Regional cerebral blood flow and oxygen metabolism in normal pressure hydrocephalus after subarachnoid hemorrhage

To clarify the pathophysiology of normal pressure hydrocephalus (NPH) after subarachnoid hemorrhage, the authors measured cerebral blood flow (CBF), cerebral oxygen metabolic rates (CMRO2), the cerebral oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in eight normal volunteers, six SAH patients with NPH, and seven patients without NPH by 15O-labeled gas and positron emission tomography (PET). In the NPH group, PET revealed a decrease in CBF in the lower regions of the cerebral cortex and a diffuse decrease in CMRO2. The decrease in CBF in the lower frontal, temporal, and occipital cortices was significantly greater in the NPH than in the non-NPH group. Reduction of CMRO2 was also more extensive in the NPH group, and both CBF and CMRO2 were more markedly decreased in the lower frontal region. OEF was increased in all areas in both of the patient groups, but the increase was not significant in most areas. CBF, CMRO2 and OEF did not significantly differ between the non-NPH group and the normal volunteers. There was no significant difference in CBV among the three groups. These results indicate that NPH involves impairment of cerebral oxygen metabolism in the lower regions of the cerebral cortex, particularly in the lower frontal region.     

Hemodynamic and metabolic effects of cerebral revascularization

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.     

Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Sequential changes in cerebral blood flow and metabolism in patients with subarachnoid haemorrhage

Summary Haemodynamic and metabolic sequences were investigated in nine patients having subarachnoid haemorrhage (SAH) up to 3 months following aneurysmal rupture, using positron emission tomography (PET). In the pre-spasm stage (2–4 days after SAH) cerebral blood flow (CBF, ml/100 ml/min) was 45±11, the cerebral metabolic rate of oxygen (CMRO₂, ml/100 ml/min) was 2.68±0.50, and cerebral blood volume (CBV, ml/100 ml) was 5.5±1.2. CBF within the normal range and a relatively low CMRO₂, indicated relative hyperaemia. This was possibly due to the direct toxic effect of SAH on the brain metabolism. CBV was considerably elevated. The spasm stage (6–15 days after SAH) showed CBF values of 39±7, CMRO₂ values of 2.42±0.50, and CBV values of 5.4±1.7. CBF decreased significantly (p<0.05 vs pre-spasm stage), and CMRO₂ also tended to decrease, while they were coupling. It is likely that this may have been induced by vasospasm. Thereafter, the PET parameters normalized gradually. During all the stages studied, significant laterality of the PET parameters was not observed. This may be because SAH and vasospasm provide diffuse pathophysiological conditions for the entire brain and cerebral arteries.     

Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats

In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 levels after experimental SAH in rats (injection of 0.07 mL of autologous blood into the cisterna magna). Four groups of Sprague-Dawley male rats were studied at predetermined PaCO2 levels: group A: normocapnia (5.01-5.66 kPa [38.0-42.0 mm Hg]); group B: slight hyperventilation (4.34-5.00 kPa [32.5-37.5 mm Hg]); group C: moderate hyperventilation (3.67-4.33 kPa [27.5-32.4 mm Hg]); group D: profound hyperventilation (3.00-3.66 kPa [22.5-27.4 mm Hg]). Each of the four groups included eight rats with SAH and eight sham-operated controls. CBF was determined by the intracarotid Xe method; CMRo2, CMRglc, and CMRlac were obtained by cerebral arteriovenous differences. In both SAH rats and controls, hyperventilation decreased CBF in proportion to the decrement in PaCO2 without affecting either CMRO2, CMRglc, or CMRlac. In groups C and D, CBF decreased by 20%-35%, but CMRs were maintained by a compensatory increase in oxygen extraction fraction (OEF). The results show that even profound hyperventilation in this model of SAH is associated with an adequate increase in OEF so that CMRs of oxygen, glucose, and lactate remain similar to levels observed in normocapnic conditions.     

Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.

