Safety and efficacy of brain biopsy: Results from a single institution retrospective cohort study.

Introduction: Brain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution. Materials and methods: This single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded. Results: Data from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error. Discussion and conclusion: This study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

Handling Severe Intraoperative Hemorrhage and Avoiding Iatrogenic Stroke During Brain Tumor Surgery: Techniques for Prevention of Hemorrhagic and Ischemic Complications.

BACKGROUND: Nationwide databases show that iatrogenic stroke and postoperative hematoma are among the commonest complications in brain tumor surgery, with a 10-year incidence of 16.3/1000 and 10.3/1000, respectively. However, techniques for handling severe intraoperative hemorrhage and dissecting, preserving, or selectively obliterating vessels traversing the tumor are sparse in the literature. METHODS: Records of the senior author's intraoperative techniques during severe haemorrhage and vessel preservation were reviewed and analyzed. Intraoperative media demonstrations of key techniques were collected and edited. In parallel, a literature search investigating technique description in handling severe intraoperative hemorrhage and vessel preservation in tumor surgery was undertaken. Histologic, anesthetic, and pharmacologic prerequisites of significant hemorrhagic complications and hemostasis were analyzed. RESULTS: The senior author's techniques for arterial and venous skeletonization, temporary clipping with cognitive or motor mapping, and ION monitoring were categorized. Vessels interfacing with tumor are labeled intraoperatively as supplying/draining the tumor, or traversing en passant, while supplying/draining functional neural tissue. Intraoperative techniques of differentiation were analyzed and illustrated. Literature search found 2 vascular-related complication domains in tumor surgery: perioperative management of excessively vascular intraparenchymal tumors and lack of intraoperative techniques and decision processes for dissecting and preserving vessels interfacing or traversing tumors. CONCLUSIONS: Literature searches showed a dearth of complication-avoidance techniques in tumor-related iatrogenic stroke, despite its high prevalence. A detailed preoperative and intraoperative decision process was provided along with a series of case illustrations and intraoperative videos showing the techniques required to reduce intraoperative stroke and associated morbidity addressing a void in complication avoidance of tumor surgery.

Practical, Stereotactic, Low-Profile Technique for Transcortical/Transventricular Colloid Cyst Removal Independent of Ventricular Size: Technical Note and Analysis of Approaches.

BACKGROUND: In the presence of a dilated foramen of Monro, a transcortical, transforaminal approach is considered the safest and simplest approach for resection of colloid cysts. However, in the presence of small or normal frontal horns, numerous microsurgical approaches and, often complicated, variations have been described, invariably employing forms of stereotactic navigation. OBJECTIVE: To report an alternative, accurate, microsurgical stereotactic low-profile technique. METHODS: The small frontal horn is stereotactically targeted as previously described. Routine equipment is used to accurately create a novel, rigid, atraumatic surgical corridor. RESULTS: After a 7-mm corticotomy, a peel-away catheter carrying the AxiEM stylet engages the target set as the frontal horn. All joints of the endoscope holder are locked, allowing only catheter advancement (y axis) while lateral (x axis) or anteroposterior (z axis) movements are secure. Two, 7-mm retractor blades are inserted. The extremely consistent anatomy of the foramen of Monro allows en bloc microsurgical removal without unnecessary coagulation of cyst wall or choroid plexus. CONCLUSION: Despite a plethora of approaches to the rostral third ventricle, in the presence of normal or small frontal horns, including creation of transcallosal/interforniceal, suprachoroidal (or transchoroidal), and sub-choroidal, colloid cyst resection does not necessarily need to be convoluted. Technical nuances of an accurate, practical, minimally invasive technique are described.

Intraoperative stimulation mapping of thalamocortical tracts in asleep and awake settings: novel electrophysiological, anatomical, and tractographic paradigms.

OBJECTIVE: Despite the disabling deficits of motor apraxia and sensory ataxia resulting from intraoperative injury of the superior thalamocortical tracts (TCTs), region-specific electrophysiological localization is currently lacking. Herein, the authors describe a novel TCT mapping paradigm. METHODS: Three patients, 1 asleep and 2 awake, underwent glioma resection affecting primarily the somatosensory cortex and underlying TCT. Stimulation was performed at the median, ulnar, and posterior tibial nerves. Parameters comprised single anodal pulses (duration 200-500 µsec, 2.1-4.7 Hz) with a current ranging from 10 to 25 mA. Recordings were captured with a bipolar stimulation probe, avoiding the classic collision technique. Positive localization sites were used to tractographically reconstruct the TCT in the third case. RESULTS: Employing one electrophysiological paradigm, the TCT was localized subcortically in all 3 cases by using a bipolar probe, peak range of 19.6-29.2 msec, trough of 23.3-34.8 msec, stimulation range of 10-25 mA. In the last case, tractographic reconstruction of the TCT validated a highly accurate TCT localization within a specific region of the posterior limb of the internal capsule. CONCLUSIONS: The authors describe the first electrophysiological technique for intraoperative localization and protection of the TCT in both asleep and awake craniotomies with tractographic validation, while avoiding the collision paradigm. None of the above paradigms have been previously reported. More data are required to further validate this technique.

