Pre- and Intraoperative Management of Brainstem Lesions

Brainstem cavernous malformation (BSCM) is a typical brainstem pathology that can lead to significant neurological morbidity. Before making a surgical decision for a patient with BSCM, it is essential to balance the surgery against the natural history of BSCM since individualized risk assessment is crucial for a comprehensive understanding of the natural course of conservatively treated BSCMs (Chapter 2). In patients with symptomatic and accessible BSCMs, surgery is recommended, however, in some deep-seated locations, surgery is more controversial because of the relatively high morbidity and mortality rates. Therefore, the timing of the surgical option still needs further investigation (Chapter 3). For the surgical treatment in patients with BSCMs, although many safe entry zones (SEZs) into the brainstem have been proposed, it is still debatable on some of them (Chapter 4). Intraoperative direct stimulation is a promising technique in brain surgeries involving eloquent areas. It has been reported to assist in preserving the motor tracts during the resection of (sub)cortical lesions. However, it is sparsely explored for mapping and monitoring the corticospinal tract in brainstem surgery (Chapter 5). In this thesis, we have investigated safe brainstem surgery from two aspects - preoperative evaluation and intraoperative direct stimulation. The results promote a better understanding of the hemorrhage rate in untreated BSCM before surgical recommendation and help on the timing of surgical decision-making. In addition, this thesis sheds light on the limitation of SEZs in surgical planning for patients with BSCM and the clinical value of direct stimulation for monitoring and mapping of the corticospinal tract during brainstem surgery. These findings contribute to safe surgical planning and lesion resection for brainstem pathologies, especially for the BSCMs

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

A review of neurophysiological mapping procedures of the brain and spinal cord

Surgical procedures of the brain and spine that require manipulation of, and near nervous structures, require unique considerations in their approach. Over the past 100 years, techniques have been developed and refined for localization of specific structures allowing for safer, more accurate interventions. These include the pre-operative use of Electroencephalography (EEG) in combination with radiographical imaging and intraoperative neurophysiological techniques rooted in electrophysiology. Since the introduction of EEG and electrical cortical stimulation, physicians have had the tools to diagnose neurological conditions while also being able to complete surgical interventions with a level of safety. By the 1920’s and 1930’s, the efforts of Hans Berger and Frederic and Erna Gibbs to develop and utilize EEG led to accurate pre-operative diagnoses of epilepsy along with their associated foci. Within that same time, the efforts of Wilder Penfield to develop and implement electrical cortical stimulation in awake patients during neurosurgery led to broad understandings of the organization and function of regions of the brain. Both EEG and cortical stimulation in combination quicky became useful beyond research in mapping the regions of the brain and led to rapid improvements in the accuracy of epilepsy surgery. Over preceding decades, these techniques continued to evolve with the latest research and technology. Additionally, their utilization has expanded from epilepsy surgery to resection for neoplasms of the central nervous system. In contemporary surgery, EEG and cortical stimulation still serve as the backbone of mapping techniques, but novel techniques are continually explored and improve patient outcomes. These advances include modern intraoperative neurophysiological monitoring, improved stimulation techniques, and additional utilization beyond the brain. This review highlights the conceptual underpinning of electrical neurophysiological mapping techniques as well as their implementation and future considerations. The review covers the pre-operative mapping of the brain using EEG, intraoperative mapping of the brain using cortical and subcortical mapping, and spinal cord mapping of the dorsal column and anterolateral tracts. The techniques and theory of each are summarized along with discussions on implementation and efficacy. Additional emphasis is placed on the need for standardization of their use to improve patient outcomes and recommendations for future research and development

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review

Purpose: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. Methods: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. Results: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). Conclusions: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity

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

Interactive Diffusion Tensor Tractography Visualization for Neurosurgical Planning

BACKGROUND: Diffusion tensor imaging (DTI) infers the trajectory and location of large white matter tracts by measuring the anisotropic diffusion of water. DTI data may then be analyzed and presented as tractography for visualization of the tracts in 3 dimensions. Despite the important information contained in tractography images, usefulness for neurosurgical planning has been limited by the inability to define which are critical structures within the mass of demonstrated fibers and to clarify their relationship to the tumor. OBJECTIVE: To develop a method to allow the interactive querying of tractography data sets for surgical planning and to provide a working software package for the research community. METHODS: The tool was implemented within an open source software project. Echo-planar DTI at 3 T was performed on 5 patients, followed by tensor calculation. Software was developed that allowed the placement of a dynamic seed point for local selection of fibers and for fiber display around a segmented structure, both with tunable parameters. A neurosurgeon was trained in the use of software in < 1 hour and used it to review cases. RESULTS: Tracts near tumor and critical structures were interactively visualized in 3 dimensions to determine spatial relationships to lesion. Tracts were selected using 3 methods: anatomical and functional magnetic resonance imaging-defined regions of interest, distance from the segmented tumor volume, and dynamic seed-point spheres. CONCLUSION: Interactive tractography successfully enabled inspection of white matter structures that were in proximity to lesions, critical structures, and functional cortical areas, allowing the surgeon to explore the relationships between them

