Author: cba

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Complication rates after autologous cranioplasty following decompressive craniectomy

Acta Neurochirurgica (2024) 166:380

The reimplantation of autologous bone grafts after decompressive craniectomy (DC) is still up for debate. The objective of this study was to analyze the surgical revision rate for autologous cranioplasties in our center, aiming to identify predictors for procedure-related-complications.

Methods A retrospective single-center study was conducted for adult patients who underwent autologous cranioplasty after DC. The primary endpoint was the complication rate in terms of surgical revision and removal of the bone graft: infection, new onset seizures, dislocation, haemorrhage, osteolysis, wound dehiscence and cerebrospinal fluid (CSF) fistula. Demographic data, medical records, surgical reports and imaging studies were analysed and risk factors for complications were evaluated.

Results 169 consecutive patients were included. The median interval between DC and cranioplasty was 84 days. Mean age was 51 ± 12.4 years. 26 patients (15.3%) had revision surgery for following reasons. n = 9 implant dislocations (5.3%), n = 7 osteolysis (3.6%), n = 6 infections (3.6%), n = 5 had re-bleedings (3%), n = 5 wound dehiscences (3%), and n = 2 CSF fistulas (1.2%). 18 patients developed new seizures (10.7%). Bi- and multivariate analysis revealed three independent risk factors, simultaneous ventriculo-peritoneal (VP) shunting increased the risk for material dislocation (p < 0.001); large bone grafts (> 193.5 cm2 ) increased the risk for osteolysis (p = 0.001) and bifrontal cranioplasties were associated with higher risk for infections (p = 0.04).

Conclusion The complication rates in our study were comparable to previously reported data for autologous or artificial cranioplasties. As osteolysis was correlated to larger bone grafts, a synthetic alternative should be considered in selected cases.

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Endoscopic Retrolabyrinthine Craniotomy for Exposure of the Trigeminal Nerve Root Entry Zone

Operative Neurosurgery 27:464–470, 2024

Exposure of the root entry zone (REZ) of the trigeminal nerve (TN) for microvascular decompression is commonly obtained with a retrosigmoid approach, with or without endoscopic assistance. We hypothesized that adequate exposure of the TN REZ could be obtained through an endoscopic retrolabyrinthine (RL) approach. We aim to quantify exposure of the REZ of the TN using endoscopic RL approach, with and without drilling of the suprameatal tubercle of the internal auditory canal.

METHODS: Surgical dissection was performed bilaterally on 3 embalmed cadaveric human heads at the anatomy laboratory of the House Institute. Heads were scanned for volumetric analysis using 3D Slicer software both before and after dissection. Extent of exposure was quantified in 2 ways: first, by assessment of the surgeon’s ability to visualize 16 predetermined anatomic landmarks with the endoscope and second, we estimated the “working” area by placing fiducials under the fully endoscopic view and calculating the resultant 3D volume.

RESULTS: Using the standard endoscopic RL approach, anaverageof 13.8 landmarks (range 12-16) was visualized. The estimated working volume exposed by the RL on each side of each head varied from 189.28 to 527.85 mm3 . Drilling of the suprameatal tubercle provided both increases in landmark visualization and, on average, an additional 55 mm 3 of working volume.

CONCLUSION: The endoscopic RL approach is a viable alternative to the standard retrosigmoid approach. Potential advantages of the RL include a more lateral trajectory that minimizes the need for cerebellar retraction and a shorter working distance and shallower angle to the cerebellopontine angle. Potential disadvantages include longer surgery time, increased technical difficulty of exposure, and potential for cerebrospinal fluid leak and or hearing loss.

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Standard operating procedure and surgical technique innovation in fully endoscopic microvascular decompression for trigeminal neuralgia

Acta Neurochirurgica (2024) 166:351

Microvascular decompression (MVD) is a well-established and effective treatment for primary trigeminal neuralgia (TN). Endoscopy has been implemented to provide a comprehensive view of neurovascular conflict and minimizes the damages of brain retraction during MVD.

Objectives To preliminarily evaluate the surgical safety and efficacy of fully endoscopic microvascular decompression (EMVD) for primary TN with surgeon performing two-hand manipulation and assistant holding endoscope.

