Minimally Invasive Surgery of Deep-Seated Brain Lesions Using Tubular Retractors and Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging Tractography Guidance: The Minefield Paradigm

Operative Neurosurgery 24:656–664, 2023

Surgical treatment of deep-seated brain lesions is a major challenge for neurosurgeons. Recently, tubular retractors have been used to help neurosurgeons in achieving the targeting and resection of deep lesions.

OBJECTIVE: To describe a novel surgical approach based on the combination of tubular retractors and preoperative mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging (DTI) tractography for the safe resection of deep-seated lesions.

METHODS: Ten consecutive patients affected by deep-seated brain lesions close to eloquent motor/language/visual pathways underwent preoperative nTMS mapping of motor/language cortical areas and nTMS-based DTI tractography of adjacent eloquent white matter tracts, including optic radiations. The nTMS-based information was used to plan the optimal surgical trajectory and to guide the insertion of tubular retractors within the brain parenchyma without causing injury to the eloquent cortical and subcortical structures. After surgery, all patients underwent a new nTMS-based DTI tractography of fascicles close to the tumor to verify their structural integrity.

RESULTS: Gross total resection was achieved in 8 cases, subtotal resection in 1 case, and a biopsy in 1 case. No new postoperative deficits were observed, except in 1 case where a visual field defect due to injury to the optic radiations occurred. Postoperative nTMS-based DTI tractography showed the integrity of the subcortical fascicles crossed by tubular retractors trajectory in 9 cases.

CONCLUSION: The novel strategy combining tubular retractors with functional nTMS-based preoperative mapping enables a safe microsurgical resection of deep-seated lesions through the preservation of eloquent cortical areas and subcortical fascicles, thus reducing the risk of new permanent deficits.

Predictive factors for post operative seizures following meningioma resection in patients without preoperative seizures: a multicenter retrospective analysis

Acta Neurochirurgica (2023) 165:1333–1343

Meningiomas are the most common primary brain tumor and represent 35% of all intracranial neoplasms. However, in the early post-operative period approximate 3–5% of patients experience an acute symptomatic seizure. Establishing risk factors for postoperative seizures will identify those patients without preoperative seizures at greatest risk of postoperative seizures and may guide antiseizure medications (ASMs) management.

Methods Adult seizure naïve patients who underwent primary resection of a World Health Organization (WHO) Grade 1–3 meningioma at the three Mayo Clinic Campuses between 2012–2022 were retrospectively reviewed. Multivariate regression analyses were used to identify radiological, surgical, and management features with the development of new-onset seizures in patients undergoing meningioma resection.

Results Of 113 seizure naïve patients undergoing meningioma resection 11 (9.7%) experienced a new-onset post-operative seizure. Tumor volume ≥ 25 cm 3 (Odds Ratio (OR) 5.223, 95% Confidence Interval (CI) 1.546 – 17.650, p = 0.008) and cerebral convexity meningiomas (OR 4.742, 95% CI 1.255 – 14.336, p = 0.016) were most associated with new onset postoperative seizures in multivariate analysis. ASMs and corticosteroid therapies did not display a significant difference among those with and without a new onset postoperative seizure.

Conclusion In the current study, a larger tumor volume (≥ 25 cm3 ) and/or convexity meningiomas predicted the development of new onset post-operative seizures. Those who present with these factors should be counseled for their increased risk of new onset post-operative seizures and may benefit from prophylactic ASMs therapy.

Initial experience with magnetic resonance–guided focused ultrasound stereotactic surgery for central brain lesions in young adults

J Neurosurg 137:760–767, 2022

Magnetic resonance–guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown.

METHODS The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children’s Hospital in Miami, Florida, are presented. Patients 15–22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA).

RESULTS In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort.

CONCLUSIONS This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms. Clinical trial registration no.: NCT03028246


Supraorbital and mini-pterional keyhole craniotomies for brain tumors

J Neurosurg 136:1314–1324, 2022

The authors’ objective was to compare the indications, outcomes, and anatomical limits of supraorbital (SO) and mini-pterional (MP) craniotomies in patients with intra- and extraaxial brain tumors, and to assess approach selection, utility of endoscopy, and surgical field overlap.

METHODS A retrospective analysis was conducted of all brain tumor patients who underwent an SO or MP approach. The analyzed characteristics included pathology, endoscopy use, extent of resection, length of stay (LOS), and complications. On the basis of preoperative MRI data, tumor heatmaps were constructed to compare surgical access provided by both routes, including coronal projection heatmaps for parasellar tumors.

