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Megan M. Finneran, Sarah Graber, Kim Poppleton, Allyson L. Alexander, C. Corbett Wilkinson, Brent R. O’Neill, Todd C. Hankinson, and Michael H. Handler

OBJECTIVE

Prior to 2019, the majority of patients at Children’s Hospital Colorado were admitted to the pediatric intensive care unit (PICU) following Chiari malformation (CM) decompression surgery. This study sought to identify the safety and efficacy of postoperative general ward management for these patients.

METHODS

After a retrospective baseline assessment of 150 patients, a quality improvement (QI) initiative was implemented, admitting medically noncomplex patients to the general ward postoperatively following CM decompression. Twenty-one medically noncomplex patients were treated during the QI intervention period. All patients were assessed for length of stay, narcotic use, time to ambulation, and postoperative complications.

RESULTS

PICU admission rates postoperatively decreased from 92.6% to 9.5% after implementation of the QI initiative. The average hospital length of stay decreased from 3.4 to 2.6 days, total doses of narcotic administration decreased from 12.3 to 8.7, and time to ambulation decreased from 1.8 to 0.9 days. There were no major postoperative complications identified that were unsuitable for management on a conventional pediatric medical/surgical nursing unit.

CONCLUSIONS

Medically noncomplex patients were safely admitted to the general ward postoperatively at Children’s Hospital Colorado after decompression of CM. This approach afforded decreased length of stay, decreased narcotic use, and decreased time to ambulation, with no major postoperative complications.

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Stephanie Schipmann, Dorothee Cäcilia Spille, Marco Gallus, Sebastian Lohmann, Michael Schwake, Nils Warneke, Eric Suero Molina, Walter Stummer, and Markus Holling

OBJECTIVE

The outbreak of COVID-19 and the sudden increase in the number of patients requiring mechanical ventilation significantly affected the management of neurooncological patients. Hospitals were forced to reallocate already scarce human resources to maximize intensive care unit (ICU) capacities, resulting in a significant postponement of elective procedures for patients with brain and spinal tumors, who traditionally require elective postoperative surveillance on ICU or intermediate care wards. This study aimed to characterize those patients in whom postoperative monitoring is required by analyzing early postoperative complications and associated risk factors.

METHODS

All patients included in the analysis experienced benign or malignant cerebral or intradural tumors and underwent surgery between September 2017 and May 2019 at University Hospital Münster, Germany. Patient data were generated from a semiautomatic, prospectively designed database. The occurrence of adverse events within 24 hours and 30 days postoperatively—including unplanned reoperation, postoperative hemorrhage, CSF leakage, and pulmonary embolism—was chosen as the primary outcome measure. Furthermore, reasons and risk factors that led to a prolonged stay on the ICU were investigated. By performing multivariable logistic regression modeling, a risk score for early postoperative adverse events was calculated by assigning points based on beta coefficients.

RESULTS

Eight hundred eleven patients were included in the study. Eleven patients (1.4%) had an early adverse event within 24 hours, which was either an unplanned reoperation (0.9%, n = 7) or a pulmonary embolism (0.5%, n = 4) within 24 hours. To predict the incidence of early postoperative complications, a score was developed including the number of secondary diagnoses, BMI, and incision closure time, termed the SOS score. According to this score, 0.3% of the patients were at low risk, 2.5% at intermediate risk, and 12% at high risk (p < 0.001).

CONCLUSIONS

Postoperative surveillance in cranial and spinal tumor neurosurgery might only be required in a distinct patient collective. In this study, the authors present a new score allowing efficient prediction of the likelihood of early adverse events in patients undergoing neurooncological procedures, thus helping to stratify the necessity for ICU or intermediate care unit beds. Nevertheless, validation of the score in a multicenter prospective setting is needed.

Open access

Jeffrey J. Hébert, Tyler Adams, Erin Cunningham, Dana El-Mughayyar, Neil Manson, Edward Abraham, Niels Wedderkopp, Erin Bigney, Eden Richardson, Amanda Vandewint, Chris Small, George Kolyvas, Andre le Roux, Aaron Robichaud, Michael H. Weber, Charles Fisher, Nicolas Dea, Stephan du Plessis, Raphaele Charest-Morin, Sean D. Christie, Christopher S. Bailey, Y. Raja Rampersaud, Michael G. Johnson, Jerome Paquet, Andrew Nataraj, Bernard LaRue, Hamilton Hall, and Najmedden Attabib

OBJECTIVE

Anterior cervical discectomy and fusion (ACDF) is often described as the gold standard surgical technique for cervical spondylotic radiculopathy. Although outcomes are considered favorable, there is little prognostic evidence to guide patient selection for ACDF. This study aimed to 1) describe the 24-month postoperative trajectories of arm pain, neck pain, and pain-related disability; and 2) identify perioperative prognostic factors that predict trajectories representing poor clinical outcomes.

