Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case.

BACKGROUND: Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial. OBSERVATIONS: A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality. LESSONS: The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112.

To scan or not to scan? A retrospective cohort study analysing the efficacy of routine post-operative CT after brain biopsy.

PURPOSE: Postoperative management following elective cranial surgery, particularly after biopsy procedures, varies significantly across neurosurgical centres. Routine postoperative head CT scans, traditionally performed to detect complications such as intracranial bleeding or cerebral oedema, lack substantial evidence supporting their necessity. METHODS: This study is a retrospective cohort analysis conducted at a regional neurosurgical department of 236 patients who underwent brain biopsies between 2018 and 2022. Patient data, including demographics, surgical details, and postoperative outcomes, were collected and analysed. The outcomes investigated were the incidence and impact of postoperative CT scans on time to discharge, management changes, and the influence of preoperative anticoagulation. RESULTS: Out of 236 patients, 205 (86.86%) underwent postoperative CT scans. There was no significant relationship between postoperative hematoma, as detected on a CT scan, and neurological deficit (p = 0.443), or between preoperative anticoagulation and postoperative bleeding on CT scans (p = 0.464). Patients who had postoperative CT scans had a significantly longer length of stay (LOS) compared to those who did not (p < 0.001). Intraoperative bleeding was a predictor of hematoma on postoperative CT (p = 0.017) but not of postoperative neurological deficit. The routine postoperative CT scan showed limited predictive value for symptomatic deficits, with a positive predictive value of 6.67% and a negative predictive value of 96.88%. CONCLUSIONS: Routine postoperative CT scans after brain biopsies do not significantly impact management or improve patient outcomes but are associated with longer hospital stays. CT scans should be reserved for patients showing clinical signs of complications rather than used as a routine procedure after a brain biopsy.

Predictors of short-term anxiety outcome in subthalamic stimulation for Parkinson's disease.

The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on anxiety in Parkinson's disease (PD) are understudied. We identified clinical predictors of STN-DBS effects on anxiety in this study. In this prospective, open-label, multicentre study, we assessed patients with anxiety undergoing STN-DBS for PD preoperatively and at 6-month follow-up postoperatively. We assessed the Hospital Anxiety and Depression Scale (HADS-anxiety and depression subscales), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-motor (SCOPA-M)-activities of daily living (ADL) and -motor complications, Non-Motor Symptom Scale (NMSS), PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose. We tested changes at follow-up with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We identified patients with a clinically relevant anxiety improvement of anxiety based on a designated threshold of ½ standard deviation of baseline HADS-anxiety. Moreover, we investigated predictors of HADS-anxiety changes with correlations and linear regressions. We included 50 patients with clinically relevant baseline anxiety (i.e., HADS-anxiety ≥ 8) aged 63.1 years ± 8.3 with 10.4 years ± 4.5 PD duration. HADS-anxiety improved significantly at 6-month follow-up as 80% of our cohort experienced clinically relevant anxiety improvement. In predictor analyses, worse baseline SCOPA-ADL and NMSS-urinary domain were associated with greater HADS-anxiety improvements. HADS-anxiety and PDQ-8 changes correlated moderately. Worse preoperative ADL and urinary symptoms predicted favourable postoperative anxiety outcome, which in turn was directly proportionate to greater QoL improvement. This study highlights the importance of detailed anxiety assessments alongside other non-motor and motor symptoms when advising and monitoring patients undergoing STN-DBS for PD.

Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

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.

Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells.