RESULTS From 2007 to 2020, 158 patients underwent 173 (84.8%) SO craniotomies and 30 patients underwent 31 (15.2%) MP craniotomies; 71 (34.8%) procedures were reoperations. Of these 204 operations, 110 (63.6%) SO and 21 (67.7%) MP approaches were for extraaxial tumors (meningiomas in 65% and 76.2%, respectively). Gliomas and metastases together represented 84.1% and 70% of intraaxial tumors accessed with SO and MP approaches, respectively. Overall, 56.1% of tumors accessed with the SO approach and 41.9% of those accessed with the MP approach were in the parasellar region. Axial projection heatmaps showed that SO access extended along the entire ipsilateral and medial contralateral anterior cranial fossa, parasellar region, ipsilateral sylvian fissure, medial middle cranial fossa, and anterior midbrain, whereas MP access was limited to the ipsilateral middle cranial fossa, sylvian fissure, lateral parasellar region, and posterior aspect of anterior cranial fossa. Coronal projection heatmaps showed that parasellar access extended further superiorly with the SO approach compared with that of the MP approach. Endoscopy was utilized in 98 (56.6%) SO craniotomies and 7 (22.6%) MP craniotomies, with further tumor resection in 48 (49%) and 5 (71.4%) cases, respectively. Endoscope-assisted tumor removal was clustered in areas that were generally at farther distances from the craniotomy or in angled locations such as the cribriform plate region where microscopic visualization is limited. Gross-total or neartotal resection was achieved in 120/173 (69%) SO approaches and 21/31 (68%) MP approaches. Major complications occurred in 11 (6.4%) SO approaches and 1 (3.2%) MP approach (p = 0.49). The median LOS decreased to 2 days in the last 2 years of the study.

CONCLUSIONS This clinical experience suggests the SO and MP craniotomies are versatile, safe, and complementary approaches for tumors located in the anterior and middle cranial fossae and perisylvian and parasellar regions. The SO route, used in 85% of cases, achieved greater overall reach than the MP route. Both approaches may benefit from expanded visualization with endoscopy.


Outcome of glioblastoma resection in patients 80 years of age and older

Acta Neurochirurgica (2022) 164:373–383

Objective To evaluate the role and possible complications of tumor resection in the management of glioblastoma (GBM) in a series of patients 80 years of age and older with review of literature.

Methods The authors retrospectively analyzed cases involving patients 80 years or older who underwent biopsy or initial resection of GBM at their hospital between 2007 and 2018. A total of 117 patients (mean age 82 years) met the inclusion criteria; 57 had resection (group A) and 60 had biopsy (group B). Functional outcomes and survival at follow-up were analyzed.

Results Group A differed significantly from group B at baseline in having betterWHO performance status, better ASA scores, more right-sided tumors, and no basal ganglia or “butterfly” gliomas. Nevertheless, 56% of group A patients had an ASA score of 3. Median survival was 9.5 months (95% CI 8–17 months) in group A, 4 months (95% CI 3.5–6 months) in group B, and 17.5 months (95% CI 12–24 months) in the 56% of group A patients treated with resection and Stupp protocol. Rates of postoperative neurologic and medical complications were almost identical in the 2 groups, but the rate of surgical site complications was substantially greater in group A (12% vs 5%). There was no significant difference in mean preoperative and postoperative KPS scores (group A).

Conclusions In selected patients 80 years or older, radical removal of GBM was associated with acceptable survival and a low perioperative complication rate which is comparable to that of a biopsy. Although the median survival of the whole group was lower than reported for younger patients, a subgroup amenable to radical surgery and Stupp protocol achieved a median survival of 17.5 months.

Tumor location and reduction in functional MRI estimates of language laterality

J Neurosurg 135:1674–1684, 2021

Brain tumors located close to the language cortex may distort functional MRI (fMRI)–based estimates of language dominance. The nature of this distortion, and whether this is an artifact of numerous confounders, remains unknown. The authors hypothesized tumor bias based on laterality estimates independent of confounders and that the effects are the greatest for tumors proximal to Broca’s area.

METHODS To answer this question, the authors reviewed more than 1113 patients who underwent preoperative fMRI to match samples on 11 known confounders (tumor location, size, type, and grade; seizure history; prior neurosurgery; aphasia presence and severity; and patient age, sex, and handedness). The samples included 30 patients with left hemisphere tumors (15 anterior and 15 posterior) and 30 with right hemisphere tumors (15 anterior and 15 posterior), thus totaling 60 patients (25 women; 18 left-handed and 4 ambidextrous; mean age 47 [SD 14.1] years). Importantly, the authors matched not only patients with left and right hemisphere tumors but also those with anterior and posterior tumors. Standard fMRI laterality indices (LIs) were calculated using whole-brain and region of interest (ROI) approaches (Broca’s and Wernicke’s areas).

