Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as evaluated by apparent diffusion coefficient changes.

OBJECTIVE: The aims of this study were to investigate the early changes in the mean apparent diffusion coefficient (ADC) after severe subarachnoid hemorrhage (SAH), as a marker of ischemic damage, and to examine the effects of moderate hypothermia, induced at various time points, on ADC changes. METHODS: ADC maps were calculated from diffusion-weighted, blipped-epi, spin echo, magnetic resonance imaging sequences (2.35-T BIOSPEC 24/40 scanner; Bruker Medizin Technik GmbH, Karlsruhe, Germany) for 21 anesthetized (0.45-1% halothane, temperature-adjusted/30% oxygen/69% nitrogen) and ventilated Wistar rats. After baseline scanning, bolus injection of 0.5 ml of autologous arterial blood or artificial cerebrospinal fluid (control group), into the cisterna magna, was performed. Serial scanning was performed for 3 hours after injection, using normothermic or hypothermic (32 degrees C) rats. In an additional series of experiments, hypothermia was initiated either immediately or 60 minutes after normothermic SAH. The water contents of the removed brains were calculated using the wet/dry weight method. RESULTS: The ADC values did not change in the control group but decreased to 88.6+/-5.2% (P < 0.05 versus baseline) after SAH and remained significantly decreased throughout the experiment in normothermia. An injection of blood during hypothermia caused an initial decrease in ADC to 96.1+/-5.6% (P < 0.05 versus baseline); values continuously increased and reached normal levels within 60 minutes. Delayed hypothermia also normalized ADC values within the observation period. The brain water content in the control group was 80.3+/-0.1%, that after SAH in normothermia was 81.1+/-0.7%, and that after SAH in hypothermia was 79.3+/-0.5%. CONCLUSION: This model of severe SAH in rats causes significant ADC changes, which are reversible by application of moderate hypothermia even when it is induced after a 60-minute delay. These findings support the concept of moderate hypothermia exerting a neuroprotective effect in severe SAH.

Management of severe traumatic brain injury by decompressive craniectomy.

OBJECTIVE: The beneficial effect of decompressive craniectomy in the treatment of head trauma patients is controversial. The aim of our study was to assess the value of unilateral decompressive craniectomy in patients with severe traumatic brain injury. METHODS: We retrospectively investigated 49 patients who underwent decompressive craniectomy. Intracranial pressure, cerebral perfusion pressure, therapy intensity level, and cranial computed tomographic scan features (midline shift, visibility of ventricles, gyral pattern, and mesencephalic cisterns) were evaluated before and after craniectomy. The gain of intracranial space was calculated from cranial computed tomographic scans. Patient outcome was graded using the Glasgow Outcome Scale. RESULTS: Thirty-one patients (63.3%) underwent rapid surgical decompression within 4.5 +/- 3.8 hours after trauma; in 18 patients (36.7%), delayed surgical decompression was performed 56.2 +/- 57.0 hours after injury. Patients younger than 50 years or patients who underwent rapid surgical decompression had a significantly better outcome than older patients or patients who underwent delayed surgical decompression. Craniectomy significantly decreased midline shift and improved visibility of the mesencephalic cisterns. The state of the mesencephalic cisterns correlated with the distance of the lower border of the craniectomy to the temporal cranial base. Alterations in intracranial pressure, cerebral perfusion pressure, and therapy intensity level were not significant. The overall mortality of the patients corresponded to the reports of the Traumatic Coma Data Bank (1991). CONCLUSION: Although there was a significant decrease in midline shift after craniectomy, this did not translate into decompressive craniectomy demonstrating a beneficial effect on patient outcome.

Mild and moderate hypothermia (alpha-stat) do not impair the coupling between local cerebral blood flow and metabolism in rats.

BACKGROUND AND PURPOSE: The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS: Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS: Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.

Relationship between local cerebral blood flow and metabolism during mild and moderate hypothermia in rats.

BACKGROUND: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls. RESULTS: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05). CONCLUSIONS: Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.

Rapid active internal core cooling for induction of moderate hypothermia in head injury by use of an extracorporeal heat exchanger.

