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.

Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: Osimertinib versus platinum-pemetrexed for T790M mutation-positive advanced non-small cell lung cancer.

BACKGROUND: This study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to osimertinib and platinum-pemetrexed according to the plasma T790M status. METHODS: Tumor tissue biopsy samples were tested for T790M during screening with the cobas EGFR Mutation Test (cobas tissue). Plasma samples were collected at screening and at the baseline and were retrospectively analyzed for EGFR mutations with the cobas EGFR Mutation Test v2 (cobas plasma), droplet digital polymerase chain reaction (ddPCR; Biodesix), and next-generation sequencing (NGS; Guardant360, Guardant Health). RESULTS: With cobas tissue test results as a reference, the plasma T790M positive percent agreement (PPA) was 51% (110 of 215 samples) by cobas plasma, 58% (110 of 189) by ddPCR, and 66% (136 of 207) by NGS. Plasma T790M detection was associated with a larger median baseline tumor size (56 mm for T790M-positive vs 39 mm for T790M-negative; P < .0001) and the presence of extrathoracic disease (58% for M1b-positive vs 39% for M0-1a-positive; P = .002). Progression-free survival (PFS) was prolonged in randomized patients (tissue T790M-positive) with a T790M-negative cobas plasma result in comparison with those with a T790M-positive plasma result in both osimertinib (median, 12.5 vs 8.3 months) and platinum-pemetrexed groups (median, 5.6 vs 4.2 months). CONCLUSIONS: PPA was similar between ddPCR and NGS assays; both were more sensitive than cobas plasma. All 3 test platforms are suitable for routine clinical practice. In patients with tissue T790M-positive NSCLC, an absence of detectable plasma T790M at the baseline is associated with longer PFS, which may be attributed to a lower disease burden.

Patient-reported experience measures in patients undergoing navigated transcranial magnetic stimulation (nTMS): the introduction of nTMS-PREMs.

BACKGROUND: Patient-reported experience measures (PREMs) are a unique measure of experience of patients which can help address the quality of care of the patients. OBJECTIVE: Our aim of the study is to collect quality of care outcomes with our newly navigated transcranial magnetic stimulation patient-reported experience measure (nTMS-PREMs) questionnaire among neurosurgical patients undergoing nTMS. METHODS: A single-centre prospective nTMS-PREMs 19-item questionnaire study was performed between February 2018 and December 2018 on patient referred for nTMS at our hospital. The Data was analysed using Likert scale, linear and logistic regression using statistical software (STATA 13.0®). RESULTS: Fifty patient questionnaires were collected (30 males, 20 females, mean age of 47.6 ± 2.1 years) among which 74% of patients underwent both motor and language mapping with a mean duration of 103.3 ± 5.1 min. An overall positive response was noted from the results of the questionnaire, tiredness and anxiety being the common effects noted. Patients with the left-sided disease appreciated more the conditions provided in our laboratory (Q4, p = 0.040) and increasing age was related to less confidence and trust (Q6, p = 0.038) in the staff performing the exam. Younger patients tolerated nTMS better than older patients (> 65 years). PubMed literature search resulted in no relevant articles on the use of PREMs in nTMS patients. CONCLUSION: nTMS is a well-tolerated non-invasive tool and nTMS-PREMS provides a promising role in identifying the unmet needs of the patients and improving the quality of their care.

Recurrent sampling and ventriculostomy-associated infections: a case-control study.