METHODS

In this retrospective cohort study, patients with cervical spondylotic radiculopathy who underwent ACDF at 1 of 12 orthopedic or neurological surgery centers were recruited. Potential outcome predictors included demographic, health, clinical, and surgery-related prognostic factors. Surgical outcomes were classified by trajectories of arm pain intensity, neck pain intensity (numeric pain rating scales), and pain-related disability (Neck Disability Index) from before surgery to 24 months postsurgery. Trajectories of postoperative pain and disability were estimated with latent class growth analysis, and prognostic factors associated with poor outcome trajectory were identified with robust Poisson models.

RESULTS

The authors included data from 352 patients (mean age 50.9 [SD 9.5] years; 43.8% female). The models estimated that 15.5%–23.5% of patients followed a trajectory consistent with a poor clinical outcome. Lower physical and mental health–related quality of life, moderate to severe risk of depression, and longer surgical wait time and procedure time predicted poor postoperative trajectories for all outcomes. Receiving compensation and smoking additionally predicted a poor neck pain outcome. Regular exercise, physiotherapy, and spinal injections before surgery were associated with a lower risk of poor disability outcome. Patients who used daily opioids, those with worse general health, or those who reported predominant neck pain or a history of depression were at greater risk of poor disability outcome.

CONCLUSIONS

Patients who undergo ACDF for cervical spondylotic radiculopathy experience heterogeneous postoperative trajectories of pain and disability, with 15.5%–23.5% of patients experiencing poor outcomes. Demographic, health, clinical, and surgery-related prognostic factors can predict ACDF outcomes. This information may further assist surgeons with patient selection and with setting realistic expectations. Future studies are needed to replicate and validate these findings prior to confident clinical implementation.

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Hrishikesh Raghuram, Thomas Looi, Samuel Pichardo, Adam C. Waspe, and James M. Drake

OBJECTIVE

Intraventricular hemorrhage (IVH) is a neurovascular complication due to premature birth that results in blood clots forming within the ventricles. Magnetic resonance–guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse clots. The authors designed and constructed a robotic MRgHIFU platform to treat the neonatal brain that facilitates ergonomic patient positioning. The clot lysis efficacy of the platform is quantified using a brain phantom and clinical MRI system.

METHODS

A thermosensitive brain-mimicking phantom with ventricular cavities was developed to test the clot lysis efficacy of the robotic MRgHIFU platform. Whole porcine blood was clotted within the phantom’s cavities. Using the MRgHIFU platform and a boiling histotripsy treatment procedure (500 W, 10-msec pulse duration, 1.0% duty cycle, and 40-second duration), the clots were lysed inside the phantom. The contents of the cavities were vacuum filtered, and the remaining mass of the solid clot particles was used to quantify the percentage of clot lysis. The interior of the phantom’s cavities was inspected for any collateral damage during treatment.

RESULTS

A total of 9 phantoms were sonicated, yielding an average (± SD) clot lysis of 97.0% ± 2.57%. Treatment resulted in substantial clot lysis within the brain-mimicking phantoms that were apparent on postsonication T2-weighted MR images. No apparent collateral damage was observed within the phantom after treatment. The results from the study showed the MRgHIFU platform was successful at lysing more than 90% of a blood clot at a statistically significant level.

CONCLUSIONS

The robotic MRgHIFU platform was shown to lyse a large percentage of a blood clot with no observable collateral damage. These results demonstrate the platform’s ability to induce clot lysis when targeting through simulated brain matter and show promise toward the final application in neonatal patients.

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Benjamin T. Himes, Cori E. Fain, Zachariah P. Tritz, Cody L. Nesvick, Helen J. Jin-Lee, Philipp A. Geiger, Timothy E. Peterson, Mi-Yeon Jung, and Ian F. Parney

OBJECTIVE

The profound immunosuppression found in glioblastoma (GBM) patients is a critical barrier to effective immunotherapy. Multiple mechanisms of tumor-mediated immune suppression exist, and the induction of immunosuppressive monocytes such as myeloid-derived suppressor cells (MDSCs) is increasingly appreciated as a key part of this pathology. GBM-derived extracellular vesicles (EVs) can induce the formation of MDSCs. The authors sought to identify the molecular consequences of these interactions in myeloid cells in order to identify potential targets that could pharmacologically disrupt GBM EV–monocyte interaction as a means to ameliorate tumor-mediated immune suppression. Heparin-sulfate proteoglycans (HSPGs) are a general mechanism by which EVs come into association with their target cells, and soluble heparin has been shown to interfere with EV-HSPG interactions. The authors sought to assess the efficacy of heparin treatment for mitigating the effects of GBM EVs on the formation of MDSCs.

