Bayesian networks for Risk Assessment and postoperative deficit prediction in intraoperative neurophysiology for brain surgery.

PURPOSE: To this day there is no consensus regarding evidence of usefulness of Intraoperative Neurophysiological Monitoring (IONM). Randomized controlled trials have not been performed in the past mainly because of difficulties in recruitment control subjects. In this study, we propose the use of Bayesian Networks to assess evidence in IONM. METHODS: Single center retrospective study from January 2020 to January 2022. Patients admitted for cranial neurosurgery with intraoperative neuromonitoring were enrolled. We built a Bayesian Network with utility calculation using expert domain knowledge based on logistic regression as potential causal inference between events in surgery that could lead to central nervous system injury and postoperative neurological function. RESULTS: A total of 267 patients were included in the study: 198 (73.9%) underwent neuro-oncology surgery and 69 (26.1%) neurovascular surgery. 50.7% of patients were female while 49.3% were male. Using the Bayesian Network´s original state probabilities, we found that among patients who presented with a reversible signal change that was acted upon, 59% of patients would wake up with no new neurological deficits, 33% with a transitory deficit and 8% with a permanent deficit. If the signal change was permanent, in 16% of the patients the deficit would be transitory and in 51% it would be permanent. 33% of patients would wake up with no new postoperative deficit. Our network also shows that utility increases when corrective actions are taken to revert a signal change. CONCLUSIONS: Bayesian Networks are an effective way to audit clinical practice within IONM. We have found that IONM warnings can serve to prevent neurological deficits in patients, especially when corrective surgical action is taken to attempt to revert signals changes back to baseline properties. We show that Bayesian Networks could be used as a mathematical tool to calculate the utility of conducting IONM, which could save costs in healthcare when performed.

Transcranial Magnetic Stimulation-Based Machine Learning Prediction of Tumor Grading in Motor-Eloquent Gliomas.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a well-established preoperative mapping tool for motor-eloquent glioma surgery. Machine learning (ML) and nTMS may improve clinical outcome prediction and histological correlation. METHODS: This was a retrospective cohort study of patients who underwent surgery for motor-eloquent gliomas between 2018 and 2022. Ten healthy subjects were included. Preoperative nTMS-derived variables were collected: resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr)-abnormal if above 10%-and cortical excitability score-number of abnormal iRMTrs. World Health Organization (WHO) grade and molecular profile were collected to characterize each tumor. ML models were fitted to the data after statistical feature selection to predict tumor grade. RESULTS: A total of 177 patients were recruited: WHO grade 2-32 patients, WHO grade 3-65 patients, and WHO grade 4-80 patients. For the upper limb, abnormal iRMTr were identified in 22.7% of WHO grade 2, 62.5% of WHO grade 3, and 75.4% of WHO grade 4 patients. For the lower limb, iRMTr was abnormal in 23.1% of WHO grade 2, 67.6% of WHO grade 3%, and 63.6% of WHO grade 4 patients. Cortical excitability score (P = .04) was statistically significantly related with WHO grading. Using these variables as predictors, the ML model had an accuracy of 0.57 to predict WHO grade 4 lesions. In subgroup analysis of high-grade gliomas vs low-grade gliomas, the accuracy for high-grade gliomas prediction increased to 0.83. The inclusion of molecular data into the model-IDH mutation and 1p19q codeletion status-increases the accuracy of the model in predicting tumor grading (0.95 and 0.74, respectively). CONCLUSION: ML algorithms based on nTMS-derived interhemispheric excitability assessment provide accurate predictions of HGGs affecting the motor pathway. Their accuracy is further increased when molecular data are fitted onto the model paving the way for a joint preoperative approach with radiogenomics.

Post-craniotomy coronal suture diastases in a transformed lower grade glioma.

Cranial suture diastases are an uncommon clinical entity, with post craniotomy diastases being a previously undescribed finding in literature to our best knowledge. Herein, we report a case of a 28-year-old adult who underwent a second-stage low-grade glioma surgery 7 months after initial surgery. This study presents coronal suture diastases adjacent to the previously performed craniotomy. After literature and pathophysiology review, we found it to be unique and that the craniotomy can resemble the mechanical stress of trauma.

Butterfly gliomas: a time for stratified management?

