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Doo-Sik Kong, Yong Hwy Kim, Won-Jae Lee, Young-Hoon Kim, and Chang-Ki Hong

OBJECTIVE

Trigeminal schwannoma is a rare CNS tumor and involves the multicompartmental skull base. Recently, the endoscopic transorbital approach (ETOA) has emerged as a technique for minimally invasive surgery. The objective of this study was to evaluate the optimal indications and clinical outcomes of the ETOA for trigeminal schwannomas based on their tumor classification.

METHODS

Between September 2016 and February 2022, the ETOA was performed in 50 patients with trigeminal schwannoma at four tertiary hospitals. There were 15 men and 35 women in the study, with a mean age of 46.9 years. All tumors were classified as type A (predominantly involving the middle cranial fossa), type B (predominantly involving the posterior cranial fossa), type C (dumbbell-shaped tumors involving the middle and posterior fossa), or type D (involvement of the extracranial compartment). Type D tumors were also subclassified by ophthalmic division (D1), maxillary division (D2), and mandibular division (D3). Clinical outcome was analyzed, including extent of resection and surgical morbidities.

RESULTS

In this study, overall gross-total resection (GTR) was performed in 35 (70.0%) of 50 patients and near-total resection (NTR) in 9 patients (18.0%). The mean follow-up period was 21.9 (range 1–61.7) months. There was no tumor regrowth or recurrence during the follow-up period. Based on the classification, there were 17 type A tumors, 20 type C, and 13 type D. There were no type B tumors. Of the 13 type D tumors, 7 were D1, 1 D2, and 5 D3. For type A tumors, GTR or NTR was achieved using an ETOA in 16 (94.1%) of 17 patients. Eighteen (90.0%) of 20 patients with type C tumors attained GTR or NTR. Ten (76.9%) of 13 patients with type D tumors underwent GTR. Statistical analysis showed that there was no significant difference in the extent of resection among the tumor subtypes. Surgical complications included transient partial ptosis (n = 4), permanent ptosis (n = 1), transient diplopia (n = 7), permanent diplopia (n = 1), corneal keratopathy (n = 7), difficulties in mastication (n = 5), and neuralgic pain or paresthesia (n = 14). There were no postoperative CSF leaks or enophthalmos during follow-up.

CONCLUSIONS

This study showed that trigeminal schwannomas can be effectively treated with a minimally invasive ETOA in all tumor types, except those predominantly involving the posterior fossa (type B). For the extracranial compartments, D2 or D3 tumor types often require an ETOA combined with the endoscopic endonasal approach, while D1 tumor types can be treated using an ETOA alone.

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Takahiro Sasaki, Jun Watanabe, Xingyao He, Hiroaki Katagi, Amreena Suri, Yukitomo Ishi, Kouki Abe, Manabu Natsumeda, William H. Frey II, Peng Zhang, and Rintaro Hashizume

OBJECTIVE

Diffuse midline gliomas, including diffuse intrinsic pontine gliomas (DIPGs), are among the most malignant and devastating childhood brain cancers. Despite aggressive treatment, nearly all children with these tumors succumb to their disease within 2 years of diagnosis. Due to the anatomical location of the tumors within the pons, surgery is not a treatment option, and distribution of most systematically administered drugs is limited by the blood-brain barrier (BBB). New drug delivery systems that bypass the BBB are desperately needed to improve outcomes of DIPG patients. Intranasal delivery (IND) is a practical and noninvasive drug delivery system that bypasses the BBB and delivers the drugs to the brain through the olfactory and trigeminal neural pathways. In this study, the authors evaluated the efficacy of nanoliposomal (LS) irinotecan (CPT-11) and an active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38), using IND in DIPG patient-derived xenograft models.

