohort followed by EC/IC bypass on 36 of the 45 patients yielded 23.2 additional QALYs at a cost of $20,000 per QALY, compared with medical therapy alone. A more specific PET threshold, which identified 18 surgical candidates, gained 22.6 QALYs at less cost than medical therapy alone. The results were sensitive to the perioperative stroke rate and the stroke risk reduction conferred by EC/IC bypass surgery. CONCLUSION: If postoperative stroke rates are similar to stroke rates observed in the EC/IC Bypass Trial, EC/IC bypass will be cost-effective in patients with symptomatic carotid occlusion who have increased OEF. A clinical trial of medical therapy versus PET followed by EC/IC bypass (if OEF is elevated) is warranted.

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.

Maternal hydrocephalus and pregnancy.

Women with cerebrospinal fluid (CSF) shunts for correction of hydrocephalus are rapidly joining the reproductive age population. These patients can have uncomplicated pregnancies and spontaneous vaginal deliveries. Careful attention to signs of CSF shunt malfunction, historical and ultrasonic screening for familial hydrocephalus, and antibiotic prophylaxis for delivery are recommended. Management of the first and second stages of labor is discussed. There is no apparent advantage to any particular technique for intrapartum analgesia.

Hemodynamic effects of middle cerebral artery stenosis and occlusion.

BACKGROUND AND PURPOSE: Middle cerebral artery (MCA) stenosis and occlusion may cause ischemic symptoms through both hemodynamic and embolic mechanisms. The purpose of this investigation was to determine the hemodynamic effects of these lesions. METHODS: Ten patients with angiographically confirmed symptomatic occlusion (n = 5) or stenosis (n = 5) of the M1 segment of the MCA were studied by clinical examination, arteriography, and positron emission tomography (PET). Arterial supply to the distal MCA territory was classified from a review of the angiogram as being through the stenosis or from pial collaterals from anterior or posterior cerebral arteries. Regional measurements of cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism, oxygen extraction fraction, and ratio of cerebral blood volume/cerebral blood flow (mean vascular transit time, MTT) were obtained using PET. Hemodynamic status was categorized from PET scans as stage 0, normal hemodynamics; stage 1, autoregulatory vasodilatation (increased MTT); or stage 2, increased oxygen extraction fraction. RESULTS: Of five patients with MCA occlusion, three had autoregulatory vasodilatation (stage 1) and two had increased oxygen extraction fraction distal to the lesion (stage 2). The MCA territory was supplied solely by pial collaterals in all five patients. Four of the five patients with focal MCA stenosis had normal hemodynamics (stage 0). One patient had stage 1 hemodynamic status. Blood flow to the MCA territory was through the stenosis in all patients; no pial collaterals were identified. CONCLUSION: The frequency of hemodynamic compromise in patients with MCA occlusion is high. Pial collateralization is not a specific sign of increased oxygen extraction fraction in patients with MCA occlusion.

Intraoperative digital subtraction angiography: a review of 112 consecutive examinations.

PURPOSE: To examine the effect of intraoperative angiography on neurosurgery and angiographic technical success, safety, and accuracy. METHODS: Angiographic studies, surgical reports, and hospital records were reviewed retrospectively for 112 consecutive procedures in which intraoperative angiography was performed during neurosurgery. The results of conventional postoperative angiograms in 28 of the 112 procedures were also reviewed. A portable digital subtraction angiography unit was used for all patients. Decisions in the operating room were based on review of stored videotaped images. RESULTS: Eighteen studies were obtained in 14 patients after arteriovenous malformation resection. Unsuspected residual nidus was identified and resected in 3 patients. The intraoperative angiogram also altered therapy for 2 patients undergoing staged resections of arteriovenous malformations. Sixty-six studies were performed after aneurysm clipping, with clinically significant changes in surgical therapy made in 5 patients. Of 28 examinations after carotid endarterectomy, 3 led to revision. Two complications of angiography occurred. One led to a permanent neurologic deficit, yielding a complication rate of 1.5% for stroke. Two examinations could not be completed because of technical factors. Two false-negative examinations were identified on postoperative studies. One patient with a normal intraoperative study after carotid endarterectomy thrombosed the repaired internal carotid artery after surgery. CONCLUSIONS: Intraoperative angiography altered surgery in 13 of 112 procedures on 104 patients. This study supports the use of intraoperative angiography in arteriovenous malformation resection and in complex aneurysm surgery, but not for routine carotid endarterectomy.