Brain metastasis resection: the impact of fluorescence guidance (MetResect study)

Neurosurg Focus 55(2):E10, 2023

Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection.

METHODS Analyzing their institution’s prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences.

RESULTS In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival.

CONCLUSIONS Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Minimally invasive modification of the Goel-Harms atlantoaxial fusion technique

Neurosurg Focus 54(3):E14, 2023

The Goel-Harms atlantoaxial screw fixation technique for the treatment of atlantoaxial instability and unstable odontoid fractures is reliable and reproducible for a variety of anatomies. The drawbacks of the technique are the potential for significant bleeding from the C2 nerve root venous plexus and the risks associated with posterior midline exposure and retraction, such as pain and wound complications. The authors developed a minimally invasive surgical (MIS) modification of the Goel-Harms technique using intra-articular grafting to facilitate placement of percutaneous lateral mass and pars screws with extended tabs for minimally invasive subfascial rod placement. The objective of this study was to present the authors’ first series of 5 patients undergoing minimally invasive modification in comparison with 51 patients undergoing open atlantoaxial fusion.

METHODS A retrospective analysis of patient comorbid conditions, blood loss, length of surgery, and length of stay was performed on patients undergoing Goel-Harms instrumented fusion (GHIF) for unstable odontoid fractures performed between 2016 and 2021.

RESULTS Patients undergoing the minimally invasive procedure showed significantly less blood loss than those undergoing the open atlantoaxial fusion procedure, with a median blood loss of 30 ml compared with 150 ml using the open technique (p < 0.01). The patients showed no significant differences in length of stay (2 days for MIS vs 4 days for open atlantoaxial fusion, p = 0.25). There were no significant differences in length of surgery for MIS, but a possible trend toward increased operative duration (234 vs 151 minutes, p = 0.112).

CONCLUSIONS In this small pilot study, it was shown that MIS-GHIF can be performed with decreased blood loss in atlantoaxial instability and odontoid fractures. This technique may allow for greater and safer application of the procedure in the elderly and infirm.


Intraoperative confocal laser endomicroscopy: prospective in vivo feasibility study of a clinical-grade system for brain tumors

J Neurosurg 138:587–597, 2023

The authors evaluated the feasibility of using the first clinical-grade confocal laser endomicroscopy (CLE) system using fluorescein sodium for intraoperative in vivo imaging of brain tumors.

METHODS A CLE system cleared by the FDA was used in 30 prospectively enrolled patients with 31 brain tumors (13 gliomas, 5 meningiomas, 6 other primary tumors, 3 metastases, and 4 reactive brain tissue). A neuropathologist classified CLE images as interpretable or noninterpretable. Images were compared with corresponding frozen and permanent histology sections, with image correlation to biopsy location using neuronavigation. The specificities and sensitivities of CLE images and frozen sections were calculated using permanent histological sections as the standard for comparison. A recently developed surgical telepathology software platform was used in 11 cases to provide real-time intraoperative consultation with a neuropathologist.

RESULTS Overall, 10,713 CLE images from 335 regions of interest were acquired. The mean duration of the use of the CLE system was 7 minutes (range 3–18 minutes). Interpretable CLE images were obtained in all cases. The first interpretable image was acquired within a mean of 6 (SD 10) images and within the first 5 (SD 13) seconds of imaging; 4896 images (46%) were interpretable. Interpretable image acquisition was positively correlated with study progression, number of cases per surgeon, cumulative length of CLE time, and CLE time per case (p ≤ 0.01). The diagnostic accuracy, sensitivity, and specificity of CLE compared with frozen sections were 94%, 94%, and 100%, respectively, and the diagnostic accuracy, sensitivity, and specificity of CLE compared with permanent histological sections were 92%, 90%, and 94%, respectively. No difference was observed between lesion types for the time to first interpretable image (p = 0.35). Deeply located lesions were associated with a higher percentage of interpretable images than superficial lesions (p = 0.02). The study met the primary end points, confirming the safety and feasibility and acquisition of noninvasive digital biopsies in all cases. The study met the secondary end points for the duration of CLE use necessary to obtain interpretable images. A neuropathologist could interpret the CLE images in 29 (97%) of 30 cases.

CONCLUSIONS The clinical-grade CLE system allows in vivo, intraoperative, high-resolution cellular visualization of tissue microstructure and identification of lesional tissue patterns in real time, without the need for tissue preparation.

