Publications by authors named "Ricardo J Komotar"

365 Publications

Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

Neurosurg Rev 2021 Nov 13. Epub 2021 Nov 13.

Department of Neurological Surgery, University of Miami, Miami, FL, USA.

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.
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http://dx.doi.org/10.1007/s10143-021-01690-3DOI Listing
November 2021

Oncolytic Virotherapy for Melanoma Brain Metastases, a Potential New Treatment Paradigm?

Brain Sci 2021 Sep 23;11(10). Epub 2021 Sep 23.

Department of Neurological Surgery, University of Miami, Miami, FL 33146, USA.

Introduction: Melanoma brain metastases remain a devastating disease process with poor prognosis. Recently, there has been a surge in studies demonstrating the efficacy of oncolytic virotherapy for brain tumor treatment. Given their specificity and amenability to genetic modification, the authors explore the possible role of oncolytic virotherapy as a potential treatment option for patients with melanoma brain metastases.

Methods: A comprehensive literature review including both preclinical and clinical evidence of oncolytic virotherapy for the treatment of melanoma brain metastasis was performed.

Results: Oncolytic virotherapy, specifically T-VEC (Imlygic™), was approved for the treatment of melanoma in 2015. Recent clinical trials demonstrate promising anti-tumor changes in patients who have received T-VEC; however, there is little evidence for its use in metastatic brain disease based on the existing literature. To date, only two single cases utilizing virotherapy in patients with metastatic brain melanoma have been reported, specifically in patients with treatment refractory disease. Currently, there is not sufficient data to support the use of T-VEC or other viruses for intracranial metastatic melanoma. In developing a virotherapy treatment paradigm for melanoma brain metastases, several factors must be considered, including route of administration, need to bypass the blood-brain barrier, viral tumor infectivity, and risk of adverse events.

Conclusions: Evidence for oncolytic virotherapy treatment of melanoma is limited primarily to T-VEC, with a noticeable paucity of data in the literature with respect to brain tumor metastasis. Given the promising findings of virotherapy for other brain tumor types, oncolytic virotherapy has great potential to offer benefits to patients afflicted with melanoma brain metastases and warrants further investigation.
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http://dx.doi.org/10.3390/brainsci11101260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534242PMC
September 2021

Using smartphone-based accelerometers to gauge postoperative outcomes in patients with NPH: Implications for ambulatory monitoring.

Surg Neurol Int 2021 13;12:464. Epub 2021 Sep 13.

Department of Neurological Surgery, University of Miami, Miami, Florida, United States.

Background: The surgical treatment of normal pressure hydrocephalus (NPH) with shunting remains controversial due to the difficulty in distinguishing such pathology from other neurological conditions that can present similarly. Thus, patients with suspected NPH should be carefully selected for surgical intervention. Historically, clinical improvement has been measured by the use of functional grades, alleviation of symptoms, and/or patient/family-member reported surveys. Such outcome analysis can be subjective, and there is difficulty in quantifying cognition. Thus, a push for a more quantifiable and objective investigation is warranted, especially for patients with idiopathic NPH (INPH), for which the final diagnosis is confirmed with postoperative clinical improvement. We aimed to use Apple Health (Apple Inc., Cupertino, CA) data to approximate physical activity levels before and after shunt placement for NPH as an objective outcome measurement. The patients were contacted and verbally consented to export Apple Health activity data. The patient's physical activity data were then analyzed. A chart review from the patient's EMR was performed to understand and better correlate recovery.

Case Description: Our first patient had short-term improvements in activity levels when compared to his preoperative activity. The patient's activity level subsequently decreased at 6 months and onward. This decline was simultaneous to new-onset lumbar pain. Our second patient experienced sustained improvements in activity levels for 12 months after his operation. His mobility data were in congruence with his subjectively reported improvement in clinical symptoms. He subsequently experienced a late-decline that began at 48-months. His late deterioration was likely confounded by exogenous factors such as further neurodegenerative diseases coupled with old age.

Conclusion: The use of objective activity data offers a number of key benefits in the analysis of shunted patients with NPH/INPH. In this distinctive patient population, detailed functional outcome analysis is imperative because the long-term prognosis can be affected by comorbid factors or life expectancy. The benefits from using smartphone-based accelerometers for objective outcome metrics are abundant and such an application can serve as a clinical aid to better optimize surgical and recovery care.
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http://dx.doi.org/10.25259/SNI_112_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492411PMC
September 2021

Prognosticating survival of pineal parenchymal tumors of intermediate differentiation (PPTID) by grade.

J Neurooncol 2021 Nov 4;155(2):165-172. Epub 2021 Oct 4.

Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.

Background: Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health Organization (WHO) Grades 2 or 3. The rarity of these tumors in adults has left a number of clinical management questions open. Correspondingly, the aim of this study was to aggregate a large PPTID cohort with sufficient statistical power from a large national cancer database to analyze prognostic parameters.

Methods: All PPTID patients aged over 18 years in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized and survival was modeled using Kaplan-Meier and Cox regression analyses.

