Peter Schmiedek

Management of severe traumatic brain injury by decompressive craniectomy.

OBJECTIVEnThe 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.nnnMETHODSnWe 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.nnnRESULTSnThirty-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).nnnCONCLUSIONnAlthough there was a significant decrease in midline shift after craniectomy, this did not translate into decompressive craniectomy demonstrating a beneficial effect on patient outcome.

Characterization of Angiogenesis and Microcirculation of High–Grade Glioma: An Intravital Multifluorescence Microscopic Approach in the Athymic Nude Mouse:

The current study follows angiogenesis and microcirculatory changes associated with malignant glioma growth by means of an intravital fluorescence microscopic approach, which allows for the direct and continuous visualization of the glioma microvasculature and its quantitative analysis. Fluorescently labeled C6 rat glioma cells (5 × 105) were implanted into dorsal skinfold chamber preparations of athymic nude mice. Glioma growth, vascularization, microhemodynamics, vascular permeability, and leukocyte–endothelial cell interactions were simultaneously followed over a 22-day observation period using intravital epiillumination microscopy and a multifluorescent labeling technique. Analysis of the process of glioma vascularization revealed three stages with distinct microvascular characteristics: avascular stage (days 0 to 6), lag of glioma growth but initial glioma-induced angiogenesis within the host tissue in peritumoral areas; early vascular stage (days 6 to 14), glioma cell proliferation associated with a spatially homogeneous development of a glioma microvasculature; and late vascular stage (days 14 to 22), exponential tumor growth and expansion (> 400 mm3) with high vascular densities in the peritumoral region and reduced vascularization (microvascular perfusion) in the glioma center. Within the center, the functional vessel length per area correlated inversely with glioma size (P<0.01). In the peritumoral region, functional vessel length per area was independent of glioma size, indicating persistent, high angiogenic activity throughout the observation period. Thus, the microvasculature of mature gliomas revealed a microvascular zonal division with a progressive reduction of the functional vessel length per area within the tumor center. The perfusion failure of individual microvessels within the glioma center was partly compensated by an increase of diameters (P<0.05), and thus by an increase of blood flow in these functional microvessels (P<0.05) over time. Histologic analysis demonstrated both expanding and infiltrating growth patterns, as well as focal necroses on day 22. These are the first data from repeated in vivo analysis of glioma growth, vascularization, and microcirculation.

Effect of Intra-Arterial Papaverine on Regional Cerebral Blood Flow in Hemodynamically Relevant Cerebral Vasospasm

Background and Purpose — It remains controversial whether the intra-arterial administration of papaverine (IAP) is effective in reversing vasospasm-associated cerebral hypoperfusion after aneurysmal subarachnoid hemorrhage. The aim of the present study was to continuously assess regional cerebral blood flow (rCBF) during and after IAP with the use of quantitative, bedside thermal diffusion flowmetry. Methods — Eight patients with cerebral vasospasm after subarachnoid hemorrhage (mean flow velocity >120 cm/s; angiographic vessel constriction >33%; hemispheric cerebral blood flow [CBF] <32 mL/100 g per minute) were prospectively entered into the study. Before IAP, thermal diffusion microprobes were implanted into the white matter of each affected vascular territory (n=10) for rCBF monitoring. During and after IAP (300 mg papaverine/50 mL saline over 1 hour), mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, thermal diffusion rCBF (TD-rCBF), and cerebrovascular resistance (CVR) were recorded continuously. Results — IAP significantly increased TD-rCBF from 7.3±1.6 to 37.9±6.6 mL/100 g per minute (mean±SEM), indicating reversal of cerebral hypoperfusion. This TD-rCBF response was dependent on the degree of cerebral vasospasm and reduced perfusion within the vascular territory. Long-term analysis of TD-rCBF, however, demonstrated that this beneficial effect of IAP on cerebral hypoperfusion was only transient: within 3 hours after treatment, TD-rCBF and CVR returned to baseline values. Furthermore, a lack of correlation between transcranial Doppler sonography and thermal diffusion flowmetry suggested that transcranial Doppler sonography is not suited for CBF-based neuromonitoring after IAP. Conclusions — IAP is not effective in permanently reversing cerebral hypoperfusion in patients with cerebral vasospasm. The need to validate alternative therapeutic strategies that seek to improve cerebral perfusion in vasospasm warrants continued development of CBF-based neuromonitoring strategies.

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

OBJECTIVEnModerate 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.nnnMETHODSnIn 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.nnnRESULTSnCooling 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.nnnCONCLUSIONnThe 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.