Exoscope improves visualization and extent of hippocampal resection in temporal lobectomy

Acta Neurochirurgica (2023) 165:259–263

Anterior temporal lobectomy (ATL) is a safe and well-validated procedure in the treatment of temporal lobe epilepsy (TLE), but is a challenging technique to master and still confers a risk of morbidity and mortality due to the complex anatomy of the mesial temporal lobe structures. Automated robotic 3D exoscopes have been developed to address limitations traditionally associated with microscopic visualization, allowing for ergonomic, high-definition 3D visualization with hands-free control of the robot. Given the potential advantages of using such a system for visualization of complex anatomy seen during mesial structure resection in ATL, this group sought to investigate impact on the percentage of hippocampal resection in both exoscope and microscope guided procedures.

Methods We conducted a retrospective analysis of 20 consecutive patients undergoing standard ATL for treatment of medically refractory TLE at our institution. Using pre-operative and post-operative imaging, the coronal plane cuts in which either the head, body, or tail of the hippocampus appeared were counted. The number of cuts in which the hippocampus appeared were multiplied by slice thickness to estimate hippocampal length.

Results Mean percentage of hippocampal resection was 61.1 (SD 13.1) and 76.5 (SD 6.5) for microscope and exoscope visualization, respectively (p = 0.0037).

Conclusion Use of exoscope for mesial resection during ATL has provided good visualization for those in the operating room and the potential for a safe increase in hippocampal resection in our series. Further investigation of its applications should be evaluated to see if it will improve outcomes.

Frameless neuronavigation‑assisted brain biopsy with electromagnetic tracking

Acta Neurochirurgica (2022) 164:3317–3322

In recent years, thanks to several technological innovations, stereotactic cerebral biopsies have evolved from frame-based to frameless neuronavigation-assisted techniques.

Methods The authors provide herein a detailed step-by-step description of the technique, shedding light on surgical tips and how to avoid complications. The practical application of the technique is demonstrated with a high-quality video.

Conclusion The neuronavigation-assisted brain biopsy with electromagnetic tracking is a “true frameless” procedure. It represents a simple, safe, and effective innovation for frameless biopsy of cerebral lesions. This technique is time efficient, offering a high degree of accuracy required for the establishment of a definitive diagnosis, enabling optimal further treatment, and thus improving patient outcome.

Technical Assessment of Microvascular Decompression for Trigeminal Neuralgia Using a 3-Dimensional Exoscope

Operative Neurosurgery 23:374–381, 2022

Detailed anatomic visualization of the root entry zone of the trigeminal nerve is crucial to successfully perform microvascular decompression surgery (MVD) in patients with trigeminal neuralgia.

OBJECTIVE: To determine advantages and disadvantages using a 3-dimensional (3D) exoscope for MVD surgery.

METHODS: A 4K 3D exoscope (ORBEYE) was used by a single surgical team for MVD in a retrospective case series of 8 patients with trigeminal neuralgia in a tertiary center. Clinical and surgical data were collected, and advantages/disadvantages of using the exoscope for MVD were recorded after each surgery. Descriptive statistics were used to summarize the data.

RESULTS: Adequate MVD of the trigeminal nerve root was possible in all patients by exclusively using the exoscope. It offered bright visualization of the cerebellopontine angle and the root entry zone of the trigeminal nerve that was comparable with a binocular operating microscope. The greatest advantages of the exoscope included good optical quality, the pronounced depth of field of the image for all observers, and its superior surgeon ergonomics. Disadvantages were revealed with overexposure at deep surgical sites and the lack of endoscope integration. In 6 patients, facial pain improved significantly after surgery (Barrow Neurological Institute pain intensity score I in 5 and III in 1 patient), whereas it did not in 2 patients (Barrow Neurological Institute score IV and V). No complications occurred.

CONCLUSION: Utilization of a 3D exoscope for MVD is a safe and feasible procedure. Surgeons benefit from better ergonomics, excellent image quality, and an improved experience for observers.

Double dose of 5-aminolevulinic acid and its effect on protoporphyrin IX accumulation in low-grade glioma

J Neurosurg 137:943–952, 2022

Administration of 5-aminolevulinic acid (5-ALA) does not regularly elicit fluorescence in low-grade glioma (LGG) at currently established doses and timing of administration. One explanation may be differences in blood-brain barrier (BBB) integrity compared to high-grade glioma. The authors hypothesized that for a BBB semipermeable to 5-ALA there might be a relationship between plasma 5-ALA concentration and its movement into the brain. A higher dose would elicit more 5-ALA conversion into protoporphyrin IX (PPIX). The authors present a case series of patients harboring LGG who received higher doses of 5-ALA.

