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Background: Petroclival tumors and ventrolateral lesions of the pons present unique surgical challenges. This cadaveric study provides qualitative and quantitative anatomic comparison for an anterior petrous apicectomy through the transcranial middle fossa (TMF) and expanded endoscopic transsphenoidal-transclival approaches., Methods: In 10 silicone-injected heads, the petrous apex and clivus were drilled extradurally using middle fossa and endonasal approaches. With in situ and frameless stereotactic navigation, we defined consistent points to compare working areas, bone removal volumes, approach angles, and surgical freedom., Results: Mean exposed TMF area (21.03 ± 3.46 cm 2 ) achieved a 44.71 ± 4.13° working angle to the brainstem between cranial nerves V and VI. Kawase's rhomboid area measured 1.76 ± 0.34 cm 2 , and bone removal averaged 1.20 ± 0.12 cm 3 at the petrous apex. Surgical freedom on the lateral brainstem was higher halfway between cranial nerves V and VI at the center of the rhomboid compared with midline at the basilar sulcus (P < 0.01). After clivectomy and petrous apicectomy, mean exposed expanded endoscopic transsphenoidal-transclival area was 5.29 ± 0.66 cm 2 . Approach from either nostril showed no statistically significant differences in surgical freedom at the foramen lacerum and midpoint basilar sulcus. At the petrous apex, bone volume removed and area exposed were significantly larger for the TMF approach (P < 0.001)., Conclusions: Expanded transclival anterior petrosectomy through the TMF approach provides an adequate corridor to lesions in the upper ventrolateral pons. The expanded endoscopic transsphenoidal-transclival approach better fits midline lesions not extending laterally beyond cranial nerve VI and C3 carotid when evaluating normal anatomic parameters., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the association between operative duration and complications after vestibular schwannoma (VS) surgery., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: One hundred forty-eight patients undergoing vestibular schwannoma resection in a single institution., Intervention: Vestibular schwannoma resection., Main Outcome Measures: Operative duration, surgical approach, tumor size, and postoperative complications., Results: Forty-one patients underwent middle cranial fossa (MCF) approach, 46 underwent translabyrinthine (TL) approach, and 61 underwent retrosigmoid (RS) approach. The mean operative duration overall was 407 minutes (MCF-339 min, TL-450 min, RS 420 min). When controlling for tumor size, there was no difference in procedure duration by approach (OR 0.92, CI 0.82-1.02, p=0.11).When controlling for approach, there was a significant increase in procedure duration by tumor size (OR 1.36, CI 1.23-1.50, p < 0.0001). Increased procedure duration was not associated with 30-day readmission (p = 0.82), cerebrospinal fluid leak (CSF) (p = 0.84), return to the operating room (p = 0.75), postoperative deep vein thrombosis (p = 1.0), postoperative stroke (p = 0.23), or postoperative wound complications (p = 0.70). Longer operative time was associated with increased hospital length of stay (p = 0.04). However, when controlling for tumor size and surgical approach, hospital length of stay was no longer associated with increased procedure duration (OR 1.15, CI 0.98-1.33, p = 0.3)., Conclusion: Increased operative duration was associated with larger tumor size; however contrary to previous reports, increased operative duration was not associated with postoperative complications.

Objective: Determine whether elevated body mass index (BMI) is associated with postoperative complications after vestibular schwannoma (VS) surgery., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Two hundred six patients undergoing surgery for VS between 2010 and 2017, grouped into obese and nonobese patients., Intervention: Surgery for VS resection., Main Outcome Measures: Postoperative facial nerve outcomes, length of hospital stay, presence of postoperative cerebrospinal fluid leak, 30-day readmission, return to the operating room, wound complications, cardiovascular and thromboembolic complications., Results: After excluding 1 patient for missing BMI, our cohort included 205 patients. Seventy-nine patients (38.5%) were obese (mean BMI 36.2 kg/m, range 30-55.1) and the remaining 126 (61.5%) were nonobese (mean BMI 25.0, range 18.8-29.8 kg/m). Compared with nonobese patients, obesity was not associated with postoperative cerebrospinal fluid leak (OR 1.1, 95% CI 0.93-1.1), length of hospital stay (OR 0.98, 95% CI 0.65-1.47), 30-day readmission rates (1.04, 95% CI 0.95-1.14), return to operating room (OR 1.05, 95% CI 0.98-1.11), or other wound-related complications (OR 0.99, 95% CI 0.94-1.04)., Conclusion: In this cohort, elevated BMI was not associated with an increased risk for postoperative complications after VS surgery. Our findings may mitigate concerns associated with surgical management of VS in obese patients.

Objective  Evaluate the cerebrospinal fluid (CSF) leak rate after the middle cranial fossa (MCF) approach to vestibular schwannoma (VS) resection. Design  Retrospective case series. Setting  Quaternary referral academic center. Participants  Of 161 patients undergoing the MCF approach for a variety of skull base pathologies, 66 patients underwent this approach for VS resection between 2007 and 2017. Main Outcome Measure  Postoperative CSF leak rate. Results  There were two instances of postoperative CSF leak (3.0%). Age, gender, and BMI were not significantly associated with CSF leak. In the two cases with CSF leakage, tumors were isolated to the internal auditory canal (IAC) and both underwent gross total resection. Both CSF leaks were successfully treated with lumbar drain diversion. For the 64 cases that did not have a CSF leak, 51 were isolated to the IAC, 1 was located only in the cerebellopontine angle (CPA), and 12 were located in both the IAC and CPA. 62 patients underwent gross total resection and 2 underwent near-total resection. Mean maximal tumor diameter in the CSF leak group was 4.5 mm (range: 3-6 mm) versus 10.2 mm (range: 3-19 mm) in patients with no CSF leak ( p  = 0.03). Conclusions  The MCF approach for VS resection is a valuable technique that allows for hearing preservation and total tumor resection and can be performed with a low CSF leakage rate. This rate of CSF leak is less than the reported rates in the literature in regard to both translabyrinthine and retrosigmoid approaches.

