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Tomokatsu Hori, Mikhail Chernov, Yasir A. Alshebib, Yuichi Kubota, Seigo Matsuo, Hideki Shiramizu, and Yoshikazu Okada

OBJECTIVE

The objective of this study was to evaluate the long-term outcomes after resection of brainstem cavernous malformations (BSCMs) and to assess the usefulness of the Lawton grading system in these cases.

METHODS

This retrospective study analyzed 46 consecutive patients with BSCMs operated on between July 1990 and December 2020. Outcomes at the last follow-up were defined as favorable (modified Rankin Scale [mRS] score 0–2) or unfavorable (mRS score > 2).

RESULTS

The study cohort comprised 24 men (52%) and 22 women (48%), ranging in age from 8 to 78 years old (median 37 years). In 19 patients (41%), the preoperative mRS score was > 2. All patients had hemorrhagic BSCM. There were 12 (26%) mesencephalic, 19 (41%) pontine, 7 (15%) medullary, and 8 (17%) cerebellar peduncle lesions, with a maximal diameter ranging from 5 to 40 mm (median 15 mm). In total, 24 BSCMs (52%) had bilateral extension crossing the brainstem midline. Lawton grades of 0, I, II, III, IV, V, and VI were defined in 3 (7%), 2 (4%), 10 (22%), 11 (24%), 8 (17%), 7 (15%), and 5 (11%) cases, respectively. Total resection of BSCMs was attained in 43 patients (93%). There were no perioperative deaths. Excluding the 3 most recent cases, the length of follow-up ranged from 56 to 365 months. The majority of patients demonstrated good functional recovery, but regress of the preexisting oculomotor nerve deficit was usually incomplete. No new hemorrhagic events were noted after total resection of BSCMs. In 42 patients (91%), the mRS score at the time of last follow-up was ≤ 2 (favorable outcome), and in 18 (39%), it was 0 (absence of neurological symptoms). Forty-four patients (96%) demonstrated clinical improvement and 2 (4%) had no changes compared with the preoperative period. Multivariate analysis revealed that only lower Lawton grade had a statistically significant independent association (p = 0.0280) with favorable long-term outcome. The area under the receiver operating characteristic curve for prediction of favorable outcome with 7 available Lawton grades of BSCM was 0.93.

CONCLUSIONS

Resection of hemorrhagic BSCMs by an experienced neurosurgeon may be performed safely and effectively, even in severely disabled patients. In the authors’ experience, preexisting oculomotor nerve palsy represents the main cause of permanent postoperative neurological morbidity. The Lawton grading system effectively predicts long-term outcome after surgery.

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Luigi Albano, Hansen Deng, Zhishuo Wei, Lena Vodovotz, Ajay Niranjan, and L. Dade Lunsford

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I–IV VS after radiosurgery.

METHODS

A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification.

RESULTS

Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ± 2.82 cm3 (range 0.12–18.77 cm3) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18–54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS.

CONCLUSIONS

Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

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Caple A. Spence, Sonia V. Eden, Brenton Pennicooke, Owoicho Adogwa, Langston T. Holly, Babu G. Welch, Nnenna Mbabuike, Edjah Nduom, and William W. Ashley Jr.

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Jürgen Beck, Ulrich Hubbe, Jan-Helge Klingler, Roland Roelz, Luisa Mona Kraus, Florian Volz, Niklas Lützen, Horst Urbach, Kristin Kieselbach, and Christian Fung

OBJECTIVE

Spinal CSF leaks cause spontaneous intracranial hypotension (SIH). Surgical closure of spinal CSF leaks is the treatment of choice for persisting leaks. Surgical approaches vary, and there are no studies in which minimally invasive techniques were used. In this study, the authors aimed to detail the safety and feasibility of minimally invasive microsurgical sealing of spinal CSF leaks using nonexpandable tubular retractors.

METHODS

Consecutive patients with SIH and a confirmed spinal CSF leak treated at a single institution between April 2019 and December 2020 were included in the study. Surgery was performed via a dorsal 2.5-cm skin incision using nonexpandable tubular retractors and a tailored interlaminar fenestration and, if needed, a transdural approach. The primary outcome was successful sealing of the dura, and the secondary outcome was the occurrence of complications.

RESULTS

Fifty-eight patients, 65.5% of whom were female (median age 46 years [IQR 36–55 years]), with 38 ventral leaks, 17 lateral leaks, and 2 CSF venous fistulas were included. In 56 (96.6%) patients, the leak could be closed, and in 2 (3.4%) patients the leak was missed because of misinterpretation of the imaging studies. One of these patients underwent successful reoperation, and the other patient decided to undergo surgery at another institution. Two other patients had to undergo reoperation because of insufficient closure and a persisting leak. The rate of permanent neurological deficit was 1.7%, the revision rate for a persisting or recurring leak was 3.4%, and the overall revision rate was 10.3%. The rate of successful sealing during the primary closure attempt was 96.6% and 3.4% patients needed a secondary attempt. Clinical short-term outcome at discharge was unchanged in 14 patients and improved in 25 patients, and 19 patients had signs of rebound intracranial hypertension.

