Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Normalization of Peri-Arteriovenous Malformation Hemodynamics Prior to Direct Microsurgery: 2-Dimensional Operative Video.

Arteriovenous malformations (AVMs) are highly complex vascular lesions characterized by abnormal connections between arteries and an intervening nidus. Definitive and safe treatment of AVMs may require the combination of multiple treatment modalities to address the various complex features of the AVM.1 Endovascular embolization can be used as an adjuvant to surgery in order to control deep feeders, reduce flow, and address high-risk features such as aneurysms. In addition, by progressively reducing the AVM flow, staged embolization can lead to normalization of peri-AVM hemodynamics and therefore may decrease the risk of postresection hemorrhage.2,3 In this operative video, we present a case of a 41-yr-old female who presented with progressively worsening left-sided hemiparesis. Magnetic resonance imaging (MRI) and angiography revealed a complex right fronto-parietal AVM with significant associated edema, likely due to the vascular steal phenomenon. The area of edema, which included the motor cortex, was thought to be at high risk for postoperative hemorrhage from normal perfusion pressure breakthrough. We therefore decided to proceed with staged presurgical embolization to gradually normalize the perilesional hemodynamics, and therefore possibly reduce the risk of postoperative morbidity. The patient underwent 3 embolization sessions at 6-wk intervals. An MRI after the last embolization showed near-complete resolution of the fluid-attenuated inversion-recovery (FLAIR) signal around the AVM. Microsurgical resection was performed on the day after the last embolization. The patient tolerated the procedure well and was discharged at her neurological baseline with mild contralateral hemiparesis, which has continued to improve at follow-up. Postoperative angiography showed complete resection of the AVM. The patient consented to the procedure as shown in this operative video and gave informed written consent for use of her images in publication.

Microvascular Decompression Technique for Trigeminal Neuralgia Using a Vascular Clip.

Microvascular decompression (MVD) surgery is a well-established, effective treatment option for trigeminal neuralgia1 and hemifacial spasm.2 In 1967, Janetta et al3 introduced the concept of MVD surgery and pioneered the Janetta technique in which Teflon felt implants are placed between the trigeminal nerve and offending vessel. Though many cases are successfully managed with Teflon interposition, alternative techniques have been developed with the objective to alleviate vascular compression symptoms indefinitely, including transposition using biological glue,4 vascular clips,5,6 and a variety of "sling" techniques.7 In Video 1, we demonstrate a fenestrated clip transposition technique in the treatment of trigeminal neuralgia. We present the case of a 72-year-old female who presented with classic trigeminal neuralgia pain along the V2 and V3 distributions. Magnetic resonance imaging revealed evident compression of the trigeminal nerve by the superior cerebellar artery (SCA). A retrosigmoid craniotomy was performed, and the vascular loop of the SCA was visualized compressing the root entry zone with significant indentation of the trigeminal nerve. Wide arachnoid dissection along the SCA was carried out in order to mobilize the SCA away from the nerve. A small slit was created in the undersurface of the tentorium, and then the SCA loop was transposed to the tentorium using a fenestrated aneurysm clip. The postoperative course was uneventful, and the patient had complete resolution of her facial pain at 6-month follow-up. This method is likely an effective and durable method of decompression for trigeminal neuralgia.

Prediction of Outcomes for Ruptured Aneurysm Surgery.

Background and Purpose- Predicting long-term functional outcomes after intracranial aneurysmal rupture can be challenging. We developed and validated a scoring system-the Southwestern Aneurysm Severity Index-that would predict functional outcomes at 1 year after clipping of ruptured aneurysms. Methods- Ruptured aneurysms treated microsurgically between 2000 and 2014 were included. Outcome was defined as Glasgow Outcome Score (ranging from 1, death, to 5, good recovery) at 1 year. The Southwestern Aneurysm Severity Index is composed of multiple prospectively recorded patient demographic, clinical, radiographic, and aneurysm-specific variables. Multivariable analyses were used to construct the best predictive models for patient outcomes in a random 50% of the cohort and validated in the remaining 50%. A scoring system was created using the best model. Results- We identified 527 eligible patients. The Glasgow Outcome Score at 1 year was 4 to 5 in 375 patients (71.2%). In the multivariable logistic regression, the best predictive model for unfavorable outcome included intracerebral hemorrhage (odds ratio [OR], 2.53; 95% CI, 1.55-4.13), aneurysmal size ≥20 mm (OR, 6.07; 95% CI, 1.92-19.2), intraventricular hemorrhage (OR, 2.56; 95% CI, 1.15-5.67), age >64 (OR, 3.53; 95% CI, 1.70-7.35), location (OR, 1.82; 95% CI, 1.10-3.03), and hydrocephalus (OR, 2.39; 95% CI, 1.07-5.35). The Southwestern Aneurysm Severity Index predicts Glasgow Outcome Score at 1 year with good discrimination (area under the receiver operating characteristic curve, derivation: 0.816, 95% CI, 0.759-0.873; validation: 0.803, 95% CI, 0.746-0.861) and accurate calibration ( R2=0.939). Conclusions- The Southwestern Aneurysm Severity Index has been internally validated to predict 1 year Glasgow Outcome Scores at initial presentation, thus optimizing patient or family counseling and possibly guiding therapeutic efforts.