Butterfly glioblastomas (bGBM) are a rare subset of WHO grade IV tumours that carry a poor prognosis with a median survival ranging between 3.3 to 6 months. Given their poor prognosis, there is debate over whether histological diagnosis with a biopsy or any surgical or oncological intervention alters disease progression. With this in mind, we reviewed our experience as a high-volume unit to evaluate management decisions and outcomes. A retrospective analysis was undertaken (January 2009 to June 2021) of the electronic patient records of a large neurosurgical centre. We assessed patient demographics, initial clinical presentation, tumour characteristics, clinical management and overall survival (Kaplan-Meier estimator, log-rank analysis and cox proportional hazard analysis). Eighty cases of bGBM were identified. These patients were managed with biopsy ± adjuvant therapy (36), with radiotherapy alone without biopsy (3), or through surgical resection (3). Thirty-eight cases of suspected bGBM were managed conservatively, receiving no oncological treatment or surgical resection/biopsy for histological diagnosis. Those managed conservatively and with radiotherapy without biopsy were diagnosed at neuro-oncology multidisciplinary meeting (MDT) based on clinical presentation and radiological imaging. No significant difference in survival was seen between conservative management compared with single adjuvant treatment (p = 0.69). However, survival was significantly increased when patients received dual adjuvant chemoradiotherapy following biopsy or resection (p = 0.002). A Cox Proportional Hazards model found that survival was significantly impacted by the oncology treatment (p < 0.001), but was not significantly related to potential confounding variables such as the patient's age (p = 0.887) or KPS (p = 0.057). Butterfly glioblastoma have a poor prognosis. Our study would suggest that unless a patient is planned for adjuvant chemoradiotherapy following biopsy, they should be managed conservatively. This avoids unnecessary procedural interventions with the associated morbidities and costs.

Cortical-Subcortical Functional Preservation and Rehabilitation in Neuro-Oncology: Tractography-MIPS-IONM-TMS Proof-of-Concept Study.

Surgical management of deep-seated brain tumors requires precise functional navigation and minimally invasive surgery. Preoperative mapping using navigated transcranial magnetic stimulation (nTMS), intraoperative neurophysiological monitoring (IONM), and minimally invasive parafascicular surgery (MIPS) act together in a functional-sparing approach. nTMS also provides a rehabilitation tool to maximize functional recovery. This is a single-center retrospective proof-of-concept cohort study between January 2022 and June 2023 of patients admitted for surgery with motor eloquent deep-seated brain tumors. The study enrolled seven adult patients, five females and two males, with a mean age of 56.28 years old. The lesions were located in the cingulate gyrus (three patients), the central core (two patients), and the basal ganglia (two patients). All patients had preoperative motor deficits. The most common histological diagnosis was metastasis (five patients). The MIPS approach to the mid-cingulate lesions involved a trajectory through the fronto-aslant tract (FAT) and the fronto-striatal tract (FST). No positive nTMS motor responses were resected as part of the outer corridor for MIPS. Direct cortical stimulation produced stable motor-evoked potentials during the surgeries with no warning signs. Gross total resection (GTR) was achieved in three patients and near-total resection (NTR) in four patients. Post-operatively, all patients had a deterioration of motor function with no ischemia in the postoperative imaging (cavity-to-CST distance 0-4 mm). After nTMS with low-frequency stimulation in the contralateral motor cortex, six patients recovered to their preoperative functional status and one patient improved to a better functional condition. A combined Tractography-MIPS-IONM-TMS approach provides a successful functional-sparing approach to deep-seated motor eloquent tumors and a rehabilitation framework for functional recovery after surgery.

Intraoperative Neuromonitoring of the Visual Pathway in Asleep Neuro-Oncology Surgery.

Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective cohort study of patients admitted for asleep surgery of intra-axial lesions in visual eloquent areas. Demographic and clinical information, data from tractography and visual evoked potentials (VEPs) monitoring were recorded and correlated with visual outcomes. Thirty-nine patients were included (20 females, 19 males; mean age 52.51 ± 14.08 years). Diffuse intrinsic glioma was noted in 61.54% of patients. There was even distribution between the temporal, occipital and parietal lobes, while 55.26% were right hemispheric lesions. Postoperatively, 74.4% remained stable in terms of visual function, 23.1% deteriorated and 2.6% improved. The tumour infiltration of the optic radiation on tractography was significantly related to the visual field deficit after surgery (p = 0.016). Higher N75 (p = 0.036) and P100 (p = 0.023) amplitudes at closure on direct cortical VEP recordings were associated with no new postoperative visual deficit. A threshold of 40% deterioration of the N75 (p = 0.035) and P100 (p = 0.020) amplitudes correlated with a risk of visual field deterioration. To conclude, direct cortical VEP recordings demonstrated a strong correlation with visual outcomes, contrary to transcranial recordings. Invasion of the optic radiation is related to worse visual field outcomes.