Methods Retrospective clinical analysis of 189 patients with primary TN underwent EMVD between June 2019 and August 2022 was performed. By analyzing the intraoperative situation, the outcomes of postoperative symptoms and the main complications, we evaluated the reliability and effectivity of the operative technique in the treatment of primary TN.

Results We summarized the standard operating procedure of EMVD for primary TN with surgeon performing two-hand manipulation and assistant holding endoscope. In addition, acicular bipolar electrocoagulation technique was developed to handle venous compression. During the follow-up period, good pain relief was achieved in 178 patients (94.2%) and recurrence of pain was observed in 4 patients (2.1%). Postoperative temporary complications included trigeminal dysesthesias (7 patients, 4.8%), cerebrospinal fluid leak (2 patients, 1.1%), hearing difficulty (3 patient, 1.6%), facial paresis (2 patients, 1.1%) and vertigo (5 patients, 2.7%). There were no cases of intracranial hemorrhage, cerebellar swelling and death.

Conclusion This EMVD technique is reliable and effective, and can be used as a routine surgical procedure for primary TN.

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Fenestrated clipping of previously coiled posterior‑superiorly projecting anterior communicating artery aneurysms

Acta Neurochirurgica (2024) 166:395

Anterior communicating artery (ACOM) aneurysms are among the most common aneurysms associated with aneurysmal subarachnoid hemorrhage (International Study of Unruptured Intracranial Aneurysms I (N Engl J Med 339:17251733, 1998), Wiebers (Lancet 362:103-110, 2003)). Surgical clipping of posterior-superiorly projecting ACOM aneurysms can be challenging, as the ipsilateral A2 can interfere with clip trajectory and ACOM perforating vessels obstructed from view. Intraluminal coils can further increase the difficulty of the procedure.

Method The relevant surgical anatomy with illustration is presented. A video detailing our technique on an illustrative case is provided.

Conclusion Surgical clipping of posterior-superiorly projecting ACOM aneurysms can require complex clip configurations. We describe the key steps of posterior-superiorly projecting ACOM aneurysm clipping through a lateral supraorbital craniotomy and fenestrated tandem clipping.

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Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma

J Neurosurg 141:945–954, 2024

Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition, particularly among the elderly. Various treatment options exist, but recurrence rates remain high. This systematic review and meta-analysis aims to assess the efficacy and safety of tranexamic acid (TXA) in the management of CSDH.

METHODS The authors conducted a comprehensive literature search adhering to the 2020 PRISMA guidelines, involving three primary databases (Scopus, PubMed, and Web of Science) that were searched for articles compiled from inception until October 20, 2023. The primary outcome was recurrence of CSDH, and secondary outcomes included complications and SDH volume following TXA treatment. The mean difference and odds ratios with 95% confidence intervals were calculated using the random-effects model.

RESULTS A total of 5 studies, involving 643 patients in the TXA group and 736 patients in the non-TXA group, met the inclusion criteria. The meta-analysis revealed that TXA use led to a significantly lower CSDH recurrence (OR 0.35, 95% CI 0.23–0.53; p < 0.01) without increasing complications (OR 1.84, 95% CI 0.43–7.95; p = 0.42). Additionally, TXA users had a significantly lower CSDH volume compared to the non-TXA group at 3-month follow-up (mean difference −4.56, 95% CI −8.76 to −0.36; p = 0.03).

CONCLUSIONS The findings suggest that TXA might be a promising agent for reducing the risk of CSDH recurrence without elevating the risk of complications. However, these results should be interpreted cautiously due to the limited number of studies included and the methodological heterogeneity. Further large-scale randomized controlled trials are needed to confirm these findings.