The CAMINO Intracranial Pressure Device in Clinical Practice: Reliability, Handling Characteristics and Complications

Summaryu2003Intracranial pressure monitoring has a key role in the management of patients developing increased intracranial pressure (ICP). We adopted the Camino fiberoptic system for intracranial pressure measurement in 1993 in our neurosurgical department. The aim of this study was to investigate reliability, handling characteristics and complication rate of the Camino intracranial pressure device.u2003In an eighteen month period, we prospectively investigated 118 patients with intracranial pathology undergoing Camino fiberoptic intraparenchymal or intraventricular ICP monitoring. The assessment of reliability of ICP monitoring according to patients clinical condition, to cranial computed tomography (CCT) findings and ICP waveform was carried out. Position of the probe and intracranial bleeding complications related to probe insertion were confirmed by CCT. Technical complications, as well as infections due to the device, were documented. In vivo recalibration was performed in 22 patients. At the end of the measuring period the drift of the probe was evaluated and the accuracy of the fiberoptic device was measured by performing a two point calibration.u2003Recordings of intracranial pressure were carried out with 136 Camino devices (104 parenchymal, 32 ventricular) in 118 patients with an average measuring time of 94.1±79.1 hrs. One hundred and fifteen Camino intracranial pressure devices (85.2%) demonstrated reliability according to the predetermined clinical parameters. The actual mean drift after removal of the devices was 3.4 mmHg±3.2 with an actual daily drift of 3.2±17.2 mmHg. Recorded complications included infection (0.7%), intraparenchymal haematoma (5.1%), and a high complication rate (23.5%) with regard to technical aspects. The Camino intracranial pressure system offers reliable ICP measurements in an acceptable percentage of devices, and the advantage of in vivo recalibration. The high incidence of technical complications identifies a need for improvement in the fiberoptic cable and the fixation system.

Targeting angiogenesis inhibits tumor infiltration and expression of the pro‐invasive protein SPARC

The solid growth of high‐grade glioma appears to be cri‐tically dependent on tumor angiogenesis. It remains unknown, however, whether the diffuse infiltration of glioma cells into healthy adjacent tissue is also dependent on the formation of new tumor vessels. Here, we analyze the relationship between tumor angiogenesis and tumor cell infiltration in an experimental glioma model. C6 cells were implanted into the dorsal skinfold chamber of nude mice, and tumor angiogenesis was monitored by intravital fluorescence videomicroscopy. Glioma infiltration was assessed by the extent of tumor cell invasion into the adjacent chamber tissue and by expression of SPARC, a cellular marker of glioma invasiveness. To test the hypothesis that glioma angiogenesis and glioma infiltration are codependent, we assessed tumor infiltration in both the presence and the absence of the angiogenesis inhibitor SU5416. SU5416 is a selective inhibitor of the VEGF/Flk‐1 signal‐transduction pathway, a critical pathway implicated in angiogenesis. Control tumors demonstrated both high angiogenic activity and tumor cell invasion accompanied by strong expression of SPARC in invading tumor cells at the tumor–host tissue border. SU5416‐treated tumors demonstrated reduced vascular density and vascular surface in the tumor periphery accompanied by marked inhibition of glioma invasion and decreased SPARC expression. A direct effect of SU5416 on glioma cell motility and invasiveness was excluded by in vitro migration and invasion assays. These results suggest a crucial role for glioma‐induced angiogenesis as a prerequisite for diffuse tumor invasion and a possible therapeutic role for anti‐angiogenic compounds as inhibitors of both solid and diffuse infiltrative tumor growth. Int. J. Cancer 87:261–268, 2000.

Specific pattern of growth factor distribution in chronic subdural hematoma (CSH): evidence for an angiogenic disease.

Summary.Summary.Background: The aim of this prospective study was to evaluate the significance of growth factors as determinants of the pathological degree of neovascularisation found in the parietal neomembrane of chronic subdural hematoma (CSH). Thus far the pathogenesis of the vascularisation has not been elucidated.Method: The concentrations of growth factors, i.e. vascular endothelial derived growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) were determined using ELISA technique in hematoma fluid and serum of 20 patients with uni- or bilateral CSH. For comparison, growth factor concentrations were determined in cerebrospinal fluid (CSF) of patients undergoing diagnostic myelography.Findings: Concentrations of VEGF and bFGF were significantly (p<0.001) increased in the hematoma fluid as compared with serum (VEGFh=8,142 pg/ml, bFGFh=8.7 pg/ml versus VEGFs=368 pg/ml, bFGFs=1.8 pg/ml). In contrast, PDGF concentration was significantly (p<0.001) lower in the hematoma (PDGFh=3,456 pg/ml versus PDGFs=31,937 pg/ml). The serum levels for VEGF, bFGF and PDGF in CSH patients lay within the range of normal volunteers. No growth factors were found in normal CSF.Interpretation: These results reveal a specific distribution pattern of growth factors in CSH patients. This pattern suggests that CSH may be considered a member of the angiogenic disease family.