CONCLUSIONS

Minimally invasive surgery with tubular retractors and a tailored interlaminar fenestration and, if needed, a transdural approach is safe and effective for the treatment of spinal CSF leaks. The authors suggest performing a minimally invasive closure of spinal CSF leaks in specialized centers.

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*Shahab Aldin Sattari, Wuyang Yang, Risheng Xu, James Feghali, Rafael J. Tamargo, and Judy Huang

OBJECTIVE

Pediatric deep brain arteriovenous malformations (bAVMs) represent a unique management challenge given their higher cumulative risk of hemorrhage as well as a higher risk of treatment. Better understanding of hemorrhage risk in this patient population will lead to a better decision-making process for patient management.

METHODS

The authors retrospectively reviewed their institutional bAVM database from 1990 to 2019 and included patients younger than 21 years who had deep-seated bAVMs. They present the annual hemorrhage risk, during the natural history and after treatment, and functional outcomes.

RESULTS

Thirty-one pediatric patients were included in this study (13 males and 18 females) with a mean age of 11.8 (SD 4.4) years. The most frequent presenting symptoms were headache (54.8%), weakness (38.7%), and seizure (22.6%). The mean follow-up duration was 13.14 (SD 12.5) years, during which 7 (22.6%) AVMs were obliterated, 10 (32.3%) individuals experienced hemorrhage, and the modified Rankin Scale score worsened in 8 (25.8%) patients. The annual natural history risk of hemorrhage was 3.24% per patient, and the overall annual hemorrhage risk after treatment was 1.98% per patient. In particular, the risk was reduced to 0.64% per patient in the stereotactic radiosurgery (SRS) group. Non-White race showed a trend of higher rupture at presentation (OR 5 [95% CI 0.84–41.68], p = 0.09). Female sex was associated with higher odds (OR 13.076 [95% CI 1.424–333.591], p = 0.048) and SRS was associated with lower odds (OR 0.122 [95% CI 0.011–0.862], p = 0.049) of follow-up hemorrhage.

CONCLUSIONS

Given the substantial cumulative risk of lifelong hemorrhagic stroke in pediatric patients, timely definitive treatment is warranted. SRS may be beneficial when the risk-benefit profile is deemed acceptable.

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William J. Ares, Brian T. Jankowitz, Peter Kan, Alejandro M. Spiotta, Peter Nakaji, Jason D. Wilson, Kyle M. Fargen, Edwin Ramos, Jody Leonardo, and Ramesh Grandhi

OBJECTIVE

Burnout and work-life balance have been noted to be problems for residents across all fields of medicine, including neurosurgery. No studies to date have evaluated how these factors may contribute to issues outside of the hospital, specifically residents’ home lives. This study aimed to evaluate the interplay between home life and work life of neurosurgical residents, specifically from the point of view of residents’ significant others.

METHODS

Online surveys were distributed to the significant others of neurosurgical residents at 12 US neurosurgery residencies. Residents’ partners were asked about relationship dynamics, their views on neurosurgery residency (work-life balance and burnout), and their views of neurosurgery as a career.

RESULTS

The majority of residents’ significant others (84%) reported being satisfied with their relationship. Significant others who reported dissatisfaction with their relationship were more likely to report frustration with work-life balance and more likely to report their resident partner as having higher levels of burnout.

CONCLUSIONS

From the perspective of neurosurgery residents’ significant others, higher perceived levels of burnout and lower satisfaction with work-life balance are correlated with lower levels of relationship satisfaction. These findings speak to the complex interplay of work life and home life and can be used to inform future interventions into improving the quality of life for both the resident and the significant other.

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MirHojjat Khorasanizadeh, Max Shutran, Clemens M. Schirmer, Mohamed M. Salem, Andrew J. Ringer, Ramesh Grandhi, Alim P. Mitha, Michael R. Levitt, Brian T. Jankowitz, Philipp Taussky, Ajith J. Thomas, Justin M. Moore, and Christopher S. Ogilvy

OBJECTIVE

Flow diverters have revolutionized the endovascular treatment of intracranial aneurysms. Here, the authors present the first large-scale North American multicenter experience using the Flow Redirection Endoluminal Device (FRED) in the treatment of cerebral aneurysms.

METHODS

Consecutive cerebral aneurysms treated with FRED at 7 North American centers between June 2020 and November 2021 were included. Data collected included patient demographic characteristics, aneurysm characteristics, periprocedural and long-term complications, modified Rankin Scale (mRS) scores, and radiological follow-up.