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Comparison of biportal endoscopic and microscopic tubular paraspinal approach for foraminal and extraforaminal lumbar disc herniation

J Neurosurg Spine 41:473–482, 2024

Foraminal and extraforaminal lumbar disc herniation (FELDH) is an important pathological condition that can lead to lumbar radiculopathy. The paraspinal muscle–splitting approach introduced by Reulen and Wiltse is a reasonable surgical technique. Minimally invasive procedures using a tubular retractor system have also been introduced. However, surgical treatment is considered more challenging for FELDH than for central or subarticular lumbar disc herniations (LDHs). Some researchers have proposed uniportal extraforaminal endoscopic lumbar discectomy through a posterolateral approach as an alternative for FELDH, but heterogeneous clinical results have been reported. Recently, the biportal endoscopic (BE) paraspinal approach has been suggested as an alternative. The aim of this study was to compare the clinical outcomes of BE and microscopic tubular (MT) paraspinal approaches for decompressive foraminotomy and lumbar discectomy (paraLD) in patients with FELDH.

METHODS Ninety-one consecutive patients with unilateral lumbar radiculopathy and FELDH underwent paraLD. Demographic and perioperative data were collected. Clinical outcomes were evaluated using the visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) for spinal disability, and the modified Macnab criteria for patient satisfaction. Postoperative complications and reoperation rates were also evaluated.

RESULTS In total, 76 patients were included in the final analysis. Among them, 43 underwent BE paraLD (group A) and the remaining 33 underwent MT paraLD (group B). The demographic and preoperative data were not statistically different between the groups. All patients showed significant improvements in VAS back, VAS leg, and ODI scores compared with baseline values (p < 0.05). The improvement in VAS back scores was significantly better in group A than in group B on postoperative day 2 (p < 0.001). However, all clinical parameters were comparable between the two groups after postoperative year 1 (p > 0.05). According to the modified Macnab criteria, 86.1% and 72.7% of the patients had excellent or good outcomes in groups A and B, respectively. No intergroup differences were observed (p = 0.367). In addition, there were no differences in the total operation time or amount of surgical drainage. Postoperative complications were not significantly different between the two groups (p = 0.301); however, reoperation rates were significantly higher in group B (p = 0.035).

CONCLUSIONS BE paraLD is an effective treatment for FELDH and is an alternative to MT paraLD. In particular, BE paraLD has advantages of early improvement in postoperative back pain and low reoperation rates.

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Visualization of the nervus intermedius during microvascular decompression in hemifacial spasm: anatomical study

J Neurosurg 141:1049–1055, 2024

The surgical anatomy of the nervus intermedius (NI) is highly variable. The aim of this study was to describe the anatomy of the NI during endoscope-assisted microvascular decompression (MVD) in hemifacial spasm (HFS), and the involvement of the nerve in the vascular conflict.

METHODS The authors reviewed a prospectively maintained database for MVDs performed between 2002 and 2022 and extracted clinical data including patient demographics, symptoms, and offending vessel(s). Operative videos and photographs were analyzed retrospectively in an attempt to identify the NI.

RESULTS Endoscopic identification of the NI was possible in 139 of 435 MVDs. The anatomy is very variable. In 79 (56.8%) patients, a single-bundle pattern was detected, whereas a multiple-bundle pattern was identified in 60 (43.2%) patients. Overall the most common pattern was a single-bundle type A (49.7%). In 20.1%, a multiple-bundles type A was identified. In 4.3%, a single-bundle type B was detected. In 2.9% a single-bundle type C was found, and in just 0.7% a multiple-bundles type C was detected. A multiple-origin pattern (type D) was found in 31 patients (22.3%). The NI was frequently involved in the neurovascular conflict (approximately 85%). The type of NI or vascular compression pattern did not affect the results regarding the outcome or recurrence of HFS.

CONCLUSIONS The anatomy of the NI is for the first time evaluated endoscopically in MVD for HFS. The nerve had various anatomical patterns that were clearly identified. Further studies to evaluate the compression patterns in relation to NI neuralgia are warranted.

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How Accurate Is Frameless Fiducial—Free Deep Brain Stimulation?

Operative Neurosurgery 27:431–439, 2024

Frameless deep brain stimulation (DBS) offers advantages in terms of patient comfort and reduced operative time. However, the need for bony fiducial markers for localization remains a drawback due to the time-consuming and uncomfortable procedure. An alternative localization method involves the direct tracking of an intraoperative 3-dimensional scanner. This study aims to assess the accuracy of the NexFrame frameless DBS system in conjunction with the O-Arm (Medtronic Inc.), both with and without fiducial markers.