Delayed treatment of ruptured brain AVMs: is it ok to wait?

OBJECTIVE Despite a hemorrhagic presentation, many patients with arteriovenous malformations (AVMs) do not require emergency resection. The timing of definitive management is not standardized in the cerebrovascular community. This study was designed to evaluate the safety of delaying AVM treatment in clinically stable patients with a new hemorrhagic presentation. The authors examined the rate of rehemorrhage or neurological decline in a cohort of patients with ruptured brain AVMs during a period of time posthemorrhage. METHODS Patients presenting to the authors' institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion criteria were ruptured AVMs that required emergency surgery involving resection of the AVM, prior treatment of AVM at another institution, or treatment of lesions within 4 weeks for other reasons (subacute surgery). The primary outcome measure was time from initial hemorrhage to treatment failure (defined as rehemorrhage or neurological decline as a direct result of the AVM). Patient-days were calculated from the day of initial rupture until the day AVM treatment was initiated or treatment failed. RESULTS Of 102 ruptured AVMs in 102 patients meeting inclusion criteria, 7 (6.9%) failed the treatment paradigm. Six patients (5.8%) had a new hemorrhage within a median of 248 days (interquartile range 33-1364 days). The total "at risk" period was 18,740 patient-days, yielding a rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve (11.8%) of 102 patients were found to have an associated aneurysm. In this group there was a single (8.3%) new hemorrhage during a total at-risk period of 263 patient-days until the aneurysm was secured, yielding a rehemorrhage risk of 11.4% per patient-month. CONCLUSIONS It is the authors' practice to rehabilitate patients after brain AVM rupture with a plan for elective treatment of the AVM. The present data are useful in that the findings quantify the risk of the authors' treatment strategy. These findings indicate that delaying intervention for at least 4 weeks after the initial hemorrhage subjects the patient to a low (< 1%) risk of rehemorrhage. The authors modified the treatment paradigm when a high-risk feature, such as an associated intracranial aneurysm, was identified.

The 2016 AANS Presidential Address: Leading the way.

This AANS presidential address focuses on enduring values of the neurosurgical profession that transcend the current political climate. The address was delivered by Dr. Batjer during a US presidential election year, but the authors have intentionally avoided discussing the current chaos of the American health care system in the knowledge that many pressing issues will change depending on the outcome of the 2016 elections. Instead, they have chosen to focus on clarifying what neurosurgeons, and the American Association of Neurological Surgeons, in particular, stand for; identifying important challenges to these fundamental principles and values; and proposing specific actions to address these challenges. The authors cite "de-professionalism" and commoditization of medicine as foremost among the threats that confront medicine and surgery today and suggest concrete action that can be taken to reverse these trends as well as steps that can be taken to address other significant challenges. They emphasize the importance of embracing exceptionalism and never compromising the standards that have characterized the profession of neurosurgery since its inception.

Microsurgical Treatment of Previously Coiled Intracranial Aneurysms: Systematic Review of the Literature.

OBJECTIVE: To assess indications, complications, clinical outcomes, and technical nuances of microsurgical treatment of previously coiled intracranial aneurysms. METHODS: A systematic review of the literature was performed using PubMed/MEDLINE and EMBASE databases from January 1990 to December 2013. English-language articles reporting on microsurgical treatment of previously coiled intracranial aneurysms were included. Articles that involved embolization materials other than coils were excluded. Data on aneurysm characteristics, indications for surgery, techniques, complications, angiographic obliteration rates, and clinical outcomes were collected. RESULTS: The literature review identified 29 articles reporting on microsurgical clipping of 375 previously coiled aneurysms. Of the aneurysms, 68% were small (<10 mm). Indications for clipping included the presence of a neck remnant (48%) and new aneurysmal growth (45%). Rebleeding before clipping was reported in 6% of cases. Coil extraction was performed in 13% of cases. The median time from initial coiling to clipping was 7 months. The angiographic cure rate was 93%, with morbidity and mortality of 9.8% and 3.6%, respectively. CONCLUSIONS: Microsurgical clipping of previously coiled aneurysms can result in high obliteration rates with relatively low morbidity and mortality in select cases. Considerations for microsurgical strategies include the presence of sufficient aneurysmal tissue for clip placement and the potential need for temporary occlusion or flow arrest. Coil extraction is not needed in most cases.

