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As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.

BACKGROUND The diagnosis of glioblastoma (GBM) in infants aged ≤ 1 year is extremely rare, and its comparability to the more common adult diagnosis is underexplored. Correspondingly, the objective of this study was to interrogate a national cancer database to elucidate the typical survival and clinical profile of this demographic. METHODS All GBM patients aged ≤ 1 year in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 86 patients satisfied criteria for entry into study, making up 0.08% of all GBM diagnoses in the database. There were 32 (37%) females and 54 (63%) males. Irrespective of treatment, median OS was 67.3 months (95% CI, 46-91), which was distinct from all other ages and pediatric age groups. There were 74 (86%) treated by surgery, 51 (59%) treated by chemotherapy, and 17 (20%) treated by radiation therapy. Multivariable analysis demonstrated that Hispanic status (HR = 3.41, P = 0.02) and the presence of comorbidity (HR = 3.24, P = 0.01) independently predicted shorter OS, whereas treatment with chemotherapy (HR = 0.18, P

Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health Organization (WHO) Grades 2 or 3. The rarity of these tumors in adults has left a number of clinical management questions open. Correspondingly, the aim of this study was to aggregate a large PPTID cohort with sufficient statistical power from a large national cancer database to analyze prognostic parameters. All PPTID patients aged over 18 years in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized and survival was modeled using Kaplan–Meier and Cox regression analyses. A total of 103 adult PPTID patients were identified in the NCDB with 63 (61%) WHO Grade 2 and 40 (39%) WHO Grade 3 tumors. Overall, mean age was 53 ± 18 years with even gender distribution. A total of 75 (73%) patients underwent surgical resection for diagnosis, with gross total resection (GTR) was the most common resection outcome in 50/75 (67%). Chemotherapy was utilized in 18 (17%) patients, and radiation therapy in 37 (36%) patients. Overall, 5-year survival rate was estimated to be 54% (95% CI 42–64%), with mean survival was 84 (95% CI 69–99) months. Patients with Grade 2 tumors survived statistically longer than Grade 3 tumor counterparts (P

There exists no consensus in the literature regarding the impact of pre-stereotactic radiosurgery (SRS) embolization on obliteration rates and clinical outcome after radiosurgery treatment of intracranial arteriovenous malformations (AVM). We performed a systematic review of four databases and included studies with at least 10 patients evaluating obliteration rates of intracranial AVMs treated with SRS alone (SRS cohort) and combined pre-SRS embolization followed by SRS (E + SRS cohort). Meta-analytic results were pooled together via random-effects models. A total of 43 studies, with 7103 patients, were included in our analysis. Among our included patients, complete obliteration was achieved in 51.5% (964/1871) of patients in the E + SRS cohort as compared to 61.5% (3217/5231) of patients in the SRS cohort. Meta-analysis of the pooled data revealed that obliteration was significantly lower in the E + SRS cohort (pooled OR = 0.64, 95% CI = 0.54-0.75, p 0.0001). The use of pre-SRS embolization was significantly associated with lower AVM obliteration rates when compared to treatment with SRS alone. Our analysis seeks to provide a macroscopic insight into the complex interaction between pre-SRS embolization and brain AVM obliteration rates and prognosis. Pre-SRS embolization may still be beneficial in select patients, and further studies are needed to identify patients who benefit from neoadjuvant AVM embolization.

Intracranial mixed vascular malformations (MVMs) are defined as any combination of a developmental venous anomaly (DVA), cerebral cavernous malformation (CCM), capillary telangiectasia (CTG), or arteriovenous malformation (AVM) within a single, contiguous lesion. However, most MVMs described in the literature contain only 2 pathologically discrete malformations; juxtaposition of 3 or more abnormalities in a single lesion remains exceedingly rare. We present the case of a 19-month-old female with new onset focal seizures and a 4-cm right basal ganglia lesion initially believed to be an embryonal neoplasm. She subsequently underwent gross total resection (GTR) of the lesion via a transsylvian-transinsular approach. Intraoperatively, the lesion appeared to be heterogenous and highly vascular, with areas of purplish-gray friable tissue. Pathology confirmed the lesion to be a MVM containing a CCM, CTG, and a DVA. This appears to be the first reported case of such a lesion confirmed on pathology in the literature.

Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors. With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0–1 years in group 1, 1–2 years in group 2, and 2–3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.

Magnetic resonance-guided laser interstitial thermal therapy (LITT) has been increasingly used to treat a number of intracranial pathologies, though its use in the posterior fossa has been limited to a few small series. We performed a multi-institutional review of targets in the posterior fossa, reporting the efficacy and safety profile associated with laser ablation in this region of the brain. A retrospective review of patients undergoing LITT in the posterior fossa was performed from August 2010 to March 2020. Patient demographic information was collected alongside the operative parameters and patient outcomes. Reported outcomes included local control of the lesion, postoperative complications, hospital length of stay, and steroid requirements. 58 patients across four institutions underwent LITT in the posterior fossa for 60 tumors. The median pre-ablation tumor volume was 2.24 cm3. 48 patients (50 tumors) were available for follow-up. An 84% (42/50) overall local control rate was achieved at 9.5 months median follow up. There were two procedural complications, including insertional hemorrhage and laser misplacement and 12/58 (21%) patients developed new neurological deficits. There was one procedure related death. The median length of hospital stay was 1 day, with 20.7% of patients requiring discharge to a rehabilitation facility. LITT is an effective approach for treating pathology in the posterior fossa. The average target size is smaller than what has been reported in the supratentorial space. Care must be taken to prevent injury to surrounding structures given the close proximity of critical structures in this region.

