Volker Seifert

Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow.

OBJECTIVEWe report our initial clinical experience with a new method for intraoperative blood flow assessment. The purposes of the study were to assess the use of indocyanine green (ICG) video angiography in neurovascular cases, to assess the handling and image quality, to compare the findings with postoperative angiographic results, and to evaluate the clinical value of the method in a preliminary feasibility study. METHODSFourteen patients with aneurysms (n = 12) or spinal (n = 1) or intracranial (n = 1) dural fistulae were included. Before and/or after aneurysm or dural fistula occlusion, ICG (25 mg) was injected intravenously. A near-infrared laser excitation light source (&lgr; = 780 nm) illuminated the operating field. The intravascular fluorescence of ICG (maximal &lgr; = 835 nm) was recorded by a nonintensified video camera, with optical filtering to block ambient and laser light for collection of only ICG-induced fluorescence. RESULTSA total of 21 investigations were performed for 14 patients. For the 17 successful ICG video angiographic investigations, image quality and resolution were excellent, allowing intraoperative real-time assessment of the cerebral circulation. ICG angiographic results could be divided into arterial, capillary, and venous phases, comparable to those observed with digital subtraction angiography. In all cases, the postoperative angiographic results corresponded to the intraoperative ICG video angiographic findings. In three cases, the information provided by intraoperative ICG angiography significantly changed the surgical procedure. CONCLUSIONICG video angiography is simple and provides real-time information on the patency of arterial and venous vessels of all relevant diameters, including small and perforating arteries (<0.5 mm), and the visible aneurysm sac. It may be a useful adjunct to improve the quality of neurovascular procedures and to document the intraoperative vascular flow.

Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial.

BACKGROUND Intraoperative MRI is increasingly used in neurosurgery, although there is little evidence for its use. We aimed to assess efficacy of intraoperative MRI guidance on extent of resection in patients with glioma. METHODS In our prospective, randomised, parallel-group trial, we enrolled adults (≥18 years) with contrast enhancing gliomas amenable to radiologically complete resection who presented to Goethe University (Frankfurt, Germany). We randomly assigned patients (1:1) with computer-generated blocks of four and a sealed-envelope design to undergo intraoperative MRI-guided surgery or conventional microsurgery (control group). Surgeons and patients were unmasked to treatment group allocation, but an independent neuroradiologist was masked during analysis of all preoperative and postoperative imaging data. The primary endpoint was rate of complete resections as established by early postoperative high-field MRI (1·5 T or 3·0 T). Analysis was done per protocol. This study is registered with ClinicalTrials.gov, number NCT01394692. FINDINGS We enrolled 58 patients between Oct 1, 2007, and July 1, 2010. 24 (83%) of 29 patients randomly allocated to the intraoperative MRI group and 25 (86%) of 29 controls were eligible for analysis (four patients in each group had metastasis and one patient in the intraoperative MRI group withdrew consent after randomisation). More patients in the intraoperative MRI group had complete tumour resection (23 [96%] of 24 patients) than did in the control group (17 [68%] of 25, p=0·023). Postoperative rates of new neurological deficits did not differ between patients in the intraoperative MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1·0). No patient for whom use of intraoperative MRI led to continued resection of residual tumour had neurological deterioration. One patient in the control group died before 6 months. INTERPRETATION Our study provides evidence for the use of intraoperative MRI guidance in glioma surgery: such imaging helps surgeons provide the optimum extent of resection. FUNDING None.

Intra- and postoperative complications in lumbar disc surgery.