Assessing informative tract segmentation and nTMS for pre-operative planning.

BACKGROUND: Deep learning-based (DL) methods are the best-performing methods for white matter tract segmentation in anatomically healthy subjects. However, tract annotations are variable or absent in clinical data and manual annotations are especially difficult in patients with tumors where normal anatomy may be distorted. Direct cortical and subcortical stimulation is the gold standard ground truth to determine the cortical and sub-cortical lo- cation of motor-eloquent areas intra-operatively. Nonetheless, this technique is invasive, prolongs the surgical procedure, and may cause patient fatigue. Navigated Transcranial Magnetic Stimulation (nTMS) has a well-established correlation to direct cortical stimulation for motor mapping and the added advantage of being able to be acquired pre-operatively. NEW METHOD: In this work, we evaluate the feasibility of using nTMS motor responses as a method to assess corticospinal tract (CST) binary masks and estimated uncertainty generated by a DL-based tract segmentation in patients with diffuse gliomas. RESULTS: Our results show CST binary masks have a high overlap coefficient (OC) with nTMS response masks. A strong negative correlation is found between estimated uncertainty and nTMS response mask distance to the CST binary mask. COMPARISON WITH EXISTING METHODS: We compare our approach (UncSeg) with the state-of-the-art TractSeg in terms of OC between the CST binary masks and nTMS response masks. CONCLUSIONS: In this study, we demonstrate that estimated uncertainty from UncSeg is a good measure of the agreement between the CST binary masks and nTMS response masks distance to the CST binary mask boundary.

IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma.

Hypertrophic pachymeningitis is a rare disorder of the dura mater of the spine or brain. It can be caused by inflammatory, infective or neoplastic conditions or can be idiopathic. We report a man with hypertrophic pachymeningitis and bilateral chronic subdural haematoma caused by IgG4-related disease. We highlight the diagnostic challenges and discuss possible underlying mechanisms of subdural haematoma formation in inflammatory conditions. Isolated IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma is very rare; previously reported cases have suggested a possible predilection for men in their sixth decade, presenting with headache as the dominant symptom. Given the rarity and complexity of the condition, it should be managed in a multidisciplinary team setting.

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Neurosurgical Management of Central Nervous System Lymphoma: Lessons Learnt from a Neuro-Oncology Multidisciplinary Team Approach.

Central nervous system lymphoma (CNSL) represents one of the most aggressive forms of extranodal lymphoma. The gold standard for CNSL diagnosis remains the stereotactic biopsy, with a limited role for cytoreductive surgery that has not been supported by historical data. Our study aims to provide a comprehensive overview of neurosurgery's role in the diagnosis of systemic relapsed and primary CNSL, with an emphasis on the impact on management and survival. This is a single center retrospective cohort study with data collected between August 2012 and August 2020, including patients referred with a potential diagnosis of CNSL to the local Neuro-oncology Multidisciplinary Team (MDT). The concordance between the MDT outcome and histopathological confirmation was assessed using diagnostic statistics. A Cox regression is used for overall survival (OS) risk factor analysis, and Kaplan-Meier statistics are performed for three prognostic models. The diagnosis of lymphoma is confirmed in all cases of relapsed CNSL, and in all but two patients who underwent neurosurgery. For the relapsed CNSL group, the highest positive predictive value (PPV) is found for an MDT outcome when lymphoma had been considered as single or topmost probable diagnosis. Neuro-oncology MDT has an important role in establishing the diagnosis in CNSL, not only to plan tissue diagnosis but also to stratify the surgical candidates. The MDT outcome based on history and imaging has good predictive value for cases where lymphoma is considered the most probable diagnosis, with the best prediction for cases of relapsed CNSL, questioning the need for invasive tissue diagnosis in the latter group.

H3 G34-mutant high-grade gliomas: integrated clinical, imaging and pathological characterisation of a single-centre case series.

