Ivan Ng

Effects of head posture on cerebral hemodynamics: its influences on intracranial pressure, cerebral perfusion pressure, and cerebral oxygenation.

OBJECTIVESeverely head-injured patients have traditionally been maintained in the head-up position to ameliorate the effects of increased intracranial pressure (ICP). However, it has been reported that the supine position may improve cerebral perfusion pressure (CPP) and outcome. We sought to determine the impact of supine and 30 degrees semirecumbent postures on cerebrovascular dynamics and global as well as regional cerebral oxygenation within 24 hours of trauma. METHODSPatients with a closed head injury and a Glasgow Coma Scale score of 8 or less were included in the study. On admission to the neurocritical care unit, a standardized protocol aimed at minimizing secondary insults was instituted, and the influences of head posture were evaluated after all acute necessary interventions had been performed. ICP, CPP, mean arterial pressure, global cerebral oxygenation, and regional cerebral oxygenation were noted at 0 and 30 degrees of head elevation. RESULTSWe studied 38 patients with severe closed head injury. The median Glasgow Coma Scale score was 7.0, and the mean age was 34.05 ± 16.02 years. ICP was significantly lower at 30 degrees than at 0 degrees of head elevation (P = 0.0005). Mean arterial pressure remained relatively unchanged. CPP was slightly but not significantly higher at 30 degrees than at 0 degrees (P = 0.412). However, global venous cerebral oxygenation and regional cerebral oxygenation were not affected significantly by head elevation. All global venous cerebral oxygenation values were above the critical threshold for ischemia at 0 and 30 degrees. CONCLUSIONRoutine nursing of patients with severe head injury at 30 degrees of head elevation within 24 hours after trauma leads to a consistent reduction of ICP (statistically significant) and an improvement in CPP (although not statistically significant) without concomitant deleterious changes in cerebral oxygenation.

Cerebral oxygenation, vascular reactivity, and neurochemistry following decompressive craniectomy for severe traumatic brain injury

OBJECT This study addresses the changes in brain oxygenation, cerebrovascular reactivity, and cerebral neurochemistry in patients following decompressive craniectomy for the control of elevated intracranial pressure (ICP) after severe traumatic brain injury (TBI). METHODS Sixteen consecutive patients with isolated TBI and elevated ICP, who were refractory to maximal medical therapy, underwent decompressive craniectomy over a 1-year period. Thirteen patients were male and 3 were female. The mean age of the patients was 38 years and the median Glasgow Coma Scale score on admission was 5. RESULTS Six months following TBI, 11 patients had a poor outcome (Group 1, Glasgow Outcome Scale [GOS] Score 1-3), whereas the remaining 5 patients had a favorable outcome (Group 2, GOS Score 4 or 5). Decompressive craniectomy resulted in a significant reduction (p < 0.001) in the mean ICP and cerebrovascular pressure reactivity index to autoregulatory values (< 0.3) in both groups of patients. There was a significant improvement in brain tissue oxygenation (PbtO(2)) in Group 2 patients from 3 to 17 mm Hg and an 85% reduction in episodes of cerebral ischemia. In addition, the durations of abnormal PbtO(2) and biochemical indices were significantly reduced in Group 2 patients after decompressive craniectomy, but there was no improvement in the biochemical indices in Group 1 patients despite surgery. CONCLUSIONS Decompressive craniectomy, when used appropriately in protocol-driven intensive care regimens for the treatment of recalcitrant elevated ICP, is associated with a return of abnormal metabolic parameters to normal values in patients with eventually favorable outcomes.

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

A collaborative virtual reality environment for neurosurgical planning and training.

OBJECTIVE We have developed a highly interactive virtual environment that enables collaborative examination of stereoscopic three-dimensional (3-D) medical imaging data for planning, discussing, or teaching neurosurgical approaches and strategies. MATERIALS AND METHODS The system consists of an interactive console with which the user manipulates 3-D data using hand-held and tracked devices within a 3-D virtual workspace and a stereoscopic projection system. The projection system displays the 3-D data on a large screen while the user is working with it. This setup allows users to interact intuitively with complex 3-D data while sharing this information with a larger audience. RESULTS We have been using this system on a routine clinical basis and during neurosurgical training courses to collaboratively plan and discuss neurosurgical procedures with 3-D reconstructions of patient-specific magnetic resonance and computed tomographic imaging data or with a virtual model of the temporal bone. Working collaboratively with the 3-D information of a large, interactive, stereoscopic projection provides an unambiguous way to analyze and understand the anatomic spatial relationships of different surgical corridors. In our experience, the system creates a unique forum for open and precise discussion of neurosurgical approaches. CONCLUSION We believe the system provides a highly effective way to work with 3-D data in a group, and it significantly enhances teaching of neurosurgical anatomy and operative strategies.