OBJECT: Recently, concern has been raised that hyperventilation following severe traumatic brain injury (TBI) could lead to cerebral ischemia. In acute ischemic stroke, in which the baseline metabolic rate is normal, reduction in cerebral blood flow (CBF) below a threshold of 18 to 20 ml/100 g/min is associated with energy failure. In severe TBI, however, the metabolic rate of cerebral oxygen (CMRO2) is low. The authors previously reported that moderate hyperventilation lowered global hemispheric CBF to 25 ml/100 g/min but did not alter CMRO2. In the present study they sought to determine if hyperventilation lowers CBF below the ischemic threshold of 18 to 20 ml/100 g/ min in any brain region and if those reductions cause energy failure (defined as a fall in CMRO2). METHODS: Two groups of patients were studied. The moderate hyperventilation group (nine patients) underwent hyperventilation to PaCO2 of 30 +/- 2 mm Hg early after TBI, regardless of intracranial pressure (ICP). The severe hyperventilation group (four patients) underwent hyperventilation to PaCO2 of 25 +/- 2 mm Hg 1 to 5 days postinjury while ICP was elevated (20-30 mm Hg). The ICP, mean arterial blood pressure, and jugular venous O2 content were monitored, and cerebral perfusion pressure was maintained at 70 mm Hg or higher by using vasopressors when needed. All data are given as the mean +/- standard deviation unless specified otherwise. The moderate hyperventilation group was studied 11.2 +/- 1.6 hours (range 8-14 hours) postinjury, the admission Glasgow Coma Scale (GCS) score was 5.6 +/- 1.8, the mean age was 27 +/- 9 years, and eight of the nine patients were men. In the severe hyperventilation group, the admission GCS score was 4.3 +/- 1.5, the mean age was 31 +/- 6 years, and all patients were men. Positron emission tomography measurements of regional CBF, cerebral blood volume, CMRO2, and oxygen extraction fraction (OEF) were obtained before and during hyperventilation. In all 13 patients an automated search routine was used to identify 2.1-cm spherical nonoverlapping regions with CBF values below thresholds of 20, 15, and 10 ml/ 100 g/min during hyperventilation, and the change in CMRO2 in those regions was determined. In the regions in which CBF was less than 20 ml/100 g/min during hyperventilation, it fell from 26 +/- 6.2 to 13.7 +/- 1 ml/ 100 g/min (p < 0.0001), OEF rose from 0.31 to 0.59 (p < 0.0001), and CMRO2 was unchanged (1.12 +/- 0.29 compared with 1.14 +/- 0.03 ml/100 g/min; p = 0.8). In the regions in which CBF was less than 15 ml/100 g/min during hyperventilation, it fell from 23.3 +/- 6.6 to 11.1 +/- 1.2 ml/100 g/min (p < 0.0001), OEF rose from 0.31 to 0.63 (p < 0.0001), and CMRO2 was unchanged (0.98 +/- 0.19 compared with 0.97 +/- 0.23 ml/100 g/min; p = 0.92). In the regions in which CBF was less than 10 ml/100 g/min during hyperventilation, it fell from 18.2 +/- 4.5 to 8.1 +/- 0 ml/100 g/min (p < 0.0001), OEF rose from 0.3 to 0.71 (p < 0.0001), and CMRO2 was unchanged (0.78 +/- 0.26 compared with 0.84 +/- 0.32 ml/100 g/min; p = 0.64). CONCLUSIONS: After severe TBI, brief hyperventilation produced large reductions in CBF but not energy failure, even in regions in which CBF fell below the threshold for energy failure defined in acute ischemia. Oxygen metabolism was preserved due to the low baseline metabolic rate and compensatory increases in OEF; thus, these reductions in CBF are unlikely to cause further brain injury.     

The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism

Using positron emission tomography with 15O-labelled CO2 O2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO2) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol.     

Effect of labetalol on cerebral blood flow, oxygen metabolism and autoregulation in healthy humans

We have studied the effects of labetalol on cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) in eight healthy volunteers. CBF was measured by single photon emission computerized tomography before and during infusion of labetalol. CMRO2 was calculated as CBF x cerebral arteriovenous oxygen content difference (CaO2-CvO2). CBF autoregulation was tested during infusion of labetalol by changing arterial pressure and estimating relative changes in global CBF from changes in (CaO2-CvO2). CBF before and during infusion of labetalol was 67 and 65 ml/100 g min-1, respectively (P > 0.05). CMRO2 was 2.9 and 2.8 ml/100 g min-1, respectively (P > 0.05). CBF autoregulation was preserved in all subjects. The lower limit of CBF autoregulation was 88 mm Hg (94% of baseline mean arterial pressure). We conclude that labetalol did not influence global or regional CBF, or CMRO2, and CBF autoregulation was preserved.      