Combined brain language connectivity and intraoperative neurophysiologic techniques in awake craniotomy for eloquent-area brain tumor resection

Speech processing can be disturbed by primary brain tumors (PBT). Improvement of presurgical planning techniques decrease neurological morbidity associated to tumor resection during awake craniotomy. The aims of this work were: 1. To perform Diffusion Kurtosis Imaging based tractography (DKI-tract) in the detection of brain tracts involved in language; 2. To investigate which factors contribute to functional magnetic resonance imaging (fMRI) maps in predicting eloquent language regional reorganization; 3. To determine the technical aspects of accelerometric (ACC) recording of speech during surgery. DKI-tracts were streamlined using a 1.5T magnetic resonance scanner. Number of tracts and fiber pathways were compared between DKI and standard Diffusion Tensor Imaging (DTI) in healthy subjects (HS) and PBT patients. fMRI data were acquired using task-specific and resting-state paradigms during language and motor tasks. After testing intraoperative fMRI’s influence on direct cortical stimulation (DCS) number of stimuli, graph-theory measures were extracted and analyzed. Regarding speech recording, ACC signals were recorded after evaluating neck positions and filter bandwidths. To test this method, language disturbances were recorded in patients with dysphonia and after applying DCS in the inferior frontal gyrus. In contrast, HS reaction time was recorded during speech execution. DKI-tract showed increased number of arcuate fascicle tracts in PBT patients. Lower spurious tracts were identified with DKI-tract. Intraoperative fMRI and DCS showed similar stimuli in comparison with DCS alone. Increased local centrality accompanied language ipsilateral and contralateral reorganization. ACC recordings showed minor artifact contamination when placed at the suprasternal notch using a 20-200 Hz filter bandwidth. Patients with dysphonia showed decreased amplitude and frequency in comparison with HS. ACC detected an additional 11% disturbances after DCS, and a shortening of latency within the presence of a loud stimuli during speech execution. This work improved current knowledge on presurgical planning techniques based on brain structural and functional neuroimaging connectivity, and speech recordingA função linguística do ser humano pode ser afetada pela presença de tumores cerebrais (TC) A melhoria de técnicas de planeamento pré-cirurgico diminui a morbilidade neurológica iatrogénica associada ao seu tratamento cirúrgico. O objetivo deste trabalho é: 1. Testar a fiabilidade da tractografia estimada por difusor de kurtose (tract-DKI), dos feixes cerebrais envolvidos na linguagem 2. Identificar os fatores que contribuem para o mapeamento linguagem por ressonância magnética funcional (RMf) na predição da neuroplasticidade. 3. Identificar aspetos técnicos do registo da linguagem por accelerometria (ACC). A DKI-tract foi estimada após realização de RM cerebral com 1.5T. O número e percurso das fibras foi avaliado. A RMf foi adquirida durante realização de tarefas linguísticas, motoras, e em repouso. Foi testada influência dos mapas de ativação calculados por RMf, no número de estímulos realizados durante a estimulação direta cortical (EDC) intraoperatória. Medidas de conectividade foram extraídas de regiões cerebrais. A posição e filtragem de sinal ACC foram estudadas após vocalização de palavras. O sinal ACC obtido em voluntários foi comparado com doentes disfónicos, após estimulação do giro inferior frontal, e após a adição de um estímulo sonoro perturbador durante vocalização. A tract-DKI estimou um elevado número de fascículos do feixe arcuato com menos falsos negativos. Os mapas linguísticos de RMf intraoperatória, não influenciou a EDC. Medidas de centralidade aumentaram após neuroplasticidade ipsilateral e contralateral. A posição supraesternal e a filtragem de sinal ACC entre 20-200Hz demonstrou menor ruido de contaminação. Este método identificou diminuição de frequência e amplitude em doentes com disfonia, 11% de erros linguísticos adicionais após estimulação e diminuição do tempo de latência quando presente o sinal sonoro perturbador. Este trabalho promoveu a utilização de novas técnicas no planeamento pré-cirúrgico do doente com tumor cerebral e alterações da linguagem através do estudo de conectividade estrutural, funcional e registo da linguagem

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)