METHODS

In vitro responses to LS-CPT-11 and LS-SN-38 in DIPG cells were evaluated with cell viability, colony formation, and apoptosis assays. The cellular uptakes of rhodamine-PE (Rhod)–labeled LS-CPT-11 and LS-SN-38 were analyzed with fluorescence microscopy. Mice bearing DIPG patient-derived xenografts were treated with IND of LS-control (empty liposome), LS-CPT-11, or LS-SN-38 by IND for 4 weeks. In vivo responses were measured for tumor growth by serial bioluminescence imaging and animal subject survival. The concentration of SN-38 in the brainstem tumor administered by IND was determined by liquid chromatography–mass spectrometry (LC-MS). Immunohistochemical analyses of the proliferative and apoptotic responses of in vivo tumor cells were performed with Ki-67 and TUNEL staining.

RESULTS

LS-SN-38 inhibited DIPG cell growth and colony formation and increased apoptosis, outperforming LS-CPT-11. Rhod-labeled LS-SN-38 showed intracellular fluorescence signals beginning at 30 minutes and peaking at 24 hours following treatment. LC-MS analysis revealed an SN-38 concentration in the brainstem tumor of 0.66 ± 0.25 ng/ml (5.43% ± 0.31% of serum concentration). IND of LS-SN-38 delayed tumor growth and significantly prolonged animal survival compared with IND of LS-control (p < 0.0001) and LS-CPT-11 (p = 0.003). IND of LS-SN-38 increased the number of TUNEL-positive cells and decreased the Ki-67–positive cells in the brainstem tumor.

CONCLUSIONS

This study demonstrates that IND of LS-SN-38 bypasses the BBB and enables efficient and noninvasive drug delivery to the brainstem tumor, providing a promising therapeutic approach for treating DIPG.

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David C. Lauzier, Samuel J. Cler, Anna L. Huguenard, Arindam R. Chatterjee, and Joshua W. Osbun

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Ebtesam Abdulla, Mrinmoy Kundu, Sabrina Rahman, and Md M. Rahman

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Emma Kofoed Lauridsen, Urszula Maria Ciochon, Anders Tolver, Mark Bech Knudsen, Laura Giraldi, Jacob Bertram Springborg, Lars Bøgeskov, Lars Poulsgaard, Tiit Mathiesen, Karin Piil, and Kåre Fugleholm

OBJECTIVE

Subfrontal meningiomas grow insidiously in areas with high cerebral compliance and a relative scarcity of eloquent function. Symptoms develop progressively, are nonspecific, and include anosmia, changes in personality and cognition, depressive symptoms, headaches, visual disturbances, and seizures. Patients with subfrontal meningiomas carry the highest risk of developing psychological symptoms, which makes patient-reported outcome in terms of long-term health-related quality of life (HRQOL), anxiety, and depression of particular importance. This observational study aimed to investigate long-term HRQOL, anxiety, and depression in patients with subfrontal meningiomas who underwent a bifrontal craniotomy (subfrontal) approach between 2008 and 2017 at a single tertiary center. Correlations between preoperative, perioperative, and postoperative factors and HRQOL, anxiety, and depression were analyzed to detect prognostic factors.

METHODS

Seventy-seven consecutive patients who underwent operations at Rigshospitalet, Copenhagen, Denmark, between 2008 and 2017 were retrospectively analyzed. Patients were prospectively invited to respond to the Functional Assessment of Cancer Therapy–General, Functional Assessment of Cancer Therapy–Brain, and Hospital Anxiety and Depression Scale. Information regarding preoperative, perioperative, and postoperative factors were collected from the patients’ medical records and scans.

RESULTS

Patients with subfrontal meningiomas exhibited better HRQOL and lower levels of anxiety and depression than general populations and other meningioma and glioblastoma cohorts. The only statistically significant prognostic factors for long-term HRQOL were number of symptoms at diagnosis and whether patients were discharged home or to a local hospital postoperatively. Tumor and peritumoral brain edema volumes were not prognostic factors.

