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Background: We evaluated restenosis rates at the cephalic arch after percutaneous angioplasty and stenting procedures in patients with brachial artery to cephalic vein arteriovenous fistula (BCAVF) hemodialysis access. Methods: We used data from adult hemodialysis patients treated at a national network of 44 outpatient interventional facilities during Oct 2011–2015. We included data from patients with BCAVF who received an exclusive angioplasty, or stent with angioplasty, for treatment of cephalic arch stenosis and had ≥ 1 subsequent evaluation of the cephalic arch. Median percent restenosis per month at cephalic arch and days between encounters was calculated from the 1st index to 2nd procedure, and for up to 4 subsequent encounters. Analyses were stratified by intervention and device types. Results: We identified a cohort of 3,301 patients (mean age 62.2 ± 13.9 years, 58.5% male, 33.2% white race) with a BCAVF who had an angioplasty, or stent, at the cephalic arch for an index and ≥ 1 follow-up procedure. Between the 1st index to 2nd procedure, patients who received an angioplasty (n = 2,663) or stent (n = 933) showed a median decrease of 18.9% and 16.5% in luminal diameter per month and a median time of 93 and 91 days between encounters, respectively. Restenosis and day rates were similar for standard versus high-pressure angioplasties. Bare metal stents showed 10.1 percentage point higher restenosis rate compared to stent grafts. Restenosis rates and time to restenosis were relatively consistent across subsequent encounters. Conclusions: Findings suggest hemodialysis patients with a BCAVF who require an angioplasty or stent to treat a stenosis at the cephalic arch will have stenosis reformed at a rate of 18.9% and 16.5% per month after the first intervention, respectively. Findings suggest patients are at risk of having significant lesions at the cephalic arch within 3 months after the previous intervention.

Background We evaluated restenosis rates at the cephalic arch after percutaneous angioplasty and stenting procedures in patients with brachial artery to cephalic vein arteriovenous fistula (BCAVF) hemodialysis access. Methods We used data from adult hemodialysis patients treated at a national network of 44 outpatient interventional facilities during Oct 2011–2015. We included data from patients with BCAVF who received an exclusive angioplasty, or stent with angioplasty, for treatment of cephalic arch stenosis and had ≥1 subsequent evaluation of the cephalic arch. Median percent restenosis per month at cephalic arch and days between encounters was calculated from the 1st index to 2nd procedure, and for up to 4 subsequent encounters. Analyses were stratified by intervention and device types. Results We identified a cohort of 3301 patients (mean age 62.2 ± 13.9 years, 58.5% male, 33.2% white race) with a BCAVF who had an angioplasty, or stent, at the cephalic arch for an index and ≥ 1 follow-up procedure. Between the 1st index to 2nd procedure, patients who received an angioplasty (n = 2663) or stent (n = 933) showed a median decrease of 18.9 and 16.5% in luminal diameter per month and a median time of 93 and 91 days between encounters, respectively. Restenosis and day rates were similar for standard versus high-pressure angioplasties. Bare metal stents showed 10.1 percentage point higher restenosis rate compared to stent grafts. Restenosis rates and time to restenosis were relatively consistent across subsequent encounters. Conclusions Findings suggest hemodialysis patients with a BCAVF who require an angioplasty or stent to treat a stenosis at the cephalic arch will have stenosis reformed at a rate of 18.9 and 16.5% per month after the first intervention, respectively. Findings suggest patients are at risk of having significant lesions at the cephalic arch within 3 months after the previous intervention.

Angiographically occult cerebral vascular malformations (AOVMs) are usually found in the supratentorial brain parenchyma. Uncommonly, AOVMs can be found within the cavernous sinus or basal cisterns and can be associated with cranial nerves. AOVMs involving the intracranial segment of the spinal accessory nerve have not been described. A 46-year-old female patient presented with a history of episodic frontal headaches and episodes of nausea and dizziness, as well as gait instability progressing over 6 months prior to evaluation. Imaging revealed a well-circumscribed 3-cm extraaxial T1-weighted isointense and T2-weighted hyperintense contrast-enhancing mass centered in the region of the right lateral cerebellomedullary cistern. The patient underwent resection of the lesion. Although the intraoperative appearance was suggestive of a cavernous malformation, some histological findings were atypical, leading to the final diagnosis of vascular malformation, not otherwise specified. The patient’s postoperative course was uneventful with complete resolution of symptoms. To the authors’ knowledge, this is the first report of an AOVM involving the intracranial portion of the accessory nerve. For any AOVM located within the cerebellomedullary cistern or one suspected of involving a cranial nerve, the authors recommend including immunohistochemistry with primary antibody to neurofilament in the histopathology workup.

OBJECT Blister aneurysms of the supraclinoid part of the internal carotid artery (ICA) are known for their high morbidity and mortality rates related to treatment, regardless of whether the treatment is surgical or endovascular. However, this grim prognosis is based on results that indiscriminately group all blister aneurysms together without taking into account the heterogeneous appearance of these lesions. The goal of this study was 2-fold: to determine whether different blister aneurysm morphologies present different pitfalls, which would then require different surgical strategies, as well as to determine whether there are identifiable subgroups of these types of aneurysms based on morphology. METHODS The authors reviewed the charts, cerebral catheter angiograms, surgical reports, and intraoperative videos of all ICA blister aneurysms treated surgically at the Centre Hospitalier de l'Université de Montréal from 2005 to 2012 to investigate whether there was a relationship between morphology and pitfalls, and whether different surgical strategies had been used according to these pitfalls. During this review process the authors noted 4 distinct morphological aspects. These 4 aspects led to a review of the English and French literature on blister aneurysms in which imaging was available, to determine whether other cases could also be classified into the same 4 subgroups based on these morphological aspects. RESULTS The retrospective review of the authors’ series of 10 patients allowed a division into 4 distinct subtypes: Type I (classic), Type II (berry-like), Type III (longitudinal), and Type IV (circumferential). These subtypes may at times be progressive stages in the arterial anomaly, and could represent a continuum. Each subtype described in this paper presented its own pitfalls and required specific surgical adaptations. Upon reviewing the literature the authors retained 35 studies involving a total of 61 cases of blister aneurysms, and all cases were able to be classified into 1 of these 4 distinct subtypes. CONCLUSIONS Although they share some common characteristics, blister aneurysms may be divided into distinct subtypes, suggestive of a continuum. Such a classification with a detailed description of each type of blister aneurysm would allow for better recognition to anticipate complications during intervention and better assess the different treatment strategies according to the subtypes.