Lesions located in subcortical areas are difficult to safely access. Tubular retractors have been increasingly used successfully with low complication profile to access lesions by minimizing brain retraction trauma and distributing pressure radially. Both binocular operative microscope and monocular exoscope are utilized for lesion visualization through tubular retractors. We present the largest multi-surgeon, multi-institutional series to determine the efficacy and safety profile of a transcortical-transtubular approach for intracranial lesion resections with both microscopic and exoscopic visualization. We reviewed a multi-surgeon, multi-institutional case series including transcortical-transtubular resection of intracranial lesions using either BrainPath (NICO, Indianapolis, Indiana) or ViewSite Brain Access System (VBAS, Vycor Medical, Boca Raton, Florida) tubular retractors (n = 113). One hundred thirteen transtubular resections for intracranial lesions were performed. Patients presented with a diverse number of pathologies including 25 cavernous hemangiomas (21.2%), 15 colloid cysts (13.3%), 26 GBM (23.0%), two meningiomas (1.8%), 27 metastases (23.9%), 9 gliomas (7.9%) and 9 other lesions (7.9%). Mean lesion depth below the cortical surface was 4.4 cm, and mean lesion size was 2.7 cm. A gross total resection was achieved in 81 (71.7%) cases. Permanent complication rate was 4.4%. One patient (0.8%) experienced one early postoperative seizure ( 1 week follow-up). Mean post-operative hospitalization length was 4.1 days. Tubular retractors provide a minimally invasive operative corridor for resection of intracranial lesions. They provide an effective tool in the neurosurgical armamentarium to resect subcortical lesions with a low complication profile.

The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from Kaplan–Meier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.

Although non-enhancing lesions suspicious for glioma are usually assumed to be low grade glioma (LGG), some high grade glioma (HGG) do not enhance, which may lead to a delay in biopsy and/or resection, diagnosis, and treatment initiation. Thus, there is a clear need for a large-sample study that quantifies the rate of malignant, non-enhancing gliomas. We retrospectively reviewed our series of 561 consecutive surgically treated gliomas with tissue diagnosis, 111 of which were non-enhancing, to determine the prevalence of high-grade histology in radiographically presumed LGG. Relative expression of tumor markers were also reported for non-enhancing lesions to investigate genetic correlates. We identified 561 surgically treated gliomas with tissue diagnosis from August 2012 to July 2018 and found that 111 patients (19.8%) demonstrated non-enhancing lesions suspicious for glioma on preoperative MRI. Thirty-one (27.9%) of the non-enhancing lesions were classified as HGGs (WHO Grade III or IV). Non-enhancing lesions were four times more likely to be HGG in patients older than 60 years than patients younger than 35 years (41.2% vs. 11.4%, Pearson Chi2 p

Hair-sparing techniques in cranial neurosurgery have gained traction in recent years and previous studies have shown no difference in infection rates, yet limited data exists evaluating the specific closure techniques utilized during hair-sparing craniotomies. Therefore, it was the intention of this study to evaluate the rate of surgical site infections (SSIs) and perioperative complications associated with using an absorbable intradermal barbed suture for skin closure in hair-sparing supratentorial craniotomies for tumor in order to prove non-inferiority to traditional methods. A retrospective review of supratentorial craniotomies for tumor by a single surgeon from 2011 to 2017 was performed. All perioperative adverse events and wound complications, defined as a postoperative infection, wound dehiscence, or CSF leak, were compared between three different groups: (1) hair shaving craniotomies + transdermal polypropylene suture/staples for scalp closure, (2) hair-sparing craniotomies + transdermal polypropylene suture/staples for scalp closure, and (3) hair-sparing craniotomies + absorbable intradermal barbed suture for scalp closure. Two hundred sixty-three patients underwent hair shaving + transdermal polypropylene suture/staples, 83 underwent hair sparing + transdermal polypropylene suture/staples, and 100 underwent hair sparing + absorbable intradermal barbed suture. Overall, 2.9% of patients experienced a perioperative complication and 4.3% developed a wound complication. In multivariable analysis, the use of a barbed suture for scalp closure and hair-sparing techniques was not predictive of any complication or 30-day readmission. Furthermore, the absorbable intradermal barbed suture cohort had the lowest overall rate of wound complications (4%). Hair-sparing techniques using absorbable intradermal barbed suture for scalp closure are safe and do not result in higher rates of infection, readmission, or reoperation when compared with traditional methods.

Most data evaluating the relationship of post-mechanical thrombectomy (MT) blood pressure (BP) management and outcomes of patients with large vessel occlusion (LVO) focus on early BP control within the first 24 h. We investigated the correlation of daily BP trends up to the third day following MT with patient outcomes. We retrospectively reviewed our prospectively maintained database for LVO patients treated with MT from February 2015 to December 2017. Recorded BP values for 72 h post-reperfusion were reviewed. Daily peak systolic and diastolic blood pressures (SBP, DBP) were extracted for each day post-procedure. The association and importance between BP increments of 10 mmHg and mortality, hemorrhage, and functional independence (FI = mRS ≤ 2) was analyzed in a multivariable logistic regression and random forest (RF) analyses modeling. A total of 212 thrombectomies were included. An increase in peak 24-h SBP was independently associated with higher likelihood of symptomatic hemorrhage (OR 1.2, p = 0.048) and decreased functional independence (OR 0.85, p = 0.03). Higher day 2 and day 3 peak SBP was strongly correlated with decreased functional independence and higher mortality. Third day SBP