Background: Aberrant expression and activation of epidermal growth factor receptor (EGFR) resulted in approval of several forms of EGFR inhibitors in the treatment of patients with a wide range of epithelial cancers. However, no EGFR inhibitor has yet been approved for the treatment of patients with brain cancer, indicating that targeting EGFR alone may not be sufficient in some patients. Methods: In this study, we investigated the role of all members of the EGFR family, other growth factor receptors, cell-cycle proteins, and downstream cell signaling pathways (e.g., mitogen-activated protein kinase (MAPK), serine/threonine protein kinase (AKT), signal transducer and activator of transcription (STAT3), Src, Abelson murine leukemia viral oncogene homolog (Abl)) on the growth of a panel of human brain cancer cell lines (HBCCLs). We examined the growth response of HBCCLs to treatment with 17 targeted agents compared to two cytotoxic drugs. Results: Of the targeted agents, the irreversible pan-human epidermal growth factor receptor (HER) inhibitors neratinib and afatinib were more effective than erlotinib and lapatinib at inhibiting the growth of all HBCCLs, and the cyclin-dependent kinase (CDK)1/2/5/9 inhibitor dinaciclib was the most potent targeted agent. We found that treatment with Src/Abl/c-kit inhibitor dasatinib, signal transducer and activator of transcription (STAT3) inhibitor stattic, Abl/platelet-derived growth factor receptor (PDGFR)α/vascular endothelial growth factor (VEGFR)2/fibroblast growth factor receptor (FGFR)1 inhibitor ponatinib, and the tropomyosin receptor kinase (TRK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS)/anaplastic lymphoma kinase (ALK) inhibitor entrectinib, also inhibited the growth of all HBCCLs. Interestingly, these agents were more effective in inhibiting growth of HBCCLs when proliferating at a slower rate. In addition to inhibiting the proliferation of HBCCLs, treatment with neratinib, dinaciclib, dasatinib, stattic and trametinib inhibited the migration of brain tumor cell line A172. Conclusions: Notably, we found that treatment with neratinib in combination with palbociclib (CDK4/6 inhibitor), or miransertib (AKT1/2/3 inhibitor) resulted in synergistic growth inhibition of all HBCCLs. Our results support that repurposing drugs like neratinib in combination with the palbociclib or miransertib may be of therapeutic potential in brain cancer and warrants further investigations.

No evidence for an association of voxel-based morphometry with short-term non-motor outcomes in deep brain stimulation for Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson's disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.

Radiogenomic biomarkers for immunotherapy in glioblastoma: A systematic review of magnetic resonance imaging studies.

Background: Immunotherapy is an effective "precision medicine" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. Methods: A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results: Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Conclusions: Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS.

Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma© which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.

Incidence and Risk Factors of Surgical Site Infection After Cranial Surgery for Patients with Brain Tumors: A Systematic Review and Meta-analysis.

BACKGROUND: Surgical site infections after craniotomy (SSI-CRANs) are a serious adverse event given the proximity of the wound to the central nervous system. SSI-CRANs are associated with substantial patient morbidity and mortality. Despite the importance and recognition of this event in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to SSI-CRAN specifically in patients after brain tumor surgery. METHODS: Systematic searches of Medline, Embase, and Cochrane Central were undertaken. The primary outcome was the incidence of SSI-CRAN at 30 and 90 days. Secondary outcomes were risk factors for SSI-CRAN. RESULTS: Thirty-seven studies reporting 91,907 patients with brain tumors who underwent cranial surgery were included in the meta-analysis. Pooled incidence of SSI-CRAN at 30 and 90 days was 4.03% (95% CI: 2.94%-5.28%, I2 = 97.3) and 6.17% (95% CI: 3.16%-10.07%, I2 = 97.3), respectively. Specifically, incidence of SSI-CRAN following surgery for posterior fossa tumors was the highest at 9.67% (95% CI: 5.98%-14.09%, I2 = 75.5). Overall pooled incidence of readmission within 30 days and reoperation due to SSI-CRAN were 13.9% (95% CI: 12.5%-15.5%, I2 = 0.0) and 16.3% (95% CI: 5.4%-31.3%, I2 = 72.9), respectively. Risk factors for SSI-CRAN included reintervention (risk ratio [RR] 1.58, 95% CI: 1.22-2.04, I2 = 0.0), previous radiotherapy (RR 1.69, 95% CI: 1.20-2.38, I2 = 0.0), longer duration of operation (mean difference 64.18, 95% CI: 3.96-124.40 minutes, I2 = 90.3) and cerebrospinal fluid (CSF) leaks (RR 14.26, 95% CI: 2.14-94.90, I2 = 73.2). CONCLUSIONS: SSI-CRAN affects up to 1 in 14 patients with brain tumors. High-risk groups include those with reintervention, previous radiotherapy, longer duration of operation, and CSF leaks. Further prospective studies should focus on bundles of care that will reduce SSI-CRAN.