RESULTS Tumors close to Broca’s area in the left hemisphere decreased LIs independently of known confounders. At the whole-brain level, this appeared to reflect a decrease in LI values in patients with left anterior tumors compared with patients with right anterior tumors. ROI analysis replicated these findings. Broca’s area LIs were significantly lower (p = 0.02) in patients with left anterior tumors (mean LI 0.28) when compared with patients with right anterior tumors (mean LI 0.70). Changes in Wernicke’s area–based LIs did not differ as a function of the tumor hemisphere. Therefore, in patients with left anterior tumors, it is essential to assess language laterality using left posterior ROIs. In all remaining tumor groups (left posterior tumors and right hemisphere tumors), language laterality derived from the anterior language ROI was the most robust measure of language dominance.

CONCLUSIONS Patients with tumors close to Broca’s area showed more bilateral fMRI language maps independent of known confounders. The authors caution against the assumption that this reduced language laterality suggests no or little risk to language function following tumor resection in the left inferior frontal gyrus. Their results address how to interpret fMRI data for neurosurgical purposes, along with theoretical questions of contralesional functional compensation and disinhibition.


Is There a Role for Surgical Resection of Multifocal Glioblastoma? A Retrospective Analysis of 100 Patients

Neurosurgery 89:1042–1051, 2021

Glioblastoma with multiple localizations (mGBMs) can be defined as multifocal, where enhancing lesions present a connection visible on magnetic resonance imaging fluid-attenuated inversion recovery imaging, or multicentric, in the absence of a clear dissemination pathway.

OBJECTIVE: To evaluate the role of the extent of resection (EOR) in the treatment of mGBMs and its correlation with overall survival (OS) and progression free survival (PFS).

METHODS: One hundred patients with mGBMs were treated at our Institution between 2009 and 2019. Clinical, radiological, and follow-up datawere collected. EOR of the contrastenhancing part of lesions was classified as gross total resection (GTR, absence of tumor remnant), subtotal resection (STR, residual tumor < 30% of the initial mass), partial resection (PR, residual tumor>30% of the initialmass), and needle or open biopsy (residual tumor > 75% of the initial mass).

RESULTS: Approximately 15% of patients underwent GTR, 14% STR, 32% PR, and 39% biopsy. Median OS was 17 mo for GTR, 11 mo for STR, 7 mo for PR, and 5 mo for biopsy. Greater EOR was associated with a significantly longer OS than biopsy. GTR and STR were associated with a longer PFS in Kaplan-Meier survival analyses. After adjusting for age, Karnofsky performance status (KPS), number of lesions, and adjunctive therapy in multivariable Cox regression analyses, GTR, STR, and PR were still associated with OS, but only GTR remained associated with PFS.

CONCLUSION: Our study suggests that EOR may positively influence survival of patients with mGBM. Surgical resection can be a reasonable option when performance and access to adjuvant treatment can be preserved.

Alterations in Functional Connectomics Associated With Neurocognitive Changes Following Glioma Resection

Neurosurgery 88,(3)2021: 544–551

Decline in neurocognitive functioning (NCF) often occurs following brain tumor resection. Functional connectomics have shown how neurologic insults disrupt cerebral networks underlying NCF, though studies involving patients with brain tumors are lacking.

OBJECTIVE: To investigate the impact of brain tumor resection upon the connectome and relationships with NCF outcome in the early postoperative period.

METHODS: A total of 15 right-handed adults with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysiswas applied to rs-fMRI connectivity matrices to calculate network properties. Network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests.Associations between pre- to postoperative change in network and NCF measures were determined with Spearman rank-order correlations (ρ).

RESULTS: A majority of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and a composite index. Regarding connectomic properties, betweenness centrality and assortativity were significantly smaller postoperatively, and reductions in these measures were associated with better NCF outcomes. Significant inverse associations (ρ = −.51 to −.78, all P < .05) were observed between change in language, executive functioning, and learning and memory, and alterations in segregation, centrality, and resilience network properties.

CONCLUSION: Decline in NCF was common shortly following resection of glioma involving eloquent brain regions, most frequently in verbal learning/memory and executive functioning. Better postoperative outcomes accompanied reductions in centrality and resilience connectomic measures.

