Faculty Bibliography

OBJECT: Awake craniotomy for removal of intraaxial tumors within or adjacent to eloquent brain regions is a well-established procedure. However, awake craniotomy failures have not been well characterized. In the present study, the authors aimed to analyze and assess the incidence and causes for failed awake craniotomy. METHODS: The database of awake craniotomies performed at Tel Aviv Medical Center between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if conversion to general anesthesia was required, or if adequate mapping or monitoring could not have been achieved. RESULTS: Of 488 patients undergoing awake craniotomy, 424 were identified as having complete medical, operative, and anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these 424 patients were considered failures. The main causes of failure were lack of intraoperative communication with the patient (n = 18 [4.2%]) and/or intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p < 0.001) and treatment with phenytoin (p = 0.0019) were related to failure due to lack of communication. History of seizures (p = 0.03) and treatment with multiple antiepileptic drugs (p = 0.0012) were found to be related to failure due to intraoperative seizures. Compared with the successful awake craniotomy group, a significantly lower rate of gross-total resection was achieved (83% vs 54%, p = 0.008), there was a higher incidence of short-term speech deterioration postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was longer (4.9 +/- 6.2 days vs 8.0 +/- 10.1 days, p < 0.001). Significantly more major complications occurred in the failure group (4 [14.8%] of 27) than in the successful group (16 [4%] of 397) (p = 0.037). CONCLUSIONS: Failures of awake craniotomy were associated with a lower incidence of gross-total resection and increased postoperative morbidity. The majority of awake craniotomy failures were preventable by adequate patient selection and avoiding side effects of drugs administered during surgery.

The impact of enrollment in a clinical study on the survival of patients with glioblastoma has not been established. We retrospectively analyzed 564 patients with newly diagnosed glioblastoma treated between 1995 and 2008. They were divided into those enrolled in a clinical trial and randomized to a treatment or control arm, and those not enrolled and who received best standard of care (BSC). The three groups were matched for age and Karnofsky performance scale (KPS) score at presentation, and included only patients who underwent at least one tumor resection. Survival analysis was performed and multivariate Cox proportional hazards model and recursive partitioning analysis (RPA) identified predictors of survival. Following the matching process, 261 patients remained to form the final cohort. Of the 124 patients enrolled in a study, 81 (31.0%) were randomized to the treatment and 43 (16.5%) to the control arms. The overall median survival for the BSC (n=137), control, and treatment groups was 11.57 months (95% confidence interval [CI], 10.41-12.73), 16.27 months (95% CI, 14.10-18.43) and 16.10 months (95% CI, 14.34-17.86), respectively (p=0.002). Participation in a clinical trial, regardless of the arm, was a significant predictor of survival, as were age and KPS at diagnosis. The RPA also demonstrated a favorable impact of participation in a clinical trial. Additional tumor resections and various treatment modalities were administered with significantly higher frequency among patients enrolled in clinical studies. Thus, enrollment in a clinical study carried a significant survival advantage for patients with glioblastoma, raising practical and ethical issues regarding the quality of care of patients who receive "standard" therapy.

BACKGROUND: Freezing of gait (FOG) is defined as an episodic inability to generate effective stepping in the absence of any known cause other than parkinsonism or high-level gait disorders. METHODS: We present a 59-year-old male with acute, progressive episodes of FOG. Imaging studies revealed a dural arteriovenous fistula (DAVF) associated with edema of the globus pallidus interna (GPi). Cerebral angiography confirmed the diagnosis of DAVF and demonstrated an occluded straight sinus and a retrograde blood flow of deep cerebral veins. RESULTS: After endovascular closure of the DAVF, a major improvement of FOG was observed concomitant with striking near resolution of GPi congestion. CONCLUSIONS: This reversal of the clinical course, correlated with changes in imaging studies, suggests a major role of the GPi in the pathology of FOG.