CONCLUSIONS

Patients with subfrontal meningiomas exhibited better long-term postoperative HRQOL and were less likely to have anxiety or depression than the reference populations. This information on long-term prognosis is very valuable for patients, next of kin, and neurosurgeons and has not been previously studied in detail.

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MirHojjat Khorasanizadeh, Max Shutran, Alfonso Garcia, Alejandro Enriquez-Marulanda, Justin Moore, Christopher S. Ogilvy, and Ajith J. Thomas

OBJECTIVE

Middle meningeal artery (MMA) embolization (MMAE) is a new therapeutic modality for chronic subdural hematoma (cSDH). There is limited evidence comparing various MMAE procedural techniques, resulting in significant variations in technique and procedural planning. The objective of this study was to compare outcomes of MMAE by the number and location of MMA branches that were embolized.

METHODS

A single-center retrospective study of patients with cSDH treated by MMAE was conducted. Clinical outcomes, need for re-intervention, and changes in hematoma size were compared between different MMAE techniques.

RESULTS

Ninety-four cSDHs in 78 patients were included. Embolization of the proximal trunk only, distal branches only, or proximal trunk plus distal branches resulted in similar rates of need for rescue surgery (7.4%, 13.0%, and 6.8%, respectively; p = 0.66) and rates of reducing the volume of the hematoma by at least 50% (74.1%, 80.0%, and 77.5%, respectively; p = 0.88). Embolization of only one branch had similar outcomes to embolization of more than one branch, as rescue surgery rates were 9.3% and 7.8% (p = 0.80), and rates ≥ 50% volume reduction were 75.6% and 78.3% (p = 0.76), respectively. Selective embolization of the dominant MMA branch was not associated with significantly different outcomes.

CONCLUSIONS

Outcomes of distal, proximal, or combined proximal and distal MMAE in cSDH are not significantly different. Embolization of more than one branch is not associated with improved treatment efficacy. Arguably, targeting any location in the MMA provides sufficient flow restriction to enable spontaneous hematoma resolution. Accordingly, a technical planning algorithm for cSDH MMAE is suggested.

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Nutdanai Neti, Panai Laohaprasitiporn, Yuwarat Monteerarat, Roongsak Limthongthang, and Torpon Vathana

OBJECTIVE

Nerve transfer surgery has been a mainstay treatment of brachial plexus injury, with varying success rates. Patients undergoing unsuccessful surgery are left with a useless limb for at least 2 years. Preoperative prediction has become a topic of interest to avoid an unsuccessful nerve transfer surgery. This study aimed to find strong predictive factors and develop a prediction model for unsuccessful functional elbow flexion recovery 2 years after a nerve transfer surgery in patients with brachial plexus injury.

METHODS

This retrospective study reviewed the medical records of 987 patients with traumatic brachial plexus injury who underwent brachial plexus surgery by five hand and microsurgery surgeons at a single tertiary care referral center from December 2001 to July 2018. Four hundred thirty-three patients were eligible for analysis. Patient demographic data, injury factors, surgical details, and postoperative factors were collected. Multivariable logistic regression was used to identify strong prognostic factors for unsuccessful nerve transfer surgery for elbow flexion. A simplified model was developed by rounding the coefficient to the nearest 0.5 score or an integer. Both original and simplified models were validated using the Hosmer-Lemeshow goodness-of-fit test and bootstrapping.

RESULTS

A full, original prognostic model from a stepwise backward logistic regression consisted of a BMI ≥ 23 kg/m2 (p = 0.015), smoking (p = 0.046), total arm–type injury (p = 0.033), donor nerve (p < 0.001), associated upper-extremity fracture (p = 0.013), and associated ipsilateral vascular injury (p = 0.095). The areas under the receiver operating characteristic curve of the original and simplified models were 0.765 and 0.766, respectively. The Hosmer-Lemeshow test showed good agreement of predicted and observed probability of the original (p = 0.49) and simplified (p = 0.19) models. Bootstrapping estimated an average optimism (1.9%) in the original model and minimal optimism (0.1%) in the simplified model.