How I do it: retrosigmoid intradural inframeatal petrosectomy

Acta Neurochirurgica (2021) 163:649–653

Lesions infiltrating the petrous temporal bone are some of the most complex to treat surgically. Many approaches have been developed in order to address these lesions, including endoscopic endonasal, anterior petrosectomy, posterior petrosectomy, and retrosigmoid.

Method We describe in a stepwise fashion the surgical steps of the retrosigmoid intradural inframeatal petrosectomy.

Conclusion The retrosigmoid intradural inframeatal petrosectomy may afford satisfactory exposure with limited drilling and minimal disruption of perilesional anatomical structures. It can provide excellent surgical results, especially for soft tumors, while minimizing surgical morbidity.

Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation

Neurosurgery 87:E338–E346, 2020

Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality- of-life (QoL) data.

OBJECTIVE: To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms.

METHODS: Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur.

RESULTS: A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors.

CONCLUSION: Results from the ongoing LAANTERN registry demonstrate that LITT stabi- lizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real- world registry and comparative to published literature.

Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients

Neurosurgery. 2019 Dec 1;85(6):762-772

Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM).

OBJECTIVE: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort.

METHODS: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines.

RESULTS: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (<70 yr, P=.02) and tumor volume (<11 cc, P=.03) were favorable prognostic factors for OS.

CONCLUSION: Themaximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patientswith nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA.

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

J Neurosurg 131:724–734, 2019

The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.

METHODS Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.

RESULTS Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.

CONCLUSIONS Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

Resection of primary motor cortex tumors

J Neurosurg 129:961–972, 2018

Brain tumors involving the primary motor cortex are often deemed unresectable due to the potential neurological consequences that result from injury to this region. Nevertheless, we have challenged this dogma for many years and used asleep, as well as awake, intraoperative stimulation mapping to maximize extent of resection. It remains unclear whether these tumors can be resected with acceptable morbidity, whether performing the surgery with the patient awake or asleep impacts extent of resection, and how stimulation mapping influences outcomes.

METHODS A retrospective chart review was performed on the senior author’s cohort to identify patients treated between 1998 and 2016 who underwent resection of tumors that were located within the primary motor cortex. Clinical notes, operative reports, and radiographic images were reviewed to identify intraoperative stimulation mapping findings and functional outcomes following tumor resection. Extent of resection was quantified volumetrically. Characteristics of patients were analyzed to identify factors associated with postoperative motor deficits.

RESULTS Forty-nine patients underwent 53 resections of tumors located primarily within the motor cortex. Stimulation mapping was performed in all cases. Positive cortical sites for motor response were identified in 91% of cases, and subcortical sites in 74%. Awake craniotomy was performed in 65% of cases, while 35% were done under general anesthesia. The mean extent of resection was 91%. There was no statistically significant difference in extent of resection in cases done awake compared with those done under general anesthesia. New or worsened postoperative motor deficits occurred in 32 patients (60%), and 20 patients (38%) had a permanent deficit. Of the permanent deficits, 14 were mild, 4 were moderate, and 2 were severe (3.8% of cases). Decreased intraoperative motor response and diffusion restriction on postoperative MRI were associated with permanent deficit. Awake motor mapping surgery was associated with increased diffusion signal on postoperative MRI.

CONCLUSIONS Resection of tumors from the primary motor cortex is associated with an increased risk of motor deficit, but most of these deficits are transient or mild and have little functional impact. Excellent extent of resection can be achieved with intraoperative stimulation mapping, suggesting that these tumors are indeed amenable to resection and should not be labeled unresectable. Injury to small perforating or en passage blood vessels was the most common cause of infarction that led to moderate or severe deficits. Awake motor mapping was not superior to mapping done under general anesthesia with regard to long-term functional outcome.


Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection

J Neurosurg 128:1690–1697, 2018

The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination.

METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620–640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis.

RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery.

CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional bluelight excitation. Clinical trial registration no.: NCT02191488 (

Intraoperative perception and estimates on extent of resection during awake glioma surgery: overcoming the learning curve

J Neurosurg 128:1410–1418, 2018

There is ample evidence that extent of resection (EOR) is associated with improved outcomes for glioma surgery. However, it is often difficult to accurately estimate EOR intraoperatively, and surgeon accuracy has yet to be reviewed. In this study, the authors quantitatively assessed the accuracy of intraoperative perception of EOR during awake craniotomy for tumor resection.

