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David Satzer and Daniel J. Guillaume

Object

Brainstem dysfunction occurs in a minority of patients with myelomeningocele (MMC), most of whom have Chiari Type II malformation. Some surgeons advocate early identification of these patients for craniocervical decompression to avoid significant mortality. The auditory brainstem response has been found to be abnormal in most children with MMC. The present study examines whether failure of routine newborn hearing screening (NHS) predicts brainstem dysfunction in MMC patients.

Methods

The charts of 40 newborns with MMC and 50 newborns without MMC who stayed in the neonatal intensive care unit were reviewed. Results of NHS, brainstem symptoms, birth demographics, and surgical history were retrospectively examined. Differences in the presence and onset of brainstem symptoms by NHS result were assessed.

Results

Failure of NHS was more common among newborns with MMC who developed brainstem symptoms (31%, 4 of 13 patients) than among newborns without MMC (0%, 0 of 50 patients; p = 0.001). Among the 40 newborns with MMC, brainstem symptoms were more common in those who failed NHS (80%, 4 of 5 patients) than in those who passed (26%, 9 of 35 patients; p = 0.031). Respiratory symptom onset occurred later in patients who failed NHS (median 16 months) than among those who passed (median 0 months; p = 0.022). The positive and negative predictive values of NHS for brainstem dysfunction in MMC were 0.80 and 0.74, respectively.

Conclusions

Results of NHS may help predict future brainstem dysfunction in patients with MMC and may be useful to incorporate into prognostic assessment and surgical decision making.

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Daniel J. Guillaume and Su-Chun Zhang

✓ The primary therapeutic goal of embryonic stem cell (ESC) research is cell replacement therapy. During the last decade, great strides have been made in developing in vitro protocols for differentiating human ESCs into neuroepithelial progenitors. More recent progress has been made in further directing them into becoming cells with specialized regional and neurotransmitter identities, such as midbrain dopaminergic and spinal motor neurons. Along with directed differentiation, other current efforts are aimed at efficient enrichment, avoidance of immune rejection, demonstration of functional integration, genetic modification to regulate neurotransmitter and factor release, directed axon growth, in vivo cell tracking, and measures to ensure safety. This review will focus on the potential of ESCs as a source of transplantable cells for use in cell replacement therapy.

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Daniel J. Guillaume, Stephen L. Huhn, Nathan R. Selden, and Robert D. Steiner

✓ Successful cellular replacement in the diseased human central nervous system (CNS) faces numerous hurdles. In this first installment of a 2-part review, the authors report on the preclinical challenges involved in preparing for a major Phase I trial investigating the safety of human neural stem cell transplantation in a lysosomal storage disorder. Specifically, they discuss choice of the ideal disease for treatment, best donor cell type and source for implantation, the in vitro and in vivo methods used to estimate safety and efficacy, the challenges to noninvasive tracking of cells after transplantation, and the unique issues related to the immunology of CNS cellular transplantation.

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Nathan R. Selden, Daniel J. Guillaume, Robert D. Steiner, and Stephen L. Huhn

✓ Cellular replacement therapy attempts to improve functioning of the diseased human central nervous system (CNS). In this second installment of a 2-part review, the authors discuss the major challenges to the translation of in vitro and animal studies of neural stem cell (NSC) therapy in the clinical setting. This analysis details the problems unique to the design of clinical trials using human NSCs, outlines patient selection practices, describes surgical techniques for cellular transplantation, and reviews the regulatory issues and ethical concerns in trials involving neurologically impaired children.

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Vyom Unadkat, Dhiraj J. Pangal, Guillaume Kugener, Arman Roshannai, Justin Chan, Yichao Zhu, Nicholas Markarian, Gabriel Zada, and Daniel A. Donoho

OBJECTIVE

While the utilization of machine learning (ML) for data analysis typically requires significant technical expertise, novel platforms can deploy ML methods without requiring the user to have any coding experience (termed AutoML). The potential for these methods to be applied to neurosurgical video and surgical data science is unknown.

METHODS

AutoML, a code-free ML (CFML) system, was used to identify surgical instruments contained within each frame of endoscopic, endonasal intraoperative video obtained from a previously validated internal carotid injury training exercise performed on a high-fidelity cadaver model. Instrument-detection performances using CFML were compared with two state-of-the-art ML models built using the Python coding language on the same intraoperative video data set.