OBJECT Review of morbidities and mortality has been the primary method used to assess surgical quality by physicians, hospitals, and oversight agencies. The incidence of reoperation has been proposed as a candidate quality indicator for surgical care. The authors report a comprehensive assessment of reoperations within a neurosurgical department and discuss how such data can be integrated into quality improvement initiatives to optimize value of care delivery. METHODS All neurosurgical procedures performed in the main operating room or the outpatient surgery center at the Ronald Reagan UCLA Medical Center and UCLA Santa Monica Medical Center from July 2008 to December 2012 were considered for this study. Interventional radiology and stereotactic radiosurgery procedures were excluded. Early reoperations within 7 days of the index surgery were reviewed and their preventability status was evaluated. RESULTS The incidence of early unplanned reoperation was 2.6% (occurring after 183 of 6912 procedures). More than half of the patients who underwent early unplanned reoperation initially had surgery for shunt-related conditions (34.4%) or intracranial tumor (23.5%). Shunt failure was the most common indication for early unplanned reoperation (34.4%), followed by postoperative bleeding (20.8%) and postoperative elevated intracranial pressure (9.8%). The average time interval (± SD) between the index surgery and reoperation was 3.0 ± 1.9 days. The average length of stay following reoperation was 12.1 ± 14.4 days. CONCLUSIONS This study enabled an in-depth assessment of reoperations within an academic neurosurgical practice and identification of strategic opportunities for department-wide quality improvement initiatives. The authors provide a nuanced discussion regarding the use of absolute reoperations as a quality indicator for neurosurgical patient populations.

Pituitary tumors including pituitary adenomas and related lesions such as craniopharyngiomas and Rathke’s cleft cysts present with a wide range of hormonal and neurological signs and symptoms resulting in a variety of referral pathways. A multidisciplinary approach to the diagnostic evaluation and treatment plan is essential to optimise outcomes. The patient is seen by each member of the team, including neurosurgeon, endocrinologist, head & neck surgeon, nurse practitioner and in some instances neuro-ophthalmologist, oncologist, radiation oncologist and interventional neuroradiologist. Appropriate investigations are undertaken and a further meeting arranged at which all opinions are discussed. A reasoned treatment regimen is recommended, taking into consideration the patient’s wishes and overall medical condition. This manuscript describes the team approach currently employed in the Brain Tumor Center and Pituitary Disorders Program at Providence Saint John’s Health Center & John Wayne Cancer Institute. When referring pituitary patients to this centre, health care professionals and patients alike are experiencing the positive benefits received from a patient-centred, multidisciplinary approach.

Background Determining ‘”value’” in health care, defined as outcomes per unit cost, depends on accurately measuring cost. We used time-driven activity-based costing (TDABC) to determine the cost of care in men with benign prostatic hyperplasia (BPH) – a common urologic condition. Methods We implemented TDABC across the entire care pathway for BPH including primary and specialist care in both inpatient and outpatient settings. A team of expert stakeholders created detailed process maps, determined space and product costs, and calculated personnel capacity cost rates. A model pathway was derived from practice guidelines and calculated costs were applied. Results Although listed as ‘optional’ in practice guidelines, invasive diagnostic testing can increase costs by 150% compared with the standalone urology clinic visit. Of five different surgical options, a 400% cost discrepancy exists between the most and least expensive treatments. Conclusions TDABC can be used to measure cost across an entire care pathway in a large academic medical center. Sizable cost variation exists between diagnostic and surgical modalities for men with BPH. Implications As financial risk is shifted toward providers, understanding the cost of care will be vital. Future work is needed to determine outcome discrepancy between the diagnostic and surgical modalities in BPH.

Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia.Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented.Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia.Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.

Objective In July 2011, the UCLA Health System released its current time-out process protocol used across the Health System. Numerous interventions were performed to improve checklist completion and time-out process observance. This study assessed the impact of the current protocol for the time-out on healthcare providers' safety attitude and operating room safety climate. Methods All members involved in neurosurgical procedures in the main operating room of the Ronald Reagan UCLA Medical Center were asked to anonymously complete an online survey on their overall perception of the time-out process. Results The survey was completed by 93 of 128 members of the surgical team. Overall, 98.9% felt that performing a pre-incision time-out improves patient safety. The majority of respondents (97.8%) felt that the team member introductions helped to promote a team spirit during the case. In addition, 93.5% felt that performing a time-out helped to ensure all team members were comfortable to voice safety concerns throughout the case. All respondents felt that the attending surgeon should be present during the time-out and 76.3% felt that he/she should lead the time-out. Unanimously, it was felt that the review of anticipated critical elements by the attending surgeon was helpful to respondents' role during the case. Responses revealed that although the time-out brings the team together physically, it does not necessarily reinforce teamwork. Conclusion The time-out process favorably impacted team members' safety attitudes and perception as well as overall safety climate in neurosurgical ORs. Survey responses identified leadership training and teamwork training as two avenues for future improvement.

Object Care providers have put significant effort into optimizing patient safety and quality of care. Value, defined as meaningful outcomes achieved per dollar spent, is emerging as a promising framework to redesign health care. Scarce data exist regarding cost measurement and containment for episodes of neurosurgical care. The authors assessed how cost measurement and strategic containment could be used to optimize the value of delivered care after the implementation and maturation of quality improvement initiatives. Methods A retrospective study of consecutive patients undergoing microvascular decompression was performed. Group 1 comprised patients treated prior to the implementation of quality improvement interventions, and Group 2 consisted of those treated after the implementation and maturation of quality improvement processes. A third group, Group 3, represented a contemporary group studied after the implementation of cost containment interventions targeting the three most expensive activities: pre-incision time in the operating room (OR) and total OR time, intraoperative neuromonitoring (IOM), and bed assignment (and overall length of stay [LOS]). The value of care was assessed for all three groups. Results Forty-four patients were included in the study. Average preparation time pre-incision decreased from 73 to 65 to 45 minutes in Groups 1, 2, and 3, respectively. The average total OR time and OR cost were 434 minutes and $8513 in Group 1; 348 minutes and $7592 in Group 2; and 407 minutes and $8333 in Group 3. The average cost for IOM, excluding electrode needles, was $1557, $1585, and $1263, respectively, in Groups 1, 2, and 3. Average total cost for bed assignment was $5747, $5198, and $4535, respectively, in Groups 1, 2, and 3. The average total LOS decreased from 3.16 days in Group 1 to 2.14 days in Group 3. Complete relief of or a significant decrease in preoperative symptomatology was achieved in 42 of the 44 patients, respectively. Overall, the average cost of a surgical care episode (index hospitalization + readmission/reoperation) decreased 25% from Group 1 to 3. Conclusions Linking cost-containment and cost-reduction strategies to ongoing outcome improvement measures is an important step toward the optimization of value-based delivery of care.