Results: A total of 103 adult PPTID patients were identified in the NCDB with 63 (61%) WHO Grade 2 and 40 (39%) WHO Grade 3 tumors. Overall, mean age was 53 ± 18 years with even gender distribution. A total of 75 (73%) patients underwent surgical resection for diagnosis, with gross total resection (GTR) was the most common resection outcome in 50/75 (67%). Chemotherapy was utilized in 18 (17%) patients, and radiation therapy in 37 (36%) patients. Overall, 5-year survival rate was estimated to be 54% (95% CI 42-64%), with mean survival was 84 (95% CI 69-99) months. Patients with Grade 2 tumors survived statistically longer than Grade 3 tumor counterparts (P < 0.01). Overall, older age (HR 1.09, P < 0.01) was associated with shorter survival, whereas GTR (HR 0.43, P = 0.02) was associated with longer survival. Both these parameters were significant within Grade 2 and Grade 3 subgroup analyses as well.

Conclusions: PPTID are rare tumors with expected mean survival more than 5 years, although Grade 2 tumors are expected to survive longer than Grade 3 tumors. Age and gross total resection are significant independent predictors of survival in PPTID overall, as well as within Grade 2 and Grade 3 subgroups separately. The prognostic role and benefit of adjuvant therapy is yet to be elucidated, mandating more molecular and biologic research be done to further optimize clinical management in the future.
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http://dx.doi.org/10.1007/s11060-021-03863-yDOI Listing
November 2021

Supralesional Ablation Volumes Are Feasible in the Posterior Fossa and May Provide Enhanced Symptomatic Relief.

Oper Neurosurg (Hagerstown) 2021 Nov;21(6):418-425

University of Miami Miller School of Medicine, Department of Neurological Surgery, Miami, Florida, USA.

Background: Laser interstitial thermal therapy (LITT) for posterior fossa lesions remains rare as the small size of the infratentorial compartment, proximity to the brainstem, and thickness/angulation of the occipital bone creates barriers to procedural success. Furthermore, evaluation of the effect of ablation volume on outcomes is limited.

Objective: To analyze our institutional experience with LITT in the posterior fossa stratifying perioperative and long-term outcomes by ablation volumes.

Methods: Seventeen patients with posterior fossa lesions treated with LITT from 2013 to 2020 were identified. Local progression-free survival (PFS), overall survival, steroid dependence, and edema reduction were evaluated with Kaplan-Meier analysis grouped by ablation volume. Preoperative, postoperative, and last known Karnofsky Performance Status (KPS) were compared using a matched paired t test.

Results: No differences in pathology, preoperative KPS, or preoperative lesion volume were found between patients with total (100%-200% increase in pre-LITT lesion volume) versus radical (>200% increase in pre-LITT lesion volume) ablations. Patients who underwent radical ablation had a higher postoperative KPS (93 vs 82, P = .02) and higher KPS (94 vs 87, P = .04) and greater reduction in perilesional edema at last follow-up (P = .01). Median follow-up was 80.8 wk.

Conclusion: Despite obvious anatomical challenges, our results demonstrate that radical ablations are both feasible and safe in the posterior fossa. Furthermore, radical ablations may lead to greater decreases in perilesional edema and improved functional status both immediately after surgery and at last follow-up. Thus, LITT should be considered for patients with otherwise unresectable or radioresistant posterior fossa lesions.
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http://dx.doi.org/10.1093/ons/opab332DOI Listing
November 2021

Is endoscopic resection a useful technique for a cavernous sinus sellar cavernoma? A case report and literature review.

Br J Neurosurg 2021 Aug 18:1-8. Epub 2021 Aug 18.

Department of Neurological Surgery, Lois Pope Life Center, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Cavernous sinus cavernous malformations (CSCMs) is a vascular malformation of the cavernous sinus. Nowadays, there is an increasing preference to withhold using the terms cavernoma or cavernous hemangioma in order to stop considering these lesions as vascular neoplasms. These lesions are highly vascularized making surgical resection a challenge, mainly in endoscopic approaches. We present a case of this tumor treated in our institution with an endoscopic endonasal approach and incomplete resection. Because of the strenuous resection through this approach, we systematically reviewed the reported endoscopic cases of CSCMs to determine their intraoperative complications, results and tumor features.

Methods: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, one database (PubMed) and crossed references were queried for CSCMs from 1948 to 2020. Data regarding demographic features, clinical presentation, MRI features, surgical results and overall pathology features extracted.

Results: Eighteen patients were selected (including our case). The mean age was 50.4 ± 14 years. Pituitary dysfunction and cavernous sinus nerve compression were the most reported symptoms. Only five cases (27%) reported a gross total resection (GTR) through endoscopic endonasal approach. Intraoperative bleeding was the most frequent intraoperative complication.

Conclusion: We present a comprehensive analysis of every reported CSCM treated through endoscopic approach. Partial or subtotal resection are the most used techniques because of the intraoperative bleeding and the adherence to surrounding structures. Radiotherapy is a very good option for patients with incomplete resections.
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http://dx.doi.org/10.1080/02688697.2021.1958154DOI Listing
August 2021

Ventriculostomy supply cart decreases time-to-external ventricular drain placement in the emergency department.

Surg Neurol Int 2021 19;12:362. Epub 2021 Jul 19.

Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, United States.

Background: Minimizing time-to-external ventricular drain (EVD) placement in the emergency department (ED) is critical. We sought to understand factors affecting time-to-EVD placement through a quality improvement initiative.

Methods: The use of process mapping, root cause analyses, and interviews with staff revealed decentralized supply storage as a major contributor to delays in EVD placement. We developed an EVD "crash cart" as a potential solution to this problem. Time-to-EVD placement was tracked prospectively using time stamps in the electronic medical record (EMR); precart control patients were reviewed retrospectively.

Results: The final cohorts consisted of 33 precart and 18 postcart cases. The mean time-to-EVD in the precart group was 99.09 min compared to 71.88 min in the postcart group (two-tailed -test, = 0.023). Median time-to-EVD was 92 min in the precart group compared to 64 min in the postcart group (rank sum test, = 0.0165). Postcart patients trended toward improved outcomes with lower modified Rankin score scores at 1 year, but this did not reach statistical significance (two-tailed -test, = 0.177).

Conclusion: An EVD "crash cart" is a simple intervention that can significantly reduce time-to-EVD placement and may improve outcomes in patients requiring an EVD.
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http://dx.doi.org/10.25259/SNI_371_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330128PMC
July 2021

Augmented reality head-mounted display-based incision planning in cranial neurosurgery: a prospective pilot study.

Neurosurg Focus 2021 08;51(2):E3

1Department of Neurological Surgery, University of Miami Miller School of Medicine; and.

Objective: Monitor and wand-based neuronavigation stations (MWBNSs) for frameless intraoperative neuronavigation are routinely used in cranial neurosurgery. However, they are temporally and spatially cumbersome; the OR must be arranged around the MWBNS, at least one hand must be used to manipulate the MWBNS wand (interrupting a bimanual surgical technique), and the surgical workflow is interrupted as the surgeon stops to "check the navigation" on a remote monitor. Thus, there is need for continuous, real-time, hands-free, neuronavigation solutions. Augmented reality (AR) is poised to streamline these issues. The authors present the first reported prospective pilot study investigating the feasibility of using the OpenSight application with an AR head-mounted display to map out the borders of tumors in patients undergoing elective craniotomy for tumor resection, and to compare the degree of correspondence with MWBNS tracing.

Methods: Eleven consecutive patients undergoing elective craniotomy for brain tumor resection were prospectively identified and underwent circumferential tumor border tracing at the time of incision planning by a surgeon wearing HoloLens AR glasses running the commercially available OpenSight application registered to the patient and preoperative MRI. Then, the same patient underwent circumferential tumor border tracing using the StealthStation S8 MWBNS. Postoperatively, both tumor border tracings were compared by two blinded board-certified neurosurgeons and rated as having an excellent, adequate, or poor correspondence degree based on a subjective sense of the overlap. Objective overlap area measurements were also determined.

Results: Eleven patients undergoing craniotomy were included in the study. Five patient procedures were rated as having an excellent correspondence degree, 5 had an adequate correspondence degree, and 1 had poor correspondence. Both raters agreed on the rating in all cases. AR tracing was possible in all cases.

Conclusions: In this small pilot study, the authors found that AR was implementable in the workflow of a neurosurgery OR, and was a feasible method of preoperative tumor border identification for incision planning. Future studies are needed to identify strategies to improve and optimize AR accuracy.
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http://dx.doi.org/10.3171/2021.5.FOCUS20735DOI Listing
August 2021

Robotic guidance platform for laser interstitial thermal ablation and stereotactic needle biopsies: a single center experience.

J Robot Surg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14th Terrace (D4-6), Miami, FL, 33146, USA.

While laser ablation has become an increasingly important tool in the neurosurgical oncologist's armamentarium, deep seated lesions, and those located near critical structures require utmost accuracy during stereotactic laser catheter placement. Robotic devices have evolved significantly over the past two decades becoming an accurate and safe tool for stereotactic neurosurgery. Here, we present our single center experience with the MedTech ROSA ONE Brain robot for robotic guidance in laser interstitial thermal therapy (LITT) and stereotactic biopsies. We retrospectively analyzed the first 70 consecutive patients treated with ROSA device at a single academic medical center. Forty-three patients received needle biopsy immediately followed by LITT with the catheter placed with robotic guidance and 27 received stereotactic needle biopsy alone. All the procedures were performed frameless with skull bone fiducials for registration. We report data regarding intraoperative details, mortality and morbidity, diagnostic yield and lesion characteristics on MRI. Also, we describe the surgical workflow for both procedures. The mean age was 60.3 ± 15 years. The diagnostic yield was positive in 98.5% (n = 69). Sixty-three biopsies (90%) were supratentorial and seven (10%) were infratentorial. Gliomas represented 54.3% of the patients (n = 38). There were two postoperative deaths (2.8%). No permanent morbidity related to surgery were observed. We did not find intraoperative technical problems with the device. There was no need to reposition the needle after the initial placement. Stereotactic robotic guided placement of laser ablation catheters and biopsy needles is safe, accurate, and can be implemented into a neurosurgical workflow.
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http://dx.doi.org/10.1007/s11701-021-01278-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276839PMC
July 2021

Emergent Radiotherapy for Leukemia-Induced Cranial Neuropathies Refractory to Intrathecal Therapy.