BACKGROUND: External ventricular drain (EVD) insertion is a common neurosurgical procedure with a significant risk of ventriculostomy-associated infections (VAIs), other morbidities and mortality. Several risk factors have been identified but their effect is unclear. OBJECTIVE: Our primary objective was to assess whether recurrent EVD sampling increased the risk of VAIs. The secondary objective was to explore the effect of sampling frequency, duration of EVD stay, presence of cerebrospinal fluid leak and concurrent infections. METHODS: Ours was a retrospective, single-centre, age-matched, case control study of 83 patients and 249 controls who underwent EVD insertion between 1 January 2010 - 31 December 2016. Patients with primary CNS infections, age under 1 year and death within 5 days of EVD insertion were excluded. Blinded abstractors collected all patient data through the electronic patient record system and regression analysis was used to compare the two groups. RESULTS: Sampling the EVD more than once did not increase the risk of infection (OR 0.47, 95% CI 0.27-0.83, p = 0.01). Risk factors significantly associated with VAI included CSF leak (OR 2.06, 95% CI 1.16-3.67, p = 0.01), concurrent infection (OR 1.85, 95% CI 1.09-3.16, p = 0.02), and an EVD duration of >10 days (OR 2.28, 95% CI 1.24-4.18, p = 0.01). CONCLUSION: Our findings do not support the notion that increased sampling of EVDs is associated with a higher risk of VAI. CSF leaks, concurrent infection and long-term EVDs are also statistically significant risk factors for infection.

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.

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.

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.

The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release.

OBJECTIVES: Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood. METHODS: We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8). RESULTS: Using in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion. CONCLUSIONS: The LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.

Spontaneous lumbar intraspinal subdural abscess: a case report.

BACKGROUND: Subdural spinous abscess is a rare pathology that carries significant morbidity if not diagnosed and treated early; of the cases reported in the literature, very few are genuinely spontaneous in nature. CASE PRESENTATION: Here we demonstrate the case of an otherwise entirely fit and well 56-year-old White, British female presenting with low back pain, bilateral sciatica and sensate urinary retention; lumbar subdural spinous abscess was diagnosed on urgent magnetic resonance imaging and the patient was successfully managed with surgical evacuation and prolonged antibiotic therapy. The patient made a full neurological recovery and was followed-up in the outpatient setting 12 weeks following her initial surgery; she was pain free with normal inflammatory markers and a normal neurological examination. There have been no further consultations and a telephone call at 20 weeks confirmed that she remains well. CONCLUSIONS: This is the second case reported in the literature of a genuinely spontaneous subdural spinous abscess, which was successfully managed with surgical evacuation following prompt diagnosis. This highlights the need to ensure infective pathologies are kept at the back of one's mind even in the most unlikely circumstances, and that excellent outcomes can be achieved with early surgical intervention.

Tractography-Enhanced Biopsy of Central Core Motor Eloquent Tumours: A Simulation-Based Study.

Safe Trajectory planning for navigation guided biopsy (nBx) of motor eloquent tumours (METs) is important to minimise neurological morbidity. Preliminary clinical data suggest that visualisation of the corticospinal tract (CST) and its relation to the tumour may aid in planning a safe trajectory. In this article we assess the impact of tractography in nBx planning in a simulation-based exercise. This single centre cross-sectional study was performed in March 2021 including 10 patients with METs divided into 2 groups: (1) tractography enhanced group (T-nBx; n = 5; CST merged with volumetric MRI); (2) anatomy-based group (A-nBx; n = 5; volumetric MRI only). A biopsy target was chosen on each tumour. Volunteer neurosurgical trainees had to plan a suitable biopsy trajectory on a Stealth S8® workstation for all patients in a single session. A trajectory safety index (TSI) was devised for each trajectory. Data collection and analysis included a comparison of trajectory planning time, trajectory/lobe changes and TSI. A total of 190 trajectories were analysed based on participation from 19 trainees. Mean trajectory planning time for the entire cohort was 225.1 ± 21.97 s. T-nBx required shorter time for planning (p = 0.01). Mean trajectory changes and lobe changes made per biopsy were 3.28 ± 0.29 and 0.45 ± 0.08, respectively. T-nBx required fewer trajectory/lobe changes (p = 0.01). TSI was better in the presence of tractography than A-nBx (p = 0.04). Neurosurgical experience of trainees had no significant impact on the measured parameters despite adjusted analysis. Irrespective of the level of neurosurgical training, surgical planning of navigation guided biopsy for METs may be achieved in less time with a safer trajectory if tractography imaging is available.