Rotational vertebral artery occlusion (RVAO), or bow hunter's syndrome, most often occurs at the C1–2 level on physiological head rotation. It presents with symptoms of vertebrobasilar insufficiency (VBI). Several previously published studies have reported on subaxial sites of vertebral artery (VA) compression by head rotation. The authors report a case of subaxial spine RVAO due to adjacent-segment degeneration. A 52-year-old man presented with dizziness when rotating his head to the left. Twenty years earlier, he had undergone a C4–5 anterior cervical discectomy and fusion (ACDF) for a herniated disc. Imaging studies including a dynamic CT angiography and dynamic catheter angiography revealed occlusion of the left VA at the C3–4 level when the patient turned his head to the left, in the setting of an aberrant vertebrobasilar system. Successful treatment was achieved by surgical decompression of the left VA and C3–4 ACDF. Expedited diagnosis and treatment are dependent on the recognition of this unusual manifestation of RVAO, especially when patients present with nonspecific symptoms of VBI.

Compartment syndrome is a fairly common condition noted in patients with fractures or crush injuries to the extremities (acute compartment syndrome) and in athletes (chronic compartment syndrome). Compartments bound by fascia are found in the extremities, buttocks, and abdomen; conditions that cause intracompartmental swelling and hypertension can lead to ischemia and limb loss. This article reviews diagnosis of the problem, monitoring of compartment pressure, and appropriate treatment.

BACKGROUND Although most posterior circulation aneurysms are currently treated by endovascular means, some are not amenable to this treatment modality. The narrow working window afforded by the anterolateral and lateral surgical approaches often translates into suboptimal visualization and limited maneuverability. OBJECTIVE We present a modified technique of tentorial incision and reflection that optimizes the exposure achieved with the traditional subtemporal approach and report our clinical experience in a series of posterior circulation aneurysms. METHODS Retrospective review of patients operated via an extended subtemporal transtentorial approach for posterior circulation aneurysms. The modified tentorial incision implies dissection of the trochlear nerve along its dural canal up to its entrance into the cavernous sinus and incision of a tentorial flap that extends up to Meckel cave, which is then reflected far anterolaterally. Clinical and radiological data were reviewed. RESULTS This series comprises 18 patients (21 procedures). Ten patients presented (56%) with a subarachnoid hemorrhage. Aneurysms most frequently arose from the basilar tip (61%) and were of small size (50%) and saccular morphology (72%). Two patients underwent surgery following unsuccessful endovascular treatment. Aneurysm treatment was successful on the first attempt in 90% (19/21) and after a second attempt in 10% (2/21). Documented postoperative palsies of the oculomotor (n = 3) and trochlear (n = 1) nerves were all transient. No procedure-related mortality occurred. CONCLUSION This modified technique of tentorial incision and reflection optimizes visibility, anatomic orientation, and maneuverability by increasing the rostrocaudal and anterolateral exposure obtained via the extended subtemporal transtentorial route without permanent postoperative trochlear nerve deficit.

Object Value of care is emerging as a promising framework to restructure health care, emphasizing the importance of reporting multiple outcomes that encompass the entire care episode instead of isolated outcomes specific to care points during a patient's care. The authors assessed the impact of coordinated implementation of processes across the episode of surgical care on value of neurosurgical care, using microvascular decompression (MVD) as an example. Methods This study is a retrospective review of consecutive cases involving patients with either trigeminal neuralgia or hemifacial spasm undergoing first-time MVD. Patients were divided into 2 groups: Group 1 included patients who underwent surgery between February 2008 and November 2009 and Group 2 included those who underwent surgery between January 2011 and October 2012. The authors collected data on outcome measures spanning the entire surgical episode of care according to the Outcome Measures Hierarchy. Results Forty-nine patients were included: 20 patients in Group 1 and 29 patients in Group 2. Thirty-one patients underwent MVD for trigeminal neuralgia and 18 for hemifacial spasm. A zero mortality rate and high degree of symptom resolution were achieved in both groups. Group 2 benefited from a reduction in the average total operating room time, a decrease in the mean and median postoperative length of hospital stay, a decrease in the mean length of stay on the floor, and a reduction in the rates of complications and readmissions. Conclusions Comprehensive implementation of improvement processes throughout the continuum of care resulted in improved global outcome and greater value of delivered care. Enhanced-recovery perioperative protocols and diagnosis-specific clinical pathways are two avenues built around global care delivery that can help achieve an “optimal episode of surgical care” in every case.

Objective Patients undergoing pituitary adenoma or Rathke cleft cyst (RCC) removal are often administered perioperative glucocorticoids regardless of lesion size and preoperative adrenocorticotropic hormone/cortisol levels. To minimize unnecessary glucocorticoid therapy, we describe a protocol in which patients with normal preoperative serum cortisol and adrenocorticotropic hormone levels are given glucocorticoids only if postoperative day 1 or 2 (POD1 or POD2) cortisol levels decrease below normal. Methods A total of 207 consecutive patients undergoing endonasal surgery for an adenoma or RCC were considered for study. Of these, 68 patients with preoperative adrenal insufficiency or Cushing disease were excluded. Glucocorticoids were withheld unless POD1 or POD2 morning cortisol values were below normal (≤4 μg/dL). Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. Results The 139 patients included 119 with macroadenomas, 14 microadenomas, and 6 RCCs (follow-up, 3–41 months; median, 10 months). Nine patients (6.5%), all with macroadenomas (mean diameter, 26 ± 10 mm) had low POD1 or POD2 cortisol values and received glucocorticoids; of these, five patients were weaned off within 3–28 weeks of surgery. Overall, 12 of 139 patients (8.6%) were treated for early (n = 9) or delayed (n = 3) adrenal insufficiency but only 5 patients (3.6%) remain on glucocorticoid replacement. No patient experienced an adrenal crisis. Using morning POD1 or POD2 cortisol values >4 μg/dL as a measure of adequate hypothalamic-pituitary-adrenal axis function, yields a sensitivity of 96%, a specificity of 57%, and a positive predictive value of 98%. Conclusions In patients with normal preoperative cortisol levels undergoing endonasal removal of a pituitary adenoma or RCC, normal morning cortisol values on POD1 and POD2 reliably predicts adequate and safe adrenal function in 98% of patients. This simple protocol of withholding postoperative glucocorticoids avoids unnecessary steroid exposure and poses minimal risk to the well-informed closely monitored patient.

