Kent D. Yundt

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.

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 15O-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 100 g−1 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.

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.

Increased Oxygen Extraction Fraction Is Associated With Prior Ischemic Events in Patients With Carotid Occlusion

BACKGROUND AND PURPOSE The purpose of our study was to investigate the relationship between misery perfusion (increased oxygen extraction fraction, OEF) and baseline risk factors in patients with carotid occlusion. METHODS One-hundred seventeen patients with atherosclerotic carotid occlusion were studied prospectively by clinical evaluation, laboratory testing, and positron emission tomography (PET). PET measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and OEF were made on enrollment in the study. Increased ipsilateral OEF was identified by comparison with 18 normal control subjects. Twenty-five baseline clinical, epidemiological, and arteriographic risk factors were assessed on study entry. Student t tests, chi(2) tests, and Fisher exact tests with Bonferroni correction were used to assess statistical significance (P<.05). RESULTS Of 117 patients, 44 had increased OEF distal to the occluded carotid and 73 had normal OEFs. Thirty-nine of the 81 patients with prior ipsilateral ischemic symptoms had high OEFs (42%), whereas only 5 of the 31 asymptomatic patients had high OEFs (16%, P<.001). All of the other baseline risk factors were similar between the two groups of patients. CONCLUSIONS Investigations of the relationship between hemodynamic factors and stroke risk must take into account the lower frequency of hemodynamic abnormalities in asymptomatic patients.

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.

THE USE OF HYPERVENTILATION AND ITS IMPACT ON CEREBRAL ISCHEMIA IN THE TREATMENT OF TRAUMATIC BRAIN INJURY

Traumatic brain injury is a common occurrence in the United States, leading to approximately 190,000 deaths or long-term disabilities. Following the primary insult, secondary disturbances in cerebral blood flow (CBF) and metabolism may have deleterious effects on potentially viable neurons. Recent studies evaluating CBF immediately following head injury have revealed flows low enough to produce cerebral ischemia. Hyperventilation is used routinely to lower suspected increased intracranial pressure (ICP). Aggressive hyperventilation produces a marked reduction in CBF, which may give rise to or exacerbate cerebral ischemia, thus enhancing rather than reducing secondary injury. This article reviews the role of hyperventilation in the treatment of increased ICP and its impact on cerebral ischemia following traumatic brain injury.

Cerebral hemodynamic and metabolic changes caused by brain retraction after aneurysmal subarachnoid hemorrhage

OBJECTIVE The cerebral hemodynamic and metabolic effects of aneurysmal subarachnoid hemorrhage are complex. To investigate the impact of surgical retraction, we analyzed position emission tomography (PET) studies that measured the regional cerebral metabolic rate for oxygen, regional oxygen extraction fraction, and regional cerebral blood flow in four patients before and after right frontotemporal craniotomies for clipping of ruptured anterior circulation aneurysms. METHODS Preoperative studies were conducted 1 day before surgery and postoperative studies 6 to 17 days after surgery. No patient had hydrocephalus or intracerebral hematoma. At the time of the second PET study, none of the patients had signs of clinical vasospasm. Regional measurements were obtained from the right ventrolateral frontal and anterior temporal regions corresponding to the area of retraction and compared to the same regions in the opposite hemisphere. To establish a quantitative means to differentiate between hemodynamic and metabolic changes related to arterial vasospasm and those caused by brain retraction, we studied a second group of preoperative patients, who had undergone PET during angiographic and clinical vasospasm. RESULTS There was a 45% reduction in regional cerebral metabolic rate for oxygen (1.87 +/- 0.22 to 1.04 +/- 0.28 ml 100 g-1 min-1) and 32% reduction in regional oxygen extraction fraction (0.41 +/- 0.04 to 0.28 +/- 0.03) in the region of retraction but no change in the opposite hemisphere (paired t test; P = 0.042 and 0.003, respectively). There was no change in regional cerebral blood flow in any region. Brain retraction produced a focal area of tissue injury at the site of retractor blade placement, as compared to more diffuse vascular territory changes produced by vasospasm. CONCLUSION This reduction in the cerebral metabolic rate of oxygen and the oxygen extraction fraction indicates a primary reduction in metabolism and uncoupling of flow and metabolism (luxury perfusion). Similar findings of luxury perfusion have been reported after ischemic stroke and traumatic brain injury. Further studies will be necessary to fully understand the clinical and pathophysiological significance of these observations.

