Relationship of cerebral perfusion pressure levels to outcome in traumatic brain injury.

This study examined the relationship of cumulative percent time that cerebral perfusion pressure (CPP) fell below set thresholds to outcome in individuals with traumatic brain injury (TBI). The sample included 157 patients (16 to 89 years of age, 79%, male) admitted to an intensive care unit at an academic medical center who underwent invasive arterial blood pressure and intracranial pressure monitoring. CPP levels were recorded continuously during the first 96 hours of monitoring. Initial neurologic status was assessed using the post-resuscitation Glasgow Coma Scale. Outcome was evaluated at hospital discharge and at six months post-injury using the Extended Glasgow Outcome Scale (GOSE). The relationship of cumulative periods of low CPP to outcome was evaluated using hierarchical and binary logistic regression analysis, controlling for age, gender, and injury severity. Patients experiencing less cumulative percent time below specific CPP thresholds were more likely to have better outcome at discharge (55 mm Hg, p = .004; 60 mm Hg, p = .008; 65 mm Hg, p = .024; 70 mm Hg, p = .016). Although differences in GOSE scores at six months were not significant, those with less time below CPP thresholds were more likely to survive. Accumulated episodes of low CPP had a stronger negative relationship with outcome in patients with more severe primary brain injury.

Temporal patterns of evoked cerebral blood flow during reading.

This study describes the dynamics of flow activation by reading and investigates the potential use of repeated flow velocity measurements for the lateralization of speech. Using simultaneous transcranial Doppler recordings from both middle cerebral arteries and averaging techniques in 25 healthy volunteers, we describe the changes in blood flow velocity caused by repetitive reading tasks of variable duration in comparison with a resting state. Reading aloud evoked a characteristic temporal flow pattern in both hemispheres, consisting of three relative maxima in flow velocity during and after activation. Flow velocities lower than baseline were common during longer lasting activation. The amplitudes of two of the observed peaks decreased depending on the duration of the task. Reading silently produced a markedly different temporal pattern of activation than reading aloud. There were individually reproducible significant side to side differences. Right-handed persons (n = 15) almost without exception showed a significantly higher increase in flow velocity on the left hemisphere (e.g., reading silently 8.7% versus 5.3%; P < 0.0001). Three out of ten left-handed individuals, however, exhibited no significant side to side difference or exhibited lateralization to the right during one or more of the tasks. These findings suggest that reading induces task-specific temporal patterns of regional neuronal activity, which show habituation with longer duration of activation. Additionally, the observed side to side differences could be useful to predict language dominance.

Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies.

BACKGROUND: Withdrawal of support in patients with severe brain injury invariably leads to death. Preconceived notions about futility of care in patients with intracerebral hemorrhage (ICH) may prompt withdrawal of support, and modeling outcome in patient populations in whom withdrawal of support occurs may lead to self-fulfilling prophecies. METHODS: Subjects included consecutive patients with supratentorial ICH. Radiographic characteristics of the hemorrhage, clinical variables, and neurologic outcome were assessed. Attitudes about futility of care were examined among members of the departments of neurology and neurologic surgery through a written survey and case presentations. RESULTS: There were 87 patients with supratentorial ICH; overall mortality was 34.5% (30/87). Mortality was 66.7% (18/27) in patients with Glasgow Coma Score < or = 8 and ICH volume > 60 cm(3). Medical support was withdrawn in 76.7% (23/30) of patients who died. Inclusion of a variable to account for the withdrawal of support in a model predicting outcome negated the predictive value of all other variables. Patients undergoing surgical decompression were unlikely to have support withdrawn, and surgery was less likely to be performed in older patients (p < 0.01) and patients with left hemispheric hemorrhage (p = 0.04). Survey results suggested that practitioners tend to be overly pessimistic in prognosticating outcome based upon data available at the time of presentation. CONCLUSIONS: The most important prognostic variable in determining outcome after ICH is the level of medical support provided. Withdrawal of support in patients felt likely to have a "poor outcome" biases predictive models and leads to self-fulfilling prophecies. Our data show that individual patients in traditionally "poor outcome" categories can have a reasonable neurologic outcome when treated aggressively.

