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Sensorineural hearing loss due to delayed cerebral ischemia in bilateral auditory cortices following aneurysmal subarachnoid hemorrhage: illustrative case

William S. Dodd, Dimitri Laurent, Brandon Lucke-Wold, Katharina M. Busl, Eric Williams, and Brian L. Hoh

BACKGROUND

Recognizing rare signs of delayed cerebral ischemia (DCI) is crucial to caring for patients with subarachnoid hemorrhage. The authors presented a case of central hearing loss that occurred during the clinical course of a patient treated for aneurysmal subarachnoid hemorrhage.

OBSERVATIONS

The patient had a ruptured right posterior communicating artery aneurysm successfully treated with coil embolization but later developed severe vasospasm and DCI. She developed bilateral hearing loss, and imaging revealed DCI to the left temporal lobe and the right auditory cortex. Computed tomography angiography and digital subtraction angiography demonstrated severe vasospasm of bilateral internal carotid arteries, bilateral middle cerebral arteries, and bilateral anterior cerebral arteries. One month after hospitalization, the patient had recovered fully neurologically intact except for persistent hearing loss.

LESSONS

This case serves to teach important neuroanatomical features and discuss the unique pathophysiology of DCI affecting the auditory cortex.

Free access

Preoperative prediction of postoperative urinary retention in lumbar surgery: a comparison of regression to multilayer neural network

Ken Porche, Carolina B. Maciel, Brandon Lucke-Wold, Steven A. Robicsek, Nohra Chalouhi, Meghan Brennan, and Katharina M. Busl

OBJECTIVE

Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery.

METHODS

The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models’ performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model’s strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine).

RESULTS

Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516–0.645) when applied to the current data set.

CONCLUSIONS

This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

Free access

Minimally invasive endoscopic repair of refractory lateral skull base cerebrospinal fluid rhinorrhea: case report and review of the literature

Brandon Lucke-Wold, Erik C. Brown, Justin S. Cetas, Aclan Dogan, Sachin Gupta, Timothy E. Hullar, Timothy L. Smith, and Jeremy N. Ciporen

Cerebrospinal fluid (CSF) leaks occur in approximately 10% of patients undergoing a translabyrinthine, retrosigmoid, or middle fossa approach for vestibular schwannoma resection. Cerebrospinal fluid rhinorrhea also results from trauma, neoplasms, and congenital defects. A high degree of difficulty in repair sometimes requires repetitive microsurgical revisions—a rate of 10% of cases is often cited. This can not only lead to morbidity but is also costly and burdensome to the health care system. In this case-based theoretical analysis, the authors summarize the literature regarding endoscopic endonasal techniques to obliterate the eustachian tube (ET) as well as compare endoscopic endonasal versus open approaches for repair. Given the results of their analysis, they recommend endoscopic endonasal ET obliteration (EEETO) as a first- or second-line technique for the repair of CSF rhinorrhea from a lateral skull base source refractory to spontaneous healing and CSF diversion. They present a case in which EEETO resolved refractory CSF rhinorrhea over a 10-month follow-up after CSF diversions, wound reexploration, revised packing of the ET via a lateral microscopic translabyrinthine approach, and the use of a vascularized flap had failed. They further summarize the literature regarding studies that describe various iterations of EEETO. By its minimally invasive nature, EEETO imposes less morbidity as well as less risk to the patient. It can be readily implemented into algorithms once CSF diversion (for example, lumbar drain) has failed, prior to considering open surgery for repair. Additional studies are warranted to further demonstrate the outcome and cost-saving benefits of EEETO as the data until now have been largely empirical yet very hopeful. The summaries and technical notes described in this paper may serve as a resource for those skull base teams faced with similar challenging and otherwise refractory CSF leaks from a lateral skull base source.

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Oncolytic viral therapy: a review and promising future directions

Ramya Reddy, Sandra C. Yan, Zahra Hasanpour Segherlou, Mohammad-Reza Hosseini-Siyanaki, Jordan Poe, Carlos Perez-Vega, E. Antonio Chiocca, and Brandon Lucke-Wold

Oncolytic viral therapy is quickly emerging as a promising subset of immunotherapy, which theoretically can target tumor cells while sparing surrounding healthy cells by harnessing the replication machinery of viruses with tropism for tumor cells, resulting in direct oncolysis, and by transforming immunologically "cold" tumor into areas that elicit the host’s immune response. This review provides an overview of oncolytic viral therapy until the present day, starting with the original concept in 1912. The general mechanism of oncolytic viruses (OVs) depends on selectively integrating them into tumor cells based on genetic engineering of viral genomic material, inducing oncolysis and eliciting the host’s innate immune response. Moreover, a major component of oncolytic viral therapy has been herpes simplex virus, with talimogene laherparepvec being the only FDA-approved oncolytic viral therapy for the treatment of melanomas. This review explores the characteristics, advantages, disadvantages, and therapeutic uses of several DNA and RNA viral families. A snapshot of the oncolytic viral treatments used in the most recent and advanced clinical trials is also provided. Lastly, the challenges of implementing oncolytic viral therapy are explored, both at a molecular and clinical level, with a highlight of promising future directions. In particular, the lack of an optimal delivery method based on tumor type for oncolytic viral therapy poses a significant obstacle, even in clinical studies. Intrathecal continuous delivery of OVs is a promising prospect, potentially by adapting the novel continuous irrigation and drainage IRRAflow catheter. Further exploration and testing of the IRRAflow catheter should be undertaken.

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Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy

Brandon P. Lucke-Wold, Ryan C. Turner, Aric F. Logsdon, Linda Nguyen, Julian E. Bailes, John M. Lee, Matthew J. Robson, Bennet I. Omalu, Jason D. Huber, and Charles L. Rosen

OBJECT

Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration.

METHODS

The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors’ clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler.

RESULTS

The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase–3β. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy.

CONCLUSIONS

Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.

Free access

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort

Kira Tosefsky, Alexander D. Rebchuk, Justin Z. Wang, Yosef Ellenbogen, Richard Drexler, Franz L. Ricklefs, Thomas Sauvigny, Ulrich Schüller, Christopher B. Cutler, Brandon Lucke-Wold, Yusuf Mehkri, Sanju Lama, Garnette R. Sutherland, Michael Karsy, Brian L. Hoh, Manfred Westphal, Gelareh Zadeh, Stephen Yip, and Serge Makarenko

OBJECTIVE

Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients.

METHODS

Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022.

RESULTS

A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%–77%) and 37% (95% CI 28%–48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period.

CONCLUSIONS

This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

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2017 AANS Annual Scientific Meeting Los Angeles, CA • April 22–26, 2017