In a prospective study, 412 primary and 69 reoperations for herniated lumbar disc were observed and intra- and postoperative complications compiled. Only surgeons with the experience of more than 100 surgical procedures on lumbar discs entered this study. The complication rates of the micro- and macrosurgical techniques are compared. Intraoperative complications range from 7.8% in the microdiskectomies and 13.7% in the macrodiskectomies to 27.5% in the reoperations. Postoperative complications range from 1.4% in reoperation, 3.9% in the microdiskectomies up to 4.2% in the macrodiskectomies. The risk of complications correlates with the age of the patient and the operating time

Laser surface scanning for patient registration in intracranial image-guided surgery

OBJECTIVE To report our clinical experience with a new laser scanning-based technique of surface registration. We performed a prospective study to measure the calculated registration error and the application accuracy of laser surface registration for intracranial image-guided surgery in the clinical setting. METHODS Thirty-four consecutive patients with different intracranial diseases were scheduled for intracranial image-guided surgery by use of a passive infrared surgical navigation system. Surface registration was performed by use of a Class I laser device that emits a visible laser beam. The Polaris camera system (Northern Digital, Waterloo, ON, Canada) detects the skin reflections of the laser, which the software uses to generate a virtual three-dimensional matrix of the anatomy of each patient. An advanced surface-matching algorithm then matches this virtual three-dimensional matrix to the three-dimensional magnetic resonance therapy data set. Registration error as calculated by the computer was noted. Application accuracy was assessed by use of the localization error for three distant anatomic landmarks. RESULTS Laser surface registration was successful in all patients. For the surgical field, application accuracy was 2.4 ± 1.7 mm (range, 1–9 mm). Application accuracy was higher for the surgical field of frontally located lesions (mean, 1.8 ± 0.8 mm; n = 13) as compared with temporal, parietal, occipital, and infratentorial lesions (mean, 2.8 ± 2.1 mm; n = 21). CONCLUSION Laser scanning for surface registration is an accurate, robust, and easy-to-use method of patient registration for image-guided surgery.

Assessment of flow in perforating arteries during intracranial aneurysm surgery using intraoperative near-infrared indocyanine green videoangiography

OBJECTIVE Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries is responsible for ischemic infarction and poor outcome. The goal of this study is to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition, we analyzed the incidence of perforating vessels involved during the aneurysm surgery and the incidence of ischemic infarct caused by compromised small arteries. METHODS Sixty patients with 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co., Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries were analyzed in the microsurgical field during surgical dissection and clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography were considered for analysis. RESULTS The ICGA was able to visualize flow in all patients in whom perforating vessels were found in the microscope field. Among 36 patients whose perforating vessels were visible on ICGA, 11 (30%) presented a close relation between the aneurysm and perforating arteries. In one (9%) of these 11 patients, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate reestablishment of flow visible with ICGA without clinical consequences. Four patients (6.7%) presented with postoperative perforating artery infarct, three of whom had perforating arteries that were not visible or distant from the aneurysm. CONCLUSION The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA may provide visual information with regard to the patency of these small vessels.

Increased Risk for Postoperative Hemorrhage After Intracranial Surgery in Patients With Decreased Factor XIII Activity: Implications of a Prospective Study

Background and Purpose— The functional integrity of the hemostatic system is a prerequisite for the safe performance of neurosurgical procedures. To monitor the individual coagulation capacity of each patient, standard tests are effective to detect deficiencies involving the generation of fibrin. However, fibrin clot strength depends primarily on coagulation factor XIII, which cross-links fibrin monomers and enhances clot resistance against fibrinolysis. Therefore, factor XIII is functionally involved in both the hemostatic and fibrinolytic systems. The objective of this prospective study was to determine the incidence and clinical relevance of perioperative decreased factor XIII with respect to standard coagulation parameters and the occurrence of postoperative hematoma. Methods— In 876 patients, 910 neurosurgical procedures were performed. Prothrombin time (PT), partial thromboplastin time (PTT), platelet count, fibrinogen, and factor XIII were tested in each patient preoperatively and postoperatively. Results— Postoperative intracranial hematoma (defined as requiring surgical evacuation) occurred after 39 (4.3%) of 910 surgical procedures. Patients with postoperative hematoma had significantly lower factor XIII and fibrinogen levels preoperatively and postoperatively than patients without hematoma. In patients with postoperative hematoma, PT and platelets differed significantly only postoperatively, whereas PTT was different neither preoperatively nor postoperatively. Of the 39 patients with a postoperative hematoma, 13 (33.3%) had a postoperative factor XIII <60% compared with 61 (7%) of 867 patients without hematoma (P <0.01, Fisher’s exact test). The relative risk of developing a postoperative hematoma is therefore increased 6.4-fold in patients with postoperative factor XIII <60%. The risk is increased 12-fold in patients who additionally have postoperative decreased fibrinogen levels (<1.5 g/L) and 9-fold in patients with platelet count <150×109/L and factor XIII <60%. Conclusions— This is the first prospective study that demonstrates the association of decreased perioperative factor XIII with an increased risk of postoperative hematoma in neurosurgical patients. The risk is further increased in those patients with low factor XIII and additional abnormalities of fibrinogen, PT, platelets, and PTT. Factor XIII testing and specific replacement, as accepted for other clotting factors, may reduce the risk of postoperative hematoma.

Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome.

OBJECTIVE:The integration of functional magnetic resonance imaging (fMRI) data into neuronavigation is a new concept for surgery adjacent to the motor cortex. However, the clinical value remains to be defined. In this study, we investigated the correlation between the lesion-to-fMRI activation distance and the occurrence of a new postoperative deficit. METHODS:fMRI-integrated “functional” neuronavigation was used for surgery around the motor strip in 54 patients. During standardized paradigms for hand, foot, and tongue movements, echo-planar imaging T2* blood oxygen level-dependent sequences were acquired and processed with BrainVoyager 2000 software (Brain Innovation, Maastricht, The Netherlands). Neuronavigation was performed with the VectorVision2 system (BrainLAB, Heimstetten, Germany). For outcome analysis, patient age, histological findings, size of lesion, distance to the fMRI areas, preoperative and postoperative Karnofsky index, postoperative motor deficit, and type of resection were analyzed. RESULTS:In 45 patients, a gross total resection (>95%) was performed, and for 9 lesions (low-grade glioma, 4; glioblastoma, 5), a subtotal resection (80–95%) was achieved. The neurological outcome improved in 16 patients (29.6%), was unchanged in 29 patients (53.7%), and deteriorated in 9 patients (16.7%). Significant predictors of a new neurological deficit were a lesion-to-activation distance of less than 5 mm (P < 0.01) and incomplete resection (P < 0.05). CONCLUSION:fMRI-integrated neuronavigation is a useful concept to assess the risk of a new motor deficit after surgery. Our data suggest that a lesion-to-activation distance of less than 5 mm is associated with a higher risk of neurological deterioration. Within a 10-mm range, cortical stimulation should be performed. For a lesion-to-activation distance of more than 10 mm, a complete resection can be achieved safely. The visualization of fiber tracks is desirable to complete the representation of the motor system.

Impairment of Cerebral Perfusion and Infarct Patterns Attributable to Vasospasm After Aneurysmal Subarachnoid Hemorrhage A Prospective MRI and DSA Study

Background and Purpose— The objective of this study was to investigate disturbance of perfusion and infarct patterns attributable to cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Methods— One hundred seventeen patients with aneurysmal SAH specifically selected at high risk for CVS were enrolled in this prospective study. One hundred twelve patients underwent surgical (n=63) or endovascular (n=59) therapy. For assessment of CVS, relative diameter changes of proximal and distal vessel segments on follow-up angiography at day 7±3 after SAH were analyzed in relation to baseline measurements, and cerebral circulation times were measured. Postprocedure MRI was undertaken selectively at four time points: within 3 days, between days 4 and 6, day 7 to 14, and day 15 to 28 from onset of SAH, including perfusion- and diffusion-weighted images. Procedure-related lesions were excluded and CVS-associated infarct patterns analyzed. Results— Occurrence of angiographic CVS was as high as 87.5% between days 7 and 14 and 52.5% showed new infarcts. Eighty-one percent of the infarcts were related to severe CVS (vascular narrowing >66%) and significant (P<0.001) cerebral circulation times prolongation of 8.47±2.25 seconds (time-to-peak delay on perfusion-weighted image: 6.52±4.75 seconds), 16% were associated with moderate CVS (34% to 66% vascular narrowing; cerebral circulation times prolongation: 4.72±0.66 seconds). Besides territorial (47%), lacunar (20%), and watershed infarcts (26%), in 7%, band-like cortical lesions developed without evidence for severe CVS. Conclusions— CVS after SAH may involve the complete arterial system from the circle of Willis up to the distal vessel segments. Depending on the variable types of collateral flow, location of affected vessels segments as well as the degree of CVS may induce different infarct patterns.