Brain SPECT and the effect of cerebral angioplasty in delayed ischemia due to vasospasm.

Cerebral vasospasm is a major determinant of outcome after subarachnoid hemorrhage (SAH). Brain SPECT with 99mTc-HMPAO was obtained before and after cerebral angioplasty in 10 patients with delayed ischemia due to vasospasm. Eight patients had clinically evident neurologic improvement after the procedure. Visual interpretation and an internal-reference (cerebellum), manual, semi-quantitative region of interest (ROI) analysis revealed improvement of regional cerebral blood flow (rCBF) in 9 out of 10. There were disagreements between the visual and ROI analysis in the two that did not improve clinically. For all 10, the average increase per anterior circulation vessel dilated (n = 17) was 8.8% by comparison of the corticocerebellar ratios. For the eight that improved, the average increase was 10.5%. Brain SPECT is valuable for evaluating delayed cerebral ischemia caused by vasospasm after SAH and is useful to document the changes in rCBF induced by angioplasty. It is possible that SPECT may be useful to detect critical reductions in perfusion before clinical deficits develop, thereby offering the potential to identify candidates for early treatment with angioplasty.

bFGF enhances the protective effects of MK-801 against ischemic neuronal injury in vitro.

The neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml-t. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.

Glycine site NMDA receptor antagonists provide protection against ischemia-induced neuronal damage in hippocampal slice cultures.

Ischemia-induced neuronal injury can be reduced by glutamate antagonists acting at the N-methyl-D-aspartate (NMDA) receptor. 7-Chlorokynurenic acid and the recently synthesized compound Acea 1021 block NMDA receptors by acting at the strychnine-insensitive glycine site. The anti-ischemic properties of these compounds were tested by evaluating their ability to reduce CA1 neuronal damage in hippocampal slice cultures deprived of oxygen and glucose. Acea 1021 and 7-chlorokynurenic acid significantly reduced CA1 injury produced by oxygen and glucose deprivation in a dose-dependent manner. The neuroprotective effect of these compounds was reversed by the addition of glycine. The phencyclidine site NMDA antagonist MK-801 also provided significant protection to CA1 neurons against the same insult, and this protection was not affected by the addition of glycine. These results indicate that Acea 1021 and 7-chlorokynurenic acid can provide protection to CA1 neurons against ischemia-induced injury by a glycine-sensitive mechanism.

Neurotoxicity in organotypic hippocampal slices mediated by adenosine analogues and nitric oxide.

Adenosine (ADO) and nitric oxide (NO) have been implicated in a variety of neurophysiological actions, including induction of long-term potentiation, regulation of cerebral blood flow, and neurotoxicity/neuroprotection. ADO has been shown to promote NO release from astrocytes by a direct effect on A1 and A2 receptors, thus providing a link between actions of NO and adenosine in the brain. However, while adenosine acts as an endogenous neuroprotectant, NO is believed to be the effector of glutamate neurotoxicity. To resolve this apparent paradox, we have further investigated the effects of adenosine and NO on neuronal viability in cultured organotypic hippocampal slices exposed to sub-lethal (20') in vitro ischemia. Up to a concentration of 500 microM ADO did not cause toxicity while exposures to 100 microM of the stable ADO analogue chloroadenosine (CADO) caused widespread neuronal damage when paired to anoxia/hypoglycemia. CADO effects were significantly prevented by the ADO receptor antagonist theophylline and blockade of NO production by L-NA (100 microM). Moreover, CADO effects were mimicked by the NO donor SIN-1 (100 microM). Application of 100 microM ADO following blockade of adenosine deaminase (with 10 microM EHNA) replicated the effects of CADO. CADO, ADO + EHNA but not ADO alone caused a prolonged and sustained release of nitric oxide as measured by direct amperometric detection. We conclude that at high concentrations and/or following blockade of its enzymatic catabolism, ADO may cause neurotoxicity by triggering NO release from astrocytes. These results demonstrate for the first time that activation of pathways other than those involving neuronal glutamate receptors can trigger NO-mediated neuronal cell death in the hippocampus.