OBJECTIVE: Moderate hypothermia (32 degrees C) may limit postischemic neuronal damage and is increasingly used clinically in head injury and stroke. For the use of hypothermia as a neuroprotective agent in the prevention of ischemic damage, it is necessary to induce it as soon as possible after the insult and to keep it at the lowest safe level. Active core cooling using an extracorporeal heat exchanger may circumvent the rather slow induction speed and temperature drifts experienced with surface cooling techniques. METHODS: In eight patients with severe head injuries (Glasgow Coma Scale score, 4-5), a venovenous extracorporeal circulation was established via a percutaneously introduced double-lumen cannula in the femoral vein. A heat exchanger was connected via a pressure-controlled roller pump. In addition to standard parameters, brain white matter temperature was continuously recorded as the target temperature. Cooling was initiated as early as possible with an extracorporeal temperature of 30 degrees C and maintained at a 32 degrees C brain temperature for 48 hours, and then gradual rewarming for 24 hours. RESULTS: Cooling was able to be initiated within 6 hours and 48 minutes +/- 3 hours and 47 minutes (mean +/- standard deviation) after trauma. A brain temperature of 32 degrees C was reached within 1 hour and 53 minutes +/- 1 hour and 21 minutes after induction of cooling with a cooling speed of 3.5 degrees C per hour. Brain temperature was able to be controlled within 0.1 degrees C intervals, which was especially helpful in gradual rewarming. No cardiac abnormalities or statistically significant changes in coagulation parameters occurred. Mean platelet count decreased to 89,614+/-42,090 on Day 3 after treatment. No clinical bleeding complications or problems resulting from extracorporeal circulation occurred. Moderate hypothermia was a helpful tool for managing increased intracranial pressure; however, five patients of this series died either of their intracranial abnormalities (n = 4) or of a delayed septic shock after pneumonia (n = 1) at various points in time during therapy. The three survivors experienced either an excellent or a good recovery. CONCLUSION: The results of this investigation suggest that the use of an extracorporeal heat exchanger to achieve active core cooling is suitable for fast and accurately controllable induction, maintenance, and reversal of moderate hypothermia in emergency situations with reliable control of temperature. In this small series of highly selected patients with severe head injuries, we did not note a beneficial effect of hypothermic therapy on outcome.

Assessment of the CAMINO intracranial pressure device in clinical practice.

The purpose of this study was to investigate reliability, handling characteristics and complication rate of the CAMINO-ICP-monitor-system in clinical routine. In a case controlled study 82 patients with intracranial pathology necessitating ICP-monitoring received either a ventricular or a parenchymal CAMINO-device. Clinical assessment of curve shape and apparent reliability of the measurement was documented. Probe position and presence of hematoma was evaluated in all patients with a CT after probe insertion. Handling complications, i.e. dislocation were recorded. At the end of the measuring period the drift of the probe was checked ex vivo and a two point calibration was performed using a water column. During one year 82 patients received 95 probes (parench, 73. ventric. 22). The average measuring period was 91.3 +/- 70.6 hrs. Catheter position was verified by CCT for 67 (70.5%) probes. 92.5% of the devices were placed correctly. Clinically 88.4% of the measurements were assessed plausible, in 8.2% the displayed ICP-values were judged to be too high, in 2.1% too low. Probe drift after explanation was -0.21 mmHg/24 hrs. The mean value of the recalibrated probes in the water column corresponding to 15.8 mmHg was 14.7 +/- 1.9 mmHg. There was no correlation between neither drift nor function in the water column and the duration of the measurement. Technical complications exclusively related to the construction of the CAMINO-system like kinking of the cable, dislocation (probe pulled out) or dislocated fixation screw were too high (25.3%).