BACKGROUND: Diffuse hemispheric glioma, H3 G34-mutant, is a novel paediatric tumour type in the fifth edition of the WHO classification of CNS tumours associated with an invariably poor outcome. We present a comprehensive clinical, imaging and pathological review of this entity. METHODS: Patients with confirmed H3 G34R-mutant high-grade glioma were included in a single-centre retrospective cohort study and examined for clinical, radiological and histo-molecular data. RESULTS: Twelve patients were enrolled in the study - 7 males/5 females; the mean age was 17.5 years (10-57 years). Most patients presented with signs of raised intracranial pressure (8/12). The frontal lobe (60%) was the prevalent location, with a mixed cystic-nodular appearance (10/12) and presence of vascular flow voids coursing through/being encased by the mass (8/12), and all tumours showed cortical invasion. Nine patients had subtotal resection limited by functional margins, two patients underwent supra-total resection, and one patient had biopsy only. 5-ALA was administered to 6 patients, all of whom showed positive fluorescence. Histologically, the tumours showed a marked heterogeneity and aggressive spread along pre-existing brain structures and leptomeninges. In addition to the diagnostic H3 G34R/V mutation, pathogenic variants in TP53 and ATRX genes were found in most cases. Potential targetable mutations in PDGFRA and PIK3CA genes were detected in five cases. The MGMT promoter was highly methylated in half of the samples. Methylation profiling was a useful diagnostic tool and highlighted recurrent structural chromosome abnormalities, such as PDGFRA amplification, CDKN2A/B deletion, PTEN loss and various copy number changes in the cyclin D-CDK4/Rb pathway. Radiochemotherapy was the most common adjuvant treatment (9/12), and the average survival was 19.3 months. CONCLUSIONS: H3 G34R-mutant hemispheric glioma is a distinct entity with characteristic imaging and pathological features. Genomic landscaping of individual tumours can offer an opportunity to adapt individual therapies and improve patient management.

On Natural History and Management of Colloid Cysts: Time to Rethink?

BACKGROUND: Colloid cysts, although benign, may occasionally cause obstructive hydrocephalus and sudden death. Reliable prognostic factors for symptomatic progression have been sought, with heterogenous results. METHODS: We conducted a retrospective review of all cases of colloid cysts of the third ventricle managed at our center between 2009 and 2019. Clinical and neuroimaging characteristics were analyzed using logistic regression in relation to symptomatic status and hydrocephalus. The cutoff values for outcome prediction were calculated using the receiver operating characteristic curve analysis. RESULTS: There were 82 patients with colloid cysts, of whom 60 were asymptomatic and 22 symptomatic. None of the asymptomatic patients experienced acute neurologic decline or hydrocephalus during follow-up, whereas half (n = 11) of the symptomatic patients presented with hydrocephalus, 8 of whom had acute hydrocephalus. We found 3 putative candidate risk factors for symptomatic colloid cysts: T1-weighted magnetic resonance imaging hyperintense/mixed signal appearance (P = 0.004), location in risk zone I (P = 0.007), and a volume >236.49 mm3 (P = 0.007). Cyst diameter and volume/foramen of Monro diameter ratios had a decreasing trend over time among asymptomatic patients, providing new insights into the natural history of the disease. CONCLUSIONS: Only a few asymptomatic colloid cysts showed progression requiring surgery, with no acute deterioration or fatal events, whereas the rest remained stable over time, thus supporting a more conservative approach for this group of patients. Higher risk for developing symptomatic colloid cyst was defined by a risk score that included T1-weighted magnetic resonance imaging appearance, risk zone, and colloid cyst volume, aiding the detection of patients at risk of clinical deterioration.

Therapeutic Strategies and Challenges in the Management of Craniospinal Tumors in Pregnancy: A Ten-Year Retrospective Tertiary-Center Study, Systematic Review, and Proposal of Treatment Algorithms.

OBJECTIVE: This study aims to review therapeutic strategies in the management of craniospinal tumors in pregnant patients and the factors that may influence the management along with their influence on maternal and fetal outcomes. METHODS: A retrospective single-center cohort study was performed at a tertiary neurosurgical referral center. Pregnant patients referred to the neuro-oncology multidisciplinary meeting (MDM) with craniospinal tumor were included. Ten-year patient data were collected from hospital records and neuro-oncology MDM outcomes. A systematic review was performed of the available literature as per PRISMA guidelines. RESULTS: Twenty-five patients were identified, with a mean age of 31 years. Of these patients, 88% (n = 22) had cranial lesions and 12% (n = 3) had spinal lesions. Most of the patients had World Health Organization grade I/II tumors. Of the patients, 44% underwent surgery when pregnant, whereas in 40%, this was deferred until after the due date. Of patients, 16% did not require surgical intervention and were followed up with serial imaging in the MDM. The left lateral/park bench position was the preferred position for the spinal and posterior fossa lesions. Systematic review and retrospective data led to proposal of treatment algorithms addressing the therapeutic strategy for management of craniospinal tumors during pregnancy. Factors that may influence maternal and fetal outcomes during management of these tumors were identified, including aggressiveness of the tumor and stage of pregnancy. CONCLUSIONS: Craniospinal tumors presenting in pregnancy are challenging. The surgical management needs to be tailored individually and as part of a multidisciplinary team approach. Factors influencing maternal and fetal outcomes are to be considered during management and patient counseling.

