Somatic Mosaicism in the Pathogenesis of de novo Cerebral Arteriovenous Malformations: A Paradigm Shift Implicating the RAS-MAPK Signaling Cascade.

Cerebral arteriovenous malformations (AVMs) are leading causes of lesional hemorrhagic stroke in both the pediatric and young adult population, with sporadic AVMs accounting for the majority of cases. Recent evidence has identified somatic mosaicism in key proximal components of the RAS-MAPK signaling cascade within endothelial cells collected from human sporadic cerebral AVMs, with early preclinical models supporting a potential causal role for these mutations in the pathogenesis of these malformations. Germline mutations that predispose to deregulation of the RAS-MAPK signaling axis have also been identified in hereditary vascular malformation syndromes, highlighting the key role of this signaling axis in global AVM development. Herein, we review the most recent genomic and preclinical evidence implicating somatic mosaicism in the RAS-MAPK signaling pathway in the pathogenesis of sporadic cerebral AVMs. Also, we review evidence for RAS-MAPK dysregulation in hereditary vascular malformation syndromes and present a hypothesis suggesting that this pathway is central for the development of both sporadic and syndrome-associated AVMs. Finally, we examine the clinical implications of these recent discoveries and highlight potential therapeutic targets within this signaling pathway.

Laser scanning confocal endomicroscopy in the neurosurgical operating room: a review and discussion of future applications.

Laser scanning confocal endomicroscopy (LSCE) is an emerging technology for examining brain neoplasms in vivo. While great advances have been made in macroscopic fluorescence in recent years, the ability to perform confocal microscopy in vivo expands the potential of fluorescent tumor labeling, can improve intraoperative tissue diagnosis, and provides real-time guidance for tumor resection intraoperatively. In this review, the authors highlight the technical aspects of confocal endomicroscopy and fluorophores relevant to the neurosurgeon, provide a comprehensive summary of LSCE in animal and human neurosurgical studies to date, and discuss the future directions and potential for LSCE in neurosurgery.

Label-free microscopic assessment of glioblastoma biopsy specimens prior to biobanking [corrected].

Glioblastoma is the most common primary brain tumor with a median 12- to 15-month patient survival. Improving patient survival involves better understanding the biological mechanisms of glioblastoma tumorigenesis and seeking targeted molecular therapies. Central to furthering these advances is the collection and storage of surgical biopsies (biobanking) for research. This paper addresses an imaging modality, confocal reflectance microscopy (CRM), for safely screening glioblastoma biopsy samples prior to biobanking to increase the quality of tissue provided for research and clinical trials. These data indicate that CRM can immediately identify cellularity of tissue biopsies from animal models of glioblastoma. When screening fresh human biopsy samples, CRM can differentiate a cellular glioblastoma biopsy from a necrotic biopsy without altering DNA, RNA, or protein expression of sampled tissue. These data illustrate CRM's potential for rapidly and safely screening clinical biopsy samples prior to biobanking, which demonstrates its potential as an effective screening technique that can improve the quality of tissue biobanked for patients with glioblastoma.

Efficacy of dural venous sinus stenting in treating idiopathic intracranial hypertension with acute vision loss.

INTRODUCTION: Dural venous sinus stenting (VSS) is an effective, durable treatment for patients with idiopathic intracranial hypertension (IIH) due to underlying venous sinus stenosis. However, the use of venous sinus stenting to treat IIH with acute vision loss has rarely been described. METHODS: A retrospective chart analysis identified patients who received VSS for fulminant IIH, defined as acute (< 8 weeks) visual field loss to within the central 5° and/or a decrease in visual acuity to less than or equal to 20/50 in either eye in the presence of papilledema. RESULTS: Ten patients were identified with average patient age of 31.0 years, and all except one were female. Mean body mass index was 41.2 kg/m2. All patients presented with vision loss and some with headache and tinnitus. The average trans-stenotic gradient pre-stenting was 28.7 mmHg (range 9-62 mmHg). All patients had diminished or resolved venous gradients immediately following the procedure. At mean follow-up of 60.5 weeks, 100% had improvements in papilledema, 80.0% had subjective vision improvement, 55.6% had headache improvement and 87.5% had tinnitus improvement. 90.0% had stable or improved visual acuity in both eyes with a mean post-stenting Snellen acuity of 20/30 and an average gain of 3 lines Snellen acuity post-stenting (95% confidence intervals 0.1185-0.4286, p = 0.0018). Two patients (20.0%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in patients presenting with IIH and acute vision loss with a fairly low complication rate and satisfactory clinical outcomes.

National trends in the surgical management of metastatic lung cancer to the spine using the national inpatient sample database from 2005 to 2014.