Stereotactic radiosurgery was conceptualized to treat functional diseases of the brain. The need for devices capable of molding the radiation dose to the nuances of intracranial lesions and yet preserve brain function became a challenge. Several devices capable of performing radiosurgery of high quality became commercially available, each with advantages and disadvantages. Speed of radiosurgery delivery for cost effectiveness and comfort for the patient are currently the main developments in the field. Nuances of these devices, procedural steps of radiosurgery, and the team approach of radiosurgery are discussed in this article.

The finding of dilated, elongated, and tortuous vessels on brain imaging should prompt clinicians to determine what vascular anomaly is present. Importantly, not all suspicious serpentine flow voids are manifestations of arteriovenous malformations or arteriovenous fistulas. Other types of intracranial vasculopathies should also be considered. The authors report a rare case of dilated, tortuous, and redundant left posterior communicating artery and left P2 segment of the posterior cerebral artery identified in a young healthy adult that remained stable over a 30-year period. Dynamic and 3D images were critical for determining the type of vascular anomaly and for guiding appropriate management. The authors propose that this case represents a pure arterial malformation and discuss its distinguishing features.

The subtemporal transtentorial approach provides excellent exposure of the incisural space. Incision of the tentorium improves access to the interpeduncular cistern, basilar artery, and rostral ventral pons. Description of the starting and termination points of the tentorial incision has varied greatly. We assessed the impact on surgical exposure of freeing the trochlear nerve (TN) from its dural canal (DC) in addition to dividing and retracting the tentorium. A subtemporal approach was performed on 10 hemispheres of cadaveric specimens. Following exposure of the middle tentorial incisura, the TN is dissected from its DC over a few millimeters. Two retraction sutures are placed along the tentorial edge, posterior to the TN entrance in its DC. The tentorial incision is started between the sutures. Dissection of TN from its DC continues for a short distance. The tentorial incision is extended straight up towards the superior petrosal sinus. Dissection of the TN DC continues anteriorly, up to its entry into the cavernous sinus. The tentorial incision can then be extended, just over the entrance to Meckel’s cave, and the flap reflected far anterolateraly. Using this technique, the exposure of the interpeduncular cistern and its content increased by a mean of 8.2 mm (standard deviation [SD] 3.9 mm) in the anteroposterior axis and by 5.5 mm (SD 1.9 mm) in the rostrocaudal axis. Tentorial incision following dissection of the TN from its DC optimizes reflection of the tentorium flap anterolateraly, maximizes the exposure, and improves lighting and visibility as well as maneuverability within the interpeduncular and rostral pre-pontine cisterns.

Object Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding and removing residual adenoma after initial microscopic removal. Methods Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study. Results Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140) of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor removal in 54% (36/67) of the adenomas measuring ≥ 2 cm in diameter and in 19% (14/73) of the adenomas smaller than 2 cm in diameter (p < 0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of endocrine-active adenomas had early remission. Conclusions After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.

The supraorbital keyhole approach offers a limited access for aneurysms located at the middle cerebral artery (MCA) bifurcation with long M1 segments or proximal M2 aneurysms. Alternative minimally invasive routes centered on the pterion have been developed to address these aneurysms. Appropriate dissection and reconstruction of the temporal muscle are important for optimal exposure and best cosmetic results with the pterional keyhole craniotomy. The authors describe the technical nuances of temporal muscle dissection and reconstruction adapted to the pterional keyhole craniotomy. After incising the scalp in a curvilinear fashion behind the hairline, an interfascial dissection is performed, allowing anterior reflection of the superficial temporal fat pat and superficial temporal fascia. The temporal muscle is incised 7–10 mm below its insertion at the superior temporal line. The deep temporal fascia and temporal muscle are incised vertically, completing a T-shaped incision. Subperiosteal dissection of both muscle flaps preserves the deep temporal arteries and nerves. A craniotomy measuring 2.5–3 cm in diameter, based anteriorly at the pterion, is made over the sylvian fissure. Dissection of the sylvian fissure and of MCA aneurysms can proceed without the use of retractors. The bone flap and associated hardware is entirely covered by the temporal muscle, which is reconstructed in 2 layers: the temporal muscle/deep temporal fascia and the superficial temporal fascia. This dissection technique prevents damage to branches of the facial nerve and minimizes temporal muscle damage. Dividing the temporal muscle vertically and reflecting both parts anteriorly and posteriorly prevents suboptimal illumination and visualization under the microscope. Covering the bone flap and related hardware with a multilayer anatomical reconstruction optimizes cosmetic results.

Numerous surgical techniques have been developed and refined for the treatment of moyamoya disease. Among the indirect techniques of revascularization, encephaloduroarteriosynangiosis has been recognized as effective in promoting revascularization and reversing symptomatology. Neovascularization occurs between the donor artery, either the superficial temporal artery or the occipital artery, and the underlying ischemic cortex. Additionally, the middle meningeal artery and its dural branches have also been shown to contribute to collateral blood supply. In this report the authors describe an integrated management of the meninges for optimal revascularization. They emphasize the importance of recognizing the 3 major layers of the dura and describe a technique of dural splitting at the locus minoris resistentiae between the dura mater's vascular (middle) layer and internal median layer. Applying the dura's vascular layer to the surface of the brain after opening of the arachnoid is designed to optimize dural-pial synangiosis related to middle meningeal artery branches.

Pituitary tumors and associated neuroendocrine disorders pose significant challenges in diagnostic and therapeutic management. Optimal care of the "pituitary patient" is best provided in a multidisciplinary collaborative environment that includes not only experienced pituitary practitioners in neurosurgery and endocrinology, but also in otorhinolaryngological surgery, radiation oncology, medical oncology, neuro-ophthalmology, diagnostic and interventional neuroradiology, and neuropathology. We provide the background and rationale for recognizing pituitary centers of excellence and suggest a voluntary verification process, similar to that used by the American College of Surgeons for Trauma Center verification. We propose that pituitary centers of excellence should fulfill 3 key missions: (1) provide comprehensive care and support to patients with pituitary disorders; (2) provide residency training, fellowship training, and/or continuing medical education in the management of pituitary and neuroendocrine disease; and (3) contribute to research in pituitary disorders. As this is a preliminary proposal, we recognize several issues that warrant further consideration including center and surgeon practice volume as well as oversight of the verification process.