CONCLUSIONS

The prediction model for failed elbow flexion recovery after nerve transfer surgery in traumatic brachial plexus injury was developed with good predictive value and internal validity. An alternative treatment, i.e., primary free functioning muscle transfer, should be offered in preoperative counseling in cases of a very high risk of failure.

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Joshua S. Catapano, Dimitri Benner, Emmajane G. Rhodenhiser, Kavelin Rumalla, Christopher S. Graffeo, Visish M. Srinivasan, Ethan A. Winkler, and Michael T. Lawton

OBJECTIVE

Safe entry zones (SEZs) enable safe tissue transgression to lesions beneath the brainstem surface. However, evidence for the safety of SEZs is scarce and is based on anatomical studies, case reports, and small series.

METHODS

A cohort of 154 patients who underwent microsurgical brainstem cavernous malformation (BSCM) treatment during a 23-year period and who had preoperative MR images and intraoperative photographs or videos was retrospectively examined. This study assessed the safety of SEZs for access to deep BSCMs, preoperative MRI to predict BSCM surface proximity, and the relationships between BSCM subtype, surgical approach, and SEZs. Lesions were characterized as exophytic, superficial, or deep on the basis of preoperative MRI and intraoperative inspection. Outcomes were scored as good (modified Rankin Scale [mRS] score ≤ 2) or poor (mRS score > 2) and relative outcomes as stable/improved or worse relative to baseline (± 1 point).

RESULTS

Resections included 34 (22%) in the midbrain, 102 (66%) in the pons, and 18 (12%) in the medulla. Of those, 23 (15%) were exophytic, 57 (37%) were superficial, and 74 (48%) were deep. Established SEZs were used for 97% (n = 72) of deep lesions; the preferred SEZ associated with its subtype was used for 91% (n = 67). MR images accurately depicted exophytic BSCMs that did not require SEZ approaches (sensitivity, 96%) but overestimated the proximity of lesions superficial to brainstem surfaces (specificity, 67%), resulting in unanticipated SEZ use. Final neurological outcomes were good in 80% of patients with follow-up data (119/149), and relative outcomes were stable/improved in 93% (139/149). Outcomes for patients with brainstem transgression through an SEZ did not differ from outcomes for patients with superficial or exophytic lesions that did not require SEZ use (final mRS score ≤ 2 in 72% of all patients with deep lesions vs 82% of all patients with superficial or exophytic lesions [p = 0.10]). Among patients with follow-up, the rates of permanent new cranial nerve deficits in patients with deep BSCMs and superficial or exophytic BSCMs were 21% and 20%, respectively (p = 0.81), with no significant change in overall cranial nerve deficit (0 and −1, p = 0.65).

CONCLUSIONS

Neurological outcomes for patients with deep BSCMs were equivalent to those for superficial or exophytic BSCMs, validating the safety of SEZs for deep BSCMs. Preoperative T1-weighted MR images overestimated the lesion’s surface proximity, necessitating detailed knowledge of SEZs and readiness to use them in cases of radiological-microsurgical discordance. Most patients achieved favorable outcomes despite the transgression of eloquent brainstem tissue in and around SEZs.

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Brian F. Saway, Warren Roth, Craig D. Salvador, Muhammed Amir Essibayi, Guilherme B. F. Porto, Ehsan Dowlati, Daniel R. Felbaum, Mitchell Rock, Charles Withington, Sohum K. Desai, Ameer E. Hassan, Wondwossen G. Tekle, and Alejandro Spiotta

OBJECTIVE

Middle meningeal artery (MMA) embolization and the Subdural Evacuation Port System (SEPS) are minimally invasive treatment paradigms for chronic subdural hematoma (cSDH). Although SEPS offers acute decompression of local mass effect from a cSDH, MMA embolization has been shown to reduce the rate of cSDH recurrence. In combination, these procedures present a potentially safer strategy to a challenging pathology. The authors present a multi-institutional retrospective case series that assessed the safety, efficacy, and complications of SEPS and MMA embolization for cSDH.