METHODS A single-surgeon experience of performing awake craniotomies for tumor resection over a 17-year period was examined. Retrospective review of operative reports for quantitative estimation of EOR was recorded. Definitive EOR was based on postoperative MRI. Analysis of accuracy of EOR estimation was examined both as a general outcome (gross-total resection [GTR] or subtotal resection [STR]), and quantitatively (5% within EOR on postoperative MRI). Patient demographics, tumor characteristics, and surgeon experience were examined. The effects of accuracy on motor and language outcomes were assessed.

RESULTS A total of 451 patients were included in the study. Overall accuracy of intraoperative perception of whether GTR or STR was achieved was 79.6%, and overall accuracy of quantitative perception of resection (within 5% of postoperative MRI) was 81.4%. There was a significant difference (p = 0.049) in accuracy for gross perception over the 17- year period, with improvement over the later years: 1997–2000 (72.6%), 2001–2004 (78.5%), 2005–2008 (80.7%), and 2009–2013 (84.4%). Similarly, there was a significant improvement (p = 0.015) in accuracy of quantitative perception of EOR over the 17-year period: 1997–2000 (72.2%), 2001–2004 (69.8%), 2005–2008 (84.8%), and 2009–2013 (93.4%). This improvement in accuracy is demonstrated by the significantly higher odds of correctly estimating quantitative EOR in the later years of the series on multivariate logistic regression. Insular tumors were associated with the highest accuracy of gross perception (89.3%; p = 0.034), but lowest accuracy of quantitative perception (61.1% correct; p < 0.001) compared with tumors in other locations. Even after adjusting for surgeon experience, this particular trend for insular tumors remained true. The absence of 1p19q co-deletion was associated with higher quantitative perception accuracy (96.9% vs 81.5%; p = 0.051). Tumor grade, recurrence, diagnosis, and isocitrate dehydrogenase-1 (IDH-1) status were not associated with accurate perception of EOR. Overall, new neurological deficits occurred in 8.4% of cases, and 42.1% of those new neurological deficits persisted after the 3-month follow-up. Correct quantitative perception was associated with lower postoperative motor deficits (2.4%) compared with incorrect perceptions (8.0%; p = 0.029). There were no detectable differences in language outcomes based on perception of EOR.

CONCLUSIONS The findings from this study suggest that there is a learning curve associated with the ability to accurately assess intraoperative EOR during glioma surgery, and it may take more than a decade to be truly proficient. Understanding the factors associated with this ability to accurately assess EOR will provide safer surgeries while maximizing tumor resection.

Pediatric Clival Chordoma: A Curable Disease that Conforms to Collins’ Law

Neurosurgery 82:652–660, 2018

Skull base chordomas in children are extremely rare. Their course, management, and outcome have not been defined.

OBJECTIVE: To describe the preeminent clinical and radiological features in a series of pediatric patients with skull base chordomas and analyze the outcome of a cohort who underwent uniform treatment. We emphasize predictors of overall survival and progression-free survival, which aligns with Collins’ law for embryonal tumors.

METHODS: Thirty-one patients with a mean age of 10.7 yr (range 0.8-22) harboring skull base chordomas were evaluated. We retrospectively analyzed the outcomes and prognostic factors for 18 patients treated by the senior author, with uniform management of surgery with the aim of gross total resection and adjuvant proton-beam radiotherapy. Mean follow-up was 119.2 mo (range 8-263).

RESULTS: Abducens nerve palsy was the most common presenting symptom. Imaging disclosed large tumors that often involve multiple anatomical compartments. Patients undergoing gross total resection had significantly increased progression-free survival (P = .02) and overall survival (P = .05) compared with those having subtotal resection. Those who lived through the period of risk for recurrence without disease progression had a higher probability of living entirely free of progression (P = .03; odds ratio = 16.0). Age, sex, and histopathological variant did not yield statistical significance in survival.

CONCLUSION: Long-term overall and progression-free survival in children harboring skull base chordomas can be achieved with gross surgical resection and proton-beam radiotherapy, despite an advanced stage at presentation. Collins’ law does apply to pediatric skull base chordomas, and children with this disease have a high hope for cure.

Risk assessment of motor function using nTMS-based tractography

J Neurosurg 128:800–810, 2018

Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking (DTI FT) based on nTMS data are increasingly used for preoperative planning and resection guidance in patients suffering from motor-eloquent brain tumors. The present study explores whether nTMS-based DTI FT can also be used for individual preoperative risk assessment regarding surgery-related motor impairment.