Background Oncologic resection of the nasopharynx is challenging due to its complex and deep-seated nature. We aimed to illustrate the anatomic landmarks of endoscopic nasopharyngectomy and design a surgical training model that could facilitate learning of this technique. Methods An endoscopic endonasal dissection of the nasopharynx was completed in fresh cadaveric specimens under conditions similar to those of our operating suite. Digital data from a high-resolution CT scan were imported to an image guidance system to be used during the dissections. Results We expanded the sinonasal corridor, harvested a contralateral nasoseptal flap, and exposed the pterygopalatine and infratemporal fossae. A detailed anatomic dissection of the nasopharynx was correlated to multiplanar images provided by the image guidance system, highlighting appropriate bony, neural, and vascular landmarks. Conclusions Understanding the anatomy-based endoscopic modular approaches facilitates planning and safe execution of an oncologic nasopharyngectomy. Clinical experience remains mandatory because anatomic models fall short of clinical scenarios. © 2012 Wiley Periodicals, Inc. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Introduction Petrous apex cholesterol granulomas (PACGs) are uncommon lesions. Recurrence following transcranial or endonasal approaches to aerate the cyst occurs in up to 60% of cases. We describe the technical nuances pertinent to the endonasal endoscopic management of a recurrent symptomatic PACG and review the literature. Results A 19-year-old woman presented with a recurrent abducens nerve paresis. Four months prior, she underwent an endonasal transsphenoidal surgery (TSS) for drainage of a symptomatic PACG. Current imaging documented recurrence of the right PACG. Transsphenoidal and infrapetrous approaches were performed to obtain a wider bony opening along the petrous apex and drain the cyst. A Doyle splint was inserted into the cyst's cavity and extended out into the sphenoid sinus, maintaining patency during the healing process. Three months after surgery, the splint was removed endoscopically, allowing visualization of a patent cylindrical communication between both aerated cavities. The patient remains symptom-free and recurrence-free. Conclusion Endoscopic endonasal surgery must be adapted to manage a recurrent PACG. A TSS may not be sufficient. An infrapetrous approach with wider bony opening, extensive removal of the cyst's anterior wall, and the use of a stent are indicated for the treatment of recurrent PACG and to prevent recurrences.

Rebleeding and symptomatic vasospasm (VS) are the major causes of subsequent morbidity and mortality in patients surviving a subarachnoid hemorrhage (SAH). Although most patients present rapidly after the bleed, some may seek medical attention in a delayed fashion due to non-resolving or worsening headaches or new neurological deficits, requiring treatment during the period at risk for VS. Such patients may either present asymptomatic radiological VS on their diagnostic angiogram or present symptomatic VS confirmed on angiogram. A similar situation may occur in patients presenting within the first 48 hours after SAH with very early angiographic VS. Deciding on the optimal timing and modality of treatment in such patients with SAH and symptomatic VS on presentation is controversial. Only six observational studies that specifically assessed aneurysm treatment in the presence of symptomatic VS have been published to date. We reviewed the published literature on the management of ruptured intracranial aneurysms in the presence of symptomatic VS and suggest avenues for future studies.

Resume Les anevrismes de type phlyctene (APh) surviennent sur l’artere carotide interne (ACI) sur un site depourvu d’embranchement. Ces anevrismes ont des parois fragiles et de larges collets mal definis. Il est essentiel de les reconnaitre pour une prise en charge adequate. Diverses strategies chirurgicales et endovasculaires ont ete tentees pour ces lesions heterogenes. Elles ont ete associees a une morbidite et une mortalite elevees liees a un ressaignement, une re-croissance, des complications ischemiques et thromboemboliques. Les auteurs ont revu les elements cles concernant le diagnostic et la prise en charge des APh et ont revise les options therapeutiques actuelles.

Resume Le resaignement et le vasospasme (VS) symptomatique representent les causes majeures de morbidite et mortalite chez les patients survivant a une hemorragie sous-arachnoidienne (HSA). Bien que la plupart des patients se presentent rapidement apres une hemorragie, d’autres tardent a consulter alors que les cephalees persistent, s’accentuent ou alors qu’ils presentent de nouveaux symptomes neurologiques, necessitant une prise en charge pendant la periode a risque de VS. Ces patients peuvent presenter a l’angiographie tant du VS asymptomatique que du VS symptomatique. Une telle situation peut se presenter plus rarement dans les 48 premieres heures apres HSA avec du VS angiographique tres precoce. Le timing et les modalites de prise en charge therapeutique des patients avec une HSA anevrismale et du VS symptomatique demeurent controverses. Seulement six etudes observationnelles evaluant specifiquement le traitement des anevrismes en presence d’un VS symptomatique ont ete publiees a ce jour. Nous avons revu la litterature sur la prise en charge des anevrismes intracrâniens rompus en presence d’un VS symptomatique et suggerons des pistes pour des etudes futures.

Object Symptomatic sellar arachnoid cysts (ACs) have typically been treated via the transsphenoidal route. After sellar cyst wall fenestration, some authors have advocated cyst wall resection and increasing communication between the AC and suprasellar subarachnoid space (SAS). This study is a report of the authors' experience using a simplified approach to reinforce a defective diaphragma sellae or unseen arachnoid diverticulum by deliberately not enlarging the AC-SAS communication and obliterating the cyst cavity with adipose tissue followed by skull base reconstruction. Methods A retrospective analysis was conducted of patients who underwent an endonasal transsphenoidal obliteration of symptomatic ACs with a fat graft and skull base repair. Results Between July 1998 and September 2010, 8 patients with a sellar AC were identified (6 women and 2 men, mean age 57 years). Clinical presentation included headache, pituitary dysfunction, and visual dysfunction (4 patients each group). Maximal cyst diameter averaged 22 mm (range 15–32 mm). In all cases the sellar communication to the SAS was deliberately not enlarged. The endoscope was used for visualization in 8 of 9 procedures. Postoperatively, headache improved in all 4 patients, vision in all 4 patients, and partial resolution of endocrine dysfunction (hyperprolactinemia and/or recurrent hyponatremia) occurred in 3 (75%) of 4 patients. No new endocrinopathy, CSF leak, meningitis, or neurological deficits occurred. Two patients experienced cyst reaccumulation: 1 symptomatic recurrence was treated with reoperation at 43 months postsurgery, and 1 asymptomatic partial recurrence continued to be monitored at 29 months postsurgery. Conclusions Sellar ACs can be effectively treated using endonasal fenestration and obliteration with fat with resultant reversal of presenting symptoms in the majority of patients. This simplified technique of AC cavity obliteration without enlarging communication to the SAS has a low risk of CSF leakage, and in most cases appears to effectively disrupt cyst progression, although longer follow-up is required to monitor for cyst recurrence.