METHODS: The locations of 100 DBS leads were determined, with 50 cases using fiducial-free localization and 50 involving fiducial markers. The coordinates were compared with the expected intraoperative targets. Absolute errors in the X, Y, and Z coordinates (ΔX, ΔY, and ΔZ) were calculated, along with the vector error (Euclidean) (vector error square root Δx 2 + Δy 2 + Δz 2 ).

RESULTS: The vector error averaged 1.61 ± 0.49 mm (right) and 1.52 ± 0.60 mm (left) for the group without fiducial bone markers and 1.66 ± 0.69 (right) and 1.44 ± 0.65 mm (left) for the other cohort (P = .76 right; P = .67 left). Absolute errors in the X, Y, and Z coordinates for the fiducial-free group were 0.88 ± 0.55, 0.79 ± 0.45, and 0.79 ± 0.57 mm (right) and 0.72 ± 0.37, 0.78 ± 0.56, and 0.77 ± 0.71 mm (left). For the group with fiducial markers, these errors were 0.87 ± 0.72, 0.92 ± 0.39, and 0.86 ± 0.50 mm (right) and 0.75 ± 0.33, 0.80 ± 0.51, and 0.73 ± 0.64 mm (left) with no statistically significant difference.

CONCLUSION: Our analysis of the accuracy of NexFrame DBS, both with and without fiducial markers, using an intraoperative navigable cone-beam computed tomography, demonstrates that both techniques provide sufficient and equivalent 3-dimensional accuracy.

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Transforaminal lumbar interbody fusion subsidence

J Neurosurg Spine 41:463–472, 2024

The aims of this study were to 1) define the incidence of transforaminal lumbar interbody fusion (TLIF) interbody subsidence; 2) determine the relative importance of preoperative and intraoperative patient- and instrumentation-specific risk factors predictive of postoperative subsidence using CT-based assessment; and 3) determine the impact of TLIF subsidence on postoperative complications and fusion rates.

METHODS All adult patients who underwent one- or two-level TLIF for lumbar degenerative conditions at a multi-institutional academic center between 2017 and 2019 were retrospectively identified. Patients with traumatic injury, infection, malignancy, previous fusion at the index level, combined anterior-posterior procedures, surgery with greater than two TLIF levels, or incomplete follow-up were excluded. Interbody subsidence at the superior and inferior endplates of each TLIF level was directly measured on the endplate-facing surface of both coronal and sagittal CT scans obtained greater than 6 months postoperatively. Patients were grouped based on the maximum subsidence at each operative level classified as mild, moderate, or severe based on previously documented < 2-mm, 2- to 4-mm, and ≥ 4-mm thresholds, respectively. Univariate and regression analyses compared patient demographics, medical comorbidities, preoperative bone quality, surgical factors including interbody cage parameters, and fusion and complication rates across subsidence groups.

RESULTS A total of 67 patients with 85 unique fusion levels met the inclusion and exclusion criteria. Overall, 28% of levels exhibited moderate subsidence and 35% showed severe subsidence after TLIF with no significant difference in the superior and inferior endplate subsidence. Moderate (≥ 2-mm) and severe (≥ 4-mm) subsidence were significantly associated with decreases in cage surface area and Taillard index as well as interbody cages with polyetheretherketone (PEEK) material and sawtooth surface geometry. Severe subsidence was also significantly associated with taller preoperative disc spaces, decreased vertebral Hounsfield units (HU), the absence of bone morphogenetic protein (BMP) use, and smooth cage surfaces. Regression analysis revealed decreases in Taillard index, cage surface area, and HU, and the absence of BMP use predicted subsidence. Severe subsidence was found to be a predictor of pseudarthrosis but was not significantly associated with revision surgery.