METHODS

GBM EVs were collected from patient-derived cell line cultures via staged ultracentrifugation and cocultured with monocytes collected from apheresis cones from healthy blood donors. RNA was isolated from EV-conditioned and unconditioned monocytes after 72 hours of coculture, and RNA-sequencing analysis performed. For the heparin treatment studies, soluble heparin was added at the time of EV-monocyte coculture and flow cytometry analysis was performed 72 hours later. After the initial EV-monocyte coculture period, donor-matched T-cell coculture studies were performed by adding fluorescently labeled and stimulated T cells for 5 days of coculture.

RESULTS

Transcriptomic analysis of GBM EV–treated monocytes demonstrated downregulation of several important immunological and metabolic pathways, with upregulation of the pathways associated with synthesis of cholesterol and HSPG. Heparin treatment inhibited association between GBM EVs and monocytes in a dose-dependent fashion, which resulted in a concomitant reduction in MDSC formation (p < 0.01). The authors further demonstrated that reduced MDSC formation resulted in a partial rescue of immune suppression, as measured by effects on activated donor-matched T cells (p < 0.05).

CONCLUSIONS

The authors demonstrated that GBM EVs induce broad but reproducible reprogramming in monocytes, with enrichment of pathways that may portend an immunosuppressive phenotype. The authors further demonstrated that GBM EV–monocyte interactions are potentially druggable targets for overcoming tumor-mediated immune suppression, with heparin inhibition of EV-monocyte interactions demonstrating proof of principle.

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George K. Hanna, Mecca Madany, Angelique Sao-Mai Sy Tay, Lincoln A. Edwards, Sungjin Kim, Justin S. Michael, Miriam Nuno, Tom Thomas, Aiguo Li, Dror Berel, Keith L. Black, Xuemo Fan, Wei Zhang, Jeremy D. Rudnick, Rongfu Wang, and John S. Yu

OBJECTIVE

Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas.

METHODS

The authors explored resistance to therapy in the context of ZEB1 loss and overexpression in glioma stem cells (GSCs) and in patient data.

RESULTS

Patients with ZEB1 loss had a shorter survival time than patients with wild-type ZEB1 in both the high- and low-MGMT groups. Consistent with the clinical data, mice implanted with ZEB1 knockdown GSCs showed shortened survival compared with mice inoculated with nonsilencing control (NS) short-hairpin RNA (shRNA) GSC glioblastoma. ZEB1-deleted GSCs demonstrated increased tumorigenicity with regard to proliferation and invasion. Importantly, GSCs that lose ZEB1 expression develop enhanced resistance to chemotherapy, radiotherapy, and combined chemoradiation. ZEB1 loss may lead to increased HER3 expression through the HER3/Akt pathway associated with this chemoresistance. Conversely, overexpression of ZEB1 in GSCs that are ZEB1 null leads to increased sensitivity to chemoradiation.

CONCLUSIONS

The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.

Open access

Erin M. Ellis, S. Joy Trybula, Scott K. Adney, Paula K. J. Lee, and S. Kathleen Bandt

BACKGROUND

Focal cortical dysplasias (FCDs) are a heterogenous cluster of histopathologic entities classically associated with medically refractory epilepsy. Because there is substantial histopathologic variation among different types of FCD, there are likely multiple pathogenic mechanisms leading to these disorders. The meninges are known to play a role in cortical development, and disruption of meningeal-derived signaling pathways has been shown to impact neurodevelopment. To our knowledge, there has not yet been an investigation into whether genetic pathways regulating meningeal development may be involved in the development of FCD.

OBSERVATIONS

The authors reported a patient with refractory epilepsy and evidence of FCD on imaging who received surgical intervention and was found to have an unusual dural anomaly overlying a region of type Ic FCD. To the authors’ knowledge, this was the first report describing a lesion of this nature in the context of FCD.