METHODS Patients undergoing surgery for indeterminate glioma later diagnosed as LGG were included in this study. 5-ALA was administered at a standard dose of 20 mg/kg body weight (bw) 4 hours prior to induction of anesthesia. A subgroup of patients received a higher dose of 40 mg/kg bw. Fluorescence was evaluated visually and PPIX concentration (cPPIX) was determined ex vivo by hyperspectral measurements in freshly extracted tissue. All adverse events were recorded.

RESULTS A total of 23 patients harboring diffuse low-grade astrocytomas (n = 19) and oligodendrogliomas (n = 4) were analyzed. Thirteen patients received 20 mg/kg bw, and 10 patients received 40 mg/kg bw of 5-ALA. In the 20 mg/ kg group, 30.8% (4 of 13) of tumors harbored areas of visible fluorescence, compared to 60% of cases (n = 6 of 10) with 40 mg/kg bw. The threshold to visibility was 1 μg/ml in both groups. Measured over all biopsies, the mean cPPIX was significantly higher in the double-dose group (1.8 vs 0.45 μg/ml; p < 0.001). In non–visibly fluorescent tissue the mean cPPIX was 0.146 μg/ml in the 20 mg/kg and 0.347 μg/ml in the 40 mg/kg group, indicating an increase of 138% (p < 0.001).

CONCLUSIONS These observations demonstrate different regions with different levels of PPIX accumulation in LGG. With higher 5-ALA doses cPPIX increases, leading to more regions surpassing the visibility threshold of 1 μg/ml. These observations can be explained by the fact that the BBB in LGG is semipermeable to 5-ALA. Higher 5-ALA doses result in more PPIX conversion, an observation with implications for future dosing in LGG.

The Evolution of 5-Aminolevulinic Acid Fluorescence Visualization: Time for a Headlamp/Loupe Combination

The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy.

METHODS: We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope.

RESULTS: We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope. –

CONCLUSIONS: Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent guided glioma resection

Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system

J Neurosurg 136:323–334, 2022

Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort.

METHODS Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21–71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters).

RESULTS The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2   2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator.

CONCLUSIONS The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.


Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma

J Neurosurg 136:9–15, 2022

5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA–induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence.

METHODS Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)–based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18 F-fluoroethyl-l-tyrosine ( 18 F-FET) PET values and their role for predicting fluorescence were evaluated.

RESULTS Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18 F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18 F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence.

CONCLUSIONS This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18 F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.

Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation

Acta Neurochirurgica (2021) 163:3501–3514

The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures.

Methods Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome.

Results Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%).

Conclusions Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

Fluorescence Guidance and Intraoperative Adjuvants to Maximize Extent of Resection

Neurosurgery 89:727–736, 2021

Safely maximizing extent of resection has become the central goal in glioma surgery. Especially in eloquent cortex, the goal of maximal resection is balanced with neurological risk. As new technologies emerge in the field of neurosurgery, the standards for maximal safe resection have been elevated.

Fluorescence-guided surgery, intraoperative magnetic resonance imaging, and microscopic imaging methods are among the most well-validated tools available to enhance the level of accuracy and safety in glioma surgery. Each technology uses a different characteristic of glioma tissue to identify and differentiate tumor tissue from normal brain and is most effective in the context of anatomic, connectomic, and neurophysiologic context. While each tool is able to enhance resection, multiple modalities are often used in conjunction to achieve maximal safe resection.

This paper reviews the mechanism and utility of the major adjuncts available for use in glioma surgery, especially in tumors within eloquent areas, and puts forth the foundation for a unified approach to how leverage currently available technology to ensure maximal safe resection.

Intraoperative surveillance of the vertebral artery using indocyanine green angiography and Doppler sonography in craniovertebral junction surgeries

Neurosurg Focus 50 (1):E5, 2021

The authors sought to evaluate the usefulness of indocyanine green (ICG) angiography and Doppler sonography for monitoring the vertebral artery (VA) during craniovertebral junction (CVJ) surgery and compare the incidence of VA injury (VAI) between the groups with and without the monitoring of VA using ICG angiography and Doppler sonography.

