The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis.

Inflammation is critical in the pathobiology of atherosclerosis. An essential player in the inflammatory process in atherosclerosis are macrophages that scavenge oxidatively modified low-density lipoproteins (OxLDL) deposited in the subendothelium of systemic arteries that secrete a myriad of pro-inflammatory mediators. Here, we identified that a subunit of the Skp-Cullin-F-box ubiquitin E3 ligase apparatus, termed FBXO3, modulates the inflammatory response in atherosclerosis. Specifically, individuals with a hypofunctioning genetic variant of FBXO3 develop less atherosclerosis. FBXO3 protein is present in cells of monocytic lineage within carotid plaques and its levels increase in those with symptomatic compared with asymptomatic atherosclerosis. Further, cellular depletion or small molecule inhibition of FBXO3 significantly reduced the inflammatory response to OxLDL by macrophages without altering OxLDL uptake. Thus, FBXO3 potentiates vascular inflammation and atherosclerosis that can be effectively mitigated by a small molecule inhibitor.

Risk Factors and Reconstruction Techniques for Persistent Cerebrospinal Fluid Leak in Patients Undergoing Endoscopic Endonasal Approach to the Posterior Fossa.

Background High-flow skull base dural defects are associated with an increased risk of postoperative cerebrospinal fluid (CSF) leaks. Objective This study aimed to identify the risk factors for persistent postoperative CSF leak after endoscopic endonasal surgery (EES) and determine the ideal reconstruction strategy after initial failed repair. Methods Patients with CSF leak after intradural EES between October 2000 and February 2017 were identified. Cases with persistent CSF leak were compared with patients with similar pathologic diagnosis without a persistent leak to identify additional risk factors. Results Two hundred and twenty-three out of 3,232 patients developed postoperative CSF leak. Persistent leaks requiring more than one postoperative repair occurred in 7/223 patients (3.1%). All seven had undergone intradural approach to the posterior fossa for resection of recurrent/residual clival chordomas. This group was matched with 25 patients with recurrent/residual clival chordoma who underwent EES without postoperative CSF leak (control group). Age, gender, history of diabetes, smoking, or radiotherapy were not statistically different between the groups. Obesity (body mass index > 30) was significantly more common in the group with persistent leak (86%) compared with controls (36%) ( p = 0.02). All patients with a persistent CSF leak developed meningitis ( p = 0.001). Five patients with persistent leak required a pericranial flap to achieve definitive repair. Conclusion Multiple recurrent CSF leak after EES primarily occurs following resection of recurrent/residual posterior fossa chordoma. Obesity is a major risk factor and meningitis is universal with persistent leak. Flap necrosis may play a role in the development of persistent CSF leaks, and the use of secondary vascularized flaps, specifically extracranial-pericranial flaps, should be considered as an early rescue option in obese patients.

Seizure Risk following Open and Expanded Endoscopic Endonasal Approaches for Intradural Skull Base Tumors.

Objectives The incidence of seizures following a craniotomy for tumor removal varies between 15 and 20%. There has been increased use of endoscopic endonasal approaches (EEAs) for a variety of intracranial lesions due to its more direct approach to these pathologies. However, the incidence of postoperative seizures in this population is not well described. Methods This is a single-center, retrospective review of consecutive patients undergoing EEA or open craniotomy for resection of a cranial base tumor between July 2007 and June 2014. Patients were included if they underwent an EEA for an intradural skull base lesion. Positive cases were defined by electroencephalograms and clinical findings. Patients who underwent a craniotomy to remove extra-axial skull base tumors were analyzed in the same fashion. Results Of the 577 patients treated with an EEA for intradural tumors, 4 experienced a postoperative seizure (incidence 0.7%, 95% confidence interval [CI]: 0.002-0.02). Over the same period, 481 patients underwent a craniotomy for a skull base lesion of which 27 (5.3%, 95% CI: 0.03-0.08) experienced a seizure after surgery. The odds ratio for EEA was 0.13 (95% CI: 0.05-0.35). Both populations were different in terms of age, gender, tumor histology, and location. Conclusion This study is the largest series looking at seizure incidence after EEA for intracranial lesions. Seizures are a rare occurrence following uncomplicated endonasal approaches. This must be tempered by selection bias, as there are inherent differences in which patients are treated with either approach that influence the likelihood of seizures.

Clinical Experience with Secondary Endoscopic Reconstruction of Clival Defects with Extracranial Pericranial Flaps.

