Bilateral STA-MCA bypass for Moyamoya angiopathy associated with severe erythrodermic psoriasis.

OBJECTIVE: We report on the uncommon association between severe erythrodermic psoriasis and moyamoya angiopathy (MMA), a progressive cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis. Concomitant moyamoya and severe erythrodermic psoriasis is a rare pathology, with unknown pathogenesis. MMA with severe erythrodermic psoriasis, even in the setting of stroke, is often managed with non-curative medical intervention alone, due to concerns for surgical instability. Here we show with appropriate surgical consideration and medical management, patients can undergo curative surgical management, and remain stroke free during follow-up. CASE REPORT: The patient, a 52-year-old female, with refractory psoriasis, presented with neurological deficits, leading to the diagnosis of bilateral moyamoya arteriopathy. Patients with these co-existing conditions have historically only been medially managed, due to concerns for surgical instability and inadequate candidacy. A comprehensive stroke workup revealed severe stenosis in the internal carotid arteries. A two-stage surgical revascularization, including right superficial temporal artery-middle cerebral artery (STA-MCA) bypass and subsequent left STA-MCA bypass, was successfully performed. Postoperatively, the patient experienced a severe psoriasis flare, requiring meticulous management to ensure post-operative surgical stability. CONCLUSIONS: With appropriate medical and surgical management, the patient was amenable for curative surgical intervention. The successful surgical intervention, following medical optimization of psoriasis, demonstrated efficacy in preventing future cerebral ischemia events in this challenging patient.

Impact of surgeon rhBMP-2 cost awareness on complication rates and health system costs for spinal arthrodesis.

OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used in spinal arthrodesis procedures to enhance bony fusion. Research has suggested that it is the most cost-effective fusion enhancer, but there are significant upfront costs for the healthcare system. The primary objective of this study was to determine whether intraoperative dosing and corresponding costs changed with surgeon cost awareness. The secondary objective was to describe surgical complications before and after surgeon awareness of rhBMP-2 cost. METHODS: A retrospective medical record review was conducted to identify patients who underwent spinal arthrodesis procedures performed by a single surgeon, supplemented with rhBMP-2, from June 2016 to June 2018. Collected data included rhBMP-2 dosage, rhBMP-2 list price, and surgical complications. Expected Medicare reimbursement was calculated. Data were analyzed before and after surgeon awareness of rhBMP-2 cost. RESULTS: Forty-eight procedures were performed using rhBMP-2, 16 before and 32 after surgeon cost awareness. Prior to cost awareness, the most frequent rhBMP-2 dosage level was x-small (38.9%, n = 7), followed by large (27.8%, n = 5) and small (22.2%, n = 4). After cost awareness, the most frequent rhBMP-2 dosage was xx-small (56.8%, n = 21), followed by x-small (21.6%, n = 8) and large (13.5%, n = 5). The rhBMP-2 average cost per surgery was $4116.56 prior to surgeon cost awareness versus $2268.38 after. Two complications were observed in the pre-cost awareness surgical group; 2 complications were observed in the post-cost awareness surgical group. CONCLUSIONS: Surgeon awareness of rhBMP-2 cost resulted in use of smaller rhBMP-2 doses, decreased rhBMP-2 cost per surgery, and decreased overall hospital admission charges, without a detectable increase in surgical complications.

Cellular allograft for multilevel stand-alone anterior cervical discectomy and fusion.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the most common treatment for degenerative disease of the cervical spine. Given the high rate of pseudarthrosis in multilevel stand-alone ACDF, there is a need to explore the utility of novel grafting materials. In this study, the authors present a single-institution retrospective study of patients with multilevel degenerative spine disease who underwent multilevel stand-alone ACDF surgery with or without cellular allograft supplementation. METHODS: In a prospectively collected database, 28 patients who underwent multilevel ACDF supplemented with cellular allograft (ViviGen) and 25 patients who underwent multilevel ACDF with decellularized allograft between 2014 and 2020 were identified. The primary outcome was radiographic fusion determined by a 1-year follow-up CT scan. Secondary outcomes included change in Neck Disability Index (NDI) scores and change in visual analog scale scores for neck and arm pain. RESULTS: The study included 53 patients with a mean age of 53 ± 0.7 years who underwent multilevel stand-alone ACDF encompassing 2.6 ± 0.7 levels on average. Patient demographics were similar between the two cohorts. In the cellular allograft cohort, 2 patients experienced postoperative dysphagia that resolved by the 3-month follow-up. One patient developed cervical radiculopathy due to graft subsidence and required a posterior foraminotomy. At the 1-year CT, successful fusion was achieved in 92.9% (26/28) of patients who underwent ACDF supplemented with cellular allograft, compared with 84.0% (21/25) of patients who underwent ACDF without cellular allograft. The cellular allograft cohort experienced a significantly greater improvement in the mean postoperative NDI score (p < 0.05) compared with the other cohort. CONCLUSIONS: Cellular allograft is a low-morbidity bone allograft option for ACDF. In this study, the authors determined favorable arthrodesis rates and functional outcomes in a complex patient cohort following multilevel stand-alone ACDF supplemented with cellular allograft.

