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.

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.

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.

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.

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.

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.