Extracranial–intracranial arterial bypass surgery improves total brain blood supply in selected symptomatic patients with unilateral internal carotid artery occlusion and insufficient collateralization

It remains controversial whether extracranial–intracranial (EC–IC) arterial bypass surgery leads to a significant increase in brain blood supply, allowing the reversal of regional cerebral hypoperfusion in symptomatic patients with occlusive cerebrovascular disease and hemodynamic impairment. The aim of the present study was to determine the effects of EC–IC bypass surgery on cerebral brain-supplying blood volume flow (BVF; ml/min) from a purely hemodynamic point of view, using 2D cine phase-contrast MR imaging. Twenty-five patients with symptomatic, unilateral internal carotid artery (ICA) occlusion and hemodynamic compromise received EC–IC arterial bypass surgery. All patients underwent quantitative BVF measurements of brain-supplying arteries preoperatively and postoperatively, including the direct BVF measurement in the established EC–IC bypass after surgery. Preoperatively, total brain BVF was reduced in comparison to normal controls (595±89 vs 663±49xa0ml/min; [mean±SEM]; p=0.039). Mean BVF through the EC–IC bypass reached 84±32xa0ml/min (range: 14–177xa0ml/min), leading to a significant net increase in total BVF of 78±43xa0ml/min (range: 7–136xa0ml/min) when compared with BVF prior to surgery (p<0.001), with resulting postoperative BVF reaching values obtained in normal controls. EC–IC arterial bypass surgery increases total brain blood supply, allowing restoration of local perfusion in hemodynamically compromised brain tissue in patients with symptomatic ICA occlusion.

Glioma cell migration is associated with glioma-induced angiogenesis in vivo.

To simultaneously assess glioma cell invasion and glioma angiogenesis in vivo by non‐invasive and quantitative means, DiI‐labeled C6 glioma spheroids were implanted into the dorsal skinfold chamber preparation of nude mice (n=6). Heat‐inactivated spheroids served as controls to distinguish between active and passive cell spread. Using multi‐flourescent intravital videomicroscopy, glioma cell migration was analyzed on days 1–4, 6, and 10 and spheroid vascularization was analyzed on days 3, 6, and 10 after implantation. Additionaly, C6 glioma spheroids were implanted into the chronic cranial window of nude mice as an orthotopic implantation site (n=4). In the dorsal skinfold chamber, spheroids were vascularized within 10 days and revealed a tumor‐specific microvasculature. In parallel, individual glioma cells detached from the spheroid edge and migrated centrifugally demonstrating an affinity to tumor and host vessels. Glioma cells demonstrated a heterogeneous pattern of their regional migratory actvity (0.2–9.6 μm/h) which correlated well with regional glioma angiogenesis (r=0.733). Using the cranial window, glioma cells spread similarily demonstrating an affinity to the perivascular space of pial/subpial vessels with preference to the arteriolar segments. Intravital fluorescence microscopy represents a versatile technique to assess the complex relationship between glioma‐driven angiogenesis and glioma cell invasion.

Characterization of Direct and Indirect Cerebral Revascularization for the Treatment of European Patients with Moyamoya Disease

Background: The best revascularization strategy for moyamoya disease (MMD) remains unknown. Our aim was to characterize angiographic revascularization effects of a bilateral standardized revascularization approach, consisting of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and encephalomyosynangiosis (EMS) on one hemisphere and single EMS on the contralateral hemisphere of each patient, and to compare the effects of both revascularization strategies on cerebral hemodynamics. Methods: In 30 patients (18 females/12 males, age 8–63 years), standardized revascularization was performed. Digital subtraction angiography was performed preoperatively and at 7 days, 6 months and 12 months postoperatively. STA-MCA and EMS functions were graded I (poor), II (medium) or III (extensive) according to angiographic aspects. In 20 patients, cerebrovascular reserve capacity (CVRC) was assessed pre- and postoperatively (at 12 months) using xenon CT. Results: After 12 months, STA-MCA/EMS function was grade 1 in 40/40%, grade 2 in 27/26%, and grade 3 in 27/10% of hemispheres, respectively. Twelve months after surgery, single EMS showed grade I in 37%, grade II in 27%, and grade III in 20% of hemispheres. Combined revascularization improved CVRC significantly compared to preoperative measurement (preoperative: 16.5 ± 34.6% vs. postoperative: 60.8 ± 64.22%; p < 0.05). Single EMS did not improve CVRC significantly (preoperative: 21.8 ± 35.9% vs. postoperative: 34.8 ± 63.0%; p < 0.05). Conclusions: Combined and indirect revascularization may be successfully applied in a bilateral standardized approach. STA-MCA/EMS is superior to single EMS in restoring CVRC in adult MMD patients.