BACKGROUND: Flow diverters are recently developed stent-like endovascular devices developed to treat complex and non-coilable aneurysms. SILK is a type of flow diverter that has been used for nearly 3 years. Only sparse data about it are available. We would like to share our experience with this device. METHODS: Twenty-eight patients were treated with SILK from October 2008 to October 2010. Thirty-one treatment sessions were performed for 32 aneurysms using 31 SILKs. Twenty have been treated with SILK only and eight with SILK and adjuvant stents. Twenty-six (86%) patients performed cross-sectional imaging (MRA/CTA) for follow-up. Eighteen (64%) patients had follow-up brain angiography. RESULTS: In all patients the SILK could be deployed. No case of early or late aneurysmal rupture was noted. Five patients (17.8%) developed immediate clinical complications, which were permanent in three (10.7%). All the complications occurred in patients harboring aneurysms larger than 15 mm. In two other patients, occlusion of the SILK was noted with no clinical deficit. A complete or near-complete aneurysmal occlusion was found in brain angiography or cross-sectional imaging follow-up in 83.3% of the patients. CONCLUSIONS: SILK is a relatively simple device to use, with a low rate of technical and clinical complications and a high short-term aneurysmal occlusion rate. In aneurysms smaller than 15 mm, the results are excellent. Results are also encouraging in the larger aneurysms, taking into consideration their complexity. The device characteristics and mainly its drawbacks must be well known by the users.

BACKGROUND: Pregnant women with pathological conditions requiring a neurosurgical intervention pose a unique therapeutic challenge. Changes in normal physiology add to the complexity of patient management. We describe our experience in treating various neurosurgical diseases in parturient women. METHODS: Thirty-four pregnant and early postpartum women were treated at our center between 2003 and 2010. The general guideline used in these patients (now deserving re-evaluation based on the presented data) was to postpone surgery until the patient reached term (weeks 34-38 of gestation) unless there was evidence of a life- or function-threatening condition, in which case surgery was promptly performed. RESULTS: Sixteen patients underwent neurosurgical intervention during pregnancy between 11 to 34 weeks of gestation (7 tumor, 3 vascular, 2 VP shunt, 2 spinal, 2 trauma). Thirteen women underwent a neurosurgical procedure after delivery (12 tumor, 1 spine), and 5 women were treated conservatively (2 vascular lesions, 3 trauma). Three patients underwent abortions (one spontaneous and two elective). The other 31 women delivered at 30-42 weeks' gestation. Of 12 patients whose definitive neurosurgical procedure was initially delayed, 5 were not able to complete their pregnancy naturally. Of 21 patients that underwent a cesarean section (CS), 3 were performed urgently. Although two pairs of twins and two singletons had an initial low Apgar score (<7), the outcome for all the neonates was good. Neurosurgical outcome was satisfactory. CONCLUSIONS: Our experience demonstrates the safety of neurosurgical intervention and anesthesia during pregnancy. Delaying intervention often resulted in maternal deterioration and urgent intervention. Thus, pregnancy by itself should not be considered a major contraindication for performing a neurosurgical procedure, which should be considered early rather than late in most patients.