Subarachnoid hemorrhage (SAH) has been recognized as a risk factor for ventriculostomy-related infections (VRI). In addition to the hemorrhagic cerebrospinal fluid (CSF), the potential need for prolonged catheterization may contribute to the increased CSF infection rate in this population. The use of antibiotic-impregnated catheters (AIC) has effectively reduced the risk of VRI. Herein, we examined specifically the impact of systematic insertion of AIC on the timing of CSF infections in SAH patients. Retrospective review of patients admitted between April 2006 to March 2009 with a non-traumatic SAH who required an external ventriculostomy. Only patients with AIC were included. A meningitis or ventriculitis was diagnosed according to the published criteria of the Center for Disease Control and Prevention. This study includes 75 patients in which 97 drains were inserted. Seven infections (7/75 = 9.3%) occurred over 1,024 drainage days (DD), resulting in a rate of 6.8 infections/1,000 DD. The mean drainage time was 15.4 days in the infected AIC group compared with 10.2 days in the non-infected AIC group. No infection occurred before day 9 of drainage and 71% (5/7) occurred after more than 2 weeks of drainage. The observed timing of infections is delayed in comparison with that reported in series using non-AIC, which typically occur prior to the 10th day of drainage. In the high-risk population of non-traumatic SAH, the use of AIC delays the occurrence of infection compared with that reported with non-antibiotic-impregnated catheters. This may orient management strategies in SAH patients requiring a ventriculostomy.

The authors present a unique side-cutting instrument (NICO Myriad, Indianapolis, IN) with variable aspiration designed specifically for tumor resection. The study included retrospective review of data collected from 10/2009 to 01/2011. We detail the use of the Myriad in 31 patients with the following pathologies: meningioma (n=16), chordoma (n = 3), schwannoma (n = 3), pituitary adenoma (n = 2), metastasis (n = 3), hemangioblastoma (n = 1), craniopharyngioma (n = 1), and nasopharyngeal tumors (n = 2). Surgical approaches included expanded endonasal approach (n = 19), endoscopic brain port (n = 3), supraorbital “eyebrow” craniotomy (n = 3), retrosigmoid suboccipital craniotomy (n = 3), pterional craniotomy (n = 1), extreme far lateral (n = 1), and laminectomy (n = 1). Successful tumor resection was achieved in 30 cases. Instrument failure was noted in only one extremely fibrous meningioma. The design of this instrument facilitated maneuvering through narrow corridors while providing direct visualization of the suction aperture during tumor resection. These features allowed for tumor removal without injury to adjacent neurovascular structures. The side-cutting aspiration device allows safe and effective tumor removal. Its low profile, variable aspiration, and lack of thermal heat energy are particularly useful in tumor resection through narrow corridors, such as endonasal, port, and keyhole approaches. The multifunctional nature of the instrument (suction, scissors, and dissectors) minimizes multiple exchanges, facilitating tumor resection through these minimal access corridors.

Elongation of the anterior cerebral artery (ACA) and subsequent compression of the chiasm rarely have been reported as causes of a visual field deficit. Neither has microvascular decompression of the chiasm been described in this circumstance. The authors report on a case of progressive visual deficits caused by compression of the optic apparatus by a right elongated ACA as documented on MR imaging. Microvascular decompression was proposed as treatment. The right A1 segment was larger than usual and tortuous, transmitting its pulsations into the chiasm. A piece of Teflon was inserted between the A1 segment and the chiasm. Following surgery, the visual field deficit progressively improved. At 4 months after surgery, the patient's visual fields were normal. Therefore, an elongated ACA can compress the chiasm and result in a visual field deficit. In such circumstances when facing a progressive visual field deficit, microvascular decompression may improve vision.

Selective transsphenoidal adenomectomy is generally recommended for initial treatment of Cushing's disease (CD) because it achieves a high (70-85%) rate of remission. However, if initial surgery is not successful, the approach to persistent or recurrent CD is more complex. Because residual or recurrent adenoma is typically found at the site of the original adenoma, repeat transsphenoidal surgery is recommended including selective adenomectomy, hemihypophysectomy or total hypophysectomy. If repeat pituitary surgery does not achieve remission, then possible adjuvant therapies include radiosurgery or stereotactic radiotherapy, bilateral adrenalectomy, and/or medical therapy. In all cases of persistent or recurrent CD, successful treatment requires close collaboration of endocrinologists, radiation oncologists and neurosurgeons.

Distal choroidal artery aneurysms stemming from the lateral wall of the ventricles are rare and are mostly associated with moyamoya disease. The treatment of these aneurysms is difficult because of their deep location. The authors report the case of a 50-year-old woman followed for moyamoya disease presenting with 2 intraventricular hemorrhages. Cerebral angiography showed an aneurysm located on the left distal choroidal artery. Magnetic resonance imaging also demonstrated that the lesion protruded from the lateral wall of the trigone of the left lateral ventricle. Using MR imaging–guided stereotactic localization, the aneurysm was accurately reached endoscopically and successfully resected from the parent artery. The patient was discharged neurologically intact. To the best of the authors' knowledge, this is the first report of a successfully endoscopically treated distal anterior choroidal artery aneurysm. Endoscopic surgery may be added to the armamentarium of procedures used to treat intraventricular aneurysms.

Objective To present a review of the literature and a case series of blood blister–like aneurysms (BBA) to show that an adapted direct surgical approach enables treatment of BBA with a low complication rate. Methods A retrospective review was performed of patients treated for a ruptured BBA of the internal carotid artery (ICA) at Hopital Notre-Dame from 2005–2009. Clinicoradiologic data and intraoperative videos were analyzed. Outcome was assessed using the modified Rankin scale (mRS). Results This series includes 7 patients (4 women and 3 men) with a mean age of 44.7 (range 30–61). All patients presented with subarachnoid hemorrhage (SAH). Four angiograms were initially negative. Diameter of BBA ranged from 1.1–8.2 mm. No intraoperative or postoperative aneurysm rupture occurred in this series. Although angiograms showed expected mild stenosis of the ICA after clipping, no clinical or radiologic cerebral infarctions were observed. The outcome was favorable in all patients. Conclusions Recognition of BBA is essential for proper management. An appropriate neurosurgical strategy has enabled a significant reduction in perioperative aneurysm rupture compared with previous reports and obtains excellent functional results.