Discriminators of pseudoprogression and true progression in high-grade gliomas: A systematic review and meta-analysis.

High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91-0.95]) and DSC-MRI (AUC = 0.93 [0.90-0.95]), compared to DCE-MRI (AUC = 0.90 [0.87-0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Early repeat resection for residual glioblastoma: decision-making among an international cohort of neurosurgeons.

OBJECTIVE: The importance of extent of resection (EOR) in glioblastoma (GBM) has been thoroughly demonstrated. However, few studies have explored the practices and benefits of early repeat resection (ERR) when residual tumor deemed resectable is unintentionally left after an initial resection, and the survival benefit of ERR is still unknown. Herein, the authors aimed to internationally survey current practices regarding ERR and to analyze differences based on geographic location and practice setting. METHODS: The authors distributed a survey to the American Association of Neurological Surgeons and Congress of Neurological Surgeons Tumor Section, Society of British Neurological Surgeons, European Association of Neurosurgical Society, and Latin American Federation of Neurosurgical Societies. Neurosurgeons responded to questions about their training, practice setting, and current ERR practices. They also reported the EOR threshold below which they would pursue ERR and their likelihood of performing ERR using a Likert scale of 1-5 (5 being the most likely) in two sets of 5 cases, the first set for a patient's initial hospitalization and the second for a referred patient who had undergone resection elsewhere. The resection likelihood index for each respondent was calculated as the mean Likert score across all cases. RESULTS: Overall, 180 neurosurgeons from 25 countries responded to the survey. Neurosurgeons performed ERRs very rarely in their practices (< 1% of all GBM cases), with an EOR threshold of 80.2% (75%-95%). When presented with 10 cases, the case context (initial hospitalization vs referred patient) did not significantly change the surgeon ERR likelihood, although ERR likelihood did vary significantly on the basis of tumor location (p < 0.0001). Latin American neurosurgeons were more likely to pursue ERR in the provided cases. Neurosurgeons were more likely to pursue ERR when the tumor was MGMT methylated versus unmethylated, with a resection likelihood index of 3.78 and 3.21, respectively (p = 0.004); however, there was no significant difference between IDH mutant and IDH wild-type tumors. CONCLUSIONS: Results of this survey reveal current practices regarding ERR, but they also demonstrate the variability in how neurosurgeons approach ERR. Standardized guidelines based on future studies incorporating tumor molecular characteristics are needed to guide neurosurgeons in their decision-making on this complicated issue.

Resection of Ependymomas Infiltrating the Fourth Ventricular Floor: Anatomosurgical and Stimulation Mapping Techniques.

BACKGROUND: Despite the importance of complete, gross total resection (GTR) of fourth ventricular ependymomas, significant morbidity and/or subtotal resections are reported, particularly when the ventricular floor is infiltrated. Step-by-step technique descriptions are lacking in the literature. OBJECTIVE: To describe monitoring and stimulation mapping techniques and surgical nuances in the challenging subgroup of infiltrating fourth ventricular ependymomas by a highly illustrated, step-by-step description. Superimposed outlines of cranial nerve nuclei on the surgical field demonstrate critical anatomy and facilitate understanding in a way not previously presented. METHODS: We reviewed the microanatomical and neurophysiological prerequisites of resecting a diffusively infiltrating fourth ventricular ependymoma. RESULTS: We achieved GTR with the use of reproducible stimulating mapping and accurate cranial nerve nuclei identification. CONCLUSION: Enhanced microanatomical understanding, reproducible stimulation mapping, and meticulous resection techniques can result in GTR, even in diffusively infiltrating ependymomas.

Converting sounds to meaning with ventral semantic language networks: integration of interdisciplinary data on brain connectivity, direct electrical stimulation and clinical disconnection syndromes.