LESSONS

The dural anomaly exhibited by the patient presented what could be a potentially novel pathogenic mechanism of FCD. Resection of the cortical tissue underlying the dural anomaly resulted in improvement in seizure control. Although the pathogenesis is unclear, this case highlighted the importance of further investigation into the developmental origins of FCD, which may help elucidate whether a connection between meningeal development and FCD exists.

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Einar Ottestad and Thomas J. Wilson

OBJECTIVE

Periscapular pain has a broad differential diagnosis. Dorsal scapular neuropathy is part of that differential diagnosis but is often forgotten by clinicians, leading to delayed diagnosis, chronic pain, and potentially worse outcomes. The objective of this study was to describe our method for diagnosis, surgical technique, intraoperative findings, and outcomes in consecutive patients undergoing dorsal scapular nerve (DSN) decompression.

METHODS

A retrospective cohort study was performed to compile and describe outcomes for consecutive patients (n = 21) who underwent DSN decompression by a single surgeon during the period between August 2018 and February 2021. The primary outcome was change in visual analog scale (VAS) score for periscapular pain between baseline and 6 months postoperatively. Secondary outcomes included change in VAS score for overall pain, change in Disabilities of the Arm, Shoulder, and Hand (DASH) score, and change in the Zung Self-Rating Depression Scale (Zung SDS) between baseline and 6 and 12 months postoperatively.

RESULTS

Patients undergoing DSN decompression showed significant improvement in VAS score for periscapular pain between baseline and 6 months postoperatively (mean score 54.0 vs 26.8, respectively; p < 0.001). Fifteen of 21 patients (71%) had a good outcome (score improvement ≥ 20). Disability (as determined by DASH scores) was significantly improved at 6 and 12 months postoperatively. The only factor that was predictive of outcome was symptom duration, with longer symptom duration predicting a poor outcome.

CONCLUSIONS

Surgical treatment of dorsal scapular neuropathy is associated with significant improvements in pain and disability, and these improvements are durable. Morbidity associated with surgical treatment is low.

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Ziyad Makoshi, Nathaniel Toop, Luke G. F. Smith, Annie Drapeau, Jonathan Pindrik, Eric A. Sribnick, Jeffrey Leonard, and Ammar Shaikhouni

OBJECTIVE

Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts.

METHODS

The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence.

RESULTS

From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel.

CONCLUSIONS

At the authors’ single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.

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Brin E. Freund, Elena Greco, Lela Okromelidze, Julio Mendez, William O. Tatum IV, Sanjeet S. Grewal, and Erik H. Middlebrooks

OBJECTIVE

The authors hypothesized that the proximity of deep brain stimulator contacts to the anterior thalamic nucleus–mammillothalamic tract (ANT-MMT) junction determines responsiveness to treatment with ANT deep brain stimulation (DBS) in drug-resistant epilepsy and conducted this study to test that hypothesis.

METHODS

This retrospective study evaluated patients who had undergone ANT DBS electrode implantation and whose devices were programmed to stimulate nearest the ANT-MMT junction based on direct MRI visualization. The proximity of the active electrode to the ANT and the ANT-MMT junction was compared between responders (≥ 50% reduction in seizure frequency) and nonresponders. Linear regression was performed to assess the percentage of seizure reduction and distance to both the ANT and the ANT-MMT junction.

RESULTS

Four (57.1%) of 7 patients had ≥ 50% reduction in seizures. All 4 responders had at least one contact within 1 mm of the ANT-MMT junction, whereas the 3 patients with < 50% seizure improvement did not have a contact within 1 mm of the ANT-MMT junction. Additionally, the 4 responders demonstrated contact positioning closer to the ANT-MMT junction than the 3 nonresponders (mean distance from MMT: 0.7 mm on the left and 0.6 mm on the right in responders vs 3.0 mm on the left and 2.3 mm on the right in nonresponders). However, proximity of the electrode contact to any point in the ANT nucleus did not correlate with seizure reduction. Greater seizure improvement was correlated with a contact position closer to the ANT-MMT junction (R2 = 0.62, p = 0.04). Seizure improvement was not significantly correlated with proximity of the contact to any ANT border (R2 = 0.24, p = 0.26).

CONCLUSIONS

Obtained using a combination of direct visualization and targeted programming of the ANT-MMT junction, data in this study support the hypothesis that proximity to the ANT alone does not correlate with seizure reduction in ANT DBS, whereas proximity to the ANT-MMT junction does. These findings support the importance of direct targeting in ANT DBS, as well as imaging-informed programming. Additionally, the authors provide supportive evidence for future prospective trials using ANT-MMT junction for direct surgical targeting.