RESULTS

In total, 133 aneurysms in 116 patients were treated with 123 FRED deployment procedures and included in this study. One hundred twenty-six aneurysms (94.7%) were unruptured, 117 (88.0%) saccular, and 123 (92.5%) located in anterior circulation. The mean (range) aneurysm maximal width and neck width sizes were 7.2 (1.5–42.5) mm and 4.1 (1.0–15.1) mm, respectively. Successful FRED deployment was achieved in 122 procedures (99.2%). Adjunctive coiling was used in 4 procedures (3.3%). Radiological follow-up was available for 101 aneurysms at a median duration of 7.0 months. At last follow-up, complete occlusion was observed in 55.4% of patients, residual neck in 8.9%, and filling aneurysm in 35.6%; among cases with radiological follow-up duration > 10 months, these values were 21/43 (48.8%), 3/43 (7.0%), and 19/43 (44.2%), respectively. On multivariate regression analysis, age (OR 0.93, p = 0.001) and aneurysm neck size (OR 0.83, p = 0.048) were negatively correlated with odds of complete occlusion at latest follow-up. The retreatment rate was 6/124 (4.8%). The overall complication rate was 31/116 (26.7%). Parent vessel occlusion, covered branch occlusion, and in-stent stenosis were detected in 9/99 (9.1%), 6/63 (9.5%), and 15/99 (15.2%) cases, respectively. The FRED-related, symptomatic, thromboembolic, and hemorrhagic complication rates were 22.4%, 12.9%, 6.9%, and 0.9% respectively. The morbidity rate was 10/116 patients (8.6%). There was 1 death due to massive periprocedural internal carotid artery stroke, and 3.6% of the patients had an mRS score > 2 at the last follow-up (vs 0.9% at baseline).

CONCLUSIONS

As the first large-scale North American multicenter FRED experience, this study confirmed the ease of successful FRED deployment but suggested lower efficacy and a higher rate of complications than reported by previous European and South American studies on FRED and other flow-diverting devices. The authors recommend judicious use of this device until future studies can better elucidate the long-term outcomes of FRED treatment.

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Andrei Brînzeu and Marc Sindou

At the end of the 1950s, at the direction of Pierre Wertheimer, the first French professor of neurosurgery, the treatment of neurological and neurosurgical diseases for Lyon’s 2 million people was concentrated in a single center functioning as not only a hospital but also a campus for neuroscience. The ideas behind the structure revolve around concepts such as spatial unity, comprehensive specialized fields, a critical mass of patients, a structured training program, and essential cross-communication between areas in the same field. Through several generations of doctors, researchers, and professors, the Pierre Wertheimer Neurological and Neurosurgical Hospital in Lyon (NHL) has had an important impact on clinical practice, fundamental neuroscientific research, and specialist training. Under Wertheimer’s stewardship, functional neurosurgery became one of the fields of excellence at the NHL with contributions in pain surgery and physiology but also epilepsy surgery and surgery for spasticity. Typically, these contributions were the result of the collaboration of separate teams, ultimately laying the groundwork for a neuroscientific doctoral school. The large mass of patients treated at the NHL provided opportunities for other, more isolated insights, such as the classification of pineal tumors and contributions to interventional neuroradiology. The present work endeavors to illustrate the contributions of the NHL to neuroscience and discuss the background allowing for their occurrence.

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Mark C. Dougherty, Seiji B. Shibata, J. Jason Clark, Franklin J. Canady, Charles W. Yates, and Marlan R. Hansen

OBJECTIVE

Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5ʹ-triphosphate–competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models.

METHODS

Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees.

RESULTS

Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment.

CONCLUSIONS

The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2–associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

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Frederic A. Vallejo, Benjamin Schachner, Nathan VanderVeer-Harris, Adrian A. Torres, John Weng, Henry Chang, Robert Bollo, and John Ragheb

OBJECTIVE

Many pathways to positions of leadership exist within pediatric neurological surgery. The authors sought to investigate common trends in leadership among pediatric neurosurgery fellowship directors (FDs) and describe how formalized pediatric neurosurgical training arrived at its current state.

METHODS

Fellowship programs were identified using the Accreditation Council for Pediatric Neurosurgery Fellowships website. Demographic, training, membership, and research information was collected via email, telephone, curricula vitae, and online searches.

RESULTS

The authors’ survey was sent to all 35 identified FDs, and 21 responses were received. Response data were supplemented with curricula vitae and online data prior to analysis. FDs were predominantly male, self-identified predominantly as Caucasian, and had a mean age of 53 years. The mean duration from residency graduation until FD appointment was 13.4 years. The top training programs to produce future FDs were New York University and Washington University in St. Louis (residency) and Washington University in St. Louis (fellowship).

CONCLUSIONS

This study characterizes the current state of pediatric neurosurgery fellowship program leadership. The data serve as an important point of reference to compare with future leadership as well as contrast with neurosurgery and other surgical disciplines in general.