Objectives The aim of this study is to report the clinical outcome of extracranial pericranial flaps (ePCF) used for reconstruction of clival dural defects following failure of primary repair. Design Retrospective review of skull base database. Setting Academic medical center. Participants Patients undergoing reconstruction of clival defects with ePCF following endoscopic endonasal surgery (EES). Main outcome measures Postoperative cerebrospinal fluid (CSF) leak, meningitis, and flap necrosis. Results Seven patients (five males and two females) who underwent ePCF reconstruction for clival defects following EES were included. All patients (ages 8-64 years) had a postoperative CSF leak due to a failed primary clival reconstruction (five had one, one had two, and one had three failed CSF leak repairs prior to ePCF reconstruction). Nasoseptal and inferior turbinate (lateral nasal wall) flaps were not available for secondary reconstruction due to prior surgeries. The immediate success rate of ePCF for the reconstruction of clival defects in patients with multiple flap failures was 58%. Two patients developed CSF leaks that were successfully repaired endoscopically with the addition of free tissue grafts; one patient had partial flap necrosis that required debridement; none required an additional vascularized flap. Width of the defect, length of the defect, properties of the ePCF, and age did not demonstrate significance ( p > 0.05) for adverse outcome. Conclusion An ePCF is a reconstructive option for high-risk, large clival defects when other local and regional vascularized flaps are not available or fail. ePCFs can be used for reconstruction of clival defects in all populations, including pediatric patients.

Long-Term Outcomes After Carotid Endarterectomy: The Experience of an Average-Volume Surgeon.

BACKGROUND: Long-term outcome data for patients undergoing carotid endarterectomy (CEA) are lacking. As most of the published literature on CEA outcomes has been from high-volume providers, we wanted to investigate the outcomes of an average-volume cerebrovascular neurosurgeon. METHODS: We reviewed a single neurosurgeon's experience with CEA focusing on long-term outcomes. Most procedures (99.0%) were performed with primary closure of the arteriotomy. RESULTS: We studied 192 CEAs performed between 1998 and 2017, 77% for symptomatic disease. Two patients (1%) experienced immediate postoperative stroke. During an average follow-up of 53 months (range, 0-205 months), 2 more patients (1%) experienced ipsilateral carotid circulation stroke, and 5 patients (2.6%) experienced ipsilateral transient ischemic attacks. Five patients (2.6%) experienced contralateral transient ischemic attacks, and 6 (3.1%) experienced contralateral stroke. There were also 3 cases of (1.6%) hemorrhagic stroke and 6 cases (3.1%) of vertebrobasilar circulation stroke. The rate of ipsilateral stroke-free survival was 98.4% at 5 years post-CEA, 97.9% at 10 years post-CEA, and 97.9% at 15 years post-CEA. The rate of ipsilateral restenosis-free survival was 97.9% at 5 years post-CEA, 96.8% at 10 years post-CEA, and 96.8% at 15 years post-CEA. Six patients (3.1%) experienced restenosis >70% during follow-up. Two of these patients underwent carotid artery stenting. Almost all patients (>95%) were maintained on an antiplatelet medication and statin. CONCLUSIONS: In the hands of an average-volume cerebrovascular neurosurgeon, CEA can provide durable protection from recurrent stroke in the ipsilateral carotid distribution that extends beyond 15 years. Thus, this procedure should be considered the gold standard against which other revascularization modalities should be evaluated.

Evaluation of Intranasal Flap Perfusion by Intraoperative Indocyanine Green Fluorescence Angiography.

BACKGROUND: Vascularized intranasal flaps are the primary reconstructive option for endoscopic skull base defects. Flap vascularity may be compromised by injury to the pedicle or prior endonasal surgery. There is currently no validated technique for intraoperative evaluation of intranasal flap viability. OBJECTIVE: To evaluate the efficacy of indocyanine green (ICG) near-infrared angiography in predicting the viability of pedicled intranasal flaps during endoscopic skull base surgery through a pilot study. METHODS: ICG near-infrared fluorescence endoscopy was performed during endoscopic endonasal surgery for skull base tumors. Intraoperative and postoperative data were collected regarding enhancement of the flap body and pedicle. Fluorescence was rated qualitatively. Postoperatively, flap perfusion was evaluated via MRI-contrast enhancement in addition to clinical outcomes (cerebrospinal fluid leak and endoscopic flap appearance). RESULTS: Thirty-eight patients underwent ICG fluorescence angiography. Both the body and pedicle enhanced in 20 patients (53%), while the pedicle only enhanced for 12 patients (32%), the body only for 3 (8%), and neither for 3 (8%). When both the pedicle and body enhanced with ICG, the rate of postoperative MRI contrast enhancement was 100% and the rate of flap necrosis was 0%. The sensitivity and specificity of flap pedicle ICG enhancement for predicting postoperative flap MRI enhancement were 97% and 67%, respectively. Two of 3 patients without enhancement developed flap necrosis. CONCLUSION: ICG fluorescence angiography of intraoperative flap perfusion is feasible and correlates well with outcomes of postoperative MRI flap enhancement and flap necrosis. Additional study is needed to further refine the imaging technique and optimally characterize the clinical utility.

Bilateral coagulation of inferior hypophyseal artery and pituitary transposition during endoscopic endonasal interdural posterior clinoidectomy: do they affect pituitary function?

