Stephan Boor

Local intracerebral administration of O(6)-benzylguanine combined with systemic chemotherapy with temozolomide of a patient suffering from a recurrent glioblastoma.

SummaryThe DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a major determinant of methylating anticancer drug resistance. Inactivation of MGMT by pseudosubstrate inhibitors, such as O6-benzylguanine (O6BG), sensitizes tumor cells to O6-alkylating agents. However, systemic administration of O6BG causes depletion of MGMT in all tissues of the body. Therefore, dose reduction of O6-alkylating drugs administered together with O6BG is required in order to avoid unwished toxic side effects. To attenuate the increased systemic toxicity caused by MGMT inhibitors, local MGMT inactivation would be desirable. Here, we report on intracerebral treatment with O6BG of a patient suffering from glioblastoma. O6BG was administered weekly in the tumor cavity by means of an Ommaya reservoir. This application was well tolerated. Concomitant treatment with temozolomide (Temodal) was associated with transient tumor stabilization without detectable side effects. Although evidence is still lacking that local O6BG administration caused MGMT to be depleted in the residual tumor, the trial shows that intracerebral treatment with O6BG is feasible. It might be a safe strategy for improving glioma therapy by treatment with temozolomide (and presumably also other O6-alkylating drugs) concomitant with O6BG without augmenting drug-induced systemic side effects.

Intraoperative Navigation in der Chirurgie der Nasennebenhöhlen und der vorderen Schädelbasis

ZusammenfassungHintergrund und Fragestellung. Beim Einsatz der computerassistierten Chirurgie im Bereich der Nasennebenhöhlen und vorderen Schädelbasis sind einige Fehlerquellen zu beachten, die durch physikalische Gesetze, den technischen Entwicklungs- und individuellen Kenntnisstand des Anwenders bedingt sind. Patienten/Methodik. Anhand unserer Erfahrungen von 436 navigationsunterstützten Eingriffen werden Hard- und Softwarefehler, Fehler der Bildgebung und des -transfers, Fehler der Patientenregistrierung, Anwenderfehler und strategische Fehler analysiert. Ergebnisse. Bei optischen CAS-Systemen führt die Blockade des Sichtfeldes der Kamera zu Funktionseinschränkungen, während elektromagnetische Systeme durch ferromagnetisch aktive Materialien beeinflusst werden. In Abhängigkeit vom verwendeten Navigationsgerät ist die Schichtbildgewinnung entsprechend zu gestalten. Besonderes Augenmerk ist dabei auf den Rekonstruktionsalgorithmus zu legen. Die kopfmaskenbasierte Patientenregistrierung hat sich für endonasale Eingriffe bewährt. Schlussfolgerungen. Ein kritischer Umgang mit Navigationssystemen bei Kenntnis der physikalischen Gesetzmäßigkeiten befähigt den Anwender, Anzeichen einer Fehlfunktion zu erkennen, richtig zu interpretieren und damit den Erfolg einer navigationsunterstützten Operation zu sichern.AbstractBackground and objective. Based on physical laws, stage of technical development and the users individual skills a number of possible errors have to be considered for the application of CAS in paranasal sinus and anterior skull base surgery. Patients/methods. Based on our experiences of 436 navigated cases hard- and software errors, errors of image acquisition and transfer, errors of patient registration, user related errors as well as strategic errors are analyzed. Results. Any hindrance of the camera field leads to a limitation of functionality of optical systems in the same extent as electromagnetic systems can be affected by ferromagnetic materials. The mode of image acquisition is dependent from the CAS-system involved. The reconstruction algorithm requires particular attention. The patient registration based on the headset proved to be reliable for endonasal sinus surgery. Conclusions. In dealing with navigation devices in paranasal and anterior skull base surgery the user must pay critical attention to possible malfunction in order to guarantee a successful image guided surgical procedure.

