Intracranial pressure (ICP) monitoring is a staple of neurocritical care. The most commonly used current methods of monitoring in the acute setting include fluid-based systems, implantable transducers and Doppler ultrasonography. It is well established that management of elevated ICP is critical for clinical outcomes. However, numerous studies show that current methods of ICP monitoring cannot reliably define the limit of the brain’s intrinsic compensatory capacity to manage increases in pressure, which would allow for proactive ICP management. Current work in the field hopes to address this gap by harnessing live-streaming ICP pressure-wave data and a multimodal integration with other physiologic measures. Additionally, there is continued development of non-invasive ICP monitoring methods for use in specific clinical scenarios.

The successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan–Meier techniques. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval (P < 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 (P < 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; P < 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; P < 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a “real-life” MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. Cancer Immunol Res; 6(9); 1039–45. ©2018 AACR.

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

OBJECTIVE: Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy was recently approved for use in the treatment of medication-refractory essential tremor (ET). Previous work has described lesion appearance and volume on MRI up to 6 months after treatment. Here, the authors report on the volumetric segmentation of the thalamotomy lesion and associated edema in the immediate postoperative period and 1 year following treatment, and relate these radiographic characteristics with clinical outcome. METHODS: Seven patients with medication-refractory ET underwent MRgFUS thalamotomy at Brigham and Women’s Hospital and were monitored clinically for 1 year posttreatment. Treatment effect was measured using the Clinical Rating Scale for Tremor (CRST). MRI was performed immediately postoperatively, 24 hours posttreatment, and at 1 year. Lesion location and the volumes of the necrotic core (zone I) and surrounding edema (cytotoxic, zone II; vasogenic, zone III) were measured on thin-slice T2-weighted images using Slicer 3D software. RESULTS: Patients had significant improvement in overall CRST scores (baseline 51.4 ± 10.8 to 24.9 ± 11.0 at 1 year, p = 0.001). The most common adverse events (AEs) in the 1-month posttreatment period were transient gait disturbance (6 patients) and paresthesia (3 patients). The center of zone I immediately posttreatment was 5.61 ± 0.9 mm anterior to the posterior commissure, 14.6 ± 0.8 mm lateral to midline, and 11.0 ± 0.5 mm lateral to the border of the third ventricle on the anterior commissure–posterior commissure plane. Zone I, II, and III volumes immediately posttreatment were 0.01 ± 0.01, 0.05 ± 0.02, and 0.33 ± 0.21 cm ³ , respectively. These volumes increased significantly over the first 24 hours following surgery. The edema did not spread evenly, with more notable expansion in the superoinferior and lateral directions. The spread of edema inferiorly was associated with the incidence of gait disturbance. At 1 year, the remaining lesion location and size were comparable to those of zone I immediately posttreatment. Zone volumes were not associated with clinical efficacy in a statistically significant way. CONCLUSIONS: MRgFUS thalamotomy demonstrates sustained clinical efficacy at 1 year for the treatment of medication-refractory ET. This technology can create accurate, predictable, and small-volume lesions that are stable over time. Instances of AEs are transient and are associated with the pattern of perilesional edema expansion. Additional analysis of a larger MRgFUS thalamotomy cohort could provide more information to maximize clinical effect and reduce the rate of long-lasting AEs.

Purpose: The integrated histopathologic and molecular diagnoses of the 2016 WHO classification of central nervous system tumors have revolutionized patient care by improving diagnostic accuracy and reproducibility; however, the frequency and consequences of misclassification of histologically diagnosed diffuse gliomas are unknown. Experimental Design: Patients with newly diagnosed ICD-O-3 (International Classification of Diseases) histologically encoded diffuse gliomas from 2010–2015 were identified from the National Cancer Database, the misclassification rates and overall survival (OS) of which were assessed by WHO grade and 1p/19q status. In addition, misclassification rates by isocitrate dehydrogenase (IDH), ATRX, and p53 statuses were examined in an analogous multi-institutional cohort of registry-encoded diffuse gliomas. Results: Of 74,718 patients with diffuse glioma, only 74.4% and 78.8% of molecularly characterized WHO grade II and III oligodendrogliomas were in fact 1p/19q-codeleted. In addition, 28.9% and 36.8% of histologically encoded grade II and III “oligoastrocytomas”, and 6.3% and 8.8% of grade II and III astrocytomas had 1p/19q-codeletion, thus molecularly representing oligodendrogliomas if also IDH mutant. OS significantly depended on accurate WHO grading and 1p/19q status. Conclusions: On the basis of 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically encoded oligodendrogliomas, astrocytomas, and glioblastomas are approximately 21%–35%, 6%–9%, and 9%, respectively; with significant clinical implications. Our findings suggest that when compared with historical histology-only classified data, in national registry, as well as, institutional databases, there is the potential for false-positive results in contemporary trials of molecularly classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Critically, findings from diffuse glioma clinical trials and historical cohorts using prior histology-only WHO schemes must be cautiously reinterpreted.