CASE REPORT Case 1 A 31-year-old female consulted for polydipsia and polyuria ongoing since a few weeks. She reported weight gain over the last eight months and amenorhea with galactorhea for the last four months. Physical examination revealed no abnormalities other than a decreased visual acuity in the left eye already noticed by the patient over the past three months. Biochemical and hematological data were within normal range. Endocrine work-up showed slightly increased prolactine, decreased luteinizing hormone/follicle stimulating hormone (LH/FHS), decreased free T4 and compensated insipidus diabetes. Magnetic resonance imaging (MRI) demonstrated a sellar cystic lesion with suprasellar extension, displacing the optic chiasm upwardly. The lesion was iso-intense on T1WI and slightly hyperintense on T2WI (Figure 1). The lesion’s rim enhanced following gadolinium injection. The stalk did not enhance. The preoperative diagnosis was a non-secreting cystic macroadenoma. The lesion was approached by an endoscopic endonasal transsphenoidal route. After opening a thin capsule beneath the dura, a whitish viscous substance spontaneously leaked out of the sella (Figure 2). After the mucoid substance was completely aspirated, the angled endoscope enabled a view inside the cavity and removal of free floating fragments of the capsule, sparing the pituitary gland. Intra-operative pathological findings were suggestive of an inflammatory process. In light of this information, the cavity was irrigated and surgery terminated. Post-operatively, the patient fully recovered her visual field defect. Currently two years following surgery, the patient remains on replacement treatment. Her follow-up MRI showed no lesion recurrence. The definitive pathological assessment showed fragments of pituitary tissue, with residual acini among tissue infiltrated with T and B lymphocytes and plasmocytes. A few giant cells were identified in the specimen. One of the fragments was lined by squamous cells, suggestive of a ruptured RCC with secondary hypophysitis (Figure 3). Special stains for micro-organisms yielded negative findings. Hypophysitis Secondary to a Ruptured Rathke Cleft Cyst

Object Conventional imaging demonstrates intertwined fibers of the cerebral white matter as a homogeneous substrate. Recently, diffusion tensor imaging has allowed 3D reconstruction of these fiber bundles. The goal of this study was to analyze the modifications of the association fibers induced by an arteriovenous malformation (AVM) in the parietotemporooccipital (PTO) associative area and their clinical significance. Methods The authors analyzed the long association fibers in seven patients harboring an AVM in or near the PTO region in relation with the fibers' clinical manifestation. The fibers include the arcuate fasciculus (AF), the occipitofrontal fasciculus (OFF), and the inferior longitudinal fasciculus (ILF). These structures were compared with the contra-lateral bundles. Results The modification of the tracts could establish a pattern signature depending on the specific location of the vascular malformation. There was a positive correlation between the degree of modifications of OFF and ILF fiber tracts and visual deficits. Alteration of the AF correlated with a speech disorder and the risk of postoperative deficits. Conclusions Diffusion tensor imaging enables in vivo dissection of fiber tracts coursing through the PTO area. Depending on the location of the AVMs, long association fibers are variously modified. These findings correlate with clinical manifestations and may predict outcome after surgery.

✓ The authors report the case of a 34-year-old woman who presented with increasing headaches. Neuroimaging revealed bilateral anomalous vessels arising at the level of each ophthalmic artery, coursing rostromedially to join the anterior communicating artery (ACA), which harbored an aneurysm. Intraoperatively, the authors identified an abnormal gyral segmentation of the frontoorbital region, with a median gyrus separated from the olfactory tracts on each side by the gyrus rectus. No interhemispheric fissure was observed in the exposed area. This is the first report in the literature of an abnormal gyral segmentation in association with an infraoptic course of an ACA. Recognition of this possible gyral abnormality in association with this vascular anomaly is relevant for surgical exposure and treatment of aneurysms by clip placement.

OBJECT While malpractice litigation has had many negative impacts on health care delivery systems, information extracted from lawsuits could potentially guide toward venues to improve care. The authors present a comprehensive review of lawsuits within a tertiary academic neurosurgical department and report institutional and departmental strategies to mitigate liability by integrating risk management data with quality improvement initiatives. METHODS The Comprehensive Risk Intelligence Tool database was interrogated to extract claims/suits abstracts concerning neurosurgical cases that were closed from January 2008 to December 2012. Variables included demographics of the claimant, type of procedure performed (if any), claim description, insured information, case outcome, clinical summary, contributing factors and subfactors, amount incurred for indemnity and expenses, and independent expert opinion in regard to whether the standard of care was met. RESULTS During the study period, the Department of Neurosurgery received the most lawsuits of all surgical specialties (30 of 172), leading to a total incurred payment of $4,949,867. Of these lawsuits, 21 involved spinal pathologies and 9 cranial pathologies. The largest group of suits was from patients with challenging medical conditions who underwent uneventful surgeries and postoperative courses but filed lawsuits when they did not see the benefits for which they were hoping; 85% of these claims were withdrawn by the plaintiffs. The most commonly cited contributing factors included clinical judgment (20 of 30), technical skill (19 of 30), and communication (6 of 30). CONCLUSIONS While all medical and surgical subspecialties must deal with the issue of malpractice and liability, neurosurgery is most affected both in terms of the number of suits filed as well as monetary amounts awarded. To use the suits as learning tools for the faculty and residents and minimize the associated costs, quality initiatives addressing the most frequent contributing factors should be instituted in care redesign strategies, enabling strategic alignment of quality improvement and risk management efforts.