CONCLUSIONS Patient-level risk factors for TLIF subsidence included decreased HU and increased preoperative disc height. Intraoperative risk factors for TLIF subsidence were decreased cage surface area, PEEK cage material, bullet cages, posterior cage positioning, smooth cage surfaces, and sawtooth surface designs. Severe subsidence predicted TLIF pseudarthrosis; however, the causality of this relationship remains unclear.

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Feasibility, Clinical Potential, and Limitations of Trans-Burr Hole Ultrasound for Postoperative Evaluation of Chronic Subdural Hematoma: A Prospective Pilot Study

Neurosurgery 95:924–931, 2024

Chronic subdural hematoma (CSDH) is commonly managed through burr hole surgery. Routine follow-up using computed tomography (CT) imaging is frequently used at many institutions, contributing to significant radiation exposure. This study evaluates the feasibility, safety, and reliability of trans-burr hole sonography as an alternative postoperative imaging modality, aiming to reduce radiation exposure by decreasing the frequency of CT scans.

METHODS: We conducted a prospective pilot study on 20 patients who underwent burr hole surgery for CSDH. Postoperative imaging included both CT and sonographic examinations through the burr hole. We assessed the ability to measure residual subdural fluid thickness under the burr hole sonographically compared with CT, the occurrence of complications, and the potential factors affecting sonographic image quality. The Pearson correlation coefficient was used to demonstrate relationships between CT and ultrasound and axial and coronal ultrasound.

RESULTS: Sonography through the burr hole was feasible in 73.5% of cases, providing measurements of residual fluid that closely paralleled CT findings, with an average discrepancy of 1.2 mm for axial and 1.4 mm for coronal sonographic views. A strong positive correlation was found between axial and coronal ultrasound (r = 0.955), CT and axial ultrasound (r = 0.936), and CT and coronal ultrasound (r = 0.920). The primary obstacle for sonographic imaging was the presence of air within the burr hole or the subdural space, which typically resolved over time after surgery.

CONCLUSION: Trans-burr hole sonography emerges as a promising technique for postoperative monitoring of CSDH, with the potential to safely reduce reliance on CT scans and associated radiation exposure in selected patients. Our results support further investigation into the extended use of sonography during the follow-up phase. Prospective multicenter studies are recommended to establish the method’s efficacy and to explore strategies for minimizing air presence postsurgery.

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Surgical Anatomy of the Retrosigmoid Approach With Transtentorial Extension: Protecting the 4th Cranial Nerve

Operative Neurosurgery 27:357–364, 2024

The retrosigmoid approach with transtentorial extension (RTA) allows us to address posterior cranial fossa pathologies that extend through the tentorium into the supratentorial space. Incision of the tentorium cerebelli is challenging, especially for the risk of injury of the cranial nerve (CN) IV. We describe a tentorial incision technique and relevant anatomic landmarks.

METHODS: The RTA was performed stepwise on 5 formalin-fixed (10 sides), latex-injected cadaver heads. The porus trigeminus’s midpoint, the lateral border of the suprameatal tubercle (SMT)’s base, and cerebellopontine fissure were assessed as anatomic landmarks for the CN IV tentorial entry point, and relative measurements were collected. A clinical case was presented.

RESULTS: The tentorial opening was described in 4 different incisions. The first is curved and starts in the posterior aspect of the tentorium. It has 2 limbs: a medial one directed toward the tentorium’s free edge and a lateral one that extends toward the superior petrosal sinus (SPS). The second incision turns inferiorly, medially, and parallel to the SPS down to the SMT. At that level, the second incision turns perpendicular toward the tentorium’s free edge and ends 1 cm from it. The third incision proceeds posteriorly, parallel to the free edge. At the cerebellopontine fissure, the incision can turn toward and cut the tentorium-free edge (fourth incision). On average, the CN IV tentorial entry point was 12.7 mm anterior to the SMT base’s lateral border and 20.2 mm anterior to the cerebellopontine fissure. It was located approximately in the same coronal plane as the porus trigeminus’s midpoint, on average 1.9 mm anterior.

CONCLUSION: The SMT and the cerebellopontine fissure are consistently located posterior to the CN IV tentorial entry point. They can be used as surgical landmarks for RTA, reducing the risk of injury to the CN IV.