Cureus 2021 May 24;13(5):e15212. Epub 2021 May 24.

Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, USA.

Neurologic symptoms from leukemic infiltration of the central nervous system are an oncologic emergency, and expeditious treatment is required to preserve function. We report the case of a 44-year-old patient with relapsed acute myeloid leukemia (AML) who developed sub-acute cranial neuropathies refractory to treatment with intrathecal (IT) chemotherapy. The patient was therefore treated with an emergent course of whole-brain radiotherapy, resulting in immediate improvement and subsequent resolution of cranial neuropathies. This case illustrates that while central nervous system involvement by AML is rare, radiotherapy remains an effective modality to avoid long-term morbidity in patients failing to respond to systemic or IT chemotherapy.
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http://dx.doi.org/10.7759/cureus.15212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221003PMC
May 2021

A Cohort Study on Prognostic Factors for Laser Interstitial Thermal Therapy Success in Newly Diagnosed Glioblastoma.

Neurosurgery 2021 08;89(3):496-503

Department of Neurosurgery, University of Miami School of Medicine, Miami, Florida, USA.

Background: Laser interstitial thermal therapy (LITT) is a promising approach for cytoreduction of deep-seated gliomas. However, parameters contributing to treatment success remain unclear.

Objective: To identify extent of ablation (EOA) and time to chemotherapy (TTC) as predictors of improved overall and progression-free survival (OS, PFS) and suggest laser parameters to achieve optimal EOA.

Methods: Demographic, clinical, and survival data were collected retrospectively from 20 patients undergoing LITT for newly diagnosed glioblastoma (nGBM). EOA was calculated through magnetic resonance imaging-based volumetric analysis. Kaplan-Meier and multivariate Cox regression were used to examine the relationship between EOA with OS and PFS accounting for covariates (age, isocitrate dehydrogenase-1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase hypermethylation). The effect of laser thermodynamic parameters (power, energy, time) on EOA was identified through linear regression.

Results: Median OS and PFS for the entire cohort were 36.2 and 3.5 mo respectively. Patient's with >70% EOA had significantly improved PFS compared to ≤70% EOA (5.2 vs 2.3 mo, P = .01) and trended toward improved OS (36.2 vs 11 mo, P = .07) on univariate and multivariate analysis. Total laser power was a significant predictor for increased EOA when accounting for preoperative lesion volume (P = .001). Chemotherapy within 16 d of surgery significantly predicted improved PFS compared to delaying chemotherapy (9.4 vs 3.1 mo, P = .009).

Conclusion: Increased EOA was a predictor of improved PFS with evidence of a trend toward improved OS in LITT treatment of nGBM. A strategy favoring higher laser power during tumor ablation may achieve optimal EOA. Early transition to chemotherapy after LITT improves PFS.
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http://dx.doi.org/10.1093/neuros/nyab193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364818PMC
August 2021

Perioperative Complications in Endoscopic Endonasal versus Transcranial Resections of Adult Craniopharyngiomas.

World Neurosurg 2021 08 18;152:e729-e737. Epub 2021 Jun 18.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA. Electronic address:

Background: Adult craniopharyngiomas are low-grade tumors of the pituitary infundibulum that can be locally aggressive and frequently present with profound visual deficits and endocrinopathies. Surgical resection remains the preferred initial treatment for these lesions, and recently endoscopic endonasal approaches (EEAs) have become increasingly used. However, minimal data exist comparing these techniques with traditional transcranial (TC) methods. The purpose of this study was to evaluate perioperative differences in EEA and TC approaches for adult craniopharyngiomas over the past several decades.

Methods: Craniopharyngioma surgeries in the Nationwide Inpatient Sample from 1998 to 2014 were identified. Complication rates, mortality rates, and annual treatment trends were stratified by procedure. Annual caseload was assessed with linear regression, and multivariate logistic regression models were created to determine predictors of inpatient mortality and perioperative complications.

Results: From 1998-2014, a significant increase in EEAs for craniopharyngiomas (+4.36/year, r = 0.80, P < 0.0001) was observed. In contrast, no increase in TC surgeries for these lesions was seen. In multivariate analysis, EEAs were more likely to experience postoperative cerebrospinal fluid leak (odds ratio = 2.61, P < 0.0001). However, EEAs were protective against all other perioperative complications including diabetes insipidus, panhypopituitarism, visual impairment, and even mortality (odds ratio = 0.41, P = 0.0007).

Conclusions: Over the past several decades, utilization of EEAs to resect adult craniopharyngiomas has increased. EEAs appear to be associated with lower rates of perioperative mortality and complications. However, long-term, prospective studies controlling for tumor size, location, and preoperative symptomatology are needed to determine when one approach should be used preferentially over the other.
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http://dx.doi.org/10.1016/j.wneu.2021.06.066DOI Listing
August 2021

The role of human endogenous retroviruses in gliomas: from etiological perspectives and therapeutic implications.

Neuro Oncol 2021 10;23(10):1647-1655

Translational Neuroscience Center, NINDS, NIH, Bethesda, Maryland, USA.

