Validation of 3D fluoroscopy for image-guidance registration in depth electrode implantation for medically refractory epilepsy.

BACKGROUND: Frame registration is a critical step to ensure accurate electrode placement in stereotactic procedures such as stereoelectroencephalography (SEEG) and is routinely done by merging a computed tomography (CT) scan with the preoperative magnetic resonance (MR) examination. Three-dimensional fluoroscopy (XT) has emerged as a method for intraoperative electrode verification following electrode implantation and more recently has been proposed as a registration method with several advantages. METHODS: We compared the accuracy of SEEG electrode placement by frame registration with CT and XT imaging by analyzing the Euclidean distance between planned and post-implantation trajectories of the SEEG electrodes to calculate the error in both the entry (EP) and target (TP) points. Other variables included radiation dose, efficiency, and complications. RESULTS: Twenty-seven patients (13 CT and 14 XT) underwent placement of SEEG electrodes (319 in total). The mean EP and TP errors for the CT group were 2.3 mm and 3.3 mm, respectively, and 1.9 mm and 2.9 mm for the XT group, with no statistical difference (p = 0.75 and p = 0.246). The time to first electrode placement was similar (XT, 82 ± 10 min; CT, 84 ± 22 min; p = 0.858) and the average radiation exposure with XT (234 ± 55 mGy*cm) was significantly lower than CT (1245 ± 123 mGy*cm) (p < 0.0001). Four complications were documented with equal incidence in both groups. CONCLUSIONS: The use of XT as a method for registration resulted in similar implantation accuracy compared with CT. Advantages of XT are the substantial reduction in radiation dose and the elimination of the need to transfer the patient out of the room which may have an impact on patient safety and OR efficiency.

The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery.

BACKGROUND: Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability of XT to be used for the more crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation. METHODS: Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration. RESULTS: Forty-one patients underwent DBS surgery-25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XT was not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518). CONCLUSION: XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.

Resection of central nervous system lymphoma: a paradigm shift?

Central nervous system lymphomas (CNSL) are traditionally regarded as non-surgically treated tumors with a poor prognosis. Usually, only stereotactic biopsy is performed to establish the diagnosis, and most patients show disease progression within half a year. A recent study questioned this view, since patients who had surgical resection of CNSL manifestations prior to adjuvant therapy reportedly had a better outcome than patients who had biopsy only. We performed a retrospective analysis of our patient database to identify patients with CNSL who had undergone "accidental" tumor removal in our department between 2002 and 2013. Four patients had CNSL specific therapy following surgery. One patient received no further therapy because of his bad clinical status. Five patients with CNSL were treated surgically. Three patients were in complete remission at nine, thirteen and 45 months postoperatively, while two others had disease progression at 45 months, respectively. The median survival was 22.6 months. Gross total removal of CNSL may improve outcome. We present a series of five patients who had surgical resection of CNSL. While the importance of chemotherapy is beyond doubt, more data on the effect of surgery on the prognosis of patients with CNSL are needed. However, the paradigm of medical treatment only for CNSL is being challenged.

Benefit and Complications of Frame-Based Stereotactic Biopsy in Old and Very Old Patients.

OBJECTIVE: Stereotactic biopsy is an everyday procedure implemented in numerous neurosurgical departments. The procedure is performed to obtain tumor tissue of unclear diagnosis. Going in hand with low complication rates and high diagnostic yield, stereotactic biopsies can be performed in adults and children likewise for histopathologic evaluation of lesions in eloquent localizations. However, little is known about whether aged patients do benefit from stereotactic biopsy or rather the therapy that is derived from histopathologic results. In this study, we therefore focused on old (80-84 years) and very old patients (85 years and older) to evaluate whether stereotactic biopsy should be performed leading to further therapy. We also assessed the complication rates of the procedure in this aged population. METHODS: We performed a retrospective analysis of our database and included all patients older than 80 years who underwent stereotactic biopsy at our department from October 2005 until May 2016. Forty-seven patients were included in this study. These patients were divided into 2 subgroups: group 1 consisted of patients from 80 to 84 years old and group 2 of patients aged 85 years and older. All patients underwent stereotactic biopsy to establish histopathologic diagnosis. We excluded patients who underwent cyst puncture or puncture of a hemorrhage because the procedure was not performed for diagnostic purposes. We assessed gender, neuroradiologic diagnosis, Karnofsky Performance Score (KPS), number of tissue samples taken, histopathologic diagnosis, localization, postoperative hemorrhage, modality of anesthesia anticoagulation, and further therapy. RESULTS: Group 1 consisted of 34 patients and group 2 of 13 patients. KPS was 80 and 70, respectively. A histopathologic diagnosis was possible in all but 1 patient. In group 1, 61.8% of the patients agreed to further postoperative therapy (radiation, 35.3%; chemotherapy, 11.8%; combined radiochemotherapy, 11.8%; complication that prevented therapy, 2.9%), as did 53.8% of the patients in group 2 (resection, 7.7%; radiation, 15.4%; combined radiochemotherapy, 30.7%). In group 1, 38.2% declined further therapy, as did 64.1% in group 2. CONCLUSIONS: Also in old and very old patients, a final histopathologic diagnosis should be established to provide adequate therapy. Our data show that most of these aged patients want to be treated.