OBJECTIVE: The endoscopic endonasal transcavernous approach with interdural pituitary transposition provides surgical access to the posterior clinoids and interpeduncular cistern. Prior to posterior clinoidectomy, selective coagulation and transection of the inferior hypophyseal artery (IHA) is recommended to prevent uncontrolled tearing of the artery and its avulsion from the wall of the cavernous carotid artery. The authors' preliminary experience has shown that unilateral sacrifice of the IHA caused no permanent endocrine dysfunction. In this study, they investigated the pituitary function in the setting of bilateral sacrifice of IHAs and pituitary transposition. METHODS: All patients with normal preoperative pituitary function who underwent endoscopic endonasal bilateral posterior clinoidectomy with bilateral IHA sacrifice between March 2010 and December 2016 were included and retrospectively evaluated. All data regarding pituitary function were collected. The degree of pituitary gland manipulation was estimated based on tumor size on preoperative MRI. An angle between a line from the point where the gland meets the floor of the sella to the highest point of the tumor and the horizontal plane of the sellar floor, or access angle, was also measured. Posterior pituitary bright spots on pre- and postoperative T1-weighted MRI were also reported. RESULTS: Twenty patients had bilateral transcavernous posterior clinoidectomies with coagulation of both IHAs. There were 13 chordomas, 3 epidermoid cysts, 2 chondrosarcomas, 1 meningioma, and 1 hemangiopericytoma. The mean follow-up was 19 months (range 13-84 months). Two patients experienced transient diabetes insipidus (DI) requiring desmopressin, which resolved before hospital discharge. One patient (with chordoma) developed delayed permanent DI, and a second patient (with hemangiopericytoma) developed permanent DI and panhypopituitarism. The access angle was higher in the group with pituitary dysfunction (47.25° compared to 33.81°; p = 0.07). Posterior pituitary bright spots were preserved in 75% of cases with normal postoperative endocrine function. CONCLUSIONS: The endoscopic endonasal transcavernous approach to the interpeduncular cistern with pituitary transposition and bilateral sacrifice of the IHAs does not cause pituitary dysfunction in a majority of patients. When endocrine deficit occurs, it appears to be more likely to have been caused by surgical manipulation than loss of blood supply. This finding confirms clinically the crucial concept of interarterial anastomosis of pituitary vasculature proposed by anatomists.

Complete endoscopic resection of a pituitary stalk epidermoid cyst using a combined infrasellar interpituitary and suprasellar endonasal approach: case report.

Intracranial epidermoid cysts are benign lesions of epithelial origin that most frequently present with symptoms of mass effect. Although they are often associated with a high rate of residual tumor and recurrence, maximal safe resection usually leads to good outcomes. The authors report a complete resection of an uncommon pituitary stalk epidermoid cyst with intrasellar extension using a combined suprasellar and infrasellar interpituitary, endoscopic endonasal transsphenoidal approach. The patient, a 54-year-old woman, presented with headache, visual disturbance, and diabetes insipidus. Postoperatively, she reported improvement in her visual symptoms and well-controlled diabetes insipidus using 0.1 mg of desmopressin at bedtime and normal anterior pituitary gland function. One year later, she continues to receive the same dosage of desmopressin and is also taking 50 mcg of levothyroxine daily after developing primary hypothyroidism unrelated to the surgical procedure. A combined infrasellar interpituitary and suprasellar approach to this rare location for an epidermoid cyst can lead to a safe and complete resection with good clinical outcomes.

Endoscopic Endonasal Approach to the Ventral Jugular Foramen: Anatomical Basis, Technical Considerations, and Clinical Series.

BACKGROUND: Surgical exposure of the jugular foramen (JF) is challenging given its complex regional anatomy and proximity to critical neurovascular structures. OBJECTIVE: To describe the anatomical basis, surgical technique, and outcomes of a group of patients who underwent the endoscopic endonasal approach to the JF. METHODS: Five silicon-injected anatomical specimens were prepared for dissection. Additionally, a chart review was conducted through our patient database, searching for endonasal exposure of the JF. Demographic data, clinical presentation, pathological findings, extent of resection in the JF, and occurrence of complications were analyzed. RESULTS: The endonasal exposure of the JF requires 3 sequential steps: a transpterygoid, a "far-medial," and an "extreme-medial" approach. Mobilization or transection of the cartilaginous portion of the eustachian tube (ET) is necessary. In the clinical series, cranial neuropathies were the presenting symptoms in 16 patients (89%). Eighteen tumors (10 chondrosarcomas, 7 chordomas, 1 adenocarcinoma) extended secondarily into the JF. Total tumor resection was achieved in 10 patients (56%), near total (≥90%) in 6 (33%), and subtotal (<90%) in 2 (11%). ET dysfunction (75% of cases), transient palatal numbness (17%), cerebrospinal fluid leakage (17%), and lower cranial nerve palsy (17%) were the most common postoperative complications. There were no carotid artery or jugular vein injuries. CONCLUSION: The endoscopic endonasal approach to the JF requires mobilization or transection of the cartilaginous portion of the ET. This maneuver provides a safe infrapetrosal surgical route to the JF. It may be considered a valid option, in well-selected cases, for resection of malignant and recurrent cranial base tumors.