The Pan-Bcl-2 Inhibitor ()-Gossypol Triggers Autophagic Cell Death in Malignant Glioma

Antiapoptotic Bcl-2 family members suppress both apoptosis and autophagy and are of major importance for therapy resistance of malignant gliomas. To target these molecules, we used BH3 mimetics and analyzed the molecular mechanisms of cell death induced thereby. Glioma cells displayed only limited sensitivity to single-agent treatment with the BH3 mimetics HA14-1, BH3I-2′, and ABT-737, whereas the pan-Bcl-2 inhibitor (−)-gossypol efficiently induced cell death. Furthermore, (−)-gossypol potentiated cell death induced by temozolomide (TMZ) in MGMT (O6-methylguanine-DNA methyltransferase)-negative U343 cells and, to a lesser extent, in MGMT-expressing U87 cells. (−)-Gossypol triggered translocation of light chain 3 to autophagosomes and lysosomes and cytochrome c release, but cell death occurred in the absence of lysosomal damage and effector caspase activation. Lentiviral knockdown of Beclin1 and Atg5 in U87, U343, and MZ-54 cells strongly diminished the extent of cell death induced by (−)-gossypol and combined treatment with TMZ, indicating that autophagy contributed to this type of cell death. In contrast, stable knockdown of the endogenous autophagy inhibitor mammalian target of rapamycin increased autophagic cell death. Our data suggest that pan-Bcl-2 inhibitors are promising drugs that induce caspase-independent, autophagic cell death in apoptosis-resistant malignant glioma cells and augment the action of TMZ. Furthermore, they indicate that efficient killing of glioma cells requires neutralization of Mcl-1. Mol Cancer Res; 8(7); 1002–16. ©2010 AACR.

Risk of shunt-dependent hydrocephalus after occlusion of ruptured intracranial aneurysms by surgical clipping or endovascular coiling: a single-institution series and meta-analysis.

OBJECTIVETo compare the risk of shunt-dependent hydrocephalus after treatment of ruptured intracranial aneurysms by clipping versus coiling. METHODSWe analyzed 596 patients prospectively added to our database from July of 1999 to November of 2005 concerning the risk of shunt dependency after clipping versus coiling. Factors analyzed included age; sex; Hunt and Hess grade; Fisher grade; acute hydrocephalus; intraventricular hemorrhage; angiographic vasospasm; and number, size, and location of aneurysms. In addition, a meta-analysis of available data from the literature was performed identifying four studies with quantitative data on the frequency of clip, coil, and shunt dependency. RESULTSThe institutional series revealed Hunt and Hess grade, Fisher grade, acute hydrocephalus, intraventricular hemorrhage, and angiographic vasospasm as significant (P < 0.05) risk factors for shunt dependency after a univariate analysis. In a multivariate logistic regression analysis, we isolated intraventricular hemorrhage, acute hydrocephalus, and angiographic vasospasm as independent, significant risk factors for shunt dependency. The meta-analysis, including the current data, revealed a significantly higher risk for shunt dependency after coiling than after clipping (P = 0.01). CONCLUSIONClipping of a ruptured aneurysm may be associated with a lower risk for developing shunt dependency, possibly by clot removal. This might influence long-term outcome and surgical decision making.