Accounting for approximately 8% of the human genome, human endogenous retroviruses (HERVs) have been implicated in a variety of cancers including gliomas. In normal cells, tight epigenetic regulation of HERVs prevent aberrant expression; however, in cancer cells, HERVs expression remains pervasive, suggesting a role of HERVs in oncogenic transformation. HERVs may contribute to oncogenesis in several ways including insertional mutagenesis, chromosomal rearrangements, proto-oncogene formation, and maintenance of stemness. On the other hand, recent data has suggested that reversing epigenetic silencing of HERVs may induce robust anti-tumor immune responses, suggesting HERVs' potential therapeutic utility in gliomas. By reversing epigenetic modifications that silence HERVs, DNA methyltransferase, and histone deacetylase inhibitors may stimulate a viral-mimicry cascade via HERV-derived dsRNA formation that induces interferon-mediated apoptosis. Leveraging this anti-tumor autoimmune response may be a unique avenue to target certain subsets of epigenetically-dysregulated gliomas. Nevertheless, the role of HERVs in gliomas as either arbitrators of oncogenesis or forerunners of the innate anti-tumor immune response remains unclear. Here, we review the role of HERVs in gliomas, their potential dichotomous function in propagating oncogenesis and stimulating the anti-tumor immune response, and identify future directions for research.
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http://dx.doi.org/10.1093/neuonc/noab142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485438PMC
October 2021

Current experimental therapies for atypical and malignant meningiomas.

J Neurooncol 2021 Jun 5;153(2):203-210. Epub 2021 May 5.

Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.

Introduction: Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas.

Methods: We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials.

Results: There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors.

Conclusion: With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.
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http://dx.doi.org/10.1007/s11060-021-03759-xDOI Listing
June 2021

Intraoperative Stimulated Raman Histology for Anterior Skull Base Tumor Margins: Can We Improve Patient Survival and Time to Recurrence?

World Neurosurg 2021 05;149:265-266

Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, USA; Sylvestor Comprehensive Cancer Center, Miami, Florida, USA.

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http://dx.doi.org/10.1016/j.wneu.2021.03.012DOI Listing
May 2021

The Focused Neurosurgical Examination During Telehealth Visits: Guidelines During the COVID-19 Pandemic and Beyond.

Cureus 2021 Feb 23;13(2):e13503. Epub 2021 Feb 23.

Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA.

Objective:  To provide guidelines to healthcare workers for performing a focused neurological examination via telemedicine during the coronavirus disease-2019 (COVID-2019) pandemic.

Methods:  We reviewed our department's outpatient clinic visits after the implementation of a telemedicine protocol in response to the COVID-19 crisis. Crossover rates from telehealth to in-person visits were evaluated and guidelines for performing a telemedicine neurological exam were created based on the consensus of 16 neurosurgical attending providers over a four-month period.

Results:  From March 23, 2020 to July 20, 2020, some 2157 telehealth visits were performed in our department. Some 26 were converted to in-person visits by the provider request with the most cited reason for conversion being the need for a more detailed patient evaluation. Based on these experiences, we created a graphical tutorial to address the key components of the neurological exam with adaptations specific to the telehealth visit.

Conclusions:  In response to the global coronavirus pandemic, telemedicine has become an integral part of neurosurgeons' daily practice. Telemedicine failures remain low but primarily occur due to a need for more comprehensive evaluations. We provide guidelines for the neurosurgical exam during telehealth visits in an effort to assuage some of these issues.
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http://dx.doi.org/10.7759/cureus.13503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992292PMC
February 2021

Commentary: An Update of Neuroanesthesia for Intraoperative Brain Mapping Craniotomy.

Neurosurgery 2021 Mar 17. Epub 2021 Mar 17.

Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.

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http://dx.doi.org/10.1093/neuros/nyab065DOI Listing
March 2021

In Reply to the Letter to the Editor Regarding "Safety Analysis of Bilateral Laser Interstitial Thermal Therapy for Treatment of Butterfly Glioma".

World Neurosurg 2021 03;147:238

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.12.011DOI Listing
March 2021

Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Gliomas.

World Neurosurg 2021 06 5;150:e135-e143. Epub 2021 Mar 5.

Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Intraoperative pathologic diagnosis traditionally involves frozen section histopathology, which may be labor and time intensive. Indeed, a technique that streamlines the acquisition and evaluation of intraoperative histologic data may expedite surgical decision-making and shorten operative time. Stimulated Raman histology (SRH) is an emerging technology that allows for more rapid acquisition and interpretation of intraoperative histopathologic data.

Methods: A blinded, prospective cohort study was performed for 82 patients undergoing resection for a central nervous system tumor. Of these, 21 patients were diagnosed with glioma either intraoperatively or postoperatively on permanent section histology and included in this study. Time to diagnosis (TTD) and diagnostic accuracy relative to permanent section (the gold standard) were compared between SRH-based diagnosis and conventional frozen section histology. Diagnostic concordance with permanent section was also compared between frozen histopathology and SRH diagnosis.