Object Knowledge of the costs incurred through the delivery of neurosurgical care has been lagging, making it challenging to design impactful cost-containment initiatives. In this report, the authors describe a detailed cost analysis for pituitary surgery episodes of care and demonstrate the importance of such analyses in helping to identify high-impact cost activities and drive value-based care. Methods This was a retrospective study of consecutively treated patients undergoing an endoscopic endonasal procedure for the resection of a pituitary adenoma after implementation and maturation of quality-improvement initiatives and the implementation of cost-containment initiatives. Results The cost data pertaining to 27 patients were reviewed. The 2 most expensive cost activities during the index hospitalization were the total operating room (OR) and total bed-assignment costs. Together, these activities represented more than 60% of the cost of hospitalization. Although value-improvement initiatives contributed to the reduction of variation in the total cost of hospitalization, specific cost activities remained relatively variable, namely the following: 1) OR charged supplies, 2) postoperative imaging, and 3) use of intraoperative neuromonitoring. These activities, however, each contributed to less than 10% of the cost of hospitalization. Bed assignment was the fourth most variable cost activity. Cost related to readmission/reoperation represented less than 5% of the total cost of the surgical episode of care. Conclusions After completing a detailed assessment of costs incurred throughout the management of patients undergoing pituitary surgery, high-yield opportunities for cost containment should be identified among the most expensive activities and/or those with the highest variation. Strategies for safely reducing the use of the targeted resources, and related costs incurred, should be developed by the multidisciplinary team providing care for this patient population.

The treatment of musculoskeletal disorders is gaining importance as the population ages. In addition to the complications brought on by prolonged life expectancy, the growing epidemic of obesity is contributing to joint degradation. Cell-based tissue engineering has the potential to advance the current treatment for musculoskeletal disorders. This article reviews the various forms of arthritis and describes stem cell therapy as a promising treatment option.

Introduction: Radioresistant brain tumor vasculature is thought to hamper the efficiency of adjuvant cancer therapies. However, little is known regarding the signalling pathways involved in the angiogenic response to brain tumor-derived growth factors in irradiated human brain microvascular endothelial cells (HBMEC). The goal of this study is to assess the effect of ionizing radiation (IR) on HBMEC survival, migration and tubulogenesis. Methods: HBMEC were cultured and irradiated at sublethal single doses. Cell survival was assessed by nuclear cell counting and flow cytometry. HBMEC migration in response to brain tumor-derived growth factors (U-87 GF) and tubulogenesis were assayed using modified Boyden chambers and Matrigel, respectively. Results: We observed that single administration of 3-10 Gy IR doses only reduced cell survival by 30%. Radioresistant HBMEC overexpressed RhoA, a small GTPase protein regulating cellular adhesion and migration, and Rho-kinase (ROK), a serine-threonine protein kinase and one of RhoA’s major targets. HBMEC migration was induced by vascular endothelial growth factor (VEGF), but even more so in response to sphingosine-1-phosphate (S1P) and to U-87 GF. Following IR exposure, HBMEC basal migration increased more than two-fold, whereas the response to S1P and to U-87 GF was significantly diminished. Similarly, the inhibitor of ROK Y-27632 decreased HBMEC migration in response to S1P and U-87 GF. Overexpression of RhoA decreased tubulogenesis, an effect also observed in irradiated HBMEC. Conclusion: Our results suggest that radioresistant HBMEC migration response to tumor-secreted growth factors and tubulogenesis are altered following IR. The RhoA/ROK signalling pathway is involved in the IR-altered angiogenic functions and may represent a potential molecular target for enhancing the impact of radiotherapy on tumor-associated endothelial cells.

Background and Purpose:The timing of aneurysmal surgery for patients presenting within the period at risk for vasospasm (VS) is controversial. The goal of this study is to review our experience of surgically treated patients in the presence of angiographic VS.Materials and Methods:From 1990-2004, 894 consecutive patients presented with an aneurysmal subarachnoid hemorrhage (SAH) and were treated with a policy of early surgery. We retrospectively analyzed the patients that had pre-operative angiographic VS. In this study, symptomatic VS was diagnosed when a decreased level of consciousness and/or focal deficit occurred after SAH in the presence of angiographic VS without confounding factors. Functional outcome was assessed three months after SAH using the Glasgow Outcome Scale.Results:Of the 40 patients studied, 62.5% were in good clinical grade Hunt & Hess (H&H 1-2) on admission; 25%, intermediate grade (H&H 3); 12.5%, poor grade (H&H 4-5). Surgery was performed 24 hours or less after initial angiography in 87.5% of patients and less than 48 hours in 97.5%. Pre-operative symptomatic VS was diagnosed in 25%. Postoperatively, angiographic VS was documented in 87.2%. Of the 30% of patients that presented post-operative symptomatic VS, 66.7% also demonstrated pre-operative symptomatic VS. The functional outcome was favorable in 92.5% of the studied patients. Two deaths occurred in patients presenting pre-operative early radiological and symptomatic VS.Conclusion:Aneurysmal surgery, especially between 3-12 days following SAH, in the presence of asymptomatic pre-operative angiographic VS can be associated with a good outcome. Early surgery is not contra-indicated and might enable optimal treatment of VS.

The microvasculature of brain tumors has been proposed as the primary target for ionizing radiation (IR)-induced apoptosis. However, the contribution of low dose IR-induced non-apoptotic cell death pathways has not been investigated. This study aimed to characterize the effect of IR on human brain microvascular endothelial cells (HBMEC) and to assess the combined effect of epigallocatechin-3-gallate (EGCg), a green tea-derived anti-angiogenic molecule. HBMEC were treated with EGCg, irradiated with a sublethal (or =10 Gy) single dose. Cell survival was assessed 48 h later by nuclear cell counting and Trypan blue exclusion methods. Cell cycle distribution and DNA fragmentation were evaluated by flow cytometry (FC), cell death was assessed by fluorimetric caspase-3 activity, FC and immunoblotting for pro-apoptotic proteins. While low IR doses alone reduced cell survival by 30%, IR treatment was found more effective in EGCg pretreated-cells reaching 70% cell death. Analysis of cell cycle revealed that IR-induced cell accumulation in G2-phase. Expression of cyclin-dependent kinase inhibitors p21(CIP/Waf1) and p27(Kip) were increased by EGCg and IR. Although random DNA fragmentation increased by approximately 40% following combined EGCg/IR treatments, the synergistic reduction of cell survival was not related to increased pro-apoptotic caspase-3, caspase-9 and cytochrome C proteins. Cell necrosis increased 5-fold following combined EGCg/IR treatments while no changes in early or late apoptosis were observed. Our results suggest that the synergistic effects of combined EGCg/IR treatments may be related to necrosis, a non-apoptotic cell death pathway. Strategies sensitizing brain tumor-derived EC to IR may enhance the efficacy of radiotherapy and EGCg may represent such a potential agent.