Rationale and Hypothesis: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials., Methods and Design: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study., Study Outcomes: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

Background: Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr)., Objective: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes., Methods: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial., Results: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation., Conclusion: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage., Methods: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046., Findings: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012)., Interpretation: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons., Funding: National Institute of Neurological Disorders and Stroke and Genentech., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The middle cranial fossa (MCF) approach is a challenging surgical technique for the resection of small and intermediate sized, primarily intracanalicular, vestibular schwannomas (VS), with the goal of hearing preservation (HP)., Objective: To describe a decade-long, single institutional experience with the MCF approach for resection of VS., Methods: This is a retrospective cohort study of 63 patients who underwent the MCF approach for resection of VS from 2006 to 2016. Audiometric data included pure-tone average (PTA), low-tone pure-tone average (LtPTA), word recognition score, and American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification at presentation and follow-up. Patients with postoperative serviceable (AAO-HNS class A-B) and/or useful (AAO-HNS class A-C) hearing were compared to those without HP. Facial nerve function was assessed using the House-Brackmann scale., Results: The mean age and duration of follow-up were 50 ± 13 yr and 21 ± 21 mo, respectively. The mean tumor size was 10 ± 4 mm. The serviceable and usable HP rates were 54% and 50%, respectively. Some residual hearing was preserved in 71% of patients. Large tumor size (P = .05), volume (P = .03), and extrameatal tumor extension (P = .03) were associated with poor audiometric outcomes. The presence of a fundal fluid cap (P = .01) was a favorable finding. At definitive testing, LtPTA was significantly better preserved than traditional PTA (P = .01). Facial nerve outcomes, tumor control rates, and durability of audiometric outcomes were excellent. 47% of patients pursued aural rehabilitation., Conclusion: In our series, the MCF approach for VS provided excellent rates of tumor and facial nerve function, with durable serviceable HP.

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Objective: Evaluate the safety and efficacy of the ultrasonic bone aspirator (UBA) during middle cranial fossa (MCF) approach to vestibular schwannoma (VS)., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Charts of 192 consecutive VS patients over 18 years of age were reviewed to identify 65 patients who underwent MCF approach to VS resection between 2006 and 2017. A combination of UBA and high-speed drill (HSD) was used to decompress the internal auditory canal (IAC) in 25 patients and HSD alone was used in the other 40 patients., Intervention(s): Use of UBA during vestibular schwannoma surgery via MCF approach for decompression of the IAC., Main Outcome Measure(s): Postoperative facial nerve outcomes assessed by the House-Brackmann (HB) facial nerve grading scale. Rates of gross total resection (GTR) and cerebrospinal fluid (CSF) leak., Results: There were no significant differences in postoperative facial nerve function, in rate of GTR of tumor, or in rate of CSF leak. In the UBA group 24/25 (96%) had postoperative HB grade I-II compared with 36/40 (90%) in the HSD group (p-value = 0.66). GTR was achieved in 25/25 (100%) in the UBA group compared with 38/40 (95%) in the HSD group (p-value = 1). In the UBA group, there were 0/25 (0%) cases of CSF leak compared with 1/40 (2.5%) in the HSD group (p-value = 1)., Conclusions: UBA use is a safe and effective alternative or adjunct to HSD during MCF approach to expose the IAC contents. This surgical tool allows for bone removal with low risk of injury to adjacent structures.

Objectives:: Assess the utility of intraoperative transcranial facial motor-evoked potential (FMEP) monitoring in predicting and improving facial function after vestibular schwannoma (VS) resection., Study Design:: Retrospective chart review., Methods:: Data were obtained from 82 consecutive VS resections meeting inclusion criteria. Sixty-two cases were performed without FMEP and 20 with FMEP. Degradation of FMEP response was defined as a final-to-baseline amplitude ratio of 0.5 or less. House-Brackmann (HB) grade was assessed preoperatively, postoperatively, at follow-up assessments, and it was compared between pre- and post-FMEP cohorts. Positive predictive value (PPV) and negative predictive value (NPV), sensitivity, and specificity of FMEP degradation in predicting facial weakness were calculated., Results:: In the pre-FMEP group, at length of follow-up (LOF) ⩾9 months, 83.9% (52/62) of patients exhibited HB 1-2 outcome. In the post-FMEP cohort, 75.0% (15/20) exhibited HB 1-2 function at LOF ⩾9 months. There was no difference in rates of HB 1-2 outcomes between groups in the immediate postoperative period ( P = .35) or at long-term follow-up ( P = 1.0). With respect to predicting immediate postoperative facial function, FMEP demonstrated high specificity (88.9%) and moderate sensitivity (54.5%). The PPV and NPV for immediate postoperative facial function were 85.7% and 61.5%, respectively. With respect to long-term (⩾9 months LOF) facial function, intraoperative FMEP was moderately sensitive (71.4%) and highly specific (84.6%); PPV was moderate (71.4%), and NPV was high (84.6%)., Conclusions:: Intraoperative FMEP is highly specific and moderately sensitive in predicting postoperative facial function for patients undergoing VS resection, but its use may not be associated with improved facial nerve outcomes., Level of Evidence:: 4.