Collateral Vessels in Proximal Middle Cerebral Artery Occlusion: The ENDOSTROKE Study

PURPOSE To determine the impact of collateral vessel status on clinical and imaging outcomes in patients undergoing endovascular therapy (EVT) for proximal middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS There were 160 patients with proximal MCA occlusion at six centers in this institutional review board-approved multicenter EVT registry. Angiograms were analyzed at a blinded core laboratory, and collateral vessel status was assessed by using the American Society of Interventional and Therapeutic Neuroradiology (ASITN)/Society of Interventional Radiology (SIR) collateral vessel grading system, while reperfusion was assessed by using the Thrombolysis in Cerebral Infarction (TICI) scale. Good outcome was defined as a modified Rankin Scale score of 0-2 at follow-up. Binary logistic regression analysis was performed by using parameters with P < .2 in univariate analysis. RESULTS Good clinical outcome was attained in 62 (39%) of the 160 patients, and TICI 2b-3 reperfusion was achieved in 94 (59%) patients. Nineteen patients had ASITN/SIR collateral vessel grades of 0 or 1, 63 patients had a grade of 2, and 78 patients had grades of 3 or 4. Better collateral vessels were associated with higher reperfusion rates (21%, 48%, and 77% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), a higher proportion of infarcts smaller than one-third of the MCA territory (32%, 48%, and 69% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), and a higher proportion of good clinical outcome (11%, 35%, and 49% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P = .007). At multivariable analysis, collateral vessel status independently predicted reperfusion, final infarct size, and clinical outcome. Within an onset-to-treatment time (OTT) of 0-3 hours, collateral vessel status predicted final infarct size and reperfusion. Within an OTT of 3-6 hours, it additionally predicted clinical outcome, with 53% of patients with ASITN/SIR grades of 3 or 4 having a good outcome, as compared with 0% of patients with grades of 0 or 1 and 27% of patients with a grade of 2 (P = .008). CONCLUSION In this patient population, collateral vessel status independently predicted the pivotal outcome parameters of reperfusion, infarct size, and clinical outcome. These data underscore the utility of patient selection for EVT on the basis of collateral vessel status.

Technical aids in the diagnosis of brain death: a comparison of SEP, AEP, EEG, TCD and CT angiography.

BACKGROUND The use of technical aids to confirm brain death is a controversial matter. Angiography with the intra-arterial administration of contrast medium is the international gold standard, but it is not allowed in Germany except in cases where it provides a potential mode of treatment. The currently approved tests in Germany are recordings of somatosensory evoked potentials (SSEP), brain perfusion scintigraphy, transcranial Doppler ultrasonography (TCD), and electroencephalography (EEG). CT angiography (CTA), a promising new alternative, is being increasingly used as well. METHODS In a prospective, single-center study that was carried out from 2008 to 2011, 71 consecutive patients in whom brain death was diagnosed on clinical grounds underwent recording of auditory evoked potentials (AEP) and SSEP as well as EEG, TCD and CTA. RESULTS The validity of CTA for the confirmation of brain death was 94%; the validity of the other tests was: 94% for EEG, 92% for TCD, 82% for SSEP, and 2% for AEP. In 61 of the 71 patients (86%), the EEG, TCD and CTA findings all accorded with the clinical diagnosis. The diagnosis of brain death was established beyond doubt in all patients. CONCLUSION In this study, the technical aids yielded discordant results in 14% of cases, necessitating interpretation by an expert examiner. The perfusion tests, in particular, can give false-positive results in patients with large cranial defects, skull fractures, or cerebrospinal fluid drainage. In such cases, electrophysiologic tests or a repeated clinical examination should be performed instead. CTA is a promising, highly reliable new method for demonstrating absent intracranial blood flow. In our view, it should be incorporated into the German guidelines for the diagnosis of brain death.