Characterization of an anterior circulation rat subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Our aim was to demonstrate the feasibility of an angiographically controlled rat model for the study of macrocirculatory and microcirculatory changes of the anterior intracranial circulation after subarachnoid hemorrhage. METHODS: Subarachnoid hemorrhage was induced by transorbital injection of 0.3 mL of nonheparinized autologous arterial blood into the chiasmatic cistern. Changes in regional cerebral blood flow were continuously recorded with the use of laser-Doppler flowmetry over the parietal cortex. Angiographic verification of middle cerebral artery diameter was performed by carotid catheterization at baseline and 2 days after injection of blood or artificial cerebrospinal fluid. We monitored intracranial and systemic blood pressure during and after injections. RESULTS: Injection of artificial cerebrospinal fluid in the control group did not change the diameter of the middle cerebral artery. Injection of blood caused a significant arterial narrowing of 17.5%, from 0.37 +/- 0.04 mm to 0.31 +/- 0.04 mm after 2 days (P = .0001). In the control group regional cerebral blood flow decreased to 75.9 +/- 16.8% of preinjection control but quickly recovered to 99.7 +/- 19.4%. Intracranial pressure increased for 5 minutes after the injection to a maximum of 27.3 +/- 8.9 mm Hg, accompanied by a 10% decrease in mean arterial pressure. A fall in cerebral blood flow to 53.1 +/- 26.3% in blood-injected animals that recovered to only 80.7 +/- 16.9% of baseline values during the observation period of 30 minutes was noted. A peak intracranial pressure of 45.7 +/- 11.5 mm Hg occurred 2 minutes after injection with a decrease in mean arterial pressure of 13%, resulting in a markedly lower cerebral perfusion pressure than in the control group. CONCLUSIONS: An angiographically controlled model of subarachnoid hemorrhage primarily involving the anterior circulation is feasible in the rat. The resulting narrowing of the middle cerebral artery reflects moderate vasospasm and will allow further microcirculatory studies with cranial windows.

[Noninvasive quantification of cerebral blood volume and blood flow with dynamic MR tomography. Studies of probands and patients with cerebrovascular insufficiency]. / Nichtinvasive Quantifizierung des zerebralen Blutvolumens und Blutflusses mit der dynamischen MR-Tomographie. Untersuchungen an Probanden und Patienten mit zerebrovaskulärer Insuffizienz.

PURPOSE: A non-invasive MR-method for the quantification of regional cerebral blood flow (rCBF) and blood volume (rCBV) is used to examine healthy volunteers and patients with cerebrovascular disorders. MATERIALS AND METHODS: 20 healthy volunteers and 10 patients with severe cerebrovascular disorders were examined. MR imaging was performed on a 1.5 T imaging system. Before, during and following brief antecubital vein bolus injection of Gd-DTPA, a series of 32 rapid T2*-weighted gradient echo images of two different slices ere simultaneously acquired in order to measure th concentration-time-curves in the brain tissue and the arterial input function in the brain feeding arteries. From these series of images the concentration-time-curves were computed. Principles of indicator dilution analysis were applied to compute rCBF and rCBV. The volunteers underwent one examination each. All patients underwent two examinations, one before and the second after azetazolamide stimulation. RESULTS: In volunteers the measured rCBF and rCBV values are in good agreement with data from positron emission tomography studies. In patients with cerebrovascular disorders in the asymptomatic hemisphere a mean increase of rCBF of 43,45 +/- 18.04% was observed after azetazolamide stimulation. In the affected areas of the symptomatic hemisphere in 8 from 10 patients the acetazolamide test reveals a significantly reduced response to azetazolamide stimulation, indicating an exhausted cerebrovascular reserve capacity. CONCLUSION: Dynamic MR-Imaging can provide quantitative information about rCBF and rCBV. In patients with cerebrovascular disorders, this method can be applied to estimate the cerebrovascular reserve capacity.

[Titanium aneurysm clips and their advantages in diagnostic imaging]. / Titananeurysmaclips und ihre Vorteile in der bildgebenden Diagnostik.

Aneurysms clips made of a titanium alloy (TiAl6V4) were used in clinical practice for the first time. The design of the clips is identical to the routinely used Yasargil series. In 30 patients, 38 symptomatic and asymptomatic aneurysms were fixed with 45 clips. Metallurgical advantages of the new alloy are better biocompatibility, less magnetic susceptibility, and lower X-ray density. The postoperative imaging results are superior to the conventionally used alloys with respect to artifact reduction in computed tomography, angiography, and magnetic resonance imaging. With a follow-up period of 7 months, a statement on biocompatibility cannot yet be given.

[Noninvasive diagnosis of cerebral ischemia with nuclear magnetic resonance tomography and near infrared spectroscopy]. / Nichtinvasive Diagnostik zerebraler Ischämie mit Kernspintomographie und Nahe-Infrarotspektroskopie.