General Anesthesia Versus Local Anesthesia in Stereotactic Biopsies of Brain Lesions: A Prospective Randomized Study.

BACKGROUND: Stereotactic biopsy of brain lesions with unknown entities is a common neurosurgical procedure to obtain tumor tissue. Pathologists can then provide an exact diagnosis on which further therapy, such as resection, radiotherapy, or chemotherapy, can be based. These procedures can be performed under local or general anesthesia. In this prospective study, we aim to show whether stress levels are higher for patients who undergo stereotactic biopsy under local or general anesthesia. METHODS: Between January 2013 and December 2014, we screened 157 patients. Of these, 43 were included and evaluated in this study. Twenty-one patients gave their written consent and were randomized for either local or general anesthesia. A Post Traumatic Stress Score (PTSS) questionnaire was filled out by the patients preoperatively and postoperatively. Also, patients who did not agree to randomization had an opportunity to fill out the PTSS questionnaire. Twenty-two patients agreed only to fill out the stress-level questionnaire but refused randomization. These patients were evaluated as a subgroup. Scores achieved in the PTSS were compared by using the Fisher exact test. RESULTS: Among the randomized patients, 9 underwent the procedure under local anesthesia and 12 under general anesthesia. Median PTSS was 24 preoperatively in the patients who received local anesthesia versus 20 among the patients with general anesthesia (P = 0.37; Fisher exact test). Postoperatively, PTSS was 29.5 in median for patients with local anesthesia versus 23 for patients with general anesthesia (P = 0.30; Fisher exact test). Postoperatively, the PTSS showed a median increase of 5.5 points in the LA and 3 points in the GA group (P = 0.87; Fisher exact test). P values of 0.05 and lower were considered statistically significant. CONCLUSIONS: The willingness of patients to undergo randomization in this setting was low (13.3%). Within this highly selective group of patients, there was no significant difference for stress levels in patients who underwent stereotactic biopsy under local anesthesia versus general anesthesia. However, median values indicate a trend for higher stress-level values for patients undergoing local anesthesia.

Oblique Positioning of the Stereotactic Frame for Biopsies of Cerebellar and Brainstem Lesions.

BACKGROUND: Frame-based stereotactic biopsy has proven to be a safe procedure with a high diagnostic yield for patients. Different supratentorial localizations can easily be accessed by standardized stereotactic approaches. Cerebellar and brainstem lesions, however, are not easy to reach because the positioning of the frame pins often makes it impossible to address the entry point properly. METHODS: By oblique positioning of the frame, cerebellar and brainstem lesions also can easily be accessed to take tissue samples. CONCLUSION: Modification of the standardized positioning of the frame allows for safe and straightforward stereotactic access even to cerebellar and brainstem lesions.

Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma.

OBJECTIVES: To investigate the relevance of bevacizumab (BEV)-induced diffusion-restricted lesions and T1-hyperintense lesions in patients with recurrent glioblastoma. METHODS: We prospectively screened 74 BEV-treated patients with recurrent glioblastoma for (1) diffusion-restricted lesions and/or, (2) lesions with a hyperintense signal on precontrast T1-weighted images. We further evaluated overall survival (OS), histopathology of the lesions, and patterns of progression. RESULTS: Twenty-five of 74 patients (34%) developed T1-hyperintense lesions, whereas diffusion-restricted lesions could be detected in 35 of 74 patients (47%). In 21 of 74 patients (28%), the lesions displayed both features ("double-positive"). OS for patients with double-positive lesions was 13.0 months; patients with neither of these lesions had an OS of 6.6 months (p < 0.005). Histologic evaluation of double-positive lesions revealed extensive calcified necrosis in 4 of 4 patients. Notably, these double-positive lesions were rarely involved in further tumor progression. However, they were associated with an increase in distant recurrences at BEV failure. CONCLUSIONS: BEV-induced double-positive MRI lesions are a predictive imaging marker associated with a substantial survival benefit and with improved local control in patients with recurrent glioblastoma. Our data suggest that these lesions are the result of a sustained focal antitumor activity of BEV.

Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies.

BACKGROUND: In nonresectable glioblastoma (GBM), stereotactic biopsies are performed to retrieve tissue for diagnostic purposes. The analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation adds prognostic and predictive information. OBJECTIVES: The aim of the study was to detect confounding factors that limit the number of conclusive MGMT promoter methylation results. METHODS: We analyzed 71 consecutive GBM patients undergoing stereotactic biopsy on whom MGMT analysis was performed by methylation-specific polymerase chain reaction. Specimens were correlated to imaging by coregistration and prospective documentation of biopsy localization. Our findings were validated in an additional 62 GBM stereotactic biopsies. RESULTS: Our results demonstrate that the best MGMT promoter methylation results were obtained from samples (n = 71) taken in a tangential manner from tumor areas showing contrast enhancement in magnetic resonance imaging. In the additional validation series of 62 stereotactically biopsied GBM, we were able to increase the rate of conclusive MGMT promoter methylation results from 76.1 to 85.48% by strictly planning the route of biopsy in a tangential manner if possible. CONCLUSIONS: These results underline that within the contrast-enhanced tumor part, choosing the trajectory in a tangential manner increases the diagnostic yield for conclusive MGMT promoter methylation analyses in stereotactic biopsies as a basis for patient stratification and individualized therapy.

Benefit of tumor resection for recurrent glioblastoma.

In the treatment of glioblastoma (GBM) the impact of radical tumor resection as first line therapy is beyond controversy. The significance of a second resection in case of tumor-recurrence remains unclear and is an issue of debate. Since GBMs always recur, it is important to determine whether or not patients will benefit from repeat surgery. We performed a retrospective analysis of our prospectively collected database and evaluated all re-resected patients with primary GBM who underwent second surgery during a 3 years period. All patients underwent early postoperative magnetic resonance imaging. We determined survival after re-resection with regard to possible prognostic factors using Kaplan-Meier estimates and Cox regression analyses. Forty patients were included in this study. Median age was 58 years and median KPS score was 80. Average tumor volume was 5.5 cm(3). A radiologically confirmed complete resection was achieved in 29 patients (72.5 %). Median follow-up was 18.8 months, and median survival after re-resection was 13.5 months. Only complete removal of contrast enhancing tumor was significantly correlated with survival after re-resection according to multivariate analysis. There was a statistical trend for KPS score influencing survival. In contrast, time between first diagnosis and tumor-recurrence, tumor volume at recurrence, MGMT status and MSM score were not significantly correlated with survival after second surgery. In the event of tumor recurrence, patients in good clinical condition with recurrent GBM amenable to complete resection should thus not be withheld second surgery as a treatment option.

Accuracy of 3D fluoroscopy in cranial stereotactic surgery: a comparative study in phantoms and patients.

BACKGROUND: To assess the precision and accuracy of 3D fluoroscopy (XT) in phantoms and patients compared to computed tomography (CT) in localizing stereotactic probes. METHODS: Approval was obtained from the institutional research ethics board. The prospective phantom study was compared to a retrospective patient cohort. Accuracy was assessed by the mean error and precision by the mean dispersion between XT and CT with a cubic or a skull phantom containing metallic spheres installed on plates or along trajectories. Significance was assessed by Friedman's and Levene's test. Secondary endpoints were Euclidean error, other influences e.g. installed frame and radiation exposure. RESULTS: A total of 3,342 distances were assessed in 17 XT and 13 CT phantom scans. The cubic phantom showed mean distance errors of 0.33 mm (SD + -0.46 mm) for XT compared to 0.19 mm (SD + -0.83 mm) for CT scans (p = 0.0004) and a dispersion of 0.22 mm (XT) and 0.70 mm (CT). The dispersion was 0.36 mm with and 0.63 mm without a stereotactic frame (p < 0.0001). The mean Euclidean error was 0.72 mm (SD + -0.59 mm) in the skull phantom and 1.34 mm (SD + -0.82 mm) in the patient cohort. The effective dose was 0.65 mSv for the XT and 1.12 mSv for the CT. CONCLUSIONS: The accuracy of XT imaging in phantoms revealed a slightly lower accuracy but higher precision than the CT. The overall accuracy of XT was higher than that of the stereotactic frame allowing stereotactic localization with about half of the effective dose of a CT-scan.

Correlation of active contact positions with the electrophysiological and anatomical subdivisions of the subthalamic nucleus in deep brain stimulation.