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.

Deep brain stimulation of the subthalamic nucleus in Parkinson disease 2013-2023: where are we a further 10 years on?

Deep brain stimulation has been in clinical use for 30 years and during that time it has changed markedly from a small-scale treatment employed by only a few highly specialized centers into a widespread keystone approach to the management of disorders such as Parkinson's disease. In the intervening decades, many of the broad principles of deep brain stimulation have remained unchanged, that of electrode insertion into stereotactically targeted brain nuclei, however the underlying technology and understanding around the approach have progressed markedly. Some of the most significant advances have taken place over the last decade with the advent of artificial intelligence, directional electrodes, stimulation/recording implantable pulse generators and the potential for remote programming among many other innovations. New therapeutic targets are being assessed for their potential benefits and a surge in the number of deep brain stimulation implantations has given birth to a flourishing scientific literature surrounding the pathophysiology of brain disorders such as Parkinson's disease. Here we outline the developments of the last decade and look to the future of deep brain stimulation to attempt to discern some of the most promising lines of inquiry in this fast-paced and rapidly evolving field.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years: A Nonrandomized Controlled Trial.

Importance: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking. Objective: To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED). Design, Setting, and Participants: In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023. Exposure: Treatment for PD of STN-DBS or MED. Main Outcomes and Measures: Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed. Results: The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001). Conclusions and Relevance: This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments. Trial Registration: German ClinicalTrials Registry: DRKS00006735.

Impact of Preoperative Mapping and Intraoperative Neuromonitoring in Minimally Invasive Parafascicular Surgery for Deep-Seated Lesions.

BACKGROUND: Transsulcal tubular retractor-assisted minimally invasive parafascicular surgery changes the surgical strategy for deep-seated lesions by promoting a deficit-sparing approach. When integrated with preoperative brain mapping and intraoperative neuromonitoring (IONM), this approach may potentially improve patient outcomes. In this study, we assessed the impact of preoperative brain mapping and IONM in tubular retractor-assisted neuro-oncological surgery. METHODS: This retrospective single-center cohort study included patients who underwent transsulcal tubular retractor-assisted minimally invasive parafascicular surgery for resection of deep-seated brain tumors from 2016 to 2022. The cohort was divided into 3 groups: group 1, no preoperative mapping or IONM (17 patients); group 2, IONM only (25 patients); group 3, both preoperative mapping and IONM (38 patients). RESULTS: We analyzed 80 patients (33 males and 47 females) with a median age of 46.5 years (range: 1-81 years). There was no significant difference in mean tumor volume (26.2 cm3 [range 1.07-97.4 cm3]; P = 0.740) and mean preoperative depth of the tumor (31 mm [range 3-65 mm], P = 0.449) between the groups. A higher proportion of high-grade gliomas and metastases was present within group 3 (P = 0.003). IONM was related to fewer motor (P = 0.041) and language (P = 0.032) deficits at hospital discharge. Preoperative mapping and IONM were also related to shorter length of stay (P = 0.008). CONCLUSIONS: Preoperative and intraoperative brain mapping and monitoring enhance transsulcal tubular retractor-assisted minimally invasive parafascicular surgery in neuro-oncology. Patients had a reduced length of stay and prolonged overall survival. IONM alone reduces postoperative neurological deficit.

Nonenhancing motor eloquent gliomas: navigated transcranial magnetic stimulation oncobiological signature.