Minimally invasive superficial temporal artery to middle cerebral artery bypass through a minicraniotomy: benefit of three-dimensional virtual reality planning using magnetic resonance angiography

OBJECT The aim of the authors in this study was to introduce a minimally invasive superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery by the preselection of appropriate donor and recipient branches in a 3D virtual reality setting based on 3-T MR angiography data. METHODS An STA-MCA anastomosis was performed in each of 5 patients. Before surgery, 3-T MR imaging was performed with 3D magnetization-prepared rapid acquisition gradient echo sequences, and a high-resolution CT 3D dataset was obtained. Image fusion and the construction of a 3D virtual reality model of each patient were completed. RESULTS In the 3D virtual reality setting, the skin surface, skull surface, and extra- and intracranial arteries as well as the cortical brain surface could be displayed in detail. The surgical approach was successfully visualized in virtual reality. The anatomical relationship of structures of interest could be evaluated based on different values of translucency in all cases. The closest point of the appropriate donor branch of the STA and the most suitable recipient M(3) or M(4) segment could be calculated with high accuracy preoperatively and determined as the center point of the following minicraniotomy. Localization of the craniotomy and the skin incision on top of the STA branch was calculated with the system, and these data were transferred onto the patients skin before surgery. In all cases the preselected arteries could be found intraoperatively in exact agreement with the preoperative planning data. Successful extracranial-intracranial bypass surgery was achieved without stereotactic neuronavigation via a preselected minimally invasive approach in all cases. Subsequent enlargement of the craniotomy was not necessary. Perioperative complications were not observed. All bypasses remained patent on follow-up. CONCLUSIONS With the application of a 3D virtual reality planning system, the extent of skin incision and tissue trauma as well as the size of the bone flap was minimal. The closest point of the appropriate donor branch of the STA and the most suitable recipient M(3) or M(4) segment could be preoperatively determined with high accuracy so that the STA-MCA bypass could be safely and effectively performed through an optimally located minicraniotomy with a mean diameter of 22 mm without the need for stereotactic guidance.

Detection of intracranial circulatory arrest in brain death using cranial CT-angiography.

Computed tomographic‐angiography (CT‐A) is becoming more accepted in detecting intracranial circulatory arrest in brain death (BD). An international consensus about the use and the parameters of this technique is currently not established. We examined intracranial contrast enhancement in CT‐A after clinically confirmed BD, compared the results with electroencephalography (EEG) and Transcranial Doppler Ultrasonography (TCD) findings and developed a commonly applicable CT‐A protocol.

Virtual endoscopy of the inner ear and the auditory canal

Abstract To assess the role of virtual endoscopy (VE) in the examination of intracisternal structures and of the inner ear, we studied the anatomy of the labyrinth and internal auditory canal using the original CT slices and VE on the unaffected side in three female and three male patients, age range 3–46 years, with contralateral retrocochlear hearing loss. We also examined seven patients with different pathological findings. VE was performed using an advanced postprocessing program with high- resolution 3D data sets of CT (1–1.5 mm thickness, pitch 1.25) and MRI-CISS-3D (constructive interference in steady state) images of the basal cisterns (1.5 T, slice thickness 0.7–1 mm). VE provides an endoscopic-like view from a given point within the basal cisterns of vessels and nerves (on MRI) or of the structures of the inner ear (on CT). The complex anatomy and pathological changes in the inner ear can be faithfully shown. The main advantage is not basic diagnostic information but demonstration of topographically complex situations, such as the canalicular system of the inner ear, for discussion, preoperative planning and teaching.

Effect of intraarterial papaverine or nimodipine on vessel diameter in patients with cerebral vasospasm after subarachnoid hemorrhage