OBJECTIVERecent studies have proposed the superior eyelid endoscopic transorbital approach as a new minimally invasive route to access orbital lesions, mostly in otolaryngology and maxillofacial surgeries. The authors undertook this anatomical study in order to contribute a neurosurgical perspective, exploring the anterior and middle cranial fossa areas through this purely endoscopic transorbital trajectory.METHODSAnatomical dissections were performed in 10 human cadaveric heads (20 sides) using 0° and 30° endoscopes. A step-by-step description of the superior eyelid transorbital endoscopic route and surgically oriented classification are provided.RESULTSThe authors' cadaveric prosection of this approach defined 3 modular routes that could be combined. Two corridors using bone removal lateral to the superior and inferior orbital fissures exposed the middle and anterior cranial fossa (lateral orbital corridors to the anterior and middle cranial base) to unveil the temporal pole region, lateral wall of the cavernous sinus, middle cranial fossa floor, and frontobasal area (i.e., orbital and recti gyri of the frontal lobe). Combined, these 2 corridors exposed the lateral aspect of the lesser sphenoid wing with the Sylvian region (combined lateral orbital corridor to the anterior and middle cranial fossa, with lesser sphenoid wing removal). The medial corridor, with extension of bone removal medially to the superior and inferior orbital fissure, afforded exposure of the opticocarotid area (medial orbital corridor to the opticocarotid area).CONCLUSIONSAlong with its minimally invasive nature, the superior eyelid transorbital approach allows good visualization and manipulation of anatomical structures mainly located in the anterior and middle cranial fossae (i.e., lateral to the superior and inferior orbital fissures). The visualization and management of the opticocarotid region medial to the superior orbital fissure are more complex. Further studies are needed to prove clinical applications of this relatively novel surgical pathway.

Background: Various extensions of the supraorbital approach reach the lateral and parasellar middle cranial fossa regions by removing the orbital rim and greater/lesser sphenoid wings. Recent proposals of a purely endoscopic ventral transorbital pathway to these regions heighten the need to compare these surgical windows., Objective: To detail the lateral and parasellar middle cranial fossa regions and quantify exposures by 2 surgical windows (transcranial and transorbital) through anatomic study., Methods: In 5 cadaveric specimens (10 sides), dissections consisted of 3 stages: stage 1 began with the supraorbital approach via the eyebrow; stage 2, endo-orbital approach via the superior eyelid, continued with removal of lesser and greater sphenoid wings; and stage 3, extended supraorbital, re-evaluated the gains of stage 2 from the perspective of stage 1. Operative working areas were quantified in Sylvian, anterolateral temporal, and parasellar regions; bone removal volumes were measured at each stage (nonpaired Student t-test)., Results: Visualization into the anterolateral temporal and Sylvian areas, though varied in perspective, were comparable with either eyelid or transcranial routes. Compared with transcranial views through a supraorbital window, the eyelid approach significantly increased exposure in the parasellar region with wider angle of attack (P < .01) and achieved comparable bone removal volumes., Conclusion: Stage 2's unique anatomic view of the lateral and parasellar middle cranial fossa regions paves the way for possible surgical application to select pathologies typically treated via transcranial approaches. Disadvantages may be the surgeon's unfamiliarity with the anatomy of this purely endoscopic, ventral route and difficulties of dural and orbital repair., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Here is a case of an isolated orbital metastasis in a previously diagnosed metastatic breast cancer of a 46-year-old woman presenting diplopia and pain in her left eye. The magnetic resonance showed a suspected metastatic localisation in the upper left oblique muscle, which was confirmed by the fine-needle aspiration biopsy. The systemic therapy with liposomal doxorubicin as well as local stereotactic radiotherapy showed a gradual improvement of the local symptoms and signs., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: To review the current literature on the extended middle cranial fossa (xMCF) approach and to provide a comprehensive description of the relevant anatomy, indications, surgical technique, results, and complications., Recent Findings: The xMCF approach expands the surgical exposure provided by the sMCF approach, allowing access to the internal auditory canal, cerebellopontine angle, prepontine cistern, anterior petrous apex, petrous carotid artery, Meckel's cave, cavernous sinus, mid and upper clivus, and posterior lesions approaching the jugular foramen. Preservation of serviceable hearing is possible with success rates approximating 50% in vestibular schwannoma and meningioma resection, and facial nerve outcome is excellent., Summary: The xMCF is an important approach for difficult to access lesions that additionally offers the possibility of hearing preservation. This approach is also useful for vascular lesions, auditory brainstem implantation, and lesions of mid-brainstem.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

The formation of the bilirubin oxidation products (BOXes), BOX A ([4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide]) and BOX B (3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide), as well as MVM (4-methyl-3-vinylmaleimide) were synthesized by oxidation of bilirubin with H 2 O 2 without and with FeCl 3 , respectively. Compound identity was confirmed with NMR and mass spectrometry (MS; less than 1 ppm, tandem MS up to MS 4 ). UV absorption profiles, including λ max , and extinction coefficient (ε; estimated using NMR) for BOX A, BOX B, and MVM in H 2 O, 15% CH 3 CN plus 10 mM CF 3 CO 2 H, CH 3 CN, CHCl 3 , CH 2 Cl 2 , and 0.9% NaCl were determined. At longer wavelengths, λ max 's for 1) BOX A were little affected by the solvent, ranging from 295-297 nm; 2) BOX B, less polar solvent yielded λ max 's of lower wavelength, with values ranging from 308-313 nm, and 3) MVM, less polar solvent yielded λ max 's of higher wavelength, with values ranging from 318-327 nm. Estimated ε's for BOX A and BOX B were approximately 5- to 10-fold greater than for MVM.

