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Lena Mary Houlihan, Evgenii Belykh, Xiaochun Zhao, Michael G. J. O’Sullivan, and Mark C. Preul

Transorbital surgery has gained recent notoriety because of its incorporation into endoscopic skull base surgery. The use of this surgical corridor has been pervasive throughout the 20th century. It has been utilized by multiple disciplines for both clinical and experimental purposes, although its historical origin is medically and ethically controversial. Hermann Knapp first introduced the orbital surgical technique in 1874, and Rudolf Krönlein introduced his procedure in 1889. Rivalry between Walter Dandy in neurosurgery and Raynold Berke in ophthalmology further influenced methods of tackling intracranial and intraorbital pathologies. In 1946, Walter Freeman revolutionized psychosurgery by completing seemingly successful transorbital leucotomies and promoting their minimally invasive and benign surgical characteristics. However, as Freeman’s legacy came into disrepute, so did the transorbital brain access corridor, again resulting in its stunted evolution. Microsurgery and endoscopy further influenced the use, or lack thereof, of the transorbital corridor in neurosurgical approaches. Historical analysis of present goals in modern skull base surgery echoes the principles established through an approach described almost 150 years ago: minimal invasion, minimal morbidity, and priority of patient satisfaction. The progression of the transorbital approach not only reflects psychosocial influences on medical therapy, as well as the competition of surgical pioneers for supremacy, but also describes the diversification of skull base techniques, the impact of microsurgical mastery on circumferential neurosurgical corridors, the influence of technology on modernizing skull base surgery, and the advancing trend of multidisciplinary surgical excellence.

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Jakub Godzik, Bernardo de Andrada Pereira, Anna G. U. Sawa, Jennifer N. Lehrman, Randall J. Hlubek, Brian P. Kelly, and Jay D. Turner

OBJECTIVE

The objective of this study was to evaluate a novel connector design and compare it with traditional side connectors, such as a fixed-angle connector (FAC) and a variable-angle connector (VAC), with respect to lumbosacral stability and instrumentation strain.

METHODS

Standard nondestructive flexibility tests (7.5 Nm) and compression tests (400 N) were performed using 7 human cadaveric specimens (L1–ilium) to compare range of motion (ROM) stability, posterior rod strain (RS), and sacral screw bending moment (SM). Directions of motion included flexion, extension, left and right lateral bending, left and right axial rotation, and compression. Conditions included 1) the standard 2-rod construct (2R); 2) the dual-tulip head (DTH) with 4-rod construct (4R); 3) FACs with 4R; and 4) VACs with 4R. Data were analyzed using repeated-measures ANOVA.

RESULTS

Overall, there were no statistically significant differences in ROM across the lumbosacral junction among conditions (p > 0.07). Compared with 2R, DTH and FAC significantly reduced RS in extension, left axial rotation, and compression (p ≤ 0.03). VAC significantly decreased RS compared with 2R in flexion, extension, left axial rotation, right axial rotation, and compression (p ≤ 0.03), and significantly decreased RS compared with DTH in extension (p = 0.02). DTH was associated with increased SM in left and right axial rotation compared with 2R (p ≤ 0.003) and in left and right lateral bending and left and right axial rotation compared with FAC and VAC (p ≤ 0.02). FAC and VAC were associated with decreased SM compared with 2R in right and left lateral bending (p ≤ 0.03).

CONCLUSIONS

RS across the lumbosacral junction can be high. Supplemental rod fixation with DTH is an effective strategy for reducing RS across the lumbosacral junction. However, the greatest reduction in RS and SM was achieved with a VAC that allowed for straight (uncontoured) accessory rod placement.

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Aurore Sellier, Nathan Beucler, Christophe Joubert, Nicolas Desse, and Arnaud Dagain

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Mónica Patricia Herrera-Martinez, Ezequiel García-Ballestas, Ivan Lozada-Martinez, Daniela Torres-Llinás, and Luis Moscote-Salazar

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Scott R. Morrison and Chandrasekaran Kaliaperumal

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Jorge A. Gonzalez-Martinez and Patrick Y. Chauvel

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Sakibul Huq, Nivedha V. Kannapadi, Joshua Casaos, Tarik Lott, Raphael Felder, Riccardo Serra, Noah L. Gorelick, Miguel A. Ruiz-Cardozo, Andy S. Ding, Arba Cecia, Ravi Medikonda, Jeff Ehresman, Henry Brem, Nicolas Skuli, and Betty M. Tyler

OBJECTIVE

Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and group 3 (Myc driven) subtypes that are associated with the activity of eukaryotic initiation factor 4E (eIF4E), a critical mediator of translation, and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and master regulator of transcription. Recent drug repurposing efforts in multiple solid and hematologic malignancies have demonstrated that eIF4E and EZH2 are both pharmacologically inhibited by the FDA-approved antiviral drug ribavirin. Given the molecular overlap between medulloblastoma biology and known ribavirin activity, the authors investigated the preclinical efficacy of repurposing ribavirin as a targeted therapeutic in cell and animal models of medulloblastoma.