The control mechanism involved in post-subarachnoid hemorrhage vasospasm

In the present work the main relationships among cerebral blood volume (CBV), cerebrospinal fluid (CSF) dynamics, cerebral blood flow (CBF) and cerebrovascular reactivity following subarachnoid hemorrhage are critically examined and discussed. It is hypothesized that, following the rupture of an aneurysm, antagonistic mechanism which regulate CBF (through a vasodilatation of the arteriolar vessels) and CBV (through a constriction of basal intracranial arteries) are activated, due to the initial increase in intracranial pressure (ICP) the time pattern of ICP and cerebral hemodynamics in the following days can be largely different depending on the state of CSF dynamics. When the CSF outflow is not altered by blood in the subarachnoid space ICP suddenly returns to the basal value, and a normal cerebral hemodynamics is rapidly restored. By contrast, in conditions in which the normal CSF dynamics is impaired, the opposite action of mechanisms regulating CBF and CBV may lead to instability of the cerebrovascular bed, with the result of a maximal dilatation of pial vessels and a strong constriction of basal arteries (spasm). In our opinion the phenomenon of vasospasm can be better understood if the reactivity of basal intracranial arteries is analyzed as a part of the complex physiological system of cerebrovascular regulation.     

Effect on cerebral blood flow of midazolam during modified neurolept-anesthesia]

Midazolam (0.2 mg.kg-1) was administered to ten patients undergoing neurosurgical operation and its influence on CBF was studied under modified NLA. Simultaneously, the plasma concentration of midazolam was measured. Heart rate and mean arterial blood pressure showed no significant changes after injection in comparison with the control. Cerebral blood flow (CBF) decreased for about 15-20% after 5 minutes, 10 minutes and 15 minutes in comparison with the control. However, 30 minutes later, CBF showed a trend to return to the control. This change in CBF is related to the changes of cerebro-vascular resistance. We applied cerebral oxygen extraction fraction (OEF) to evaluate cerebral metabolism. OEF was constant, showing no significant changes. It is concluded that cerebral oxygen consumption (CMRO2) has decreased together with the decrease in CBF. The plasma concentration of midazolam was 250-300 ng.ml-1 or greater after 5 minutes, 10 minutes and 15 minutes. We think that the sedative dose of midazolam can also sufficiently reduce CBF and CMRO2. The results suggest that midazolam is a safe and effective agent to use for anesthesia and provides adequate sedation for patients with intracranial hypertension.     

Cerebral blood flow and metabolism following superficial temporal artery to superior cerebellar artery bypass for vertebrobasilar occlusive disease.

In order to clarify the effectiveness of extracranial-intracranial bypass operations in patients with vertebrobasilar occlusive disease, the authors used positron emission tomography to investigate the cerebral blood flow (CBF) and metabolism of eight patients undergoing superficial temporal artery (STA)-superior cerebellar artery (SCA) bypass procedures. In the preoperative studies, CBF in the region of the posterior fossa was low and the oxygen extraction fraction (OEF) was high, the so-called "misery perfusion syndrome." Such changes were evident in both the posterior circulation and the anterior circulation regions. Postoperatively, there was a significant increase in CBF, a significant decrease in the OEF not only in the region of posterior circulation but also over the entire brain, and a disappearance of the uncoupling between CBF and oxygen metabolism. The STA-SCA bypass procedure is effective in improving CBF and metabolism in patients with vertebrobasilar occlusive disease.     