Resident away rotations allow adaptive neurosurgical training.

Subspecialization of physicians and regional centers concentrate the volume of certain rare cases into fewer hospitals. Consequently, the primary institution of a neurological surgery training program may not have sufficient case volume to meet the current Residency Review Committee case minimum requirements in some areas. To ensure the competency of graduating residents through a comprehensive neurosurgical education, programs may need for residents to travel to outside institutions for exposure to cases that are either less common or more regionally focused. We sought to evaluate off-site rotations to better understand the changing demographics and needs of resident education. This would also allow prospective monitoring of modifications to the neurosurgery training landscape. We completed a survey of neurosurgery program directors and query of data from the Accreditation Council of Graduate Medical Education to characterize the current use of away rotations in neurosurgical education of residents. We found that 20% of programs have mandatory away rotations, most commonly for exposure to pediatric, functional, peripheral nerve, or trauma cases. Most of these rotations are done during postgraduate year 3 to 6, lasting 1 to 15 months. Twenty-six programs have 2 to 3 participating sites and 41 have 4 to 6 sites distinct from the host program. Programs frequently offset potential financial harm to residents rotating at a distant site by support of housing and transportation costs. As medical systems experience fluctuating treatment paradigms and demographics, over time, more residency programs may adapt to meet the Accreditation Council of Graduate Medical Education case minimum requirements through the implementation of away rotations.

Advances and innovations in brain arteriovenous malformation surgery.

Arteriovenous malformations (AVMs) of the brain are very complex and intriguing pathologies. Since their initial description by Luschka and Virchow in the middle of the 19th century, multiple advances and innovations have revolutionized their management and surgical treatment. Here, we review the historical landmarks in the surgical treatment of AVMs and then illustrate the most recent and futuristic technologies aiming to improve outcomes in AVM surgeries. In particular, we examine potential advances in patient selection, imaging, surgical technique, neuroanesthesia, and postoperative neuro-rehabilitation and quantitative assessments. Finally, we illustrate how concurrent advances in radiosurgery and endovascular techniques might present new opportunities to treat AVMs more safely from a surgical perspective.

Intracranial aneurysms in previously irradiated fields: literature review and case report.

OBJECTIVE: Radiotherapy is a common treatment for a variety of disease processes in the central nervous system; it has an ever-increasing number of indications and applications. With the life expectancy of cancer patients increasing, delayed complications of radiation have become more apparent. One such potential complication is the appearance of intracranial aneurysms in the irradiated field. The incidence and natural history of these aneurysms is not well understood. To this end, we performed a review of the literature to analyze the current state of knowledge of these rare aneurysms. Furthermore, we present a case treated at our center. METHODS: We reviewed the literature for all reported cases of intracranial aneurysms appearing in an irradiated field, including any available histopathologic analysis. All papers were included irrespective of the language in which it was published. We calculated the mean age at radiation exposure, the interval between radiation exposure, and aneurysm development and the rate of presentation. Herein we also present a case of an intracranial aneurysm in a 38-year-old patient detected in an irradiation field 33 years after the patient underwent craniospinal irradiation for a medulloblastoma. RESULTS: A total of 46 patients with 69 intracranial aneurysms in irradiation fields were reported between 1978 and 2013. The mean age at radiation exposure was 34 years, and the mean lag time between exposure and diagnosis was 12 years (range, 4 months to 50 years). The median lag time between exposure and diagnosis was shorter in patients older than 40 (6 years). Among the reported aneurysms, 83% were saccular, 9% were fusiform, and 9% were considered pseudo-aneurysms. The Median lag time was 20 years for brachytherapy, 8 years for focused radiation, 9 years for whole brain radiation, and 6 years for SRS. Among reported aneurysms, 55% presented with some form of hemorrhage: intracranial rupture with subarachnoid hemorrhage, epistaxis, or otorrhagia. Only 13% were discovered on routine follow-up or were found incidentally for work-up of unrelated neurologic symptoms. CONCLUSION: Although rarely reported, intracranial aneurysms in irradiation fields may warrant special attention when diagnosed. These aneurysms may have an inherently weaker structure and may be more prone to rupture. Their repair may also be complicated by more fragile and irregular morphology. The increasing longevity of cancer patients suggests that screening for aneurysms at irradiation sites may be warranted, but further studies are needed to validate this approach.

Pharyngo-occipital artery variant arising from the internal carotid artery impacting surgical technique during carotid endarterectomy.