Tracking protein aggregation and mislocalization in cells with flow cytometry

We applied pulse-shape analysis (PulSA) to monitor protein localization changes in mammalian cells by flow cytometry. PulSA enabled high-throughput tracking of protein aggregation, translocation from the cytoplasm to the nucleus and trafficking from the plasma membrane to the Golgi as well as stress-granule formation. Combining PulSA with tetracysteine-based oligomer sensors in a cell model of Huntingtons disease enabled further separation of cells enriched with monomers, oligomers and inclusion bodies.

Dex-ray: augmented reality neurosurgical navigation with a handheld video probe.

OBJECTIVEWe developed an augmented reality system that enables intraoperative image guidance by using 3-dimensional (3D) graphics overlaid on a video stream. We call this system DEX-Ray and report on its development and the initial intraoperative experience in 12 cases. METHODSDEX-Ray consists of a tracked handheld probe that integrates a lipstick-size video camera. The camera looks over the probes tip into the surgical field. The cameras video stream is augmented with coregistered, multimodality 3D graphics and landmarks obtained during neurosurgical planning with 3D workstations. The handheld probe functions as a navigation device to view and point and as an interaction device to adjust the 3D graphics. We tested the systems accuracy in the laboratory and evaluated it intraoperatively with a series of tumor and vascular cases. RESULTSDEX-Ray provided accurate and real-time video-based augmented reality display. The system could be seamlessly integrated into the surgical workflow. The see-through effect revealing 3D information below the surgically exposed surface proved to be of significant value, especially during the macroscopic phase of an operation, providing easily understandable structural navigational information. Navigation in deep and narrow surgical corridors was limited by the camera resolution and light sensitivity. CONCLUSIONThe system was perceived as an improved navigational experience because the augmented see-through effect allowed direct understanding of the surgical anatomy beyond the visible surface and direct guidance toward surgical targets.

Characterization of cerebrovascular reactivity after craniectomy for acute brain injury.

Analysis of slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) has been used as an index to describe cerebrovascular pressure-reactivity. It has been previously demonstrated that the pressure-reactivity index (PRx) can be used to reflect global cerebrovascular reactivity with changes in ABP. A positive PRx signifies a positive association between ABP and ICP, indicating a non-reactive vascular bed, while a negative PRx is reflective of intact cerebral autoregulation, where ABP waves provoke inversely correlated waves in ICP. To date, there has been no characterization of pressure-reactivity following decompressive craniectomy. In this prospective observational study, 33 patients who underwent surgery for acute brain injury with mass lesions for which the bone flap was left out were studied. The PRx was calculated as a moving correlation coefficient between 30 consecutive samples of values of ICP and ABP averaged for a period of 10 s. The time profiles of mean PRx values at 6-hourly intervals were analysed and compared with that in seven patients treated by medical therapy alone. The initial mean PRx 6 h after surgery was positive, indicative of disturbed pressure-reactivity. With time, PRx trended towards a more negative value, suggestive of an improving cerebrovascular autoregulatory reserve. The mean PRx 24 h after surgery was 0.28 (±0.26), while the mean PRx 72 h after surgery was 0.15 (±0.25) (p = 0.012). In contrast, the mean PRx in patients that were not decompressed did not change significantly with time (p = 0.357). Surgery in acute brain injury for which the bone flap is left out in anticipation of raised intracranial pressure in the postoperative period leads to an improved PRx as compared with controls. Craniectomy in this situation may have a contribution to the restoration of disturbed cerebrovascular pressure-reactivity.

Comparison of polyetheretherketone and titanium cranioplasty after decompressive craniectomy.