METHODS Data derived from preoperative nTMS motor mapping and subsequent nTMS-based tractography in 86 patients were analyzed. All patients suffered from high-grade glioma (HGG), low-grade glioma (LGG), or intracranial metastasis (MET). In this context, nTMS-based DTI FT of the corticospinal tract (CST) was performed at a range of fractional anisotropy (FA) levels based on an individualized FA threshold ([FAT]; tracking with 50%, 75%, and 100% FAT), which was defined as the highest FA value allowing for visualization of fibers (100% FAT). Minimum lesion-to-CST distances were measured, and fiber numbers of the reconstructed CST were assessed. These data were then correlated with the preoperative, postoperative, and follow-up status of motor function and the resting motor threshold (rMT).

RESULTS At certain FA levels, a statistically significant difference in lesion-to-CST distances was observed between patients with HGG who had no impairment and those who developed surgery-related transient or permanent motor deficits (75% FAT: p = 0.0149; 100% FAT: p = 0.0233). In this context, no patient with a lesion-to-CST distance ≥ 12 mm suffered from any new surgery-related permanent paresis (50% FAT and 75% FAT). Furthermore, comparatively strong negative correlations were observed between the rMT and lesion-to-CST distances of patients with surgery-related transient paresis (Spearman correlation coefficient [rs]; 50% FAT: rs = –0.8660; 75% FAT: rs = –0.8660) or surgery-related permanent paresis (50% FAT: rs = –0.7656; 75% FAT: rs = –0.6763).

CONCLUSIONS This is one of the first studies to show a direct correlation between imaging, clinical status, and neurophysiological markers for the integrity of the motor system in patients with brain tumors. The findings suggest that nTMSbased DTI FT might be suitable for individual risk assessment in patients with HGG, in addition to being a surgery-planning tool. Importantly, necessary data for risk assessment were obtained without significant additional efforts, making this approach potentially valuable for direct clinical use.

Efficacy and outcomes of facial nerve–sparing treatment approach to cerebellopontine angle meningiomas

J Neurosurg 127:1231–1241, 2017

Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient’s life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC).

METHODS Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve–sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated.

RESULTS According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes.

CONCLUSIONS CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.

Complications of ventricular entry during craniotomy for brain tumor resection

J Neurosurg 127:426–432, 2017

Recent studies have demonstrated that periventricular tumor location is associated with poorer survival and that tumor location near the ventricle limits the extent of resection. This finding may relate to the perception that ventricular entry leads to further complications and thus surgeons may choose to perform less aggressive resection in these areas. However, there is little support for this view in the literature. This study seeks to determine whether ventricular entry is associated with more complications during craniotomy for brain tumor resection.

METHODS A retrospective analysis of patients who underwent craniotomy for tumor resection at Henry Ford Hospital between January 2010 and November 2012 was conducted. A total of 183 cases were reviewed with attention to operative entry into the ventricular system, postoperative use of an external ventricular drain (EVD), subdural hematoma, hydrocephalus, and symptomatic intraventricular hemorrhage (IVH).

RESULTS Patients in whom the ventricles were entered had significantly higher rates of any complication (46% vs 21%). Complications included development of subdural hygroma, subdural hematoma, intraventricular hemorrhage, subgaleal collection, wound infection, urinary tract infection/deep venous thrombosis, hydrocephalus, and ventriculoperitoneal (VP) shunt placement. Specifically, these patients had significantly higher rates of EVD placement (23% vs 1%, p < 0.001), hydrocephalus (6% vs 0%, p = 0.03), IVH (14% vs 0%, p < 0.001), infection (15% vs 5%, p = 0.04), and subgaleal collection (20% vs 4%, p < 0.001). It was also observed that VP shunt placement was only seen in cases of ventricular entry (11% vs 0%, p = 0.001) with 3 of 4 of these patients having a large ventricular entry (defined here as entry greater than a pinhole [< 3 mm] entry). Furthermore, in a subset of glioblastoma patients with and without ventricular entry, Kaplan- Meier estimates for survival demonstrated a median survival time of 329 days for ventricular entry compared with 522 days for patients with no ventricular entry (HR 1.13, 95% CI 0.65–1.96; p = 0.67).

CONCLUSIONS There are more complications associated with ventricular entry during brain tumor resection than in nonviolated ventricular systems. Better strategies for management of periventricular tumor resection should be actively sought to improve resection and survival for these patients.


Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers

Acta Neurochir (2017) 159:1187–1195

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value.

Methods: The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications.

Results: nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here.

Conclusion: At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.

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