Introduction. Papaverine (P) and nimodipine (N) are the most widely used vasodilators when angiographic and symptomatic vasospasm is present after subarachnoid aneurysmatic hemorrhage (SAH). Their effect is only short-lived and no direct comparisons have been undertaken to evaluate the action of both substances directly. We retrospectively assessed the effect of either P or N on angiographic diameter reduction and capillary blood flow. Methods. Fifteen SAH patients with secured aneurysms and cerebral vasospasm received intraarterial P, fifteen similar patients received N. As the primary endpoint, pre- and post-infusion arterial diameters and capillary blood flow were rated retrospectively on angiographies and compared by RM-ANOVA. Secondary endpoints were the difference in the modified Rankin Scale between the two groups on admission and at discharge, the occurrence of delayed cerebral ischemia, the separate effects on angiographic diameter and capillary blood flow and the overall response rate to the vasodilator infusion. Results. Angiographic resolution of diameter reduction and angiographically assessed capillary blood flow together differed not significantly between both groups. P infusion dilated all angiographic demonstrable vessels while N infusion was ineffective in 16% of the patients. Capillary flow on pre- and post-infusion angiographies was not different between the two groups. Conclusion. P and N seem to differ in the effect on cerebral diameter reduction in patients with vasospasm after SAH. The clinical implications remain to be established. A multimodal approach, perhaps combining different agents for intraarterial infusion in such patients, needs to be evaluated.

Computed tomographic angiography as a useful adjunct in the diagnosis of brain death.

BACKGROUND: Because of its widespread accessibly, computed tomographic angiography (CT‐A) is a promising technique in the detection of intracranial circulatory arrest in brain death (BD). Several studies assessed this tool, but neither have standardized evaluation parameters been developed nor has information about specificity become available. METHODS: We conducted a prospective study between January 2008 and April 2012. Thirty patients were admitted to our University Hospital (16 men and 14 women; age, 18–88 years) and underwent CT‐A scanning at two occasions: immediately after the first signs of loss of brain stem reflexes and after definitive determination of brain. The results of CT‐A were compared with transcranial Doppler ultrasonography and electroencephalogram. RESULTS: In 3 of 30 patients, we observed a termination of contrast flow at the level of the skull base and foramen magnum in arterial scanning series before the clinical determination of BD. After the clinical determination of BD, the opacification of all vascular territories in arterial phase scanning was found in one case, but venous phase scanning revealed no blood return in internal cerebral veins. In all other cases, contrast filling ceased at level of skull base or below. The specificity of CT‐A in the detection of intracranial circulatory arrest was 90%, and sensitivity was 97%. CONCLUSION: CT‐A is reliable and appropriate technical investigation to detect intracranial circulatory arrest in BD. The evaluation of contrast enhancement in arterial phase scanning seems to be more reliable than that in venous phase. An international consensus about a uniformly applied CT‐A protocol for the evaluation of BD should be established. LEVEL OF EVIDENCE: Diagnostic study, level V.

An alternative projection for fluoroscopic-guided needle insertion in the foramen ovale: technical note

PurposePuncture of the ganglion Gasseri through the foramen ovale and subsequent thermocoagulation, balloon compression, or glycerin injection is a well-established technique to treat trigeminal neuralgia. However, direct puncture of the foramen is sometimes difficult. Here, the authors present a simple technique of improved biplane fluoroscopic control for insertion of the needle into the foramen ovale.MethodsThe authors evaluated an alternative oblique X-ray trajectory for the correct placement of a needle into the foramen ovale on cadaveric skull models. After determination of the ideal X-ray trajectory, 13 subsequent patients suffering from trigeminal neuralgia were subjected to intraforaminal needle placement with application of the alternative X-ray trajectory.ResultsAn oblique projection with the X-ray tube (mean rotation 20.9° and angulations 28°) aligned coaxially to the inserted needle is proposed. On cadaver skull models, this oblique trajectory appeared to be ideal for visualization of the correct needle position. In the 13 patients, an immediate needle insertion into the foramen ovale was achieved under this direct oblique fluoroscopic control. No complications were observed.ConclusionsExperimentally and clinically, the new projection demonstrated three distinct advantages over the standard submental projection: Firstly, the foramen ovale can be better visualized independent of the patients position. Secondly, needle correction or insertion can be performed much easier because of the direct fluoroscopic control. Thirdly, the correct needle position in the foramen ovale is more reliably determined than with the submental projection due to projection geometry. Further studies are needed to give evidence that the needle insertion into the foramen ovale is easier achieved with the coaxial projection than with the standard technique.