Guenther C. Feigl

Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

Magnetic Resonance Imaging Diffusion Tensor Tractography: Evaluation of Anatomic Accuracy of Different Fiber Tracking Software Packages

BACKGROUND Diffusion tensor imaging (DTI)-based tractography has become an integral part of preoperative diagnostic imaging in many neurosurgical centers, and other nonsurgical specialties depend increasingly on DTI tractography as a diagnostic tool. The aim of this study was to analyze the anatomic accuracy of visualized white matter fiber pathways using different, readily available DTI tractography software programs. METHODS Magnetic resonance imaging scans of the head of 20 healthy volunteers were acquired using a Siemens Symphony TIM 1.5T scanner and a 12-channel head array coil. The standard settings of the scans in this study were 12 diffusion directions and 5-mm slices. The fornices were chosen as an anatomic structure for the comparative fiber tracking. Identical data sets were loaded into nine different fiber tracking packages that used different algorithms. The nine software packages and algorithms used were NeuroQLab (modified tensor deflection [TEND] algorithm), Sörensen DTI task card (modified streamline tracking technique algorithm), Siemens DTI module (modified fourth-order Runge-Kutta algorithm), six different software packages from Trackvis (interpolated streamline algorithm, modified FACT algorithm, second-order Runge-Kutta algorithm, Q-ball [FACT algorithm], tensorline algorithm, Q-ball [second-order Runge-Kutta algorithm]), DTI Query (modified streamline tracking technique algorithm), Medinria (modified TEND algorithm), Brainvoyager (modified TEND algorithm), DTI Studio modified FACT algorithm, and the BrainLab DTI module based on the modified Runge-Kutta algorithm. Three examiners (a neuroradiologist, a magnetic resonance imaging physicist, and a neurosurgeon) served as examiners. They were double-blinded with respect to the test subject and the fiber tracking software used in the presented images. Each examiner evaluated 301 images. The examiners were instructed to evaluate screenshots from the different programs based on two main criteria: (i) anatomic accuracy of the course of the displayed fibers and (ii) number of fibers displayed outside the anatomic boundaries. RESULTS The mean overall grade for anatomic accuracy was 2.2 (range, 1.1-3.6) with a standard deviation (SD) of 0.9. The mean overall grade for incorrectly displayed fibers was 2.5 (range, 1.6-3.5) with a SD of 0.6. The mean grade of the overall program ranking was 2.3 with a SD of 0.6. The overall mean grade of the program ranked number one (NeuroQLab) was 1.7 (range, 1.5-2.8). The mean overall grade of the program ranked last (BrainLab iPlan Cranial 2.6 DTI Module) was 3.3 (range, 1.7-4). The difference between the mean grades of these two programs was statistically highly significant (P < 0.0001). There was no statistically significant difference between the programs ranked 1-3: NeuroQLab, Sörensen DTI Task Card, and Siemens DTI module. CONCLUSIONS The results of this study show that there is a statistically significant difference in the anatomic accuracy of the tested DTI fiber tracking programs. Although incorrectly displayed fibers could lead to wrong conclusions in the neurosciences field, which relies heavily on this noninvasive imaging technique, incorrectly displayed fibers in neurosurgery could lead to surgical decisions potentially harmful for the patient if used without intraoperative cortical stimulation. DTI fiber tracking presents a valuable noninvasive preoperative imaging tool, which requires further validation after important standardization of the acquisition and processing techniques currently available.

Neurosurgical Procedures in the Semisitting Position: Evaluation of the Risk of Paradoxical Venous Air Embolism in Patients with a Patent Foramen Ovale

OBJECTIVE To analyze the actual risk for patients with a patent foramen ovale (PFO) to experience a clinically relevant venous air embolism (VAE) during surgery performed in the semisitting position. METHODS All procedures were performed between January 2008 and December 2009, under general anesthesia and in the semisitting position. Transesophageal echocardiography (TEE) and capnometry were used intraoperatively to monitor for air bubbles in the venous system. RESULTS Of 200 consecutive patients who all were operated on in the semisitting position, 52 patients (26%) had a diagnosis of PFO. Rates of VAE in patients were graded as follows: grade 0 (no air bubbles visible, no air embolism), 23 patients (44.2%); grade I (air bubbles on TEE), 22 patients (42.3%); grade II (air bubbles on TEE with decrease of end-tidal carbon dioxide [ETCO2] ≤ 3 mm Hg), 2 patients (3.8%); grade III, air bubbles on TEE with decrease of ETCO2 >3 mm Hg, 4 patients (7.7%); grade IV, air bubbles on TEE with decrease of ETCO2 >3 mm Hg and decrease of mean arterial pressure ≥ 20% or increase of heart rate ≥ 40% (or both), 1 patient (1.9%); and grade V, VAE causing arrhythmia with hemodynamic instability requiring cardiopulmonary resuscitation, 0 patients (0%). There were no deaths in this series, and no new or unexplained, mild or severe neurologic deficits were caused by a VAE. CONCLUSIONS Under standardized anesthesia and neurosurgical protocols, patients with a PFO can be operated on safely in the semisitting position.

Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of gamma knife radiosurgery.

OBJECTIVE The most important treatment options for meningiomas are microsurgery, radiotherapy, and gamma knife radiosurgery (GKRS). The efficacy of GKRS in terms of local tumor control and tumor volume (TV) reduction can best be determined by accurate analysis of changes in tumor size in pre- and post-GKRS images. In this prospective study, we set the focus on evaluating TV changes and treatment outcome of meningiomas using a quantitative volumetric follow-up protocol after GKRS. METHODS Consecutive patients with World Health Organization Grade I and II meningiomas were included in this study. Most patients underwent a microsurgical TV reduction before being treated with GKRS. Follow-up examinations were performed according to a standardized protocol and included magnetic resonance imaging and quantitative volumetric tumor analyses as well as thorough neurological examinations. RESULTS Complete follow-up data was available for 211 patients (243 tumors) with a mean age of 57.9 years. TVs ranging from 0.1 to 48.3cm3 were treated with GKRS using prescription doses ranging from 10 to 22 Gy. The achieved overall tumor control rate determined with quantitative TV analyses after GKRS was 93.4%; a mean TV reduction of 42.1% was achieved in 74.5% of all treated patients. CONCLUSION Results of this study show that a quantitative volumetric follow-up study of meningiomas is a useful method to demonstrate the efficacy of GKRS for meningiomas. Statistically significant TV reductions with a low rate of side effects can be achieved with GKRS.

Hypericin for visualization of high grade gliomas: First clinical experience

AIMS We aimed to demonstrate that Hypericin, a component of St. Johns Wort, selectively visualizes malignant gliomas. Hypericin is known as one of the most powerful photosensitizers in nature with excellent fluorescent properties. METHODS In five patients with a recurrence of a malignant glioma a newly developed water soluble formulation of hypericin was given intravenously (0.1 mg/kg body weight) 6 h before the surgical procedure. Tumor resection was performed under white light and fluorescence mode. The intensity grade of the tissue fluorescence was categorisized by the surgeon in three grades, highly fluorescent, weakly fluorescent and not fluorescent. In these areas tissue samples were taken and investigated by two blinded independent neuropathologists. Tissue samples were histologically classified differentiating between tumor tissue, tumor necrosis, tissue with scattered tumor cells and normal brain tissue. RESULTS In all patients tumor tissue was clearly distinguishable by its typically red fluorescence color from normal brain tissue which was colored blue under a special fluorescent filter. Histological evaluation of the 110 tissue samples showed a specificity of 100% and sensitivity of 91% for one of the two neuropathologists, whereas specificity for second pathologist was 90% and sensitivity 94%. The i.v. application of Hypericin proofed to be safe in all cases and there were no side effects observed. CONCLUSION Hypericin in its water soluble form is a well tolerated drug. In addition to its high photosensitizing properties hypericin will open up interesting new therapeutic possibilities especially when used in combination with fluorescence detection and simultaneously photodynamic therapy.

Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid-induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence-guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence-guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380-430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.

Imagine your neighbor mows the lawn: a pilot study of psychological sequelae due to awake craniotomy Clinical article

OBJECT Although it has been reported that awake neurosurgical procedures are well tolerated, the long-term occurrence of general psychological sequelae has not yet been investigated. This study assessed the frequency and effects of psychological symptoms after an awake craniotomy on health-related quality of life (HRQOL). METHODS Sixteen patients undergoing an awake surgery were surveyed with a self-developed questionnaire, the Posttraumatic Stress Disorder Inventory For Awake Surgery Patients, which adopts the core components of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) posttraumatic stress disorder (PTSD) criteria. The mean time between surgery and data collection was 97.3 ± 93.2 weeks. Health-related quality of life was assessed with the 36-Item Short Form Health Survey. RESULTS Forty-four percent of the patients stated that they had experienced either repetitive distressing recollections or dreams related to the awake surgery, 18.8% stated persistent avoidance of stimuli associated with the awake surgery, and symptoms of increased arousal occurred in 62.5%. Two patients presented with postoperative psychological sequelae resembling PTSD symptoms. Younger age at surgery and female sex were risk factors for symptoms of increased arousal. The experience of intense anxiety during awake surgery appears to favor the development of postsurgical PTSD symptoms, while recurrent distressing recollections particularly affect HRQOL negatively. CONCLUSIONS In many cases awake craniotomy is necessary to preserve language and motor function. However, in some cases awake craniotomy can lead to postoperative psychological sequelae resembling PTSD symptoms. Therefore, possible long-term effects of an awake surgery should be considered and discussed with the patient when planning this type of surgery.