Optimal management of metastatic lung cancer to the spine (MLCS) incorporates a multidisciplinary approach. With improvements in lung cancer screening andnonsurgical treatment, the role for surgerymay be affected. The objective of this study is to assess trends in the surgical management of MLCS using the National Inpatient Sample (NIS) database. The NIS was queried for patients with MLCS who underwent surgery from 2005 to 2014. The frequencies of spinal decompression alone, spinal stabilization with or without (+/-) decompression, and vertebral augmentation were calculated. Statistical analysis was performed to analyze the effect of patient characteristics on outcomes. The most common procedure performed was vertebral augmentation (10719, 44.3%), followed by spinal stabilization +/- decompression (8634, 35.7%) and then decompression alone (4824, 20.0%). The total number of surgeries remained stable, while the rate of spinal stabilizations increased throughout the study period (p < 0.001). Invasive procedures such as stabilization and decompression were associated with greater costs, length of stay,complications and mortality. Increasingcomorbidity was associated with increased odds of complication, especially in patients undergoing more invasive procedures. In patients with lowpre-operative comorbidity, the type of procedure did not influence the odds of complication. Graded increases in length of stay, cost and mortality were seen with increasing complication rate.The rate of spinal stabilizations increased, which may be due to either increased early detection of disease facilitating use of outpatient vertebral augmentation procedures and/or the recognition that surgical decompression and stabilization are necessary for optimal outcome in the setting of MLCS with neurological deficit.

Current trends in incidence, characteristics, and surgical management of metastatic breast cancer to the spine: A National Inpatient Sample analysis from 2005 to 2014.

Management of metastatic breast cancer to the spine (MBCS) incorporates a multimodal approach. Improvement in screening and nonsurgical therapies may alter the trends in surgical management of MBCS. The objective of this study is to assess trends in surgical management of MBCS and short-term outcomes based on the National Inpatient Sample (NIS) database. The NIS database was queried for patients with MBCS who underwent surgery from 2005 to 2014. The weighted frequencies of spinal decompression alone, spinal stabilization +/- decompression, and vertebral augmentation were calculated. Multivariate analysis was performed to analyze the effect of patient characteristics on outcomes stratified by procedure. The most common procedure performed was vertebral augmentation (11,114, 53.4%), followed by stabilization +/- decompression (6,906, 33.2%) and then decompression alone (3,312, 13.4%). The total population-adjusted rate of surgical management for MBCS remained stable, while the rate of spinal stabilization increased (P < 0.001) and vertebral augmentation decreased (p < 0.003). The risk of complication increased with spinal stabilization and decompression compared to vertebral augmentation procedures in those with fewer comorbidities. This relative increase in risk abated in patients with higher numbers of pre-operative comorbidities. Any single complication was associated with increases in length of stay, cost, and mortality. The rate of in-hospital interventions remained stable over the study period. Stratified by procedure, the rate of stabilizations increased with a concomitant decrease in vertebral augmentations, which suggests that patients who require hospitalization for MBCS are becoming more likely to represent advanced cases that are not amenable to palliative vertebral augmentation procedures.

Factors associated with length of stay after single-level posterior thoracolumbar instrumented fusion primarily for degenerative spondylolisthesis.

BACKGROUND: The postoperative length of stay (LOS) is an important prognostic indicator for patients undergoing instrumented spinal fusion surgery. Increased LOS can be associated with higher infection rates, higher incidence of venous thromboembolisms, and a greater frequency of hospital-acquired delirium. The day of surgery and early postoperative mobilization following single-level posterior thoracolumbar stabilizations may impact the LOS. In this study, we evaluated the effects of weekday (Monday-Thursday) versus weekend (Friday-Sunday) surgery and postoperative rehabilitation services on LOS following primarily transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis (DS). METHODS: In this single-institution retrospective chart review, we identified 198 adults who received a one-level thoracolumbar instrumented fusion through a posterior only approach (2017-2019). The majority of these patients underwent TLIF for DS. A zero truncated negative binomial model was used for predictors of the primary outcome of LOS (weekday of surgery, duration of operation, first or repeat surgery, and physical therapy/ occupational therapy [PT/OT] evaluation). Covariates were sex, age, and body mass index. RESULTS: We found that operative duration, repeat surgery, and in-hospital PT/OT all significantly increased the LOS (P < 0.05). Furthermore, those undergoing weekday surgery (Monday-Thursday) had 1.29 times longer LOS than those on the weekend (Friday-Sunday), but this did not reach statistical significance (P = 0.09). CONCLUSION: In our patient sample, duration, repeat surgery, and in-hospital PT/OT increased the LOS following primarily TLIF for DS. The increased LOS in these cases is likely due to higher overall disease burden and case complexity. In addition, those patients with a greater likelihood of extended recovery and ongoing neurologic deficits are more likely to have PT/OT evaluations. Notably, LOS was not significantly impacted by the day of surgery at our institution.

Dural venous sinus stenting for treatment of pediatric idiopathic intracranial hypertension.