OBJECTIVE: Preoperative grading of nonenhancing motor eloquent gliomas is hampered by a lack of specific imaging surrogates. Tumor grading is crucial for the informed consent discussion before tumor resection. In this paper, the authors hypothesized that navigated transcranial magnetic stimulation (nTMS)-derived metrics could provide significant information to distinguish between high- and low-grade motor eloquent gliomas that present as nonenhancing tumors and therefore contribute to improving patient counseling, timing of treatment, preoperative planning, and intraoperative strategies. METHODS: The authors conducted a retrospective single-center cohort study of patients admitted for tumor surgery between January 2018 and April 2022 with a nonenhancing motor eloquent glioma and preoperative bilateral nTMS mapping. nTMS data including resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr), Cortical Excitability Score (CES), area and volume of cortical activation, and motor evoked potential (MEP) characteristics were obtained and integrated with demographic and clinical data. RESULTS: Thirty patients met the inclusion criteria, and 10 healthy participants were recruited for comparison. Seizures were the most common presenting symptom (25 patients) and WHO grade 3 the most common tumor grade (21 patients). The area and volume of functional cortical activation of both the abductor pollicis brevis and first dorsal interosseous muscles were decreased in healthy participants compared with patients with WHO grade 3 glioma (p < 0.05). An abnormal iRMTr for the lower limbs (16.7% [1/6] WHO grade 2, 76.2% [16/21] WHO grade 3, 100% [3/3] WHO grade 4; p = 0.015) and a higher CES (maximal abnormal CES: 0% [0/6] WHO grade 2, 38% [8/21] WHO grade 3, 66.7% [2/3] WHO grade 4; p = 0.010) were associated with the prediction of high-grade lesions. A total of 7280 MEPs were analyzed. A significant increase in the amplitude and a significant decrease in latency in the MEPs for the first dorsal interosseous and abductor digiti minimi muscles (p < 0.0001) were identified in healthy participants compared with WHO grade 3 glioma patients. CONCLUSIONS: Nonenhancing motor eloquent gliomas have a different impact on both anatomical and functional reorganization of motor areas according to their WHO grading.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Stratifying quality of life outcome in subthalamic stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves quality of life (QoL), motor and non-motor symptoms (NMS). However, in previous studies, 43%-49% of patients did not experience clinically relevant postoperative QoL improvement. To inform individualised prediction of postoperative QoL improvement, we developed a stratification analysis of QoL outcomes based on preoperative non-motor total burden, severity of motor progression and motor response in levodopa challenge tests. METHODS: This was a prospective, open-label, multicentre, international study with a 6-month follow-up. A distribution-based threshold identified 'QoL responders' in the PDQuestionnaire-8 Summary Index (PDQ-8 SI). After baseline stratification based on the NMS Scale, Hoehn and Yahr Scale and levodopa response assessed with the Unified PD Rating Scale-III, we compared postoperative QoL response between these strata. To assess the clinical usefulness and statistical feasibility of stratifications, we compared cumulative distribution function curves, respectively PDQ-8 within-stratum variation. RESULTS: All main outcomes improved postoperatively. Based on the 8.1 points threshold for clinically meaningful PDQ-8 SI improvement, only 80/161 patients were classified as 'QoL responders'. The absolute risk reductions for QoL non-response among respective non-motor, motor progression and levodopa response strata were 23%, 8% and 3%, respectively. Only non-motor stratification reduced PDQ-8 within-stratum variation compared with the overall cohort. CONCLUSIONS: Non-motor stratification, but not motor progression or levodopa response stratification, is clinically useful and statistically feasible for personalised preoperative prediction of postoperative QoL outcome of STN-DBS for PD. Our findings highlight that non-motor assessments are necessary components of a case-based, holistic approach of DBS indication evaluations geared towards optimising postoperative QoL outcomes. TRIAL REGISTRATION NUMBER: GermanClinicalTrialsRegister: #6735.

Awake craniotomy during pregnancy: A systematic review of the published literature.

Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.