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How I do it: surgical ligation of posteromedial tentorial dural arteriovenous fistulas

Acta Neurochirurgica (2024) 166:382

Tentorial dural arteriovenous fistulas (dAVFs) are categorized based on venous drainage and location. Although their angioarchitecture may initially appear intimidating, once “decodified,” treatment is straightforward. Posteromedial tentorial dAVFs have an arterialized draining vein that emanates from the inferior tentorium along the posterior third of the straight sinus, just slightly off the midline.

Method With the aid of anatomical dissections, intraoperative photos, and operative videos, we outline the key steps for surgical treatment of posteromedial tentorial dAVFs.

Conclusion Posteromedial tentorial dAVFs constitute a precise and well-defined subtype of tentorial dAVF for which surgical ligation has an important role.

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Accurate placement of thoracolumbar pedicle screws using a handheld iOS-based navigation device

The Spine Journal 24 (2024) 1671−1677

Accurate pedicle screw placement is a challenge with reported misplacement rates of 10% and higher. A handheld navigation device (HND) may provide accuracy equal to CT-based navigation (CT-Nav) but without the cost and complexity.

OBJECTIVE: To study the accuracy of a handheld navigation device for pedicle screw placement. STUDY DESIGN: This prospective cross-sectional study with consistently applied reference standard enrolled 20 patients undergoing 92 pedicle screw placements.

PATIENTS: Patients who underwent pedicle screw placement between May 2022 and September 2022.

OUTCOME MEASURES: Pedicle screw placement accuracy per Gertzbein−Robbins.

METHODS: Once the screw pilot hole was established, the proposed trajectory of the HND was compared with that proposed by CT-Nav. Postoperatively, screw accuracy was graded according to Gertzbein−Robbins by a blinded radiologist based on CT scans. Accuracy was compared between the two systems and published control for fluoroscopy assisted and CT-Nav placement using Bayesian posterior distribution.

RESULTS: The trajectory proposed by the HND and CT-Nav were in agreement in 98.9% (95% Exact CI; 94.09%−99.97%). The HND accuracy was 98.9% with 91 screws rated “A” and 1 rated “C”. Noninferiority to fluoroscopic placement was achieved because the one-sided normalapproximation 95% CI Lower Bound (LB) of 95.3% is greater than the Performance Goal (PG) of 83.4%. Posthoc analysis demonstrated that the probability of superiority of the HND relative to the historical accuracy rate of 91.5% for fluoroscopy assisted procedures is >0.999 and that the HND’s accuracy rate is within 4.5% of CT-Nav of 95.5% is >0.999. No adverse events or intra-operative complications associated with HND were observed. There was 1 (1.1%) intra-operative repositioning and no reoperations for any reason.

CONCLUSIONS: The accuracy rate of the HND was 98.9%, and the proposed trajectory matched with CT-Nav in 98.9% of the time. This is superior to the historical published accuracy rate for fluoroscopy-assisted procedures and equivalent to the historical published accuracy rate for CT-Nav.

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Improvement of diffusion tensor imaging–based tractography by free-water correction in nonedematous gliomas: assessment with brain mapping

J Neurosurg 141:684–694, 2024

The free-water correction algorithm (Freewater Estimator Using Interpolated Initialization [FERNET]) can be applied to standard diffusion tensor imaging (DTI) tractography to improve visualization of subcortical bundles in the peritumoral area of highly edematous brain tumors. Interest in its use for presurgical planning in purely infiltrative gliomas without peritumoral edema has never been evaluated. Using subcortical maps obtained with direct electrostimulation (DES) in awake surgery as a reference standard, the authors sought to 1) assess the accuracy of preoperative DTIbased tractography with FERNET in a series of nonedematous glioma patients, and 2) determine its potential usefulness in presurgical planning.

METHODS Based on DES-induced functional disturbances and tumor topography, the authors retrospectively reconstructed the putatively stimulated bundles and the peritumoral tracts of interest (various associative and projection pathways) of 12 patients. The tractography data obtained with and without FERNET were compared.