Numerous traditional linguistic theories propose that semantic language pathways convert sounds to meaningful concepts, generating interpretations ranging from simple object descriptions to communicating complex, analytical thinking. Although the dual-stream model of Hickok and Poeppel is widely employed, proposing a dorsal stream, mapping speech sounds to articulatory/phonological networks, and a ventral stream, mapping speech sounds to semantic representations, other language models have been proposed. Indeed, despite seemingly congruent models of semantic language pathways, research outputs from varied specialisms contain only partially congruent data, secondary to the diversity of applied disciplines, ranging from fibre dissection, tract tracing, and functional neuroimaging to neuropsychiatry, stroke neurology, and intraoperative direct electrical stimulation. The current review presents a comprehensive, interdisciplinary synthesis of the ventral, semantic connectivity pathways consisting of the uncinate, middle longitudinal, inferior longitudinal, and inferior fronto-occipital fasciculi, with special reference to areas of controversies or consensus. This is achieved by describing, for each tract, historical concept evolution, terminations, lateralisation, and segmentation models. Clinical implications are presented in three forms: (a) functional considerations derived from normal subject investigations, (b) outputs of direct electrical stimulation during awake brain surgery, and (c) results of disconnection syndromes following disease-related lesioning. The current review unifies interpretation of related specialisms and serves as a framework/thinking model for additional research on language data acquisition and integration.

CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing.

PURPOSE: Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. METHODS: Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2µT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted. RESULTS: IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). CONCLUSIONS: CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.

Pineal region tumours in the sitting position: how I do it.

BACKGROUND: Pineal region tumours remain challenging neurosurgical pathologies. METHODS: Detailed anatomical knowledge of the posterior incisural space and its variations is critical. An opaque arachnoidal membrane seals the internal cerebral and basal veins, leading to thalamic, basal ganglia, mesencephalic/pontine infarctions if injured. Medium-size tumours can be removed en-bloc with all traction/manipulation applied on the tumour side, virtually without contact of ependymal surfaces of the pulvinars or third ventricle. Sacrifice of the cerebello-mesencephalic fissure vein may be required. CONCLUSIONS: The sitting position offers superior anatomical orientation and remains safe with experienced teams. Meticulous microsurgical techniques and detailed anatomical knowledge are likely to secure safe outcomes.

Reforming support systems of newly diagnosed brain cancer patients: a systematic review.

PURPOSE: Despite the increasing incidence of currently incurable brain cancer, limited resources are placed in patients' support systems, with reactive utilisation late in the disease course, when physical and psychological symptoms have peaked. Based on patient-derived data and emphasis on service improvement, this review investigated the structure and efficacy of the support methods of newly diagnosed brain cancer patients in healthcare systems. METHODS: This systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. Articles from PubMed, Embase, and CENTRAL databases were screened with six pre-established eligibility criteria, including assessment within 6 months from diagnosis of a primary malignant brain tumour. Risk of bias was evaluated using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program (CASP) Qualitative Studies Checklist. RESULTS: Of 5057 original articles, 14 were eligible for qualitative synthesis. Four studies were cross-sectional and ten were descriptive. Information given to patients was evaluated in seven studies, communication with patients in nine, and patient participation in treatment decisions in eight. Risk of bias was low in ten studies, moderate in two, and high in two. CONCLUSIONS: Techniques promoting individualised care increased perceived support, despite poor patient-physician communication and complexity of the healthcare system. Extracted data across 14 included studies informed a set of guidelines and a four-step framework. These can help evaluate and reform healthcare services to better accommodate the supportive needs of this patient group.

Systematic review-Time to malignant transformation in low-grade gliomas: Predicting a catastrophic event with clinical, neuroimaging, and molecular markers.

BACKGROUND: Despite an initially indolent course, all WHO grade II, LGGs inevitably transform to malignant, WHO grades III and IV, without current curative options. Malignant transformation (MT) remains unpredictable with limited prognostic markers to steer timing of interventions. The aim of this study was to review and assign predictive value to specific clinical, molecular, and radiological markers impacting MT, thereby justifying timely therapeutic interventions. METHODS: Searches of MEDLINE, Embase, and Cochrane databases were conducted from inception to April 28, 2021 and outputs were analysed in accordance with PRISMA protocol. RESULTS: From an initial 5,032 articles, 33 articles were included, totalling 5672 patients. Forty-three prognostic factors were registered to significantly impact MT. These were categorised as 7 clinical; 14 neuroimaging; 8 biological/molecular; 3 volumetric; 5 topological; 3 histological; and 3 treatment-related. Following analysis, 10 factors were highlighted: the pre-operative prognosticators were 1. presentation with epileptic seizures; 2. VDE > 8 mm/y; 3. VDE > 4 mm/y; 4. rCBV > 1.75; 5. PTV ≥ 5 cm (65 ml); 6. PTV ≥ 100 ml; and 7. cortical involvement. The post-operative prognosticators were: (1) IDH-wt, (2) TP53 mutation, and (3) temozolomide monotherapy. CONCLUSIONS: The management of LGGs remains controversial, as conservative and invasive treatment may be associated with MT and impaired quality of life, respectively. Our review indicates that MT can be predicted by specific metrics in VDE, PTV, and rCBV, alongside cortical involvement. Additionally, patients with IDH-wt tumours TP53 mutations, or receiving TMZ monotherapy are more likely to undergo MT. Our data may form the basis of a predictive scoring system.