BACKGROUND: Dural venous sinus stenting (VSS) is an effective treatment for idiopathic intracranial hypertension (IIH) in adult patients. There are no published series to date evaluating safety and efficacy of VSS in pediatric patients. OBJECTIVE: To report on procedural device selection and technique as well as safety and efficacy of VSS for pediatric patients with medically refractory IIH due to underlying venous sinus stenosis. METHODS: A multi-institutional retrospective case series identified patients with medically refractory IIH aged less than 18 years who underwent VSS. RESULTS: 14 patients were identified at four participating centers. Patient ages ranged from 10 to 17 years, and 10 patients (71.4%) were female. Mean body mass index was 25.7 kg/m2 (range 15.8-34.6 kg/m2). Stenting was performed under general endotracheal anesthesia in all except two patients. The average trans-stenotic gradient during diagnostic venography was 10.6 mm Hg. Patients had stents placed in the superior sagittal sinus, transverse sinus, sigmoid sinus, occipital sinus, and a combination. Average follow-up was 1.7 years after stenting. Six patients out of 10 (60%) had reduced medication dosing, 12 of 14 patients (85.7%) had improvements in headaches, two patients (100%) with pre-stent tinnitus had resolution of symptoms, and four (80%) of five patients with papilledema had improvement on follow-up ophthalmological examinations. Two patients (14.3%) developed postprocedural groin hematomas, one patient (7.1%) developed a groin pseudoaneurysm, and one patient (7.1%) had postprocedural groin bleeding. No other procedural complications occurred. Four patients (28.6%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in a pediatric population with IIH and has a low complication rate and good clinical outcomes.

A Thoracic Surgeon Among Neurosurgeons: Edward Archibald's Forgotten Influence on the Professionalization of Neurosurgery.

Edward Archibald, Professor of Surgery at McGill University (1904-1945), Montreal, Canada, was the foremost thoracic surgeon of his generation. Although instrumental in establishing the American Board of Surgery and in standardizing surgical training, he was also influential as a neurosurgeon. Archibald, an early member invited by Harvey Cushing to join the Society of Neurological Surgeons, helped establish neurosurgery as a distinct, specialized discipline. We review Archibald's contributions to the development of neurosurgery in light of his encyclopedic 1908 monograph, "Surgical Affections and Wounds of the Head," which we compare and contrast to the contemporary treatise by Cushing in the same year. Through his writings and correspondence with Wilder Penfield and Cushing, we also describe his role in the creation of the Montreal Neurological Institute. Primary archival sources addressing the professional relationship between Archibald and Cushing and between Archibald and Penfield were consulted. Archibald's personal acquaintance with the principal neurosurgeons of the day, his insight into their personalities, their prominence in the field, and their career paths played a critical role in influencing Penfield to consider relocating to Montreal from Columbia University, despite tempting offers from Boston and Philadelphia. However, it was Archibald's support and mentorship for the creation of an academic center that finally convinced Penfield to move to McGill University. As one of the most influential surgeons of the early 20th century and a founding figure of modern neurosurgery, Archibald is an important part of neurosurgery's legacy.

Changes in the Operative Corridor in Oblique Lumbar Interbody Fusion Between Preoperative Magnetic Resonance Imaging and Intraoperative Cone-Beam Computed Tomography Using Morphometric Analysis.

Background The oblique lumbar interbody fusion or anterior-to-psoas (OLIF/ATP) technique relies on a corridor anterior to the psoas and posterior to the vasculature for lumbar interbody fusion. This is evaluated preoperatively with CT and/or MRI. To date, there have been no studies examining how intraoperative, lateral decubitus positioning may change the dimensions of this corridor when compared to preoperative imaging. Objective Our objective was to evaluate changes in the intraoperative corridor in the supine and lateral positions utilizing preoperative and intraoperative imaging. Methods We performed a retrospective analysis among patients who have undergone an OLIF/ATP approach at two tertiary care centers from 2016 to 2018 by measuring the distance between the left lateral border of the aorta or iliac vessels and anteromedial border of the psoas muscle from L1-L2 through L4-5 disc spaces. We compared this corridor between supine, preoperative MRI axial and intraoperative CT acquired in the right lateral decubitus position. Results Thirty-three patients, 15 of whom were female, were included in our study. The average age of the patients was 65.4 years and the average BMI was 31 kg/m2. The results revealed a statistically significant increase (p<.05) in the intraoperative corridor from supine to lateral decubitus positioning at all levels. However, age, BMI, and gender had no statistically significant impact on the preoperative versus intraoperative corridor. Conclusion This is the first study to provide objective evidence that lateral decubitus positioning increases the intraoperative corridor for OLIF/ATP. Our study demonstrates that lateral decubitus positioning provides a more favorable corridor for the OLIF/ATP technique from L1-L5 disc levels.