RESULTS The authors identified 21 putative tracts from 24 stimulation sites and reconstituted 49 tracts of interest. The number of streamlines of the putative tracts crossing the DES area was 26.8% higher (96.04 vs 75.75, p = 0.016) and their volume 20.4% higher (13.99 cm 3 vs 11.62 cm 3 , p < 0.0001) with FERNET than with standard DTI. Additionally, the volume of the tracts of interest was 22.1% higher (9.69 cm 3 vs 7.93 cm 3 , p < 0.0001).

CONCLUSIONS Free-water correction significantly increased the anatomical plausibility of the stimulated fascicles and the volume of tracts of interest in the peritumoral area of purely infiltrative nonedematous gliomas. Because of the functional importance of the peritumoral zone, applying FERNET to DTI could have potential implications on surgical planning and the safety of glioma resection.

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Generation and applications of synthetic computed tomography images for neurosurgical planning

J Neurosurg 141:742–751, 2024

CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis.

METHODS Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a “synthetic” CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration.

RESULTS A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion.

CONCLUSIONS The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.

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Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma

J Neurosurg 141:673–683, 2024

Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma.

METHODS Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma.

RESULTS CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation.

CONCLUSIONS The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTMbased survival models can enable clinicians to evaluate patients’ response to surgery as well as their outcomes.

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Berberine as a potential enhancer for 5-ALA–mediated fluorescence in glioblastoma

J Neurosurg 141:653–663, 2024

The prognosis of glioblastoma (GBM) correlates with residual tumor volume after surgery. In fluorescenceguided surgery, 5-aminolevulinic acid (ALA) has been used to maximize resection while avoiding neurological morbidity. However, not all tumor cells, particularly glioma stem cells (GSCs), display 5-ALA–mediated protoporphyrin IX (PpIX) fluorescence (5-ALA fluorescence). The authors searched for repositioned drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA fluorescence. In this study, they investigated whether BBR can enhance 5-ALA fluorescence in GSCs and whether BBR can be applied to clinical practice as a 5-ALA fluorescence enhancer.

METHODS The effects of BBR on 5-ALA fluorescence in glioma and GSCs were evaluated by flow cytometry (fluorescence-activated cell sorting [FACS]) analysis. As 5-ALA is metabolized for heme synthesis, the effects of BBR on mRNA expressions of 7 enzymes in the heme-synthesis pathway were analyzed. Enzymes showing significantly higher expression than control in all cells were identified and protein analysis was performed. To examine clinical availability, the detectability and cytotoxicity of BBR in tumor-transplanted mice were analyzed.

RESULTS Fluorescence microscopy revealed much more intense 5-ALA fluorescence in both GSCs and non-stem cells with 5-ALA and BBR than with 5-ALA alone. FACS showed that BBR greatly enhanced 5-ALA fluorescence compared with 5-ALA alone, and enhancement was much higher for GSCs than for glioma cells. Among the 7 enzymes examined, BBR upregulated mRNA expressions of ALA synthetase 1 (ALAS1) more highly in all cells, and activated ALAS1 through deregulating ALAS1 activity inhibited by the negative feedback of heme. An in vivo study showed that 5-ALA fluorescence with 5-ALA and BBR was significantly stronger than with 5-ALA alone, and the sensitivity and specificity of BBR-enhanced fluorescence were both 100%. In addition, BBR did not show any cytotoxicity for normal brain tissue surrounding the tumor mass.

CONCLUSIONS BBR enhanced 5-ALA–mediated PpIX fluorescence by upregulating and activating ALAS1 through deregulation of negative feedback inhibition by heme. BBR is a clinically used drug with no side effects. BBR is expected to significantly augment fluorescence-guided surgery and photodynamic therapy.

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Full-endoscopic lumbar discectomy for lumbar disc herniation in young adults: 199 consecutive cases treated by a single surgeon with a mean 3.7-year follow-up

J Neurosurg Spine 41:369–377, 2024

Lumbar disc herniation (LDH) is rare in young adults. The present study aimed to evaluate the clinical outcomes of full-endoscopic lumbar discectomy (FELD) for LDH in young adults and to determine the risk factors that predict unfavorable outcomes of FELD for LDH in young adults.