Normal Diameter of Filum terminate in Children: In vivo Measurement

The hallmarks of tethered cord syndrome are a low-lying conus medullaris and a thick filum terminale. In diagnosing the tethered cord syndrome, the thick filum terminale is often defined as that greater than 2 mm in diameter. The cutoff of 2 mm in diameter was derived from myelographic measurements a few decades ago, and the true normal diameter of the filum terminale diameter in children or adults remains unknown. We measured the diameters of the filum terminale in vivo in the operating room on 31 children (age range = 2-14 years; mean age = 5 years) undergoing selective dorsal rhizotomy for spastic cerebral palsy. None of them had clinical evidence of tethered cord syndrome. The conus medullaris and filum terminale were videotaped intraoperatively and images were transferred to an image analyzer; the filum diameters at 10 and 15 mm caudal to the conus medullaris were then measured extraoperatively using the computer graphics system. The diameter of the filum at 10 and 15 mm caudal to the conus was 1,211 +/- 209 and 1,163 +/- 245 microm (mean +/- SD), respectively. In all children except one, the conus medullaris ended above the L2 level. The data indicate that filum terminales greater than 2 mm in diameter in children are abnormally thick.

Posterior Fossa Decompression without Duraplasty in Infants and Young Children for Treatment of Chiari Malformation and Achondroplasia

Some children with Chiari malformation and achondroplasia require posterior fossa decompression that typically includes expansion of the dural tube with duraplasty. Infants and young children, however, may have a more distensible dura mater than do older patients. Furthermore, the structures that compress the hindbrain of young patients may be the bone and abnormally thickened atlantooccipital membrane, i.e., dural band, rather than the dura mater. We have treated 7 children who had Chiari malformation or achondroplasia with posterior fossa decompression without duraplasty. All children were symptomatic; 3 had Chiari-I malformations, 2 Chiari-II malformations, and 2 achondroplasia. The age range was 3 months to 2.5 years (mean 15.1 months). The exent of tonsillar herniation and other hindbrain anomalies was assessed on preoperative magnetic resonance imaging. The infants with Chiari-II malformations underwent cervical laminectomies, whereas the other young children with Chiari-I malformations or achondroplasia underwent suboccipital craniectomy as well as cervical laminectomy. In Chiari malformation, the dural band was divided; in achondroplasia, there was no identifiable dural band. Following bony decompression and division of the identifiable dural band, immediate expansion of the stenotic region with visible cerebrospinal fluid space posterior to the neural elements could be ascertained by intraoperative ultrasonography. During a follow-up period ranging from 4.5 months to 4 years (mean 22 months), all patients made improvements in their symptoms, 3 having complete resolution of their symptoms. This preliminary experience indicates that in children 2 years of age or younger, posterior fossa bony decompression without duraplasty can be effective treatment for Chiari malformations or achondroplasia.

Higher neonatal cerebral blood flow correlates with worse childhood neurologic outcome

Cerebral blood flow (CBF) in newborn infants is often below levels necessary to sustain brain viability in adults. Controversy exists regarding the effects of such low CBF on subsequent neurologic function. We determined the current childhood neurologic status and IQ in 26 subjects who had measurements of CBF performed with PET in the neonatal period between 1983 and 1989 as part of a study of hypoxic-ischemic encephalopathy. Follow-up information at ages 4 to 12 years was obtained on all 26 subjects. Ten subjects had died. All 16 survivors underwent clinical neurologic evaluation, and 14 also underwent intelligence testing. Eight had abnormal clinical neurologic evaluations; eight were normal. The mean neonatal CBF in those with abnormal childhood neurologic outcome was significantly higher than in those with normal childhood neurologic outcome (35.64 ± 11.80 versus 18.26 ± 8.62 mL 100 g-1 min-1, t = 3.36, p = 0.005). A significant negative correlation between neonatal CBF and childhood IQ was demonstrated (Spearman rank correlation r = -0.675, p = 0.008). Higher CBF was associated with lower IQ. The higher CBF in subjects with worse neurologic and intellectual outcome may reflect greater loss of cerebrovascular autoregulation or other vascular regulatory mechanisms due to more severe brain damage.