Prognostic Value of Hemorrhagic Brainstem Injury on Early Computed Tomography: A TRACK-TBI Study.

BACKGROUND: Traumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied. METHODS: Patients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups. RESULTS: Mann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p = 0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p = 0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p = 0.01). CONCLUSIONS: These findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway.

The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.

Progress in diffuse intrinsic pontine glioma: advocating for stereotactic biopsy in the standard of care.

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brainstem tumor affecting approximately 300 children in the US annually. Median survival is less than 1 year, and radiation therapy has been the mainstay of treatment for decades. Recent advances in the biological understanding of the disease have identified the H3K27M mutation in nearly 80% of DIPGs, leading to the 2016 WHO classification of diffuse midline glioma H3K27M-mutant, a grade IV brainstem tumor. Developments in epigenetic targeting of transcriptional tendencies have yielded potential molecular targets for clinical trials. Chimeric antigen receptor T cell therapy has also shown preclinical promise. Recent clinical studies, including prospective trials, have demonstrated the safety and feasibility of pediatric brainstem biopsy in the setting of DIPG and other brainstem tumors. Given developments in the ability to analyze DIPG tumor tissue to deepen biological understanding of this disease and develop new therapies for treatment, together with the increased safety of stereotactic brainstem biopsy, the authors present a case for offering biopsy to all children with suspected DIPG. They also present their standard operative techniques for image-guided, frameless stereotactic biopsy.

Pediatric functional hemispherectomy: operative techniques and complication avoidance.

Functional hemispherectomy/hemispherotomy is a disconnection procedure for severe medically refractory epilepsy where the seizure foci diffusely localize to one hemisphere. It is an improvement on anatomical hemispherectomy and was first performed by Rasmussen in 1974. Less invasive surgical approaches and refinements have been made to improve seizure freedom and minimize surgical morbidity and complications. Key anatomical structures that are disconnected include the 1) internal capsule and corona radiata, 2) mesial temporal structures, 3) insula, 4) corpus callosum, 5) parietooccipital connection, and 6) frontobasal connection. A stepwise approach is indicated to ensure adequate disconnection and prevent seizure persistence or recurrence. In young pediatric patients, careful patient selection and modern surgical techniques have resulted in > 80% seizure freedom and very good functional outcome. In this report, the authors summarize the history of hemispherectomy and its development and present a graphical guide for this anatomically challenging procedure. The use of the osteoplastic flap to improve outcome and the management of hydrocephalus are discussed.

Laser interstitial thermal therapy for pediatric atypical teratoid/rhabdoid tumor: case report.

Herein, the authors describe the successful use of laser interstitial thermal therapy (LITT) for management of metastatic craniospinal disease for biopsy-proven atypical teratoid/rhabdoid tumor in a 16-month-old boy presenting to their care. Specifically, LITT was administered to lesions of the right insula and left caudate. The patient tolerated 2 stages of LITT to the aforementioned lesions without complication and with evidence of radiographic improvement of lesions at the 2- and 6-month follow-up appointments. To the authors' knowledge, this represents the first such published report of LITT for management of atypical teratoid/rhabdoid tumor.

Spontaneous regression of an idiopathic arteriovenous fistula of the right vertebral artery.

A previously healthy 53-year-old male presented with a 2-month history of pulsatile tinnitus, worsening headaches, and neck pain. Given the clinical symptoms, a workup was initiated to assess for a vascular etiology such as a dural arteriovenous fistula.

Glioblastoma stem cells and stem cell-targeting immunotherapies.

Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM.

Nanotechnology in bone tissue engineering.

Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. FROM THE CLINICAL EDITOR: Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field.

Ventricular endoscopy in the pediatric population: review of indications.