Purpose: Artificial neural networks (ANN) are increasingly applied to complex medical problem solving algorithms because their outcome prediction performance is superior to existing multiple regression models. ANN can successfully identify symptomatic cerebral vasospasm (SCV) in adults presenting after aneurysmal subarachnoid hemorrhage (aSAH). Although SCV is unusual in children with aSAH, the clinical consequences are severe. Consequently, reliable tools to predict patients at greatest risk for SCV may have significant value. We applied ANN modeling to a consecutive cohort of pediatric aSAH cases to assess its ability to predict SCV., Methods: A retrospective chart review was conducted to identify patients < 21 years of age who presented with spontaneously ruptured, non-traumatic, non-mycotic, non-flow-related intracranial arterial aneurysms to our institution between January 2002 and January 2015. Demographics, clinical, radiographic, and outcome data were analyzed using an adapted ANN model using learned value nodes from the adult aneurysmal SAH dataset previously reported. The strength of the ANN prediction was measured between - 1 and 1 with - 1 representing no likelihood of SCV and 1 representing high likelihood of SCV., Results: Sixteen patients met study inclusion criteria. The median age for aSAH patients was 15 years. Ten underwent surgical clipping and 6 underwent endovascular coiling for definitive treatment. One patient experienced SCV and 15 did not. The ANN applied here was able to accurately predict all 16 outcomes. The mean strength of prediction for those who did not exhibit SCV was - 0.86. The strength for the one patient who did exhibit SCV was 0.93., Conclusions: Adult-derived aneurysmal SAH value nodes can be applied to a simple AAN model to accurately predict SCV in children presenting with aSAH. Further work is needed to determine if ANN models can prospectively predict SCV in the pediatric aSAH population in toto; adapted to include mycotic, traumatic, and flow-related origins as well.

Background: Minimally invasive thrombolytic evacuation of intracerebral hematoma is being investigated in the ongoing phase III clinical trial of Minimally Invasive Surgery plus recombinant Tissue plasminogen activator for Intracerebral hemorrhage Evacuation (MISTIE III)., Objective: To assess the accuracy of catheter placement and efficacy of hematoma evacuation in relation to surgical approach and surgeon experience., Methods: We performed a trial midpoint interim assessment of 123 cases that underwent the surgical procedure. Accuracy of catheter placement was prospectively assessed by the trial Surgical Center based on prearticulated criteria. Hematoma evacuation efficacy was evaluated based on absolute volume reduction, percentage hematoma evacuation, and reaching the target end-of-treatment volume of <15 mL. One of 3 surgical trajectories was used: anterior (A), posterior (B), and lobar (C). Surgeons were classified based on experience with the MISTIE procedure as prequalified, qualified with probation, and fully qualified., Results: The average hematoma volume was 49.7 mL (range 20.0-124), and the mean evacuation rate was 71% (range 18.4%-99.8%). First placed catheters were 58% in good position, 28% suboptimal (but suitable to dose), and 14% poor (requiring repositioning). Posterior trajectory (B) was associated with significantly higher rates of poor placement (35%, P = .01). There was no significant difference in catheter placement accuracy among surgeons of varying experience. Hematoma evacuation efficacy was not significantly different among the 3 surgical approaches or different surgeons' experience., Conclusion: Ongoing surgical education and quality monitoring in MISTIE III have resulted in consistent rates of hematoma evacuation despite technical challenges with the surgical approaches and among surgeons of varying experience., (Copyright © 2017 by the Congress of Neurological Surgeons)

Background: Classification of cerebrovascular malformations has revealed intermediary lesions that warrant further review owing to their unusual presentation and management. We present 2 cases of arteriovenous malformation (AVM) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies., Methods: Two cases of AVMs associated with DVA were identified, and a literature search for published cases between 1980 and 2016 was conducted. Patient demographic data and clinical features were documented., Results: In case 1, a 29-year-old female presenting with parenchymal hemorrhage and left homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral, and posterior cerebral arteries, with major venous drainage to the superior sagittal sinus. In case 2, imaging in a 34-year-old female evaluated for night tremors and incontinence revealed a left parietal AVM with venous drainage to the superior sagittal sinus. Including our 2 cases, 22 cases of coexisting AVMs and DVAs have been reported in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7 cases, embolization in 6 cases, surgical resection in 4 cases, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12 of 18)., Conclusions: Patients with coexisting AVMs and DVAs tend to have a hemorrhagic presentation. Contrary to traditional AVM management, in these cases it is important to preserve the draining vein via the DVA to ensure a safe, sustained circulatory outflow of the associated brain parenchyma while achieving safe AVM obliteration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Most high-riding distal basilar trunk aneurysms can be surgically approached via the transsylvian route and its orbitozygomatic variant. However, on rare occasions, the basilar bifurcation may be unusually high and an approach above the carotid terminus may be required., Objective: In this cadaveric study, we sought to determine the feasibility and exposure limits of the interlenticulostriate approach (ILSA)., Methods: A standard transsylvian approach was performed in 10 cerebral hemispheres of 5 formalin-fixed, silicone-injected cadaver heads. The interpeduncular cistern was exposed via the opticocarotid window, carotid-oculomotor window, and supracarotid ILSA window. The latter was measured and an aneurysm clip or ventriculostomy stylet was placed as high as possible through each corridor. Using noncontrast 3-D rotational angiography, clip/stylet positions were measured relative to the dorsum sellae., Results: ILSA provided a 9.4 × 4.6 mm mean surgical corridor, just enough room for a standard clip applier. This space was limited by the carotid bifurcation inferiorly, the lenticulostriate arteries medially and laterally, and the optic tract superiorly. There was no difference between opticocarotid and carotid-oculomotor windows, in terms of clip position (+8.9 vs +8.6 mm, respectively; P = .78). In contrast, ILSA provided significantly improved superior exposure, compared with either approaches (mean stylet position: +14.3 mm; P = .005). The exposure benefit afforded by ILSA was consistent across all 10 hemispheres, ranging from +2.5 to +8 mm., Conclusion: For high-riding distal basilar trunk aneurysms that cannot be reached via the frontotemporal orbitozygomatic approach, ILSA can provide a viable route of access. Vascular neurosurgeons should be familiarized with this approach., (Copyright © 2017 by the Congress of Neurological Surgeons)