Genomic Prognosticators and Extent of Resection in Molecularly Subtyped World Health Organization Grade II and III Gliomas-A Single-Institution, Nine-Year Data.

BACKGROUND: World Health Organization (WHO) grade II and III isocitrate dehydrogenase wild-type (IDH-wt) gliomas are often treated as WHO grade IV glioblastomas. However, cumulative evidence indicates that IDH mutation status alone is insufficient in predicting survival. The current study examines molecular and clinical markers to further prognostically stratify WHO grade II and III gliomas, in particular, IDH-wt. METHODS: A single institution's records were retrospectively reviewed for molecularly stratified WHO grade II and grade III gliomas over a 9-year period (2010-2019). Clinical data, IDH1/IDH2 status, EGFR amplification, and other molecular markers were recorded and correlated to the study outcomes. These outcomes were defined as progression-free survival (PFS), overall survival (OS), and time to malignant progression (TtMP). RESULTS: A total of 167 and 42 WHO grade II and III gliomas, respectively, were identified, totaling 209 cases with 157 IDH1/2 mutated and 52 IDH-wt tumors. The presence of IDH1/2 mutation was associated with longer OS (P < 0.0001) and PFS (P < 0.0001) but not with TtMP (P = 0.314). Lack of EGFR amplification, younger age, and greater extent of resection (EOR) (≥80%) were identified as independent, favorable OS prognostic factors. In the IDH-wt cohort, multivariate analysis indicated that older age (P = 0.003) and lesser EOR (<80%) (P = 0.007) are associated with worse OS. In addition, EGFR amplification showed a trend toward shorter OS in the IDH-wt cohort (P = 0.073). CONCLUSIONS: IDH1/2 mutation favors longer OS and PFS but does not protect from malignant progression. Lack of EGFR amplification, younger age and greater EOR are favorable OS prognosticators. In the IDH-wt cohort, older age and lesser EOR were linked to worse OS.

Mapping and anatomo-surgical techniques for SMA-cingulum-corpus callosum gliomas; how I do it.

BACKGROUND: Awake brain mapping paradigms are variable, particularly in SMA, and not personalised to each patient. In addition, subpial resections do not offer full protection to vascular injury, as the pia can be easily violated. METHODS: Mapping paradigms developed by a multidisciplinary brain mapping team. During resection, a combined subpial/interhemispheric approach allowed early identification and arterial skeletonization. Precise anatomo-surgical dissection of the affected cingulum and corpus callosum was achieved. CONCLUSIONS: In SMA-cingulum-CC tumours, a combined subpial/interhemispheric approach reduces risk of vascular injury allowing precise anatomo-surgical dissections. Knowledge of cognitive functions of affected parcels is likely to offer best outcomes.

Experience with awake throughout craniotomy in tumour surgery: technique and outcomes of a prospective, consecutive case series with patient perception data.

BACKGROUND: Awake craniotomy is the standard of care in surgery of tumours located in eloquent parts of the brain. However, high variability is recorded in multiple parameters, including anaesthetic techniques, mapping paradigms and technology adjuncts. The current study is focused primarily on patients' level of consciousness, surgical technique, and experience based on a cohort of 50 consecutive cases undergoing awake throughout craniotomy (ATC). METHODS: Data was collected prospectively for 46 patients undergoing 50 operations over 14-month period, by the senior author, including demographics, extent of resection (EOR), adverse intraoperative events, surgical morbidity, surgery duration, levels of O2 saturation and brain oedema. A prospective, patient experience questionnaire was delivered to 38 patients. RESULTS: The ATC technique was well tolerated in all patients. Once TCI stopped, all patients were immediately assessable for mapping. Despite > 75% of cases being considered inoperable/high risk, gross total resection (GTR) was achieved in 68% patients and subtotal resection in 20%. The average duration of surgery was 220 min with no episodes of hypoxia. Early and late severe deficits recorded in 12% and 2%, respectively. No stimulation-induced seizures or failed ATCs were recorded. Patient-recorded data showed absent/minimal pain during (1) clamp placement in 95.6% of patients; (2) drilling in 94.7% of patients; (3) surgery in 78.9% of patients. Post-operatively, 92.3% of patients reported willingness to repeat the ATC, if necessary. CONCLUSIONS: The current ATC paradigm allows immediate brain mapping, maximising patient comfort during self-positioning. Despite the cohort of challenging tumour location, satisfactory EOR was achieved with acceptable morbidity and no adverse intraoperative events.