METHODS In total, 344 consecutive patients enrolled who underwent CVJ surgery. Surgery was performed without intraoperative VA monitoring tools in 262 cases (control group) and with VA monitoring tools in 82 cases (monitoring group). The authors compared the incidence of VAI between groups. The procedure times of ICG angiography, change of VA flow velocity measured by Doppler sonography, and complication were investigated.

RESULTS There were 4 VAI cases in the control group, and the incidence of VAI was 1.5%. Meanwhile, there were no VAI cases in the monitoring group. The procedure time of ICG angiography was less than 5 minutes (mean [± SD] 4.6 ± 2.1 minutes) and VA flow velocity was 11.2 ± 4.5 cm/sec. There were several cases in which the surgical method had to be changed depending on the VA monitoring. The combined use of ICG angiography and Doppler sonography was useful not only to monitor VA patency but also to assess the quality of blood flow during CVJ surgery, especially in the high-risk group of patients.

CONCLUSIONS The combined use of ICG angiography and Doppler sonography enables real-time intraoperative monitoring of the VA by detecting blood flow and flow velocity. As the arteries get closer, they provide auditory and visual feedback to the surgeon. This real-time image guidance could be a useful tool, especially for high-risk patients and inexperienced surgeons, to avoid iatrogenic VAI during any CVJ surgery.

Intraoperative MRI–based elastic fusion for anatomically accurate tractography of the corticospinal tract

Neurosurg Focus 50 (1):E9, 2021

Tractography is a useful technique that is standardly applied to visualize subcortical pathways. However, brain shift hampers tractography use during the course of surgery. While intraoperative MRI (ioMRI) has been shown to be beneficial for use in oncology, intraoperative tractography can rarely be performed due to scanner, protocol, or head clamp limitations. Elastic fusion (EF), however, enables adjustment for brain shift of preoperative imaging and even tractography based on intraoperative images. The authors tested the hypothesis that adjustment of tractography by ioMRI-based EF (IBEF) correlates with the results of intraoperative neuromonitoring (IONM) and clinical outcome and is therefore a reliable method.

METHODS In 304 consecutive patients treated between June 2018 and March 2020, 8 patients, who made up the basic study cohort, showed an intraoperative loss of motor evoked potentials (MEPs) during motor-eloquent glioma resection for a subcortical lesion within the corticospinal tract (CST) as shown by ioMRI. The authors preoperatively visualized the CST using tractography. Also, IBEFs of pre- and intraoperative images were obtained and the location of the CST was compared in relation to a subcortical lesion. In 11 patients (8 patients with intraoperative loss of MEPs, one of whom also showed loss of MEPs on IBEF evaluation, plus 3 additional patients with loss of MEPs on IBEF evaluation), the authors examined the location of the CST by direct subcortical stimulation (DSCS). The authors defined the IONM results and the functional outcome data as ground truth for analysis.

RESULTS The maximum mean ± SD correction was 8.8 ± 2.9 (range 3.8–12.0) mm for the whole brain and 5.3 ± 2.4 (range 1.2–8.7) mm for the CST. The CST was located within the lesion before IBEF in 3 cases and after IBEF in all cases (p = 0.0256). All patients with intraoperative loss of MEPs suffered from surgery-related permanent motor deficits. By approximation, the location of the CST after IBEF could be verified by DSCS in 4 cases.

CONCLUSIONS The present study shows that tractography after IBEF accurately correlates with IONM and patient outcomes and thus demonstrates reliability in this initial study.

Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study

Neurosurgery 88 (1) 2021: 63–73,

Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas.

OBJECTIVE: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas.

METHODS: Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS.

RESULTS: A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P < .001) and PFS (P = .01) than astrocytomas. Multivariate analyses demonstrated improved OS for gross total resection (GTR) vs subtotal resection (STR; P = .006, hazard ratio [HR]: .23) and near total resection (NTR; P = .02, HR: .64). GTR vs STR (P = .02, HR: .54), GTR vs NTR (P = .04, HR: .49), and iMRI use (P = .02, HR: .54) were associated with longer PFS. Frontal (P = .048, HR: 2.11) and occipital/parietal (P = .003, HR: 3.59) locations were associated with shorter PFS (vs temporal). Kaplan-Meier analyses showed longer OS with increasing extent of surgical resection (EOR) (P=.03) and 1p/19q gene deletions (P=.02). PFS improved with increasing EOR (P = .01), GTR vs NTR (P = .02), and resections above STR (P = .04). Factors influencing adjuvant treatment (35.3% of patients) included age (P=.002, odds ratio [OR]: 1.04) and EOR (P=.003,OR: .39) but not glioma subtype or location. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these instances.