METHODS

Multiple in vitro assays were performed using human ONS-76 (a primitive SHH model) and D425 (an aggressive group 3 model) cells. The impacts of ribavirin on cellular growth, death, migration, and invasion were quantified using proliferation and Cell Counting Kit-8 (CCK-8) assays, flow cytometry with annexin V (AnnV) staining, scratch wound assays, and Matrigel invasion chambers, respectively. Survival following daily ribavirin treatment (100 mg/kg) was assessed in vivo in immunodeficient mice intracranially implanted with D425 cells.

RESULTS

Compared to controls, ribavirin treatment led to a significant reduction in medulloblastoma cell growth (ONS-76 proliferation assay, p = 0.0001; D425 CCK-8 assay, p < 0.0001) and a significant increase in cell death (flow cytometry for AnnV, ONS-76, p = 0.0010; D425, p = 0.0284). In ONS-76 cells, compared to controls, ribavirin significantly decreased cell migration and invasion (Matrigel invasion chamber assay, p = 0.0012). In vivo, ribavirin significantly extended survival in an aggressive group 3 medulloblastoma mouse model compared to vehicle-treated controls (p = 0.0004).

CONCLUSIONS

The authors demonstrate that ribavirin, a clinically used drug known to inhibit eIF4E and EZH2, has significant antitumor effects in multiple preclinical models of medulloblastoma, including an aggressive group 3 animal model. Ribavirin may represent a promising targeted therapeutic in medulloblastoma.

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Gonzague Guillaumet, Nozar Aghakhani, Silvia Morar, Razvan Copaciu, Fabrice Parker, and Steven Knafo

OBJECTIVE

Surgical treatment for nonforaminal syringomyelia related to spinal arachnoiditis is still controversial. The authors sought to assess respective outcomes and rates of reintervention for shunting and spinal cord untethering (arachnolysis) in spinal arachnoiditis with syringomyelia.

METHODS

This retrospective cohort study was conducted at a single reference center for syringomyelia. Patients undergoing arachnolysis and/or shunting interventions for nonforaminal syringomyelia were screened.

RESULTS

The study included 75 patients undergoing 130 interventions. Arachnolysis without shunting was performed in 48 patients, while 27 patients underwent shunting. The mean follow-up between the first surgery and the last outpatient visit was 65.0 months (range 12–379 months, median 53 months). At the last follow-up, the modified McCormick score was improved or stabilized in 83.4% of patients after arachnolysis versus 66.7% after shunting. Thirty-one (41.3%) patients underwent reintervention during follow-up, with a mean delay of 33.2 months. The rate of reintervention was 29.2% in the arachnolysis group versus 63.0% in the shunting group (chi-square = 8.1, p = 0.007). However, this difference was largely driven by the extension of the arachnoiditis: in patients with focal arachnoiditis (≤ 2 spinal segments), the reintervention rate was 21.6% for arachnolysis versus 57.1% for shunting; in patients with extensive arachnoiditis, it was 54.5% versus 65.0%, respectively. Survival analysis assessing the time to the first reintervention demonstrated a better outcome in both the arachnolysis (p = 0.03) and the focal arachnoiditis (p = 0.04) groups.

CONCLUSIONS

Arachnolysis led to fewer reinterventions than shunting in patients with nonforaminal syringomyelia. There was a high risk of reintervention for patients with extensive arachnopathies, irrespective of the surgical technique.

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Risheng Xu, Lydia Gregg, Sheng-fu Larry Lo, and Philippe Gailloud

Low-flow spinal extradural arteriovenous fistulas (SEAVFs) are frequently misdiagnosed as spinal dural arteriovenous fistulas (SDAVFs), and their true prevalence is unknown. The principal feature distinguishing low-flow SEAVFs from SDAVFs is the location of the shunt, which involves a pouch of epidural plexus in SEAVFs and a radiculomedullary vein (RMV) in SDAVFs. A venous hypertensive myelopathy comparable to the one observed with SDAVFs develops when the arterialized venous pouch of an SEAVF is connected to an RMV. Depending on the size of the epidural pouch, a low-flow SEAVF may uncommonly drain into multiple RMVs. The authors present an observation of a low-flow SEAVF whose double radiculomedullary drainage was revealed only after intraoperative digital subtraction angiography, and they discuss the surgical implications of this anatomical configuration.