Glutamate-mediated selective vulnerability to ischemia is present in organotypic cultures of hippocampus.

Ischemic damage to the brain, whether induced experimentally or observed clinically, often produces a pattern of delayed selective cell death in subfield CA1 of hippocampus which has been associated with significant neurologic deficits. The present study demonstrates that this selective vulnerability of CA1 neurons to ischemia, with relative preservation of their neighbors, is expressed in organotypic tissue culture and is prevented by the N-methyl-D-aspartate (NMDA) receptor blocker, MK-801. These data provide conclusive evidence that this selective cell death does not have a vascular etiology but is mediated by factors intrinsic to the hippocampal neurons and/or local circuitry. This model system provides an opportunity both to examine mechanisms of ischemic cell death in an avascular environment and to study methods of prevention in the absence of systemic variables.

Adenosinergic modulation of CA1 neuronal tolerance to glucose deprivation in organotypic hippocampal cultures.

Glucose deprivation produced neuronal degeneration of CA1 pyramidal neurons in hippocampal slice cultures. The effects of the adenosine agonist cyclohexyladenosine (CHA) and antagonist cyclopentylxanthine (CPX) on CA1 neuronal loss following hypoglycemia was examined using propidium iodide fluorescence as an indicator of cell death. The intensity of propidium iodide fluorescence in hippocampal area CA1 was quantified using Optimas image analysis software. Following 2 or 3 h of glucose deprivation, CPX significantly enhanced injury in the CA1 region while CHA provided significant protection. These results suggest that adenosine plays an important role in endogenous neuronal protection during hypoglycemic injury, and also supports a role for the use of adenosine agonists as neuroprotective agents.

Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology.

BACKGROUND AND PURPOSE: Oscillating flow or systolic spikes are typical Doppler-sonographic flow signals found in the presence of cerebral circulatory arrest, which if irreversible, results in brain death. The Neurosonology Research Group (NSRG) of the World Federation of Neurology (WFN) created a Task Force Group in order to evaluate the role of Doppler-sonography as a confirmatory test for determining brain death. METHODS: The available evidence from the literature has been reviewed and discussed by a group of experts, the members of the Task Force Group on cerebral death of the NSRG. RESULTS AND CONCLUSIONS: Extra- and intracranial Doppler-sonography is a useful confirmatory test to establish irreversibility of cerebral circulatory arrest as optional part of a brain death protocol. Doppler-sonography is of special value when the therapeutic use of sedative drugs renders electroencephalography unreliable. Doppler-sonographic criteria are defined and guidelines for the use of Doppler-sonography in this setting are presented.

Evaluation of brain death using transcranial Doppler.

Cerebral blood flow velocities in the middle cerebral arteries were measured using transcranial Doppler in 12 patients with conditions that ultimately resulted in brain death. All patients had sustained closed head injury, gunshot wounds to the head, or spontaneous intracerebral hemorrhages. When clinical criteria for brain death were met, a characteristic pattern was found with transcranial Doppler. This pattern consisted of reverberating flow, with forward flow in systole and retrograde flow in diastole. When this pattern was seen, there was arrest of cerebral flow, as measured by radionuclide scanning using technetium, in all patients studied. Transcranial Doppler is a useful technique for easily assessing the arrest of the cerebral circulation.

Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography.

A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels.

Emergent aneurysm clipping without angiography in the moribund patient with intracerebral hemorrhage: the use of infusion computed tomography scans.