OBJECT: Preserving motor function is a major challenge in surgery for intraaxial brain tumors. Navigation systems are unreliable in predicting the location of the corticospinal tracts (CSTs) because of brain shift and the inability of current intraoperative systems to produce reliable diffusion tensor imaging data. The authors describe their experience with elaborate neurophysiological assessment and tractography-based navigation, corrected in real time by 3D intraoperative ultrasonography (IOUS) to identify motor pathways during subcortical tumor resection. METHODS: A retrospective analysis was conducted in 55 patients undergoing resection of tumors located within or in proximity to the CSTs at the authors' institution between November 2007 and June 2009. Corticospinal tract tractography was coregistered to surgical navigation-derived images in 42 patients. Direct cortical-stimulated motor evoked potentials (dcMEPs) and subcortical-stimulated MEPs (scrtMEPs) were recorded intraoperatively to assess function and estimate the distance from the CSTs. Intraoperative ultrasonography updated the navigation imaging and estimated resection proximity to the CSTs. Preoperative clinical motor function was compared with postoperative outcome at several time points and correlated with incidences of intraoperative dcMEP alarm and low scrtMEP values. RESULTS: The threshold level needed to elicit scrtMEPs was plotted against the distance to the CSTs based on diffusion tensor imaging tractography after brain shift compensation with 3D IOUS, generating a trend line that demonstrated a linear order between these variables, and a relationship of 0.97 mA for every 1 mm of brain tissue distance from the CSTs. Clinically, 39 (71%) of 55 patients had no postoperative deficits, and 9 of the remaining 16 improved to baseline function within 1 month. Seven patients had varying degrees of permanent motor deficits. Subcortical stimulation was applied in 45 of the procedures. The status of 32 patients did not deteriorate postoperatively (stable or improved motor status): 27 of them (84%) displayed minimum scrtMEP thresholds > 7 mA. Six patients who experienced postoperative deterioration quickly recovered (within 5 days) and displayed minimum scrtMEP thresholds > 6.8 mA. Five of the 7 patients who had late (> 5 days postoperatively) or no recovery had minimal scrtMEP thresholds < 3 mA. An scrtMEP threshold of 3 mA was found to be the cutoff point below which irreversible disruption of CST integrity may be anticipated (sensitivity 83%, specificity 95%). CONCLUSIONS: Combining elaborate neurophysiological assessment, tractography-based neuronavigation, and updated IOUS images provided accurate localization of the CSTs and enabled the safe resection of tumors approximating these tracts. This is the first attempt to evaluate the distance from the CSTs using the threshold of subcortical monopolar stimulation with real-time IOUS for the correction of brain shift. The linear correlation between the distance to the CSTs and the threshold of subcortical stimulation producing a motor response provides an intraoperative technique to better preserve motor function.

OBJECT: Resection of lesions involving the supplementary motor area (SMA) may result in immediate postoperative motor and speech deficits that are reversible in most cases. In the present study the authors aimed to determine the critical involvement of SMA in the lesioned and healthy hemispheres in this functional recovery. They hypothesized that compensatory mechanisms take place following surgery in the SMA, and that these mechanisms can involve either the lesioned or the non-lesioned hemisphere. In addition, they hypothesized that a correlation will be present between the functional MR imaging (fMR) imaging-related activation in the SMA and the occurrence of a functional deficit during intraoperative cortical stimulation. METHODS: Twenty-six patients scheduled for resection of space-occupying lesions involving, or in the vicinity of, the SMA were recruited. Patients underwent an fMR imaging examination that included finger-tapping and verb-generation tests to assess for motor and language functions. Intraoperatively direct cortical stimulation (DCS) of the SMA region was performed while patients were monitored for language and motor functions using tests similar to those used for the fMR imaging. Task dysfunction during DCS assessed the critical involvement of the SMA in the tested functions. Neurological evaluations were performed prior to surgery and at 3 time points within a month following surgery. A region of interest-based approach was used to evaluate fMR imaging blood oxygen level-dependent activation level and asymmetry in the SMA. These measurements were later compared with the intraoperative DCS and neurological findings. RESULTS: Functional MR imaging showed greater activation and dominance of the SMA in the lesioned hemisphere in patients who exhibited no motor or language dysfunction during DCS. In addition, patients with the highest activation of the SMA in the lesioned hemisphere for language and motor tests showed stronger coupling of this region with ipsilateral motor and language networks. In contrast, activation in the nonlesioned hemisphere did not correspond with DCS results. CONCLUSIONS: The authors' findings demonstrate the necessity of activation in the vicinity of the lesioned SMA for functional compensation in motor and language tasks. It is possible that more effective functional coupling of the SMA with motor and language areas in the same hemisphere prevents dysfunctions following surgical intervention. Importantly, fMR imaging activation in the unaffected SMA was not sufficient for development of functional compensation and, if anything, indicated decompensation.