Background: Patients who undergo clipping of cerebral aneurysms face an inherent risk for new postoperative neurologic deficits. Intraoperative neuromonitoring (IONM) is used often for early detection of ischemic changes, while it is still potentially reversible. However, the value, safety, and efficacy of temporary clipping and multimodal IONM to minimize risks are debated. Our retrospective series examined the sensitivity and specificity of IONM using transcranial motor evoked potentials and somatosensory evoked potentials and quantified the safety of temporary clipping by duration and vascular territory., Methods: Our prospectively collected database (2010-2013) included 123 consecutive patients who underwent clipping of 133 cerebral aneurysms with use of IONM. We determined postoperative deficit rate and sensitivity and specificity of monitoring to predict these changes intraoperatively. The rate of permanent deficit after temporary clipping was correlated with duration, vascular territory, and IONM findings., Results: Of 133 clipped aneurysms, 15 instances of IONM changes occurred, including 12 temporary without new postoperative deficit and 3 permanent with new postoperative deficit. Somatosensory evoked potential monitoring predicted one of the permanent deficits and transcranial motor evoked potentials predicted the other 2 deficits., Conclusions: Multimodal IONM was highly specific and sensitive for detecting new deficits. Three patients with new deficits had temporary clipping, including 2 patients with IONM changes not temporally associated with clip placement. Our 1.1% rate of permanent neurologic deficit attributed to temporary clipping support its safety. Differences in patterns of IONM changes among vascular territories warrant further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Our pilot study evaluated the effectiveness of our telementoring-telescripting model to facilitate seamless communication between surgeons while the operating surgeon is using a microscope., Methods: As a first proof of concept, 4 students identified 20 anatomic landmarks on a dry human skull with or without telementoring guidance. To assess the ability to communicate operative information, a senior neurosurgery resident evaluated the student's ability and timing to complete a stepwise craniotomy on a cadaveric head, with and without telementoring guidance; a second portion included exposure of the anterior circulation. The mentor was able to annotate directly onto the operator's visual field, which was visible to the operator without looking away from the binocular view., Results: The students showed that they were familiar with half (50% ± 10%) of the structures for identification and none was familiar with the steps to complete a craniotomy before using our system. With the guidance of a remote surgeon projected into the visual field of the microscope, the students were able to correctly identify 100% of the structures and complete a craniotomy. Our system also proved effective in guiding a more experienced neurosurgery resident through complex operative steps associated with exposure of the anterior circulation., Conclusions: Our pilot study showed a platform feasible in providing effective operative direction to inexperienced operators while operating using a microscope. A remote mentor was able to view the visual field of the microscope, annotate on the visual stream, and have the annotated stream appear in the binocular view for the operating mentee., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome., Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134., Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar., Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status., Funding: National Institute of Neurological Disorders and Stroke., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To characterize temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes over 5 time periods in a large population-based stroke study in the United States., Methods: All SAHs among residents of the Greater Cincinnati/Northern Kentucky region at least 20 years of age were identified and verified via study physician review in 5 distinct year-long study periods between 1988 and 2010. We abstracted demographics, care patterns, and outcomes, and we compared incidence and case-fatality rates across the study periods., Results: The incidence of SAH in the 5 study periods (age-, race-, and sex-adjusted to the 2000 US population) was 8.8 (95% confidence interval 6.8-10.7), 9.2 (7.2-11.2), 10.0 (8.0-12.0), 9.0 (7.1-10.9), and 7.7 (6.0-9.4) per 100,000, respectively; the trend in incidence rates from 1988 to 2010 was not statistically significant (p = 0.22). Advanced neurovascular imaging, endovascular coiling, and neurologic intensive care unit availability increased significantly over time. All-cause 5-day (32%-18%, p = 0.01; for trend), 30-day (46%-25%, p = 0.001), and 90-day (49%-29%, p = 0.001) case-fatality rates declined from 1988 to 2010. When we included only proven or highly likely aneurysmal SAH, the declines in case-fatality were no longer statistically significant., Conclusions: Although the incidence of SAH remained stable in this population-based region, 5-day, 30-day, and 90-day case-fatality rates declined significantly. Advances in surgical and medical management, along with systems-based changes such as the emergence of neurocritical care units, are potential explanations for the reduced case-fatality., (© 2016 American Academy of Neurology.)

