Rapid Tumor DNA Analysis of Cerebrospinal Fluid Accelerates Treatment of Central Nervous System Lymphoma.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

Preoperative assessment of eloquence in neurosurgery: a systematic review.

BACKGROUND AND OBJECTIVES: Tumor location and eloquence are two crucial preoperative factors when deciding on the optimal treatment choice in glioma management. Consensus is currently lacking regarding the preoperative assessment and definition of eloquent areas. This systematic review aims to evaluate the existing definitions and assessment methods of eloquent areas that are used in current clinical practice. METHODS: A computer-aided search of Embase, Medline (OvidSP), and Google Scholar was performed to identify relevant studies. This review includes articles describing preoperative definitions of eloquence in the study's Methods section. These definitions were compared and categorized by anatomical structure. Additionally, various techniques to preoperatively assess tumor eloquence were extracted, along with their benefits, drawbacks and ease of use. RESULTS: This review covers 98 articles including 12,714 participants. Evaluation of these studies indicated considerable variability in defining eloquence. Categorization of these definitions yielded a list of 32 brain regions that were considered eloquent. The most commonly used methods to preoperatively determine tumor eloquence were anatomical classification systems and structural MRI, followed by DTI-FT, functional MRI and nTMS. CONCLUSIONS: There were major differences in the definitions and assessment methods of eloquence, and none of them proved to be satisfactory to express eloquence as an objective, quantifiable, preoperative factor to use in glioma decision making. Therefore, we propose the development of a novel, objective, reliable, preoperative classification system to assess eloquence. This should in the future aid neurosurgeons in their preoperative decision making to facilitate personalized treatment paradigms and to improve surgical outcomes.

Safe surgery for glioblastoma: Recent advances and modern challenges.

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts.

The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study.

INTRODUCTION: The main surgical dilemma during glioma resections is the surgeon's inability to accurately identify eloquent areas when the patient is under general anaesthesia without mapping techniques. Intraoperative stimulation mapping (ISM) techniques can be used to maximise extent of resection in eloquent areas yet simultaneously minimise the risk of postoperative neurological deficits. ISM has been widely implemented for low-grade glioma resections backed with ample scientific evidence, but this is not yet the case for high-grade glioma (HGG) resections. Therefore, ISM could thus be of important value in HGG surgery to improve both surgical and clinical outcomes. METHODS AND ANALYSIS: This study is an international, multicenter, prospective three-arm cohort study of observational nature. Consecutive HGG patients will be operated with awake mapping, asleep mapping or no mapping with a 1:1:1 ratio. Primary endpoints are: (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery and (2) residual tumour volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: (1) overall survival and (2) progression-free survival at 12 months after surgery; (3) oncofunctional outcome and (4) frequency and severity of serious adverse events in each arm. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID number NCT04708171 (PROGRAM-study), NCT03861299 (SAFE-trial).

Reflections on the contributions of Harvey Cushing to the surgery of peripheral nerves.

By the time Harvey Cushing entered medical school, nerve reconstruction techniques had been developed, but peripheral nerve surgery was still in its infancy. As an assistant surgical resident influenced by Dr. William Halsted, Cushing wrote a series of reports on the use of cocaine for nerve blocks. Following his residency training and a hiatus to further his clinical interests and intellectual curiosity, he traveled to Europe and met with a variety of surgeons, physiologists, and scientists, who likely laid the groundwork for Cushing's increased interest in peripheral nerve surgery. Returning to The Johns Hopkins Hospital in 1901, he began documenting these surgeries. Patient records preserved at Yale's Cushing Brain Tumor Registry describe Cushing's repair of ulnar and radial nerves, as well as his exploration of the brachial plexus for nerve repair or reconstruction. The authors reviewed Harvey Cushing's cases and provide 3 case illustrations not previously reported by Cushing involving neurolysis, nerve repair, and neurotization. Additionally, Cushing's experience with facial nerve neurotization is reviewed. The history, physical examination, and operative notes shed light on Cushing's diagnosis, strategy, technique, and hence, his surgery on peripheral nerve injury. These contributions complement others he made to surgery of the peripheral nervous system dealing with nerve pain, entrapment, and tumor.