The authors report their experience with 25 patients (mean age, 44.3 +/- 12.1 years) with an intracerebral hematoma (ICH) from a ruptured aneurysm who were emergently operated on without angiography. Instead, preoperative high-resolution infusion computed tomography (CT) scans were used to identify the aneurysm causing the hemorrhage. In all patients, the preoperative Glasgow Coma Scale score was < 5 and brain stem compression was evident. ICH was present in the frontal or temporal lobe and was often associated with intraventricular hemorrhage (n = 17) and significant (> 1 cm) midline shift (n = 18). Infusion CT scans correctly identified the aneurysm in all patients (middle cerebral artery, 18; posterior communicating artery, 2; carotid bifurcation, 3; anterior communicating artery, 2). Partial evacuation of the hematoma guided by infusion CT scan was usually required first to clip the aneurysm definitively using standard microvascular techniques. Intraoperative rupture occurred twice, and temporary clips were used on four occasions. Lobectomy (n = 8), decompressive craniotomy (n = 15), and ventriculostomy (n = 8) were required to control cerebral swelling. All patients underwent postoperative angiography to confirm aneurysm obliteration. Eleven unruptured aneurysms were subsequently identified. Nine had been predicted by infusion scan. Twelve patients survived, eight of whom were only moderately disabled and were independent at 6-months' follow-up. Of the 13 patients who died, all except one died within 4 days of admission. The authors conclude that although angiographic verification before aneurysm surgery is preferable, in the moribund patient with intracerebral hemorrhage, infusion CT scanning provides sufficient information concerning vascular anatomy to allow rational emergency craniotomy and aneurysm clipping.

Effect of transient moderate hyperventilation on dynamic cerebral autoregulation after severe head injury.

OBJECTIVE: This study was undertaken to evaluate the effect of acute moderate hyperventilation on cerebral autoregulation in head-injured patients. METHODS: Dynamic cerebral autoregulation was analyzed by use of transcranial doppler ultrasonography before and after hyperventilation in 10 patients with severe head injury. All of the patients were artificially ventilated and underwent continuous monitoring of arterial blood pressure, intracranial pressure, and end-tidal carbon dioxide. To test autoregulation, rapid transient decreases in systemic blood pressure were achieved by quickly releasing large blood pressure cuffs that were inflated around both thighs. This resulted in a drop of 24 +/- 6 mm Hg in mean systemic blood pressure, which lasted an average of 49 +/- 24 seconds. Cerebral blood flow velocity was monitored continuously in both middle cerebral arteries by use of transcranial doppler ultrasonography. The percentage change in middle cerebral artery velocity was used as an index of the change in cerebral blood flow during the autoregulatory response. The change in estimated cerebrovascular resistance, immediately after the blood pressure drop, or the rate of regulation was used to analyze the effectiveness of the cerebral autoregulation. This value was calculated by determining the rate of increase in middle cerebral artery velocity during the 1st 5 seconds after a blood pressure drop, relative to the rate of increase of the cerebral perfusion pressure. RESULTS: The average rate of regulation during normocapnia at pCO2 of 37 mm Hg was 11.4 +/- 5% per second. After reduction of the pCO2 to 28 mm Hg, the average rate of regulation improved significantly (P < 0.001) to 17.7 +/- 6% per second. Autoregulation improved, despite no significant change in the cerebral perfusion pressure during hyperventilation. The degree of improvement in autoregulation was significantly correlated with the CO2 reactivity (r = 0.45, P < 0.05) but did not correlate (r = -0.23, P = 0.33) with the change in arterial pH value after hyperventilation. CONCLUSION: These results confirm the finding that dynamic autoregulation is disturbed in severe head injury and that moderate transient hyperventilation can temporarily improve the efficiency of the autoregulatory response, probably as a result of a transient increase in vascular tone.