Background: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage., Methods: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770., Findings: Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051)., Interpretation: MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage., Funding: National Institute of Neurological Disorders and Stroke, Genentech, and Codman., Competing Interests: Declaration of Interests. IA, DFH, SWM, NU, KL, NMc, WAM, MR (R01NS046309 and U01NS062851), CBT, and PV report grants from the National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. DFH reports non-financial support from Genentech and Johnson& Johnson (Codman) during the conduct of the study, grants from NINDS outside the submitted work, and expert testimony. SWM reports personal fees from Johns Hopkins University outside the submitted work. JM reports grants from the National Institutes of Health during the conduct of the study and has a patent (C13388—primary intracerebral haemorrhage prediction employing logistic regression and features extracted from CT) pending for Johns Hopkins. ADM reports grants from the National Institutes of Health during the conduct of the study, non-financial support as the Director of the Newcastle Neurosurgery Foundation, and personal fees from Advisor to Stryker and Draeger outside the submitted work. BG reports grants from Johns Hopkins University (MISTIE National Institutes of Health grant) during the conduct of the study and grants from the National Institutes of Health Research (UK) Health Technology Assessment Programme outside the submitted work. All other authors declare no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cocaine constriction of the cerebral vasculature is thought to contribute to the ischemia associated with cocaine use. However, the mechanisms whereby cocaine elicits relevant vasoconstriction remain elusive. Indeed, proposed intra- and intercellular mechanisms based on over 3 decades of ex vivo vascular studies are, for the most part, of questionable relevancy due to the generally low contractile efficacy of cocaine combined with the use of nonresistance-type vessels. Furthermore, the significance attached to mechanisms derived from in vivo animal studies may be limited by the inability to demonstrate cocaine-induced decreased cerebral blood flow, as observed in (awake) humans. Despite these apparent limitations, we surmise that the vasoconstriction relevant to cocaine-induced ischemia is elicited by inhibition of dilator and activation of constrictor pathways because of cocaine action on the neurovascular unit (neuron, astrocyte, and vessel) and on vessels outside the unit. Furthermore, previous cocaine exposure, that is, conditions present in human subjects, downregulates and sensitizes these dilator and constrictor pathways, respectively, thereby enhancing constriction to acute cocaine. Identification of specific intra- and intercellular mechanisms requires investigations in the isolated microvasculature and the neurovascular unit from species chronically exposed to cocaine and in which cocaine decreases cerebral blood flow.

Background: Supratentorial hemangioblastomas are rare tumors, most commonly occurring in the sellar/suprasellar region, cerebrum, and ventricle. They are generally found in patients with von Hippel Lindau disease but have infrequently been reported in patients without this syndrome., Case Description: A 35-year-old woman with a history of neurofibromatosis type 1 presented to our care with visual loss and headaches. Magnetic resonance imaging of the brain demonstrated an 8-mm cystic, contrast-enhancing lesion abutting the optic chiasm and optic tracts. The patient's endocrine profile was unremarkable. The tumor was resected using an endoscopic expanded transsphenoidal approach. Pathologic evaluation was consistent with hemangioblastoma. Postoperatively, the patient experienced an improvement in her visual symptoms., Conclusions: Hemangioblastoma should be included in the differential of sellar/suprasellar mass lesions, particularly in patients with von Hippel Lindau disease. Small suprasellar lesions may be safely and effectively removed using an expanded transsphenoidal approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

Objective: Postoperative headache is an undesirable consequence of retrosigmoid vestibular schwannoma (VS) removal. An ultrasonic bone aspirator (UBA) may reduce headache by minimizing subarachnoid bone dust dispersion. The feasibility of removing internal auditory canal (IAC) bone with a UBA is unknown. This study assessed volume and duration of IAC bone removal in clinical and laboratory settings., Study Design: (1) Retrospective review of radiologic data and intraoperative videos. (2) Cadaveric temporal bone model., Setting: (1) Tertiary care medical center. (2) Laboratory., Subjects Methods: We calculated the volume of IAC bone drilled during retrosigmoid VS removal using postoperative computed tomography scans. We then measured the time spent actively drilling IAC bone by analyzing operative videos. Finally, we measured bone ablation rates in a cadaveric temporal bone model using a drill and UBA., Results: The mean ± SD volume of IAC bone removed during surgery was 0.32 ± 0.17 mL (n = 9). The time spent actively removing IAC bone with a drill was only 10.4 ± 3.5 minutes, less than a third of the total IAC opening time of 34.2 ± 13.1 minutes (n = 5). On cadaveric specimens, the UBA removed bone at 0.21 ± 0.03 or 0.35 ± 0.07 µL/s at 15% or 50% power, respectively (n = 4). This extrapolates to 15.0 ± 3.0 to 25.0 ± 3.9 minutes to remove the same 0.32 mL from surgery., Conclusions: The volume and duration of IAC bone removal during retrosigmoid VS surgery are small. Using a UBA at low power instead of a drill would extend the length of surgery by 5 to 15 minutes, with the theoretical potential for reducing headache., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Objective: Postoperative headache is not uncommon after retrosigmoid vestibular schwannoma removal. Bone dust dispersed into the subarachnoid space during drilling may be responsible. If dispersion could be reduced, headache incidence might be decreased. An ultrasonic bone aspirator (UBA) containing an integrated suction at the tip may more effectively suction bone dust created during bone removal. The objective is to determine whether a UBA results in less bone dust dispersion than a standard otologic drill., Study Design: Cadaveric temporal bone quantitative model., Setting: Laboratory., Subjects and Methods: Temporal bone blocks were placed in a watertight enclosure. Under irrigation, bone was removed by use of either a drill or a UBA. The settings of the UBA were varied. The irrigant containing bone dust was microfiltered, and bone dust was weighed. Differences were compared across groups (n = 2-9 per group). Ablation times were also recorded (n = 3 per group)., Results: Only 3% (SD = 1.6%, n = 7) of the drilled bone mass was re-collected as bone dust with the UBA under optimized settings (power = 15%, suction = 100%, irrigation = 15 mL/min) compared with 81% (SD = 10%, n = 4) with the drill and external suction (P < .001). Increasing UBA power and reducing suction led to significantly more bone dust dispersal than with optimized settings. Varying irrigation did not have a significant effect. Bone ablation time was 1.4 times longer with the UBA at 50% power compared with the drill at maximum power., Conclusions: The UBA resulted in approximately 25 times less bone dust dispersion than the otologic drill at optimized settings., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background: Supra-/transorbital approaches are mostly limited to suprasellar and anterior fossa pathologies, whereas lateral supraorbital approaches provide less retrosellar exposure and less overall operative volume, especially in the temporal region., Objective: Our cadaveric study proposes removal of the lesser and greater wings of the sphenoid bone to increase both the lateral angle typically achieved with pterional approaches and exposure to the temporal lobe and perisellar region., Methods: In 5 cadaveric specimens, our 3 steps to expand transorbital exposures included the following: step 1, standard transorbital craniotomy via a 3-cm supra-eyebrow incision; step 2, removal of the lesser sphenoid wing completed extradurally; and step 3, partial removal of the greater sphenoid wing. Operative extension in sylvian, parasellar, and anterolateral temporal exposures were quantified for each step (t test)., Results: Step 2 provided the greatest increased exposure in the sylvian and parasellar regions compared with step 3, whereas step 3 provided a significant proportion of the exposure in the lateral temporal region. Finally, the lateral view progressively increased with each subsequent step., Conclusion: Our 3-step removal of the lesser and greater wings of the sphenoid bone quantified increased sylvian, anterior temporal, and parasellar exposures for this minimally invasive approach with excellent cosmesis. Its increases the anterolateral view (similar to a subfrontal pterional approach) and offers potential applications to vascular and neoplastic (ie, sphenoid meningiomas) pathologies classically treated via a pterional or frontotemporal orbitozygomatic approach.

Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not "MCA plus" strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression.

Introduction Analysis of computed tomography perfusion (CTP) studies before and after superficial temporal artery to middle cerebral artery (STA-MCA) bypass is warranted to better understand cerebral steno-occlusive pathology. Methods Retrospective review was performed of STA-MCA bypass patients with steno-occlusive disease with CTP before and after surgery. CTP parameters were evaluated for change after STA-MCA bypass. Results A total of 29 hemispheres were bypassed in 23 patients. After STA-MCA bypass, mean transit time (MTT) and time to peak (TTP) improved. When analyzed as a ratio to the contralateral hemisphere, MTT, TTP, and cerebral blood flow (CBF) improved. There was no effect of gender, double vessel versus single vessel bypass, or time until postoperative CTP study to changes in CTP parameters after bypass. Conclusions Blood flow augmentation after STA-MCA bypass may best be assessed by CTP using baseline MTT or TTP and ratios of MTT, TTP, or CBF to the contralateral hemisphere. The failure of cerebrovascular reserve to improve after cerebral bypass may indicate irreversible loss of autoregulation with chronic cerebral vasodilation or the inability of CTP to detect these improvements.

Cerebral arteriovenous malformations (AVMs) present unique challenges to cerebrovascular specialists. Management of these lesions begins with assessing their natural history. Intervention with the goal of complete obliteration requires some component of microsurgical techniques or radiosurgery. Clinicians must weigh observation and acceptance of the natural history of these lesions versus intervention on a case-by-case basis. Microsurgical resection and radiosurgery are both well-validated tools used in selectively treating cerebral AVMs. This manuscript offers a general review of the management of cerebral AVMs with multimodality treatment recommendations.

Background: Occlusion of blood vessels using high-intensity focused ultrasound (HIFU) is a potential treatment for arteriovenous malformations and other neurovascular disorders. However, attempting HIFU-induced vessel occlusion can also cause vessel rupture, resulting in hemorrhage. Possible rupture mechanisms include mechanical effects of acoustic cavitation and heating of the vessel wall., Methods: HIFU exposures were performed on 18 ex vivo porcine femoral arteries with simultaneous passive cavitation detection. Vessels were insonified by a 3.3-MHz focused source with spatial-peak, temporal-peak focal intensity of 15,690-24,430 W/cm(2) (peak negative-pressure range 10.92-12.52 MPa) and a 50% duty cycle for durations up to 5 min. Time-dependent acoustic emissions were recorded by an unfocused passive cavitation detector and quantified within low-frequency (10-30 kHz), broadband (0.3-1.1 MHz), and subharmonic (1.65 MHz) bands. Vessel rupture was detected by inline metering of saline flow, recorded throughout each treatment. Recorded emissions were grouped into 'pre-rupture' (0-10 s prior to measured point of vessel rupture) and 'intact-vessel' (>10 s prior to measured point of vessel rupture) emissions. Receiver operating characteristic curve analysis was used to assess the ability of emissions within each frequency band to predict vessel rupture. Based on these measurements associating acoustic emissions with vessel rupture, a real-time feedback control module was implemented to monitor acoustic emissions during HIFU treatment and adjust the ultrasound intensity, with the goal of maximizing acoustic power delivered to the vessel while avoiding rupture. This feedback control approach was tested on 10 paired HIFU exposures of porcine femoral and subclavian arteries, in which the focal intensity was stepwise increased from 9,117 W/cm(2) spatial-peak temporal-peak (SPTP) to a maximum of 21,980 W/cm(2), with power modulated based on the measured subharmonic emission amplitude. Time to rupture was compared between these feedback-controlled trials and paired controller-inactive trials using a paired Wilcoxon signed-rank test., Results: Subharmonic emissions were found to be the most predictive of vessel rupture (areas under the receiver operating characteristic curve (AUROC) = 0.757, p < 10(-16)) compared to low-frequency (AUROC = 0.657, p < 10(-11)) and broadband (AUROC = 0.729, p < 10(-16)) emissions. An independent-sample t test comparing pre-rupture to intact-vessel emissions revealed a statistically significant difference between the two groups for broadband and subharmonic emissions (p < 10(-3)), but not for low-frequency emissions (p = 0.058). In a one-sided paired Wilcoxon signed-rank test, activation of the control module was shown to increase the time to vessel rupture (T - = 8, p = 0.0244, N = 10). In one-sided paired t tests, activation of the control module was shown to cause no significant difference in time-averaged focal intensity (t = 0.362, p = 0.363, N = 10), but was shown to cause delivery of significantly greater total acoustic energy (t = 2.037, p = 0.0361, N = 10)., Conclusions: These results suggest that acoustic cavitation plays an important role in HIFU-induced vessel rupture. In HIFU treatments for vessel occlusion, passive monitoring of acoustic emissions may be useful in avoiding hemorrhage due to vessel rupture, as shown in the rupture suppression experiments.