INTRODUCTION: Neuroendoscopy has greatly impacted pediatric neurosurgery over the past few decades. Improved optics and microsurgical tools have allowed neuroendoscopes to be used for a multitude of neurosurgical procedures. DISCUSSION: In this review article, we present the breadth of intraventricular neuroendoscopic procedures for the treatment of conditions ranging from hydrocephalus and brain tumors to congenital cysts and other pathologies. We critically discuss treatment indications and reported success rates for neuroendoscopic procedures. We also present novel approaches, technical nuances, and variations from recently published literature and as practiced in the authors' institution.

Endovascular management of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is characterized by formation of widespread thrombus within the cerebral venous sinus system. CVST can cause venous hypertension, venous infarcts, hemorrhage and seizures. It is managed in most cases with systemic anticoagulation through the use of heparin to resolve the thrombus. Patients that demonstrate clinical deterioration while on heparin are often treated with endovascular strategies to recanalize the sinuses. We present the case of a patient with widespread CVST, involving his superior sagittal sinuses and bilateral transverse sigmoid sinuses, who was treated with a combination of endovascular therapies. The video can be found here: http://youtu.be/w3wAGlT7h8c .

Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid.

OBJECT: In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. METHODS: Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. RESULTS: Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. CONCLUSIONS: Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.

Management of moyamoya disease: a review of current and future therapeutic strategies.

Moyamoya disease (MMD) is characterized by idiopathic, progressive stenosis of the circle of Willis and the terminal portion of the internal carotid arteries with the development of prominent small collateral vessels and a characteristic moyamoya or puff-of-smoke radiographic appearance. The incidence and prevalence of MMD varies by region, age, and sex, with higher rates in Asian and East Asian populations compared to North American or European populations. There is a bimodal distribution of patients diagnosed with MMD. Pediatric patients are more commonly diagnosed within the 1st decade of life, whereas adult patients present in the 5th or 6th decade of life. Overall, there is a nearly 2:1 female-to-male ratio. Ischemic symptoms are the most common presentation in pediatric and adult populations, but adult patients are nearly twice as likely to present with intracranial hemorrhage compared to their pediatric counterparts. Surgical revascularization is indicated in symptomatic cases, and antiplatelet therapy may be a useful adjunct to prevent recurrent symptoms. Direct and combined bypass procedures seem to be more effective in adults, whereas children respond well to indirect bypass. The identification of key genetic, molecular, and environmental factors including RNF213 and GUCY1A3 loss-of-function mutations, angiogenic growth factors, autoantibodies, CNS infections, and radiation exposure suggest multiple pathways for the development of moyamoya arteriopathy. Further research is needed to better understand the heterogeneity of pathogenetic mechanisms that lead to moyamoya and to identify novel therapeutic targets to prevent, stabilize, and treat MMD.

Combination endovascular and microsurgical treatment of partially thrombosed ruptured ICA terminus aneurysm, with common carotid artery to MCA bypass via saphenous vein graft and parent vessel sacrifice after coil embolization.

A 63-year-old woman presented with ruptured giant ICA terminus aneurysm, temporized with coil embolization and definitively treated with parent vessel sacrifice and high-flow bypass.

Ruptured traumatic pseudoaneurysm of the middle cerebral artery following minor trauma treated with an MCA-MCA bypass: A case report.

Background: Traumatic middle cerebral artery (MCA) pseudoaneurysms following minor head trauma are rare. Case Description: We report a case of a 76-year-old man who presented with a traumatic acute subdural hematoma and subarachnoid hemorrhage (SAH) from a ruptured distal right MCA pseudoaneurysm treated with evacuation of the hematoma, resection of the pseudoaneurysm, and an MCA-to-MCA bypass. Conclusion: Although traumatic pseudoaneurysms of the distal intracranial vessels are rare, patients with traumatic SAH would benefit from vascular imaging. Treatment of pseudoaneurysms of distal intracranial vessels may be treated with vessel occlusion or trapping/excision of aneurysm with revascularization.

Brain AVM surgery without endovascular embolization in a low to middle income country.

We treated a 20-year-old woman in Paraguay with a ruptured intraventricular Spetzler-Martin Grade 3 AVM, and illustrate microsurgical resection without embolization in this video.

Craniocervical dural arteriovenous fistula: Microsurgical clipping and technical nuances with ICG.

A 48-year-old male with progressive congestive myelopathy had a craniocvervical DAVF treated with surgical clipping using ICG to confirm solitary inflow.