The incidence of surgical complications is similar in good and poor grade patients undergoing repair of ruptured anterior circulation aneurysms: a retrospective review of 355 patients.

To determine how clinical grade after subarachnoid hemorrhage impacts operative characteristics and the incidence of intra- and postoperative surgical complications, we retrospectively compared the surgical management of all good grade (n = 224) and poor grade (n = 131) patients who suffered ruptured anterior circulation aneurysms between 1983 and 1993. The majority of good grade (74.2%) and poor grade (89.8%) patients underwent surgery < 3 days after subarachnoid hemorrhage. The results in this series demonstrate that severe cerebral swelling, often secondary to intracerebral hemorrhage, was significantly more frequent in poor grade patients. The incidence of complications, such as failure to occlude the aneurysm, major vessel occlusion, intraoperative aneurysm rupture, or surgical contusion, however, was similar in poor grade and good grade patients. We conclude, therefore, that except for severe cerebral swelling associated with intracerebral hemorrhage, the risk of surgical complications is similar in good and poor grade patients undergoing surgical repair of ruptured anterior circulation aneurysms.

Intraventricular hemorrhage in blunt head trauma: an analysis of 43 cases.

Before the advent of computed tomography, intraventricular hemorrhage (IVH) from any source was thought rare and invariably fatal. Although intraventricular blood is readily identifiable with computed tomography, there has been little systematic study of its significance in blunt head trauma. Forty-three patients with traumatic IVH were prospectively identified in 1 year at Harborview Medical Center (University of Washington). Most were victims of motor vehicle accidents and suffered severe head injuries. IVH occurred alone in two patients; superficial contusions and subarachnoid hemorrhage were the most common associated finding. Blood was present in only one or both lateral ventricles in 25 patients; only the 3rd or 4th ventricles in 4 and all ventricles in 14 instances. There were 3 intracerebral hematomas and 14 basal ganglion hemorrhages. All of the former and half of the latter communicated with the adjacent lateral ventricle. Extra-axial hematomas appeared more common when only the lateral ventricles were involved, whereas corpus callosum or brain-stem hemorrhage appeared more likely when all the ventricles were involved. Acute hydrocephalus was rare, and ventricular drainage was needed in only four cases. Intracranial pressure (ICP) was elevated (> 15 mm Hg) in 46% of patients. The amount of IVH was related inversely with the Glasgow Coma Scale, but not with increased ICP. The presence of IVH indicated a poor outcome, with only half of the patients being independent at a 6-month follow-up. Poor outcome was associated with increasing age, low admission Glasgow Coma Scale, the presence of space occupying lesions if only the lateral ventricles were involved, and hemorrhage in all four ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon angioplasty for the treatment of vasospasm: results of first 50 cases.

OBJECTIVE: To report the results of the first 50 consecutive patients with vasospasm secondary to subarachnoid hemorrhage treated with balloon angioplasty after failure of medical management. METHODS: Retrospective uncontrolled study of 50 consecutive patients treated with balloon angioplasty between February 1988 and July 1992. Forty-six had objective clinical deterioration despite maximal medical therapy, whereas four were treated on the basis of rapidly accelerating transcranial Doppler velocities and decreased regional blood perfusion detected by technetium-99m-exametazime brain single photon emission computed tomography. All patients had evidence of marked vasospasm demonstrated by angiography. Thirty-two (64%) and 46 (92%) patients underwent angioplasty within 12 and 18 hours, respectively. RESULTS: Of the patients with clinical evidence of vasospasm-induced ischemia, 28 (61%) showed sustained neurological improvement within 72 hours of angioplasty. Three (6%) patients deteriorated within 72 hours after angioplasty, with two (4%) patients dying immediately after angioplasty as a result of vessel rupture and the other patient's Glasgow Coma Scale score decreasing by 2. Two additional patients in poor condition with Hunt and Hess Grade V at the time of angioplasty subsequently died during hospitalization. Two other patients died as a result of unclipped aneurysms that subsequently bled 4 and 12 days after angioplasty, respectively. The improvement demonstrated clinically, angiographically, and by transcranial Doppler after angioplasty was sustained, with only one patient requiring subsequent angioplasty of a previously dilated segment (total, 170 vessel segments dilated). Two patients developed vasospasm in previously undilated segments. CONCLUSION: Timely balloon angioplasty can reverse delayed ischemic deficit caused by vasospasm in patients for whom medical therapy has failed.