RESULTS

The CFML system successfully ingested surgical video without the use of any code. A total of 31,443 images were used to develop this model; 27,223 images were uploaded for training, 2292 images for validation, and 1928 images for testing. The mean average precision on the test set across all instruments was 0.708. The CFML model outperformed two standard object detection networks, RetinaNet and YOLOv3, which had mean average precisions of 0.669 and 0.527, respectively, in analyzing the same data set. Significant advantages to the CFML system included ease of use, relatively low cost, displays of true/false positives and negatives in a user-friendly interface, and the ability to deploy models for further analysis with ease. Significant drawbacks of the CFML model included an inability to view the structure of the trained model, an inability to update the ML model once trained with new examples, and the inability for robust downstream analysis of model performance and error modes.

CONCLUSIONS

This first report describes the baseline performance of CFML in an object detection task using a publicly available surgical video data set as a test bed. Compared with standard, code-based object detection networks, CFML exceeded performance standards. This finding is encouraging for surgeon-scientists seeking to perform object detection tasks to answer clinical questions, perform quality improvement, and develop novel research ideas. The limited interpretability and customization of CFML models remain ongoing challenges. With the further development of code-free platforms, CFML will become increasingly important across biomedical research. Using CFML, surgeons without significant coding experience can perform exploratory ML analyses rapidly and efficiently.

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Daniel J. Guillaume, Kristin Knight, Carol Marquez, Dale F. Kraemer, Dianna M. E. Bardo, and Edward A. Neuwelt

Object

Cerebrospinal fluid shunting has previously been associated with hearing loss. Although the mechanism for this is unclear, it is thought that changes in CSF pressure can affect cochlear physiology via endolymph expansion in the setting of a patent cochlear aqueduct. Patients undergoing radiation and cisplatin chemotherapy are at risk for hearing loss. The authors hypothesized that the incidence and severity of hearing loss in patients undergoing radiation and chemotherapy for medulloblastoma would be greater in those with shunts than in those without shunts.

Methods

Baseline and longitudinal audiology data were collected in 33 patients with medulloblastoma who were receiving radiation and cisplatin chemotherapy. Additional data included age, sex, details of shunt placement and revision, and details of chemotherapy and radiation. Hearing sensitivity and peripheral auditory function measures included pure tone audiometry, immittance audiometry, and distortion product evoked otoacoustic emissions. Ototoxicity was determined according to the American Speech-Language-Hearing Association criteria. Severity of hearing loss was determined using the Brock hearing loss grades. Incidence of hearing loss and association with shunting was determined.

Results

Thirteen (39.4%) of the 33 patients evaluated had undergone shunt placement. Hearing loss occurred in 14 (70%) of 20 patients without shunts and in 13 (100%) of 13 patients with shunts. The difference between the rates of hearing loss in patients with shunts versus those without the devices was highly significant (p = 0.0008). The odds ratio for hearing loss in patients with a CSF shunt compared with those without a shunt was 23.49 (95% CI 4.21–131.15). Age, side of shunt, evidence of dissemination, diameter of cochlear aqueduct, and treatment protocol did not have a significant effect on shunt-related ototoxicity.

Conclusions

This study suggests an independent association between CSF shunting and hearing loss in children undergoing treatment for medulloblastoma, laying the foundation for a prospective study evaluating hearing loss in children with shunts who are not treated with ototoxic therapy.

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Mark P. Piedra, Eric M. Thompson, Nathan R. Selden, Brian T. Ragel, and Daniel J. Guillaume

Object

The object of this study was to determine if early cranioplasty after decompressive craniectomy for elevated intracranial pressure in children reduces complications.

Methods

Sixty-one consecutive cases involving pediatric patients who underwent autologous cranioplasty after decompressive craniectomy for raised intracranial pressure at a single academic children's hospital over 15 years were studied retrospectively.

Results

Sixty-one patients were divided into early (< 6 weeks; 28 patients) and late (≥ 6 weeks; 33 patients) cranioplasty cohorts. The cohorts were similar except for slightly lower age in the early (8.03 years) than the late (10.8 years) cranioplasty cohort (p < 0.05). Bone resorption after cranioplasty was significantly more common in the late (42%) than the early (14%) cranioplasty cohort (p < 0.05; OR 5.4). No other complication differed in incidence between the cohorts.

Conclusions

After decompressive craniectomy for raised intracranial pressure in children, early (< 6 weeks) cranioplasty reduces the occurrence of reoperation for bone resorption, without altering the incidence of other complications.