Lightfield hyperspectral imaging in neuro-oncology surgery: an IDEAL 0 and 1 study.

Introduction: Hyperspectral imaging (HSI) has shown promise in the field of intra-operative imaging and tissue differentiation as it carries the capability to provide real-time information invisible to the naked eye whilst remaining label free. Previous iterations of intra-operative HSI systems have shown limitations, either due to carrying a large footprint limiting ease of use within the confines of a neurosurgical theater environment, having a slow image acquisition time, or by compromising spatial/spectral resolution in favor of improvements to the surgical workflow. Lightfield hyperspectral imaging is a novel technique that has the potential to facilitate video rate image acquisition whilst maintaining a high spectral resolution. Our pre-clinical and first-in-human studies (IDEAL 0 and 1, respectively) demonstrate the necessary steps leading to the first in-vivo use of a real-time lightfield hyperspectral system in neuro-oncology surgery. Methods: A lightfield hyperspectral camera (Cubert Ultris ×50) was integrated in a bespoke imaging system setup so that it could be safely adopted into the open neurosurgical workflow whilst maintaining sterility. Our system allowed the surgeon to capture in-vivo hyperspectral data (155 bands, 350-1,000 nm) at 1.5 Hz. Following successful implementation in a pre-clinical setup (IDEAL 0), our system was evaluated during brain tumor surgery in a single patient to remove a posterior fossa meningioma (IDEAL 1). Feedback from the theater team was analyzed and incorporated in a follow-up design aimed at implementing an IDEAL 2a study. Results: Focusing on our IDEAL 1 study results, hyperspectral information was acquired from the cerebellum and associated meningioma with minimal disruption to the neurosurgical workflow. To the best of our knowledge, this is the first demonstration of HSI acquisition with 100+ spectral bands at a frame rate over 1Hz in surgery. Discussion: This work demonstrated that a lightfield hyperspectral imaging system not only meets the design criteria and specifications outlined in an IDEAL-0 (pre-clinical) study, but also that it can translate into clinical practice as illustrated by a successful first in human study (IDEAL 1). This opens doors for further development and optimisation, given the increasing evidence that hyperspectral imaging can provide live, wide-field, and label-free intra-operative imaging and tissue differentiation.

Minimally invasive approach to a deep-seated motor eloquent brain tumour: a technical note.

Deep-seated brain tumours represent a unique neurosurgical challenge as they are often surrounded by eloquent structures. We describe a minimally invasive technique using tubular retractors and intraoperative neurophysiology monitoring for open biopsy of a deep-seated lesion surrounded by the corticospinal tract. We used preoperative functional mapping with diffusion tensor imaging tractography and navigated transcranial magnetic stimulation to identify a safe surgical corridor. We also used 5-Aminolevulinic Acid induced fluorescence to identify the lesion intraoperatively and optimize tissue samples obtained for histopathological diagnosis. We found the use of these tools improved the safety of surgery and reduced the risk of surgical morbidity.

Case report: 'Photodynamics of Subependymal Giant Cell Astrocytoma with 5-Aminolevulinic acid'.

Subependymal Giant Cell Astrocytoma (SEGA) is a common diagnosis in patients with Tuberous Sclerosis. Although surgical treatment is often required, resection may entail a significant risk for cognitive function given the anatomical relation with critical structures such as the fornices and subgenual area. Therefore, target subtotal resections using minimal invasive approaches focused in the higher metabolic areas are valuable options to preserve quality of life while addressing specific problems caused by the tumor, such as hydrocephalus or progressive growth of a specific component of the tumor. In this report, the authors explore the potential role of 5-ALA in the identification of highly metabolic areas during SEGA resection in the context of minimal invasive approaches.

Spinal myxomas: review of a rare entity.