Inter-dural spinal cyst with acute thoracic compressive myelopathy: anatomical aspects of spinal dura, case report and literature review.

INTRODUCTION: Inter-dural juxta-facet spinal cysts occur rarely. They form as part of the degenerative spinal disease process and can be misdiagnosed as synovial cysts or ganglion cysts. We report the case of a thoracic inter-dural juxta-facet spinal cyst causing acute compressive thoracic myelopathy. METHODS: The data was collected retrospectively from patient records. The literature review was performed in PubMed. RESULTS: We report a case of symptomatic inter-dural juxta-facet thoracic spinal cyst. The literature review showed a variety of different spinal cysts including arachnoid cyst, discal cyst, ganglion cyst, epidermoid cyst and synovial cysts. Micro-instability and repeated microtrauma associated with degenerative changes are most likely contributors to its formation. Asymptomatic cysts can show spontaneous resolution. When symptomatic, they can be managed with surgical excision with good patient outcome. CONCLUSION: Inter-dural spinal cysts can be diagnosed and surgically excised to produce excellent post-operative outcome. High pre-operative index of suspicion of this diagnosis together with good understanding of the intraoperative anatomy are essential to avoid inadvertent dural breach.

Prognostic factors and surgical outcomes of spontaneous spinal epidural haematoma: a systematic review and meta-analysis.

Spontaneous spinal epidural haematoma (SSEH) is a rare disease defined as blood accumulation within the vertebral epidural space without a cause identified, which can lead to severe neurological deficits. We aim to provide a comprehensive understanding of the prognostic factors affecting surgical outcomes in true SSEH and propose a critical time frame for operative management. A systematic literature search was performed and registered, using OVID Medline and EMBASE, in line with the PRISMA guidelines. Relevant demographic, clinical, surgical, and outcome data were extracted. The ASIA scale was uniformly used throughout our systematic review. Statistical analysis was performed via logistic regression. Of the 1179 articles examined, we included 181 studies involving 295 adult patients surgically treated for SSEH. SSEH were most commonly found in the cervicothoracic spine, with 2-4 spinal segments most commonly involved. Multivariable logistic regression model showed that the following factors were statistically significant in the post-operative outcome: operation type (P = 0.024), pre-operative neurologic status (P < 0.001), use of warfarin (P = 0.039), and operative interval (P = 0.006). Our retrospective analysis confirms the reversibility of severe neurological deficits after surgical intervention, with a prognosis of post-operative outcomes determined by the use of warfarin, pre-operative ASIA grade, and above all surgical evacuation within 12 h.

Association of extent of resection and functional outcomes in diffuse low-grade glioma: systematic review & meta-analysis.

BACKGROUND: Surgical resection offers survival benefits in patients with diffuse low-grade glioma (DLGG) but its association with functional outcomes is uncertain. This systematic review assessed functional outcomes associated with extent of resection (EoR) in adults with DLGG. METHODS: We searched Medline, Embase and CENTRAL on the 19th of February 2021 for observational studies reporting functional outcomes after surgical resection for patients aged ≥ 18 years with a new diagnosis of supratentorial DLGG according to any World Health Organization classification of primary brain tumors. The Newcastle-Ottawa Scale (NOS) informed our risk of bias assessments. The proportion of patients returning to work within 12 months entered a random-effects meta-analysis. PROSPERO registration number CRD42021238387. RESULTS: There were seven eligible moderate to high-quality (NOS > 6) observational studies identified from 1,183 records involving 234 patients with DLGG. Functional outcomes reported included neurocognition (n = 2 studies), performance status (n = 3), quality of life (QoL) (n = 1) and return to work (n = 6). The proportion of patients who returned to work within 12 months of surgery was 84% (95% confidence interval [CI] 50-96%, I-squared = 38%, 5 studies) for gross total resection, 66% (95% CI 14-96%, I2 = 57%, 5 studies) for subtotal resection, and 31% (95% CI 4-82%, I2 = 0%, 4 studies) for partial resection. There was insufficient data on other functional outcomes for quantitative synthesis. CONCLUSION: A higher proportion of DLGG patients returned to work following gross total resection compared with those who had a subtotal or partial resection. Further studies with standardized assessments can clarify the association between EoR and different functional outcomes.