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Bharathi D. Jagadeesan, Haralabos Zacharatos, David R. Nascene, Andrew W. Grande, Daniel J. Guillaume, and Ramachandra P. Tummala

A 5-month-old infant was to be treated with elective transarterial embolization for a vein of Galen aneurysmal malformation (VGAM). A team of endovascular surgical neuroradiologists, pediatric interventional radiologists, and pediatric cardiologists attempted conventional femoral arterial access, which was unsuccessful given the small caliber of the femoral arteries and superimposed severe vasospasm. Thereafter, eventual arterial access was achieved by navigating from the venous to the arterial system across the patent foramen ovale following a right femoral venous access. Embolization was then successfully performed. At a later date, the child underwent successful transvenous balloon-assisted embolization and eventual arterial embolization with cure of the VGAM.

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Bharathi D. Jagadeesan, Andrew W. Grande, Daniel J. Guillaume, David R. Nascene, and Ramachandra P. Tummala

Dural sinus malformations (DSMs) are rare congenital malformations that can be midline or lateral in location. Midline DSMs have been reported to have a worse prognosis than lateral DSMs and have traditionally been more difficult to manage. The authors report 2 unusual manifestations of midline DSMs and their management with percutaneous transfontanelle embolization. The first patient (Case 1) presented at 21 days of life with a large midline DSM and multiple highflow dural and pial arteriovenous shunts. The child developed congestive cardiac failure and venous congestion with intracranial hemorrhage and seizures within a few weeks. The second patient (Case 2) presented with a large midline DSM found on prenatal imaging that was determined to be a purely venous malformation on postnatal evaluation. This large malformation resulted in consumptive coagulopathy and apneic episodes from brainstem compression. The patient in Case 1 was treated initially with endovascular embolization and eventually with curative percutaneous-transfontanelle embolization. The patient in Case 2 was treated with percutaneous transfontanelle embolization in combination with posterior fossa decompression and cranial expansion surgery.

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Dhiraj J. Pangal, David J. Cote, Jacob Ruzevick, Benjamin Yarovinsky, Guillaume Kugener, Bozena Wrobel, Elisabeth H. Ference, Mark Swanson, Andrew J. Hung, Daniel A. Donoho, Steven Giannotta, and Gabriel Zada

OBJECTIVE

The utility of robotic instrumentation is expanding in neurosurgery. Despite this, successful examples of robotic implementation for endoscopic endonasal or skull base neurosurgery remain limited. Therefore, the authors performed a systematic review of the literature to identify all articles that used robotic systems to access the sella or anterior, middle, or posterior cranial fossae.

METHODS

A systematic review of MEDLINE and PubMed in accordance with PRISMA guidelines performed for articles published between January 1, 1990, and August 1, 2021, was conducted to identify all robotic systems (autonomous, semiautonomous, or surgeon-controlled) used for skull base neurosurgical procedures. Cadaveric and human clinical studies were included. Studies with exclusively otorhinolaryngological applications or using robotic microscopes were excluded.

RESULTS

A total of 561 studies were identified from the initial search, of which 22 were included following full-text review. Transoral robotic surgery (TORS) using the da Vinci Surgical System was the most widely reported system (4 studies) utilized for skull base and pituitary fossa procedures; additionally, it has been reported for resection of sellar masses in 4 patients. Seven cadaveric studies used the da Vinci Surgical System to access the skull base using alternative, non–TORS approaches (e.g., transnasal, transmaxillary, and supraorbital). Five cadaveric studies investigated alternative systems to access the skull base. Six studies investigated the use of robotic endoscope holders. Advantages to robotic applications in skull base neurosurgery included improved lighting and 3D visualization, replication of more traditional gesture-based movements, and the ability for dexterous movements ordinarily constrained by small operative corridors. Limitations included the size and angulation capacity of the robot, lack of drilling components preventing fully robotic procedures, and cost. Robotic endoscope holders may have been particularly advantageous when the use of a surgical assistant or second surgeon was limited.

CONCLUSIONS

Robotic skull base neurosurgery has been growing in popularity and feasibility, but significant limitations remain. While robotic systems seem to have allowed for greater maneuverability and 3D visualization, their size and lack of neurosurgery-specific tools have continued to prevent widespread adoption into current practice. The next generation of robotic technologies should prioritize overcoming these limitations.