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury--a study of cerebral blood flow and metabolism

OBJECTIVE: To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc) and lactate (CMRLct). METHODS: Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO2 from 36 +/- 4 to 32 +/- 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO2, CMRGlc and CMRLct. RESULTS: Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml x 100 gr(-1) x min(-1) were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO2, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. CONCLUSIONS: Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions

Mean hemispheric cerebral blood flow (CBF) and intracranial pressure (ICP) were measured in 19 severely head-injured patients treated with barbiturate coma. The CBF was calculated from the clearance of tracer substance monitored by extracranial scintillation detectors after intravenous administration of xenon-133. In 11 of the patients cerebral arteriovenous oxygen differences were measured simultaneously. In all patients the effects of pronounced hyperventilation were recorded prior to initiation of barbiturate treatment. A normal CBF response to hyperventilation (delta CBF/delta PaCO2 greater than or equal to 1) was obtained in eight patients. In these patients induction of barbiturate coma was accompanied by physiological decreases in CBF and in the calculated cerebral metabolic rate of oxygen (CMRO2); they also exhibited a rapid and lasting decrease in ICP. A decreased or an abolished CO2 reactivity was recorded (delta CBF/delta PaCO2 less than 1) in 11 patients. In 10 of these 11 patients the physiological decreases in CBF and CMRO2 were not obtained during barbiturate treatment and the decrease in ICP was transitory. This study demonstrates a correlation between cerebral vasoreactivity, physiological effects of barbiturate therapy, and clinical outcome.     

Jugular venous oxygen saturation thresholds in trauma patients may not extrapolate to ischemic stroke patients: lessons from a preliminary study

The authors' first examinations of 10 patients with severe hemispheric stroke indicate that bedside monitoring of cerebral blood flow (CBF) is of clinical value as a prognostic tool for outcome and as therapy of elevated intracranial pressure (ICP). Jugular venous oximetry, which is easier to handle and provides on-line data, may also be of prognostic value in patients with ischemic stroke. No clinical studies are available on patients with hemispheric infarctions. Therefore, in a second data analysis from the same patient population, the authors' objective was to estimate the clinical value of monitoring cerebral hemodynamics and metabolism with jugular bulb catheters in treatment of severe postischemic brain edema. In 10 patients with severe hemispheric infarctions, ICP, jugular venous oxygen saturation (SjvO2), CBF, and cerebral metabolic rate of oxygen (CMRO2) were measured prospectively. A total of 101 ICP, SjvO2, and 92 CBF measurements were obtained. Only two SjvO2 values were below the critical thresholds to detect secondary ischemic events defined in trauma patients (SjvO2 < 50%). Intracranial pressure elevations more than 20 mm Hg and pupillary disturbances were treated with osmotherapy (mannitol or hypertonic NaCl hydroxyethyl starch solution) or mild hyperventilation in combination with tromethamine-buffer. In 8 of 17 pairs of measurements with treated elevated ICP, CMRO2 varied and changes of SjvO2 did not reflect changes in CBF. Jugular bulb oximetry should interpreted with caution in patients with severe hemispheric infarction. Critical thresholds defined in trauma patients may not be extrapolated to ischemic stroke.     

Cerebral blood flow and metabolism following ketamine administration

The effects of ketamine on cerebral blood flow (CBF), cerebral metabolic rate (CMRO2) and intracranial pressure (ICP) were evaluated in ventilated or spontaneously breathing goats after peripheral administration of 5 mg . kg-1 and central administration of 0.1-2.0 mg. In mechanically ventilated normocarbic goats intravenous ketamine 5 mg . kg-1 had no effect on CBF, but did produce a significant reduction in CMRO2 (4.3 +/- 0.4 vs 3.7 +/- 0.3 ml O2 . min-1/100 g) five minutes after injection. However, in spontaneously breathing goats, ketamine caused a significant increase in CBF (77 +/- 7 vs 109 +/- 12 ml . min-1/100 g), a significant reduction in CMRO2 (4.3 +/- 0.3 vs 3.8 +/- 0.4) and an increase of PCO2 from 4.5 +/- 0.5 to 5.4 +/- 0.9 kPa (34 +/- 4 to 41 +/- 7 torr). Small doses of ketamine (0.1-2.0 mg) injected directly into the cerebral circulation failed to cause any significant change in CBF. Intracranial pressure showed a significant increase from 13 +/- 3 to 19 +/- 3 mm Hg in spontaneously breathing goats and no change in ventilated goats. These data suggest that ketamine is a mild depressant of cerebral metabolic rate and has no other cerebral vascular effects.     

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.     

Negative BOLD with large increases in neuronal activity

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2)) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO(2) modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions.     

Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failure

BACKGROUND: Our previous study reported that cerebral oxygen extraction fraction (OEF) increased in hemodialysis patients with anemia. The increased OEF suggests that the cerebral vasodilatory capacity might be impaired in these patients. To clarify this issue, we measured the CO2 response in patients with anemia secondary to chronic renal failure (CRF) using positron emission tomography (PET). METHODS: Ten anemic patients with CRF (6 females and 4 males) and 6 age-matched normal controls were studied. The underlying diseases of CRF were glomerulonephritis in 8 patients, systemic lupus erythematosus (SLE) in one patient, and hypertension in one patient; in this cohort, 5 patients were on hemodialysis treatment and the remaining 5 patients were in a pre-hemodialysis state. The cerebral blood flow (CBF) was measured by the O-15 H2O bolus injection method with each patient in a resting state and during 5% CO2 inhalation. The CO2 response was estimated as the percentage change of CBF per 1 mm Hg change of PaCO2. RESULTS: The CO2 response was significantly attenuated in anemic patients with CRF in comparison to the normal controls, and it inversely correlated with the severity of anemia. There was no significant difference in the CO2 response between the hemodialysis and pre-hemodialysis patients. The CO2 response significantly correlated with CBF and the cerebral metabolic rate for oxygen (CMRO2) at rest, however, it did not correlate with OEF and cerebral blood volume (CBV). CONCLUSIONS: The present study revealed the existence of a reduced cerebral vasodilatory capacity in anemic patients with CRF, suggesting that chronic hypoxic brain damage might play a role in the impaired cerebrovascular response to CO2.     

Moyamoya disease presenting with subarachnoid hemorrhage localized over the frontal cortex: case report

BACKGROUND: In moyamoya disease, intracranial bleeding is known to occur because of the rupture of saccular aneurysms in the circle of Willis or because of the rupture of dilated, fragile moyamoya vessels. The former causes subarachnoid hemorrhage (SAH), and the latter causes intracerebral or intraventricular hemorrhage. CASE DESCRIPTION: In this report, we describe the case of a 34-year-old woman with moyamoya disease who suddenly developed headache and jacksonian seizure. Plain computed tomographic scans on admission revealed SAH localized over the left frontal cortex. The patient was diagnosed with moyamoya disease on cerebral angiography. However, no aneurysm was found on cerebral angiography. Positron emission tomography showed the reduction of CBF and its reactivity to acetazolamide and the elevation of CBV in the left hemisphere. She underwent STA to MCA anastomosis and indirect synangiosis. Intraoperative observations revealed that the pial arterioles were markedly dilated on the brain surface. The CBF in the left hemisphere significantly improved after surgery. The patient has experienced no further episode of cerebral ischemia or intracranial bleeding. CONCLUSIONS: Subarachnoid hemorrhage of unknown cause is quite rare in moyamoya disease. Based on the findings in the present case, the dilated collateral arteries on the brain surface may rupture and cause SAH over the cerebral cortex, which is the third cause of intracranial bleeding in patients with persistent cerebral ischemia due to moyamoya disease.     

Acute subdural haematoma due to ruptured intracranial aneurysms

Acute spontaneous subdural haematoma (SDH) is rarely associated with rupture of intracranial saccular aneurysm. We report our experience with four cases of non-traumatic SDHs secondary to rupture of an intracranial aneurysm and discuss the diagnosis and management of this condition. We retrospectively reviewed of four cases of acute SDH due to cerebral aneurysm rupture confirmed by cerebral angiography and surgery. Patients were evaluated using the Glasgow Coma Scale (GCS) and subarachnoid grade of the World Federation of Neurosurgical Societies (WFNS) and outcome with the Glasgow Outcome Scale (GOS). Of the 232 patients with non-traumatic subarachnoid haemorrhage (SAH) treated between 1993 and 2002, only four patients (1.72%) presented SDH due to aneurysmal rupture. The SAH grade on admission was grade IV in one patient and V in the other three. In all cases the aneurysm was located in the posterior communicating artery. Spontaneous acute SDH secondary to aneurysm rupture has been rarely reported. We suggested that timely SDH removal and aneurysmal clipping surgery should be performed in such patients, including those in poor neurological condition.