BACKGROUND AND IMPORTANCE: Extracranial carotid artery atherosclerotic stenosis typically occurs at the junction of the common carotid, external carotid and internal carotid arteries. Although rare, anatomical arterial variants can influence surgical strategy and can have a significant impact on surgical complications and patient outcome. An unusual case of atherosclerotic stenosis of the internal carotid artery (ICA) at the origin of a pharyngo-occipital variant off of the ICA is reported here. CLINICAL PRESENTATION: A 60-year-old man presented with symptomatic severe left cervical ICA stenosis. The stenosis was related to the origin of the pharyngo-occipital common trunk which arose from the ICA rather than the typical origin off of the external carotid artery. The patient underwent successful left carotid endarterectomy with special attention to this variant anatomy. CONCLUSION: Anomalies of the extracranial ICA, although rare, can influence the location of atherosclerotic disease and the surgical endarterectomy strategy. A detailed anatomical study should be performed prior to surgery to minimize risk and improve patient outcome.

Brainstem cavernous malformations: 1390 surgical cases from the literature.

OBJECTIVE: Although surgical resection of brainstem cavernous malformations (CM) has been reviewed, numerous large surgical series have been recently reported. METHODS: Eighteen new surgical series with 710 patients were found via a PubMed search, in addition to our previous meta-analysis. Complete excision, complications, and long-term outcome results were compiled across these series. They were then compared and subsequently combined with those of our previous report. RESULTS: We combined results of 68 surgical series with 1390 patients, incorporating results from our previous meta-analysis. Across 61 series, 1178 of 1291 (91%) CMs were completely excised. Of 105 partially resected CMs with ample follow-up, 65 rebled (62%). Across 46 series providing information on early neurologic morbidity, the overall rate was 45%. Specifically, 12% of patients required tracheostomy and/or gastrostomy procedures. Overall long-term condition was improved in 62% of patients across 51 series. Across 60 series, overall long-term condition was improved or the same in 84% of patients, with worsening in the remaining 16%. The overall surgical and/or cavernoma related mortality rate for all 1390 patients was 1.5%. Notably, these results did not differ significantly between our initial review and the combined data from the subsequent 18 surgical series recently reported in the literature. CONCLUSION: Surgical resection of brainstem CM continues to present a considerable challenge with resultant morbidity akin to another CM hemorrhage. We therefore prefer to offer surgery only to patients with at least one previous hemorrhage with CM pial representation. Appropriate patient counseling about expected early morbidity and the potential for long-term worsening is crucial.

Management of brainstem cavernous malformations.

OPINION STATEMENT: The risk of hemorrhage from brainstem cavernous malformations (BSCMs) ranges between 2.33 % and 4.1 % per patient-year across natural history studies and between 2.68 % and 6.8 % per patient-year across surgical series. The recurrent hemorrhage rate from BSCMs ranges between 5 % and 60 % per patient-year. Asymptomatic BSCMs tend to have a benign course, whereas symptomatic lesions often have a more aggressive course and carry an increasing risk of hemorrhage with subsequent bleeds. Hemorrhagic presentation, female gender, family history, and associating venous anomalies have been correlated with an increased risk of hemorrhage from BSCMs. MRI is the diagnostic imaging method of choice for the detection of CMs. Preoperative T1-weighted MRI can help assess the proximity of the lesion to the pial or ependymal surface of the brainstem and is thus essential to operative planning. Fluid attenuated inversion recovery (FLAIR) sequences can detect inflammatory activity and perilesional gliosis and may therefore correlate with an increased biological activity in the CM. This might help predict the aggressiveness of these lesions and their clinical activity. Due to the potential risks of surgery, conservative management with close follow-up should be the primary treatment option for patients with BSCMs. At least two clinically significant hemorrhagic episodes and an anatomical pial representation of the lesion are required before considering surgical intervention as an option because of the potential irreversible neurological damage to the patient. Life-threatening bleeds and rapidly progressive neurological deterioration are also potential indications for surgery. Complete removal of BSCMs when feasible is crucial to the prevention of future hemorrhage from BSCMs. An intraoperative ultrasound and a post-operative MRI can be used to rule out any unnoticed residual lesion. Minimizing the risk of surgery can be achieved by undergoing a case-based selection of the optimal surgical approach that allows for easy access to the lesion with minimal manipulation of normal neural tissues. Preserving any associated venous anomaly during surgery is crucial in order to avoid any undesirable hemorrhagic infarction. Advanced imaging techniques, such as diffusion tensor imaging integrated with intra-operative neuronavigation MRI, can be used to determine the anatomical relation between BSCM and the surrounding eloquent structures. Radiosurgery is not considered an effective treatment option for BSCMs. It is reserved only for extremely biologically aggressive lesions that cannot be accessed surgically.