Results: Diagnostic accuracy was not significantly different between methods (P = 1.00). Diagnostic concordance was not significantly different between methods when comparing 95% confidence intervals for kappa values (κ = 0.215; κ = 0.297; κ = 0.369). Lastly, mean TTD was significantly shorter with SRH-based diagnosis compared with frozen section (43 vs. 9.7 minutes, P < 0.0001). SRH was able to identify key features associated with varying glioma types.

Conclusions: SRH allows for rapid intraoperative diagnosis without sacrificing diagnostic accuracy. SRH may serve as a promising adjuvant to conventional histopathology to expedite intraoperative pathology consultation and surgical decision-making.
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http://dx.doi.org/10.1016/j.wneu.2021.02.122DOI Listing
June 2021

When "Peripheral" Becomes "Central": Primary and Secondary Malignant Intracerebral Nerve Sheath Tumor: A Case Report and a Systematic Review.

Neurosurgery 2021 05;88(6):1074-1087

Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, Miami, Florida, USA.

Background: The intracerebral occurrence of malignant peripheral nerve sheath tumors (MPNSTs) is exceedingly rare, and despite aggressive treatments, local recurrence and poor prognosis are very frequent. Like other brain tumors, these tumors could be primary or secondary, making the term "peripheral" an imprecise term for a primary brain tumor.

Objective: To analyze the reported cases of primary and secondary cerebral MPSNTs in terms of diagnosis, treatment, and overall survival. Additionally, we present a case of malignant intracerebral nerve sheath tumor (MINST) treated with radical surgery and radiotherapy.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, one database (PubMed) and crossed references were queried for MPNST with brain metastasis and primary MINSTs from 1971 to 2020. Data regarding demographic features, primary tumor site, risk factors, brain location of the lesion, treatment applied, and overall survival were extracted.

Results: A total of 55 patients were selected (including the reported case): 29 patients were secondary brain MPNST and 26 patients were primary MINST. The mean age was 41.8 ± 22 and 31.2 ± 23 yr, respectively. All brain metastases of MPNST (100%) had a primary tumor elsewhere in the body at the time of diagnosis. The overall survival was significantly shorter in patients with a secondary brain MPNST compared to MINST (P = .002).

Conclusion: We present a comprehensive analysis of every reported primary and secondary intracerebral MPNST. The prognosis in terms of survival is worst in the last one despite aggressive treatment. The lack of a primary MPNST in screening tests is sufficient to confirm a MINST at time of diagnosis.
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http://dx.doi.org/10.1093/neuros/nyab043DOI Listing
May 2021

Rapid Intraoperative Diagnosis of Meningiomas using Stimulated Raman Histology.

World Neurosurg 2021 06 27;150:e108-e116. Epub 2021 Feb 27.

Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Frozen section is a time- and labor-intensive method for intraoperative pathologic diagnosis. As a result, there exists a need to expedite and streamline the acquisition and interpretation of diagnostic histologic data to inform surgical decision making. Stimulated Raman histology (SRH) is an emerging technology that may serve to expedite the acquisition and interpretation of histologic data in the operating room.

Methods: A blinded, prospective cohort study of 82 patients undergoing resection for tumors of the central nervous system was performed. Twenty-six patients with diagnoses of meningioma on SRH, frozen, or permanent section were included in this subanalysis. Diagnostic time and accuracy of stimulated SRH histology images were compared with the gold standard (frozen section). Agreement of SRH and frozen section diagnosis with permanent section (true) diagnosis was also compared.

Results: Mean time-to-diagnosis was significantly shorter for SRH-mediated diagnosis compared with frozen section (9.2 vs. 35.8, P < 0.0001). Diagnostic accuracy was not significantly different between methods (P = 0.15). Diagnostic agreement was not significantly different between SRH versus frozen, SRH versus permanent, or frozen versus permanent section methods (P = 0.5, P = 0.5, P = 1.00).

Conclusions: SRH is a promising adjuvant technology that may expedite intraoperative neuropathologic consult without sacrificing diagnostic accuracy.
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http://dx.doi.org/10.1016/j.wneu.2021.02.097DOI Listing
June 2021

In Reply to the Letter to the Editor Regarding "Early Changes to Neurosurgery Resident Training During the COVID-19 Pandemic at a Large United States Academic Medical Center".

World Neurosurg 2021 02;146:423

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.11.095DOI Listing
February 2021

Clinical trials using oncolytic viral therapy to treat adult glioblastoma: a progress report.

Neurosurg Focus 2021 02;50(2):E3

Objective: Adult glioblastoma (GBM) has proven refractory to decades of innovation. Oncolytic viral therapy represents a novel therapy that uses viral vectors as both a delivery and therapeutic mechanism to target GBM cells. Despite the growing body of basic science data supporting the feasibility of viral therapy to treat GBM, the reporting of clinical trial results is heterogeneous. Correspondingly, the aim of this study was to present a contemporary summary of the progress all clinical trials have made to date.

Methods: The ClinicalTrials.gov database was reviewed in August 2020 for all possible interventional clinical trials involving viral vector-based therapy to treat adult GBM. These were then screened against selection criteria to identify pertinent clinical trials.