OBJECTIVE To characterize complication and failure rates and outcomes of patients who underwent cranioplasty with polyetheretherketone (PEEK) and titanium implants and to compare complication and failure rates between the 2 implants. METHODS A retrospective cohort study of patients who underwent cranioplasty with PEEK patient-specific implant (PEEK Optima-LT) and preformed titanium mesh at the National Neuroscience Institute, Singapore, between January 2001 and February 2012 was performed. Data related to initial decompressive craniectomy and cranioplasty, associated complications after cranioplasty, and indication for revision or removal of implants were collected. Cranioplasty failure was defined as revision or removal of a patients implant. RESULTS Overall complication rates for PEEK and titanium cranioplasty were 25.0% and 27.8%, respectively. The combined complication rate was 27.3%. A trend toward increase in exposed implant in titanium cranioplasty compared with PEEK cranioplasty was observed (P = 0.074). There were 3 of 24 (12.5%) cranioplasty failures with PEEK, and 27 of 108 (25%) cranioplasty failures with titanium (P = 0.129). Previous deep infection in patients after decompressive craniectomy was associated with cranioplasty complications (odds ratio, 23.3; confidence interval, 3.00-180.5; P = 0.003) and failure (odds ratio, 22.5; confidence interval, 2.82-179.0; P = 0.003). CONCLUSIONS The findings from this study highlight that cranioplasty is associated with significant complications, including the necessity for reoperation. It is hoped that the information in this study will provide better understanding of the risks associated with PEEK and titanium cranioplasty and contribute to decision making by the clinician and patient.

Augmented reality neurosurgical planning and navigation for surgical excision of parasagittal, falcine and convexity meningiomas

Objective. To assess the utility of pre-operative 3-dimension (3D) visualisation and surgical planning with the Dextroscope™ in combination with the use of DEX-Ray—a novel augmented reality surgical navigation platform for resection of meningiomas in the falcine, convexity and parasagittal regions. Methods and Results. Magnetic resonance imaging (MRI) and magnetic resonance venogram (MRV) images of the patients were reconstructed in 3D using the Dextroscope workstation. Using a variety of available tools, we were able to view the tumour in various surgical angles and appreciate the intricate relationship of the tumour with respect to the surrounding structures and venous anatomy. Critical draining veins both superficial and deep to the tumour were well visualised. By varying the transparency of the overlying scalp and bone we were able to preoperatively determine the ideal size of our scalp flap and bone window for surgical approach. The Dextroscope enabled us to simulate surgical opening and various trajectories of approach while the DexRay virtual reality navigation system enabled the transfer of the Dextroscope 3D planning data into the operating by displaying it in real-time video-augmented mode which further enhanced the appreciation of the tumours location in 3D space. Four patients underwent total excision of their meningioma while one patient had near total excision with a small residual remnant left behind at the medial third of the superior sagittal sinus. All 5 patients had good neurological recovery post-operatively. Conclusion. The use of the Dextroscope for pre-operative surgical planning allows for appreciation of complex anatomical relationships in 3D. This appreciation is further translated for use during surgical navigation utilizing the DEX-Ray platform that provided us with the superior advantage of allowing fast and accurate surgical resection confidently.

Cryopreservation of neurospheres derived from human glioblastoma multiforme.

Cancer stem cells have been shown to initiate and sustain tumor growth. In many instances, clinical material is limited, compounded by a lack of methods to preserve such cells at convenient time points. Although brain tumor‐initiating cells grown in a spheroid manner have been shown to maintain their integrity through serial transplantation in immune‐compromised animals, practically, it is not always possible to have access to animals of suitable ages to continuously maintain these cells. We therefore explored vitrification as a cryopreservation technique for brain tumor‐initiating cells. Tumor neurospheres were derived from five patients with glioblastoma multiforme (GBM). Cryopreservation in 90% serum and 10% dimethyl sulfoxide yielded greatest viability and could be explored in future studies. Vitrification yielded cells that maintained self‐renewal and multipotentiality properties. Karyotypic analyses confirmed the presence of GBM hallmarks. Upon implantation into NOD/SCID mice, our vitrified cells reformed glioma masses that could be serially transplanted. Transcriptome analysis showed that the vitrified and nonvitrified samples in either the stem‐like or differentiated states clustered together, providing evidence that vitrification does not change the genotype of frozen cells. Upon induction of differentiation, the transcriptomes of vitrified cells associated with the original primary tumors, indicating that tumor stem‐like cells are a genetically distinct population from the differentiated mass, underscoring the importance of working with the relevant tumor‐initiating population. Our results demonstrate that vitrification of brain tumor‐initiating cells preserves the biological phenotype and genetic profiles of the cells. This should facilitate the establishment of a repository of tumor‐initiating cells for subsequent experimental designs. STEM CELLS 2009;27:29–39