We describe the non-invasive assessment of cerebrovascular reserve capacity by means of near-infrared spectroscopy (NIRS) and magnetic resonance imaging. Both methods are compared with transcranial Doppler sonography. There is a good correlation of the three methods in the changes in cerebral oxygen saturation and in blood velocity following acetazolamide stimulation of cerebral blood flow, except found in one patient with unilateral carotid artery occlusion. In this patient we found a decreased cerebrovascular reserve capacity, revealed by a magnetic resonance technique designed to quantify CBV and CBF. We postulate a raised oxygen extraction as the cause of his changes in oxygen saturation.

Normal values of cerebrovascular reserve capacity after stimulation with acetazolamide measured by xenon 133 single-photon emission CT.

PURPOSE: To determine whether a standardized stimulation challenge with acetazolamide will be helpful for assessing the vasodilatory capacity in patients with obstructive cerebrovascular disease. METHODS: To establish normative data of the cerebrovascular reserve capacity, a group of 41 control patients was investigated. The regional cerebral blood flow was measured quantitatively before and after stimulation with acetazolamide using the xenon 133 inhalation method and dynamic single-photon emission CT. RESULTS: A significant increase of regional cerebral blood flow was found after administration of 1 g of acetazolamide. By doubling the dose no significant further increase was measured. We found no correlation of either baseline or stimulated flow values with age. However, a linear dependence between the stimulated flow values and their respective baseline values was observed. CONCLUSION: The standardized challenge with acetazolamide seems to be a reliable method to determine cerebrovascular reserve capacity quantitatively.

Improvement of cerebrovascular reserve capacity by EC-IC arterial bypass surgery in patients with ICA occlusion and hemodynamic cerebral ischemia.

Since the negative results of the international Bypass Study, extracranial-intracranial (EC-IC) bypass surgery is infrequently employed in the treatment of patients with cerebral ischemia. Newly acquired evidence concerning the pathophysiology of cerebral ischemia, however, has facilitated the identification of a small subgroup of patients with "hemodynamic" cerebral ischemia. Characteristically, these patients demonstrate severely impaired cerebrovascular reserve capacity due to occlusive disease and insufficient collateral blood supply. Over an 8-year period, 28 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had recurring episodes of focal cerebral ischemia due to unilateral internal carotid artery occlusion. Computerized tomography (CT) scans either were normal or showed evidence of border zone infarction. The cerebrovascular reserve capacity was studied using 133Xe single-photon emission CT and acetazolamide challenge and was found to be significantly impaired in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed to augment collateral flow to the ischemic hemispheres. Two patients died from myocardial infarction, one 4 days and the other 2 months postoperatively. One patient died from massive brain infarction and another suffered a postoperative stroke with incomplete recovery, resulting in a major morbidity and mortality rate of 14%. Minor morbidity included one patient with a subdural hematoma who subsequently recovered completely. The postoperative course was uneventful in 23 patients (82%). Over a mean follow-up period of almost 3 years, no patient had another episode of brain ischemia. Bypass patency was confirmed by postoperative angiography in 26 patients. Follow-up studies of cerebral blood flow (CBF) and cerebrovascular reserve capacity showed significant improvement of the latter while the resting CBF was essentially unchanged. In view of these findings, the authors conclude that EC-IC bypass surgery constitutes appropriate therapy for a subgroup of patients with recurrent focal cerebral ischemia, defined using the strict selection criteria employed in this study.

STA-MCA bypass in bilateral carotid artery occlusion: clinical results and long-term effect on cerebrovascular reserve capacity.

In this report we describe our experience with extracranial-intracranial arterial bypass surgery in a subgroup of 9 patients (mean age at surgery 61 +/- 9 years) with bilateral carotid artery occlusion, unilaterally symptomatic for occlusive cerebrovascular disease of haemodynamic origin. Haemodynamic insufficiency is characterized by a severely reduced cerebrovascular reserve capacity, measured with Xe-133 D-SPECT and acetazolamide challenge. Preoperatively, the mean baseline cerebral blood flow of 54 +/- 6 ml 100 g-1 min-1 did not change after challenge (54 +/- 5 ml 100 g-1 min-1) in the symptomatic hemisphere. Immediately following surgery an improvement in cerebrovascular reserve capacity for up to 14 +/- 8 ml 100 g-1 min-1 (1-2 years control) was noted. One patient subsequently died from a perioperative stroke, another patient died three months post-operatively from a myocardial infarction. Three patients were followed up to 4 years, four for 2 years. Patients with former transient ischaemic attacks had no further attacks, symptoms from PRIND or minor stroke did not progress further, nor did new symptoms occur. Unilateral extracranial-intracranial bypass surgery has a positive effect on clinical outcome in highly selected patients with bilateral carotid artery occlusion and cerebral ischaemia of haemodynamic origin.