Results: A total of 29 oncolytic viral therapy trials treating adult GBM were identified. The median start and expected completion years were 2014 and 2020, respectively. At the time of this writing, 10 (35%) trials were reported to have completed recruitment, whereas 7 (24%) were actively recruiting. The median target enrollment number was 36 (range 13-108), with the majority of trials being phase I (n = 18, 62%), and involving secondary GBM among other malignant glioma (n = 19, 66%). A total of 10 unique viral vectors were used across all trials, with the most common being adenovirus (n = 16, 55%). Only 2 (7%) phase I trials to date have reported outcomes on the ClinicalTrials.gov portal. Results of 12 additional clinical trials were found in academic publications, with median progression-free and overall survival times of 3 and 15 months, respectively, after the first viral dose at recurrence. The coordination of the large majority of trials originated from the US (n = 21, 72%), and the median number of testing sites per trial was 1 (range 1-15), via industry funding (n = 18 trials, 62%).

Conclusions: There are multiple early-stage oncolytic viral therapy clinical trials for adult GBM currently active. To date, limited results and outcomes are promising but scarce. The authors expect this to change in the near future because many trials are scheduled to have either nearly or actually reached their expected recruitment completion time. How exactly oncolytic viral therapy will fit into the current treatment paradigms for primary and secondary GBM remains to be seen, and will not be known until safety and toxicity profiles are established by these clinical trials.
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http://dx.doi.org/10.3171/2020.11.FOCUS20860DOI Listing
February 2021

Remote Cerebellar Hemorrhage Associated With Intra-Operative Cerebrospinal Fluid Leak: A Report of Two Rare Case Presentations and Review of the Literature.

Cureus 2020 Dec 14;12(12):e12082. Epub 2020 Dec 14.

Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA.

Remote cerebellar hemorrhage (RCH) is a rare complication following cranial or spinal neurosurgical procedures. Traditionally, RCH has been associated with frontal or frontotemporal craniotomy with supine patient positioning. Though the exact etiology is unknown, theories have described patient positioning and excessive cerebrospinal fluid (CSF) drainage intra-operatively as contributing factors to cerebellar displacement (cerebellar sag), obstruction of venous flow, and pathogenesis of RCH.  We report two cases of RCH following a prone, suboccipital craniotomy-C1 laminectomy and a temporal burr hole evacuation of a subdural hygroma. In each case, a large volume of CSF was rapidly evacuated intra-operatively. To the best of our knowledge, both instances represent relatively rare settings for RCH. Additionally, we conducted a comprehensive literature review of PubMed, EMBASE, and Web of Science for all cases of RCH in which peri-operative CSF leakage was explicitly detailed. Although RCH is thought to be a rare complication of frontotemporal and frontal craniotomies, this case report signifies that RCH may occur in the setting of sub-occipital craniotomy or even after minimally invasive burr hole procedures. For these procedures, careful symptomatic monitoring and follow-up imaging remain essential in diagnosis. Controlled CSF drainage may be useful in mediating dramatic alterations in intracranial pressure (ICP) and cerebellar sag contributing to RCH.
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http://dx.doi.org/10.7759/cureus.12082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805504PMC
December 2020

Differences Between Neurosurgical Subspecialties in Telehealth Adoption.

World Neurosurg 2021 02 16;146:e323-e327. Epub 2020 Nov 16.

Department of Neurological Surgery, University of Miami, Miami, Florida, USA. Electronic address:

Objective: The health care field has been faced with unprecedented challenges during the COVID 19 pandemic. One such challenge was the implementation of enhanced telehealth capabilities to ensure continuity of care. In this study, we aim to understand differences between subspecialties with regard to patient consent and satisfaction following telehealth implementation.

Methods: A retrospective review of the electronic medical record was performed from March 2 to May 8, 2020 to evaluate surgical consents before and after telehealth implementation. Press Ganey survey results were also obtained both pre- and posttelehealth implementation and compared.

Results: There was no significant difference in the percentage of new patients consented for surgery (after being seen via telehealth only) between the cranial and spine services. For procedures in which >10 patients were consented for surgery, the highest proportion of patients seen only via telehealth was for ventriculoperitoneal shunt placement/endoscopic third ventriculostomy for the cranial service, and lumbar laminectomy and microdiscectomy for the spine service. Additionally, the spine service experienced marked improvement in Press Ganey scores posttelehealth implementation with overall doctor ranking improving from the 29th to the 93rd percentile, and likelihood to recommend increasing from the 24th to the 94th percentile.

Conclusions: There were clear trends with regard to which pathologies and procedures were most amenable to telehealth visits, which suggests a potential roadmap for future clinic planning. Additionally, the notable improvement in spine patient satisfaction following the implementation of a telehealth program suggests the need for long-term process changes.
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http://dx.doi.org/10.1016/j.wneu.2020.10.080DOI Listing
February 2021

Building a Brain Tumor Practice: Objective Analysis of Referral Patterns and Implications for the Growth of a Subspecialty Surgical Program.

Cureus 2020 Sep 12;12(9):e10416. Epub 2020 Sep 12.

Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA.