Male sex as a risk factor for the clinical course of skull base chordomas

OBJECT Chordomas of the skull base are rare and locally invasive and have a poor prognosis. The aim of this retrospective multicenter study was to evaluate the current pattern of care and clinical course and to identify prognostic factors. METHODS A total of 47 patients (26 men; mean age 48.5 years) treated in 5 centers were included. Histology was centrally reviewed; additionally, semiquantitative N- and E-cadherin expression analysis was performed. Prognostic factors were obtained from multivariate regression models. For survival analysis the Kaplan-Meier method was used. RESULTS The median follow-up period was 5.2 years. Complete resection, incomplete resection, and extended biopsy were performed in 14.9%, 80.9%, and 4.3% of patients, respectively. Surgical morbidity was not associated with extent of resection. Adjuvant radiation therapy was performed in 30 (63.8%) of 47 patients. The median progression-free survival (PFS) was 7.3 years. Complete resection prolonged median overall survival (OS) (p = 0.04). Male patients presented with worse PFS (4.8 years vs 9.8 years; p = 0.04) and OS (8.3 years vs not reached; p = 0.03) even though complete resection was exclusively achieved in the male subpopulation. Multivariate analysis confirmed male sex as the most important risk factor for tumor progression (p = 0.04) and death (p = 0.02). Age, duration of symptoms, initial Karnofsky Performance Scale score, brainstem compression, involvement of the petrous bone, infiltration of the dura mater, modality and dose of radiation therapy, and the E- and N-cadherin expression patterns did not gain prognostic relevance. CONCLUSIONS In skull base chordomas, male patients bear a higher risk of progressive disease and death. Male patients might benefit from more aggressive adjuvant therapy and/or from a closer follow-up schedule.

Thrombophilia Due to Factor V and Factor II Mutations and Formation of a Dural Arteriovenous Fistula: Case Report and Review of a Rare Entity

Genetic mutations underlying thrombophilia are often recognized in patients with thromboembolic episodes. However, the clinical and therapeutic implications of such findings often remain unclear. We report the first case of a dural arteriovenous fistula (DAVF) in a patient with a combined factor II and factor V Leiden mutation. A 40-year-old man presented with a large left temporal and intraventricular hemorrhage. An initial angiogram showed thrombosis of the left sigmoid sinus but no evidence of a vascular malformation. One year after the hemorrhage, an angiographic study showed the appearance of a right DAVF. During the follow-up period, the patient was found to harbor heterozygosity for a mutation of factor V and a mutation of factor II. Recognition of the patients thrombophilia led to prolonged oral anticoagulation therapy to reduce the risk of a recurrent thrombotic episode. Despite the increased risk of bleeding, the therapy was considered justified. DAVFs may occur after sinus thrombosis in patients with combined factor II and factor V mutations. This observation indicates the association of multiple hematological disorders with DAVFs in individual patients. Moreover, it raises the clinical conundrum of how to manage patients with thrombophilia, intracranial hemorrhage, and DAVFs.

Posterior Cranial Fossa Gangliogliomas

Ganglioglioma (GG) is an uncommon primary lesion of the central nervous system that is typically located supratentorially. There are only a few reports of GG arising from the cerebellum. To the best of our knowledge this is the first case of a cerebellar GG with supratentorial extension and a longstanding history before its recognition. In fact, this 29-year-old male presented with an 11-year history of intermittent headaches. A cranial computerized tomography (CT) performed at the onset of his complaints failed to reveal the tumor. After a particularly longstanding cephalalgic episode, the patient underwent a new CT scan that was also negative. However, magnetic resonance (MR) imaging of the brain revealed a space-occupying lesion in the right cerebellar hemisphere with extension to the level of the superior colliculi and pineal recess. The tumor was partially removed through a midline suboccipital craniotomy and supracerebellar approach. Pathological examination of the tumor showed composition of atypical ganglion cells and astrocytes, indicating the diagnosis of cerebellar GG. At last follow-up, 24 months after surgery, the patient reported a marked improvement of his clinical condition with significant reduction of intensity and frequency of the headache. The present report illustrates how cerebellar GG may remain undetectable by CT and may therefore present with a longstanding history and nonspecific signs and symptoms. MR investigation can lead to the proper diagnosis. Even after partial removal the prognosis remains good and remission of the symptoms may be achieved. In this article, we review the literature and summarize the current understanding of infratentorial GGs.