METHODS

A retrospective review was performed of patients who underwent SEPS placement and MMA embolization for cSDH between 2018 and 2021 at three institutions.

RESULTS

One hundred patients with 136 cSDHs and a median age of 73 years underwent both SEPS placement and MMA embolization. Initial Glasgow Coma Scale scores were between 14 and 15 in 81% of patients and between 9 and 13 in 14%. The median initial midline shift (MLS) was 7 mm, with subdural hematoma (SDH) in the left hemisphere (lh) in 30% of patients, right hemisphere (rh) in 34%, and bilateral hemispheres in 36%. Follow-up was available for 86 patients: 93.4% demonstrated decreased MLS, and all patients with lhSDH and rhSDH demonstrated progressive decrease in SDH size. The overall complication rate was 4%, including 1 case of facial palsy and 3 cases of iatrogenic acute SDH. Two subjects (2%) required craniotomy for hematoma evacuation. The rate of good functional outcomes, with modified Rankin Scale (mRS) score < 2, was 89% on final follow-up and the overall mortality rate was 2%. A good mRS score on admission was associated with increased odds of functional improvement at follow-up (p < 0.001).

CONCLUSIONS

SEPS placement with MMA embolization for cSDH can be done safely and effectively reduces cSDH size with minimal perioperative morbidity.

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Guo-Chen Sun, Xu-Jun Shu, Xiao-Que Zheng, Xiao-Dong Ma, Gang Cheng, Jia-Lin Liu, Ling Chen, and Jian-Ning Zhang

OBJECTIVE

The classic transopercular or transsylvian approach to insular gliomas removes the tumor laterally through the insular cortex. This study describes a new anteroposterior approach through the frontal isthmus for insular glioma surgery.

METHODS

The authors detailed the surgical techniques for resection of insular gliomas through the transfrontal isthmus approach. Fifty-nine insular gliomas with at least Berger-Sanai zone I involvement were removed with the new approach, and extent of resection and postoperative neurological outcomes were assessed.

RESULTS

Fifty-nine patients were enrolled in the study, including 35 men and 24 women, with a mean (range) age 44.3 (19–75) years. According to the Berger-Sanai classification system, the most common tumor was a giant glioma (67.8%), followed by involvement of zones I and IV (18.6%). Twenty-two cases were Yaşargil type 3A/B, and 37 cases were Yaşargil type 5A/B. The average angle between the lateral plane of the putamen and sagittal line was 33.53°, and the average width of the isthmus near the anterior insular point was 33.33 mm. The average angle between the lateral plane of the putamen and the sagittal line was positively correlated with the width of the isthmus near the anterior insular point (r = 0.935, p < 0.0001). The median (interquartile range [IQR]) preoperative tumor volume was 67.82 (57.64–92.19) cm3. Of 39 low-grade gliomas, 26 (66.67%) were totally resected; of 20 high-grade gliomas, 19 (95%) were totally resected. The median (IQR) extent of resection of the whole group was 100% (73.7%–100%). Intraoperative diffusion-weighted imaging showed no cases of middle cerebral artery– or lenticulostriate artery–related stroke. Extent of insular tumor resection was positively correlated with the angle of the lateral plane of the putamen and sagittal line (r = −0.329, p = 0.011) and the width of the isthmus near the anterior insular point (r = −0.267, p = 0.041). At 3 months postoperatively, muscle strength grade exceeded 4 in all cases, and all patients exhibited essentially normal speech. The median (IQR) Karnofsky performance score at 3 months after surgery was 90 (80–90).

CONCLUSIONS

The transfrontal isthmus approach changes the working angle from lateral-medial to anterior-posterior, allowing for maximal safe removal of insular gliomas.