Introduction Growth of surgical caseload among specialties with a large contribution margin is an important financial objective for hospitals. In this study, we examined the diversity of referral patterns to a neurosurgeon over an eight-year interval and examined practice attributes related to surgical growth. Methods The electronic records of all patients undergoing an intracranial surgical procedure between August 2011 and August 2019 by an academic neurosurgeon were reviewed retrospectively. The Herfindahl-Hirschman index (HHI) was used to assess the distribution of referrals among community physicians who referred such patients; a value of HHI <0.15 indicates diversity. The yearly HHI trend was evaluated using meta-regression. Results The neurosurgeon's brain surgery caseload progressively increased on an annual basis from 1.4 to 12.5 cases per week between 2012 and 2018. Among the 1540 cases referred by 1775 different physicians, 78% were from three counties in southeast Florida and 8.1% from two counties in southwest Florida. The HHI declined between 2013 and 2018 by 0.023 per year (0.0046 standard error [SE], p = 0.0073) with the estimated value 0.0063 (0.0014 SE) < 0.15 in 2018 (p < 0.0001). The findings indicate that the base of referring physicians was highly diverse and that growth in caseload was accompanied by significantly less concentration of referrals. Conclusion Surgical growth in the neurosurgeon's practice resulted from a small number of referrals from many physicians, not from many referrals from a small number of physicians. Few physicians referred a sufficient number of patients to warrant attribution of the referral itself to personal knowledge of their patients' eventual outcomes. Rather, factors promoting timely access to patient care appear to have been the driving force for growth.
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http://dx.doi.org/10.7759/cureus.10416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550243PMC
September 2020

Magnetic resonance-guided laser interstitial thermal therapy for posterior fossa neoplasms.

J Neurooncol 2020 Sep 15;149(3):533-542. Epub 2020 Oct 15.

Department of Neurosurgery, Rutgers Robert Wood Johnson Medical School, 10 Plum St. 5th Floor, New Brunswick, NJ, 08901, USA.

Purpose: Magnetic resonance-guided laser interstitial thermal therapy (LITT) has been increasingly used to treat a number of intracranial pathologies, though its use in the posterior fossa has been limited to a few small series. We performed a multi-institutional review of targets in the posterior fossa, reporting the efficacy and safety profile associated with laser ablation in this region of the brain.

Methods: A retrospective review of patients undergoing LITT in the posterior fossa was performed from August 2010 to March 2020. Patient demographic information was collected alongside the operative parameters and patient outcomes. Reported outcomes included local control of the lesion, postoperative complications, hospital length of stay, and steroid requirements.

Results: 58 patients across four institutions underwent LITT in the posterior fossa for 60 tumors. The median pre-ablation tumor volume was 2.24 cm. 48 patients (50 tumors) were available for follow-up. An 84% (42/50) overall local control rate was achieved at 9.5 months median follow up. There were two procedural complications, including insertional hemorrhage and laser misplacement and 12/58 (21%) patients developed new neurological deficits. There was one procedure related death. The median length of hospital stay was 1 day, with 20.7% of patients requiring discharge to a rehabilitation facility.

Conclusions: LITT is an effective approach for treating pathology in the posterior fossa. The average target size is smaller than what has been reported in the supratentorial space. Care must be taken to prevent injury to surrounding structures given the close proximity of critical structures in this region.
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http://dx.doi.org/10.1007/s11060-020-03645-yDOI Listing
September 2020

Commentary: Computational Drug Repositioning Identifies Potentially Active Therapies for Chordoma.

Neurosurgery 2021 01;88(2):E203-E204

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida.

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http://dx.doi.org/10.1093/neuros/nyaa403DOI Listing
January 2021

Early Changes to Neurosurgery Resident Training During the COVID-19 Pandemic at a Large U.S. Academic Medical Center.

World Neurosurg 2020 12 28;144:e926-e933. Epub 2020 Sep 28.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: The coronavirus disease 2019 pandemic has led to sweeping changes in residency programs across the world, including cancellation of elective cases. The effects of safety measures on neurosurgical training remain unclear. To understand how neurosurgical residents have been affected, we analyzed the operative experience in the months leading up to and during the pandemic.

Methods: The resident and institutional case totals were tallied for a single residency program in Miami-Dade County from January 1, 2019 to June 30, 2020. A matched cohort analysis was performed before and during the pandemic to assess the effects on resident surgical training.

Results: The case totals for all levels of training were lower when restrictions were placed on elective surgeries. An average of 11 cases was logged in April 2020, a decrease from 26 cases in April 2019 (95% confidence interval, 8.7-22; P < 0.01). An average of 20 cases was logged in May 2020, a decrease from 25 cases in May 2019 (95% confidence interval, 1.2-8.8; P = 0.01). In April and May 2020, 299 (66%) and 148 (50%) fewer cases had been performed at our institution compared with April and May 2109.

Conclusions: Operative experience was reduced for residents during the months when the performance of elective cases was restricted. Our data suggest experience in some areas of neurosurgery were more affected than were others, and residents at different levels of training were also affected differently. However, the extent of the coronavirus disease 2019 pandemic on neurosurgical training is unlikely to be understood in the short term.
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http://dx.doi.org/10.1016/j.wneu.2020.09.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521299PMC
December 2020
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