CONCLUSION: EOR is a major determinant of OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS.

Intraoperative CT and cone-beam CT imaging for minimally invasive evacuation of spontaneous intracerebral hemorrhage

Acta Neurochirurgica (2020) 162:3167–3177

Minimally invasive surgery (MIS) for evacuation of spontaneous intracerebral hemorrhage (ICH) has shown promise but there remains a need for intraoperative performance assessment considering the wide range of evacuation effectiveness. In this feasibility study, we analyzed the benefit of intraoperative 3-dimensional imaging during navigated endoscopyassisted ICH evacuation by mechanical clot fragmentation and aspiration.

Methods 18 patients with superficial or deep supratentorial ICH underwent MIS for clot evacuation followed by intraoperative computerized tomography (iCT) or cone-beamCT (CBCT) imaging. Eligibility for MIS required (a) availability of intraoperative iCT or CBCT, (b) spontaneous lobar or deep ICH without vascular pathology, (c) a stable ICH volume (20–90 ml), (d) a reduced level of consciousness (GCS 5–14), and (e) a premorbid mRS ≤ 1. Demographic, clinical, and radiographic patient data were analyzed by two independent observers.

Results Nine female and 9 male patients with a median age of 76 years (42–85) presented with an ICH score of 3 (1–4), GCS of 10 (5–14) and ICH volume of 54 ± 26 ml. Clot fragmentation and aspiration was feasible in all cases and intraoperative imaging determined an overall evacuation rate of 80 ± 19% (residual hematoma volume: 13 ± 17 ml; p < 0.0001 vs. Pre-OP).Based on the intraoperative imaging results, 1/3rd of all patients underwent an immediate re-aspiration attempt. No patient experienced hemorrhagic complications or required conversion to open craniotomy. However, routine postoperative CT imaging revealed early hematoma re-expansion with an adjusted evacuation rate of 59 ± 30% (residual hematoma volume: 26 ± 37 ml; p < 0.001 vs. Pre-OP).

Conclusions Routine utilization of iCTor CBCT imaging in MIS for ICH permits direct surgical performance assessment and the chance for immediate re-aspiration, which may optimize targeting of an ideal residual hematoma volume and reduce secondary revision rates.

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas

J Neurosurg 133:1324–1331, 2020

Maximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression- free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.

METHODS A total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.

RESULTS One hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).

CONCLUSIONS Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.


Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases

J Neurosurg 133:1032–1043, 2020

Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort.

METHODS Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria.

RESULTS Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well.

CONCLUSIONS In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

Pure Apraxia of Speech After Resection Based in the Posterior Middle Frontal Gyrus

Neurosurgery DOI:10.1093/neuros/nyaa002

Apraxia of speech is a disorder of articulatory coordination and planning in speech sound production. Its diagnosis is based on deficits in articulation, prosody, and fluency. It is often described concurrent with aphasia or dysarthria, while pure apraxia of speech is a rare entity.

CLINICAL PRESENTATION: A right-handed man underwent focal surgical resection of a recurrent grade III astrocytoma in the left hemisphere dorsal premotor cortex located in the posterior middle frontal gyrus. After the procedure, he experienced significant longterm speech production difficulties. A battery of standard and custom language and articulatory assessments were administered, revealing intact comprehension and naming abilities, and preserved strength in orofacial articulators, but considerable deficits in articulatory coordination, fluency, and prosody—consistent with diagnosis of pure apraxia of speech. Tractography and resection volumes compared with publicly available imaging data from the Human Connectome Project suggest possible overlap with area 55b, an under-recognized language area in the dorsal premotor cortex and has white matter connectivity with the superior longitudinal fasciculus.

CONCLUSION: The case reported here details a rare clinical entity, pure apraxia of speech resulting from resection of posterior middle frontal gyrus. While not a classical language area, emerging literature supports the role of this area in the production of fluent speech, and has implications for surgical planning and the general neurobiology of language.


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

Acta Neurochirurgica (2020) 162:1871–1878

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 ofXT to be used for themore 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 XTwas 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.

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