Glioblastoma multiforme, a neoplasm with variable histological and biological features, is characterized by diverse imaging features, including highly heterogeneous enhancement. This reflects variable disruption of the blood brain barrier and inherent differences in the vascularity of the tumor. Experience in treating malignant glioma with antiangiogenic drugs is growing, and the most commonly used, in combination with irinotecan or other cytotoxic agents as salvage therapy, is bevacizumab, a monoclonal antibody against vascular endothelial growth factor.A 42-year-old, right-handed person with recurrent glioblastoma multiforme presented with two synchronous foci of recurrent disease in follow-up: one area with enhancement and another one nonenhancing and infiltrative, which responded differently to treatment with bevacizumab and irinotecan. Our example demonstrates the heterogeneous nature of glioblastoma multiforme and is proof of principle for antiangiogenic treatment in selected enhancing, presumably angiogenic forms of glioblastoma multiforme. Antiangiogenic treatment may be ineffective in more infiltrative, biologically different lesions.

Amyloidoma is a term referring to a tumor-like deposition of extracellular insoluble fibrillar protein. Tumor-like amyloid formation in the brain had been described in isolated cases. However no advanced radiological studies to characterize these lesions have been reported. In the report, we have describe a 59-year-old woman, presented several months prior to diagnosis with memory decline, dizziness, walking instability, and speech difficulties. MRI revealed a left basal ganglia lesion with an intraventricular component. The patient underwent a stereotactic biopsy, which confirmed the diagnosis of amyloidoma, an extensive radiographic characterization of amyloidoma using advanced MR techniques was done, including magnetic resonance spectroscopy, dynamic susceptibility contrast, susceptibility weighted image (SWI), and magnetization transfer (MTR). All advanced MR techniques were able to characterize the amyloidoma as a non-neoplastic process. This is an example where such methods can be used for differential diagnosis of atypical brain lesions.

OBJECT: Orbital tumors can be divided schematically into primary lesions, originating from the orbit itself, and secondary lesions, extending to the orbit from neighboring structures. These tumors are variable in their biological nature and in their location. The authors evaluate 41 cases of benign and malignant tumors involving the orbit and discuss the surgical challenge, which involves tumor removal, preserving visual function and cosmetic reconstruction. METHODS: The authors performed a retrospective analysis of a series of all cases involving patients who underwent surgery for treatment of orbital tumors in their hospital between December 2003 and December 2006. Data were collected from the patients' files in the hospital's outpatient clinic, operative notes, and pre- and postoperative imaging studies. RESULTS: The authors identified 41 patients who met the inclusion criteria (age range 14-82 years, mean 42.2 years, standard deviation 22.4 years). The most common presenting symptoms were proptosis and/or partial ptosis (11 cases [27%]) and headache (7 cases [17%]). In 5 (12%) cases, the tumors were primary intraorbital lesions, and in 34 cases (83%) they were secondary. Two patients had metastases to the orbit. The most common lesion types were meningioma (10 cases [24%]) and osteoma (7 cases [17%]). In 24 cases a midline approach through a frontal craniotomy or a subcranial approach was used; in 13 a lateral approach was used; and in 4 a biopsy procedure was performed. Maxillectomy through a Weber-Ferguson approach or a facial degloving approach was added in 5 cases to complete tumor removal. Duration of follow-up was 1-38 months (mean 20 months). None of the patients died as a result of the procedure, and there were relatively few complications. Excluding the patients who underwent orbital exenteration, none of the patients had visual deterioration following surgery, and most had no change in their visual condition. Two patients had temporary diplopia, 1 had a cerebrospinal fluid leak, and 1 had enophthalmos following removal of an orbital osteosarcoma. CONCLUSIONS: Orbital tumors can be treated safely using transcranial approaches in many cases. Preoperative imaging can accurately define the compartments involved and the surgical approach needed for tumor removal. A multidisciplinary team of surgeons facilitates optimal tumor removal and skull base sealing as well as good cosmetic results.