[Transcranial Doppler sonography and cerebrovascular reserve capacity]. / Transkranielle Doppler-Sonographie und zerebrovaskuläre Reservekapazität.

Measurements of blood flow velocity in the basal cerebral arteries during functional testing by means of transcranial Doppler sonography are reviewed. Special emphasis is placed on cerebrovascular reserve capacity, which we determined in two groups of patients with obstructive cerebrovascular disease and in normal persons. We discuss the value of functional testing during endovascular neuroradiological procedures.

Morphometry of intraluminal side-to-side differences in human basal cerebral arteries.

Intraindividual variability of Doppler frequencies in the basal cerebral arteries is higher than the variability in perfusion measurements. Since Doppler frequency is dependent on vessel diameter, we measured intraluminal vessel diameters post mortem. In 73 human cadavers, we measured fresh pairs of rings of the terminal internal carotid artery, the anterior and the middle cerebral artery. Mean intraluminal diameters (+/- standard deviation) for the respective vessel segments were 2.8 +/- 0.49 mm (2.72 +/- 0.49 mm), 1.61 +/- 0.37 mm (1.63 +/- 0.39 mm) and 2.10 +/- 0.38 mm (2.10 +/- 0.41 mm). The left/right ratio was 1.04 +/- 0.13, 1.05 +/- 0.35 and 1.02 +/- 0.17. Intraindividual asymmetries in intraluminal vessel diameters might be an additional factor in the interpretation of intracranial Doppler frequency measurements.

Pathophysiology of unilateral high-grade carotid artery stenosis: evaluation of intracranial haemodynamics by analysis of velocity waveforms from the middle cerebral artery.

1. Transcranial flow velocity waves were measured via Doppler sonography of the middle cerebral artery during hypo-, hyper- and normo-capnia. Applying the principle of vascular impedance, flow velocity waves were analysed in 30 young subjects, 37 elderly subjects and 18 patients with high-grade unilateral internal carotid artery disease. 2. There was evidence that the relative peak-to-peak velocity in the middle cerebral artery could serve as an index of peripheral wave reflection and cerebral resistance (CRi). The response of CRi to changes in arterial CO2 concentration (CRi reactivity) showed a clear age-dependency. However, the absolute side-to-side asymmetry of CRi reactivity (delta R) did not vary with age and could be used to define a normal range (0-4%CRi/vol.%CO2). 3. Selective angiography demonstrated no cerebral cross-flow through the anterior part of the circle of Willis in nine patients with carotid artery stenosis whose absolute delta R was above the normal range and whose CRi reactivity of the affected hemisphere was lower than that of the healthy opposite hemisphere. Conversely, another group of nine patients, whose ipsilateral CRi reactivity was higher than the contralateral CRi reactivity, demonstrated cross-flow through the anterior part of the circle of Willis. 4. delta R may be used to identify patients who have high-grade internal carotid artery stenosis and present with low cerebral vascular resistance owing to poor intracerebral collaterals.

[Hemodynamic monitoring in neuro-endovascular interventions]. / Hämodynamisches Monitoring bei neuro-endovaskulären Eingriffen.

We report on the feasibility of hemodynamic monitoring during occlusive neuro-endovascular procedures. The cerebrovascular reserve capacity as assessed by transcranial Doppler sonography was chosen as the hemodynamic parameter. A standardized stimulation of cerebral blood flow was achieved by a bolus injection of 100 mg acetazolamide (Diamox) i.v. Ten minutes after injection, the middle cerebral artery blood flow velocity of 54 arteries in 33 normal persons increased by 41% +/- 17.5 (mean +/- standard deviation). The lower threshold value was therefore set to 6% increase (mean minus 2 standard deviations). An application in a case of endovascular test- and permanent occlusion of an internal carotid artery is described.