BACKGROUND: The most effective contacts in subthalamic nucleus (STN) deep brain stimulation are reported to be dorsolateral, and suppression of synchronized oscillatory activity might be a mechanism of action. OBJECTIVES: To analyze the optimal contact position in regard to the anatomical and electrophysiological position and to determine whether oscillatory and bursty activity is more frequent around the active contact. METHODS: In 21 patients, the clinically most effective contacts were analyzed according to their relative position to the anatomical and electrophysiological STN center, which was assessed by T2-weighted MRI and microrecording. In 12 out of 21 consecutive patients, autocorrelograms of the action potentials within the vicinity of the active contact were compared to the most ventromedial reference contact. RESULTS: The isocenter of the anatomical and electrophysiological STN had a mean deviation of 0.8 mm (SD 1.45). Thirty-two out of 42 active contacts were found dorsal to the anatomical isocenter of the STN. None of the active contacts were ventral to the STN. Synchronized oscillatory or bursty activity was found in 67% of the patients within the vicinity of the active contact. In 64% of the patients, the ventromedial reference contact showed irregular activity. CONCLUSIONS: Synchronized activity in the autocorrelogram correlates with the most effective contact. The optimal localization of the finally stimulated contact is dorsal to the STN isocenter.

Efficacy and safety of local versus general anesthesia in stereotactic biopsies: a matched-pairs cohort study.

BACKGROUND: Frame-based stereotactic biopsies remain the gold standard for the diagnosis of intracerebral lesions. A major advantage is the ability to perform these procedures under local anesthesia (LA). However, there is no consensus on whether or when to use LA or general anesthesia (GA). It has been postulated that the use of LA may reduce the risk of complications. This study aims to objectify the efficacy and safety of stereotactic biopsies under LA versus GA by analyzing a prospective registry for stereotactic biopsies. METHODS: A prospective registry for stereotactic procedures was analyzed for the activities performed between May 2009 and August 2011. Inclusion criteria were patients undergoing a stereotactic biopsy. Patients with functional stereotactic procedures, cyst or abscess evacuation, and children were excluded. Of the remaining 274 patients, 204 could be randomly matched considering sex, age, American Society of Anesthesiologists (ASA) classification, and type of hospitalization. The primary endpoint was the diagnostic yield. Secondary endpoints were safety and procedural time intervals. RESULTS: Ninety-six percent of diagnosis was achieved in the LA group and 94% within the GA group. There was no significant difference in the overall complication rate. However, the rate of pulmonary complications was higher in the GA group (P=0.059). The rate of bleeding was significantly higher in the LA group (P=0.003) intraoperatively. However, no significant difference was found clinically or on routine postoperative computed tomography scan reports. There was a significant reduction in the time spent in the operating room within the LA group (P<0.001). CONCLUSIONS: The type of anesthesia may not interfere with the diagnostic yield in stereotactic biopsies. Patients operated under LA are less likely to suffer pulmonary complications. Furthermore, LA could spare hospital resources in this setting.

Postoperative MRI examinations in patients treated by deep brain stimulation using a non-standard protocol.

BACKGROUND: MRI in patients bearing deep brain stimulation (DBS) electrodes may induce cerebral lesions due to electrode heating. To avoid neurological deficits related to MRI, post-operative MRI protocol was installed in our institution. However, our protocol comprised a higher specific absorption rate (SAR) and different positioning of lead excess than the later released electrode manufacturer's guidelines. The objective was to evaluate the safety using this protocol. METHODS: Between January 2000 and May 2008, post-operative MRI was performed in all patients. In selected patients, additional MRI scans were performed with the implanted generator. MRI was acquired at 1.5 T with a RF transmit/receive head coil comprising a T2-weighted fast spin echo (FSE) and a T1-weighted inversion recovery FSE sequence. Local cranial SAR values measured up to 0.9 W/kg compared to the manufacturer's recommendation of 0.1 W/kg. Initial scans (1-7 days after surgery) were performed with externalized leads, long-term scans (>30 days after surgery) with a connected generator. New neurological deficits were assessed before and after MRI. Additional MRIs were compared to the initial postoperative MRI with emphasis on new lesions. RESULTS: In 211 patients, 243 MRIs were performed, including 212 initial post-operative MRI. In 12% (n = 24), 31 additional MRI examinations for various clinical reasons were achieved. No patients demonstrated new neurological deficits during or after MRI acquisitions. CONCLUSIONS: No complications were observed using this MRI protocol in DBS patients. Our results suggest that, within this setting, higher SAR values may be feasible for DBS patients than in the manufacturer's guidelines.