METHODS A retrospective two-center cohort study was performed between January 2015 and October 2021 at the authors’ institutions. Clinical outcomes were assessed using the visual analog scale (VAS) for low-back pain and leg pain and the Oswestry Disability Index (ODI). The modified Macnab criteria were used to evaluate clinical efficacy at the last follow-up, and the global outcomes were classified into 4 groups, namely excellent, good, fair, and poor. The fair and poor groups were defined as unfavorable outcomes.

RESULTS One hundred ninety-nine patients were analyzed in this study (mean age 18.5 years, mean BMI 25.1 kg/m 2 , male/female sex ratio 2.8). The duration from the onset of symptoms to the operation was in general prolonged with age. The VAS and ODI scores significantly improved after surgery. A total of 17 of 195 single-segment cases had unfavorable outcomes based on the modified Macnab criteria. Lateral disc herniation (OR 3.72, 95% CI 1.14–12.12, p = 0.029) and high preoperative VAS score (OR 1.98, 95% CI 1.13–3.46, p = 0.017) were identified as risk factors for unfavorable outcomes after FELD.

CONCLUSIONS FELD for LDH in young adults is safe and effective. Preoperative VAS score and lateral disc herniation are risk factors of nonfavorable outcomes after surgery and may be a useful index for surgical procedure selection.

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Longitudinal brain volumetrics in glioma survivors

J Neurosurg 141:634–641, 2024

Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT.

METHODS This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models.

RESULTS The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36–18.9 years), and the median number of time points analyzed per patient was 12 (range 2–40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (β = −0.06, p < 0.001) and use of RT (β = −1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (β = −0.08, p < 0.001), midline involvement (β = 1.31, p = 0.006), and use of RT (β = −1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (β = −0.0027, p = 0.001), tumor resection (β = −0.069, p < 0.001), use of chemotherapy (β = −0.0597, p = 0.003), and use of RT (β = −0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model.

CONCLUSIONS This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

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Intraoperative ultrasound and magnetic resonance comparative analysis in brain tumor surgery: a valuable tool to flatten ultrasound’s learning curve

Acta Neurochirurgica (2024) 166:337

Intraoperative ultrasound (IOUS) is a profitable tool for neurosurgical procedures’ assistance, especially in neuro-oncology. It is a rapid, ergonomic and reproducible technique. However, its known handicap is a steep learning curve for neurosurgeons. Here, we describe an interesting postoperative analysis that provides extra feedback after surgery, accelerating the learning process.

Method We conducted a descriptive retrospective unicenter study including patients operated from intra-axial brain tumors using neuronavigation (Curve, Brainlab) and IOUS (BK-5000, BK medical) guidance. All patients had preoperative Magnetic Resonance Imaging (MRI) prior to tumor resection. During surgery, 3D neuronavigated IOUS studies (n3DUS) were obtained through craniotomy N13C5 transducer’s integration to the neuronavigation system. At least two n3DUS studies were obtained: prior to tumor resection and at the resection conclusion. A postoperative MRI was performed within 48 h. MRI and n3DUS studies were posteriorly fused and analyzed with Elements (Brainlab) planning software, permitting two comparative analyses: preoperative MRI compared to pre-resection n3DUS and postoperative MRI to post-resection n3DUS. Cases with incomplete MRI or n3DUS studies were withdrawn from the study.

Results From April 2022 to March 2024, 73 patients were operated assisted by IOUS. From them, 39 were included in the study. Analyses comparing preoperative MRI and pre-resection n3DUS showed great concordance of tumor volume (p < 0,001) between both modalities. Analysis comparing postoperative MRI and post-resection n3DUS also showed good concordance in residual tumor volume (RTV) in cases where gross total resection (GTR) was not achieved (p < 0,001). In two cases, RTV detected on MRI that was not detected intra-operatively with IOUS could be reviewed in detail to recheck its appearance.

Conclusions Post-operative comparative analyses between IOUS and MRI is a valuable tool for novel ultrasound users, as it enhances the amount of feedback provided by cases and could accelerate the learning process, flattening this technique’s learning curve.

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