Acute traumatic posteroinferior cerebellar artery aneurysms: report of three cases.

OBJECTIVE AND IMPORTANCE: Posterior fossa subarachnoid hemorrhage secondary to blunt head trauma is rarely associated with traumatic aneurysms of the posterior circulation. CLINICAL PRESENTATION: We present three cases of posterior fossa subarachnoid hemorrhage from ruptured posteroinferior cerebellar artery (PICA) aneurysms after blunt head trauma. In each case, there was no associated penetrating injury or cranial fracture. All three patients presented with acute hydrocephalus requiring ventriculostomy. Two of the three patients had a proximal PICA aneurysm visible on emergent angiography. The remaining patient's aneurysm, although not visible on his initial angiogram, was detected on a subsequent angiogram 72 hours later. INTERVENTION: All patients underwent successful surgical clipping of their aneurysms. Two cases required sacrificing of the parent vessels because of the friable nature of the false aneurysms. In each case, severe symptomatic vasospasm occurred, requiring angioplasty. All three patients also required a ventriculoperitoneal shunt for persistent hydrocephalus. CONCLUSION: Features of these three cases and similar cases reported in the literature support the theory that vascular ruptures and traumatic aneurysms of the proximal PICA may be related to anatomic variability of the PICA as it transverses the brainstem. This variability predisposes individuals to vascular lesions, which occur in a continuum based on the severity of the injury. Posterior fossa subarachnoid hemorrhage after head injury requires a high index of suspicion and warrants aggressive diagnostic and therapeutic interventions.

The relationship of blood flow velocity fluctuations to intracranial pressure B waves.

Intracranial pressure (ICP) and continuous transcranial Doppler ultrasound signals were monitored in 20 head-injured patients and simultaneous synchronous fluctuations of middle cerebral artery (MCA) velocity and B waves of the ICP were observed. Continuous simultaneous monitoring of MCA velocity, ICP, arterial blood pressure, and expired CO2 revealed that both velocity waves and B waves occurred despite a constant CO2 concentration in ventilated patients and were usually not accompanied by fluctuations in the arterial blood pressure. Additional recordings from the extracranial carotid artery during the ICP B waves revealed similar synchronous fluctuations in the velocity of this artery, strongly supporting the hypothesis that blood flow fluctuations produce the velocity waves. The ratio between ICP wave amplitude and velocity wave amplitude was highly correlated to the ICP (r = 0.81, p less than 0.001). Velocity waves of similar characteristics and frequency, but usually of shorter duration, were observed in seven of 10 normal subjects in whom MCA velocity was recorded for 1 hour. The findings in this report strongly suggest that B waves in the ICP are a secondary effect of vasomotor waves, producing cerebral blood flow fluctuations that become amplified in the ICP tracing, in states of reduced intracranial compliance.

Intracranial vascular anastomosis using the microanastomotic system. Technical note.

The authors describe the use of a microanastomotic device to perform intracranial end-to-end vascular anastomoses. Direct end-to-end anastomosis was performed between the superficial temporal artery and branches of the middle cerebral artery (MCA) in three patients. Two patients had moyamoya disease, with severe proximal MCA disease, and one suffered an internal carotid artery occlusion with poor collateral flow. All patients reported a history of recent ischemic symptoms. Each anastomosis was accomplished in less than 15 minutes with technically satisfactory results. Postoperative angiographic studies demonstrated patency of the bypasses in all patients.