Background: After the term carotid siphon was introduced by Moniz in 1927 to describe the radiographic appearance of the intracranial internal carotid artery (ICA), the concept gained popularity in decades following in both the anatomic and the medical literature. However, as conflicting definitions persist in the delineation of proximal and distal sites, does the term carotid siphon provide the precision needed for current anatomic and clinical studies?, Methods: A PubMed search of "carotid siphon" detected >400 articles from the anatomic and medical literature during the past 6 decades. Moniz's text and figures in his original Lancet article and a compilation of other seminal historical articles and references were reviewed to trace the use of the term carotid siphon during this period., Results: Viewing the radiographic silhouette of a normal ICA, Moniz defined the carotid siphon as the series of bends and curves; an additional curvature was identified as a double siphon. Throughout Moniz's works, in text and figures, the boundaries of the carotid siphon were never delineated. Authors who followed attempted to correlate his original description of this two-dimensional radiographic projection with anatomic documentation., Conclusions: Tracing the origin and usage of the term carotid siphon during 6 decades in the medical literature shows continued discrepancy rather than consensus. The term carotid siphon is historically relevant but can now be supplanted by definitive ICA classification systems, which continue to evolve in contemporary medical and anatomic communications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlike saccular or berry aneurysms, which present more often with subarachnoid hemorrhage, fusiform aneurysms present more often with ischemic stroke or mass effect. The most time-tested treatment of fusiform vertebrobasilar aneurysms consists of flow reduction or flow reversal. Recently, flow diversion has been attempted with mixed results in the posterior circulation. Given the described pathophysiologic processes of fusiform aneurysms that may be altered with modern medical therapies, future investigators may look to medical treatment of these lesions, especially in cases of poor surgical candidates., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study investigated the involvement of sensory nerves and, in particular, neuronal transient receptor potential vanilloid (TRPV) 1 channels, in the CO(2)-mediated regulation of cerebrovascular tone. Basilar artery diameter and blood flow velocity in the ventral midbrain were determined in a rat cranial window preparation by digital imaging and laser-Doppler flowmetry, respectively. Superfusion of the basilar artery with capsaicin, a selective TRPV1 receptor agonist, caused a transient relaxation, consistent with acute desensitization of neuronal TRPV1 channels. Constriction to respiratory hypocapnia remained unaffected following capsaicin superfusion. Denervation of sensory nerves by repeated capsaicin injection of neonates also did not reduce the respiratory hypocapnia constriction of the basilar artery as well as the decreased flow velocity in the ventral midbrain in adults. These findings suggest that sensory nerves and, in particular, neuronal TRPV1 channels, do not play a role in respiratory hypocapnia constriction and decreased flow, at least in rat basilar artery and ventral midbrain., (Published by Elsevier B.V.)

Introduction: Risks associated with endovascular management remain unaddressed for post-hemorrhagic cerebral vasospasm (PHCV) caused by pathologies that cannot be secured or identified before vasospasm treatment. This retrospective study reviews our 10 year experience in the difficult scenario of subarachnoid hemorrhage (SAH) with vasospasm, including intra-arterial vasodilators or percutaneous transluminal angioplasty (PTA) to vessels feeding a ruptured unsecured lesion., Methods: 10 SAH patients with ruptured unsecured vascular lesions underwent 44 endovascular treatments for PHCV (2002-2011). We defined unsecured as an untreated aneurysm/dissection, incompletely coiled aneurysm, dissection covered with self-expanding nitinol stents, or angiographically negative SAH. Treatments were categorized by location of the ruptured unsecured (partial or complete) lesion relative to the vessel treated for vasospasm., Results: Our 10 patients with four aneurysms, four dissections, and two angiographically negative SAH accounted for 10.3% of SAH patients who underwent angiography for vasospasm. No procedure related complications occurred when treating vessels not supplying the index lesion or with angiographically negative SAH. Of the endovascular treated vessels supplying partially secured lesions, one (6.3%) fatal complication occurred; none of these patients receiving only vasodilators had complications. With endovascular treatment of PHCV with completely unsecured lesions, one (33%) complication was fatal., Conclusions: Endovascular treatment appeared safe for PHCV for vessels not supplying the index arterial lesion and for angiographically negative SAH. Vasodilators were safe for vessels harboring partially secured, ruptured lesions (eg, incompletely coiled aneurysms, stented dissections). Following two major complications, the safety of administering vasodilators or performing PTA to vessels supplying completely unsecured vascular lesions remains inconclusive and should be used cautiously.

This study investigated whether cocaine constriction of rat basilar artery in situ is mediated by nitric oxide (NO) inhibition and/or endothelin (ET)-1 release. Cocaine (3-100 µmol/l) concentration-dependently constricted the basilar artery to a maximum of 18%. Nω-nitro-L-arginine (100 µmol/l) was without effect on constriction to 3 and 10 µmol/l cocaine. PD145065 (1 and 10 µmol/l), an ETA/B receptor antagonist, variably and at most partially inhibited the 100 µmol/l cocaine constriction. Capsaicin denervation of sensory nerves innervating the basilar, which contain ET-1 and NO synthase, also failed to influence cocaine constriction. These findings suggest that cocaine constriction of cerebral vessels (1) varies with respect to the involvement of ET-1 release and (2) unlike findings in the peripheral vasculature, the constriction is not mediated by inhibition of NO., (© 2014 S. Karger AG, Basel.)