Intramuscular myxomas are rare, benign mesenchymal tumours, occurring predominantly in large skeletal muscles as large, slow-growing and painless masses. Spinal occurrence is rare, and may present incidentally, or diagnosed via localized symptoms secondary to local infiltration of surrounding structures. Differential diagnosis based on imaging includes sarcomas, meningiomas and lipomas. We discuss two contrasting cases presenting with well-circumscribed cystic paraspinal lesions indicative of an infiltrative tumour and discuss the radiological and histological differences that distinguish myxomas from similar tumours. Surgical resection of the tumour was performed in both cases, however one patient required surgical fixation due to bony erosion secondary to tumour infiltration. Immuno-histopathological analysis confirmed the diagnosis of a cellular myxoma. Follow up imaging at 6 months confirmed no symptomatic or tumour recurrence in both cases. Histological analysis is the definitive means for diagnosis to differentiate myxomas from other tumours. Recurrence is rare if full resection is achieved.

Simultaneous Motor and Visual Intraoperative Neuromonitoring in Asleep Parietal Lobe Surgery: Dual Strip Technique.

Background: The role played by the non-dominant parietal lobe in motor cognition, attention and spatial awareness networks has potentiated the use of awake surgery. When this is not feasible, asleep monitoring and mapping techniques should be used to achieve an onco-functional balance. Objective: This study aims to assess the feasibility of a dual-strip method to obtain direct cortical stimulation for continuous real-time cortical monitoring and subcortical mapping of motor and visual pathways simultaneously in parietal lobe tumour surgery. Methods: Single-centre prospective study between 19 May−20 November of patients with intrinsic non-dominant parietal-lobe tumours. Two subdural strips were used to simultaneously map and monitor motor and visual pathways. Results: Fifteen patients were included. With regards to motor function, a large proportion of patients had abnormal interhemispheric resting motor threshold ratio (iRMTr) (71.4%), abnormal Cortical Excitability Score (CES) (85.7%), close distance to the corticospinal tract­Lesion-To-Tract Distance (LTD)­4.2 mm, Cavity-To-Tract Distance (CTD)­7 mm and intraoperative subcortical distance­6.4 mm. Concerning visual function, the LTD and CTD for optic radiations (OR) were 0.5 mm and 3.4 mm, respectively; the mean intensity for positive subcortical stimulation of OR was 12 mA ± 2.3 mA and 5/6 patients with deterioration of VEPs > 50% had persistent hemianopia and transgression of ORs. Twelve patients remained stable, one patient had a de-novo transitory hemiparesis, and two showed improvements in motor symptoms. A higher iRMTr for lower limbs was related with a worse motor outcome (p = 0.013) and a longer CTD to OR was directly related with a better visual outcome (p = 0.041). At 2 weeks after hospital discharge, all patients were ambulatory at home, and all proceeded to have oncological treatment. Conclusion: We propose motor and visual function boundaries for asleep surgery of intrinsic non-dominant parietal tumours. Pre-operative abnormal cortical excitability of the motor cortex, deterioration of the VEP recordings and CTD < 2 mm from the OR were related to poorer outcomes.

Pre- and Intraoperative Mapping for Tumors in the Primary Motor Cortex: Decision-Making Process in Surgical Resection.

BACKGROUND: Lesions within the primary motor cortex (M1) and the corticospinal tract (CST) represent a significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centered treatment plan. METHODS: Patients with lesions within the M1 and CST with preoperative cortical and subcortical mapping (navigated transcranial magnetic stimulation [nTMS] and tractography), intraoperative mapping, and intraoperative provisional histologic information (smear with and without 5-aminolevulinic acid [5-ALA]) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection. RESULTS: A total of 10 patients (6 patients with metastatic precentral tumor; 1 patient with grade III and 2 patients with grade IV gliomas; 1 patient with precentral cavernoma) were included in the study. Most of the patients (60%) had a preoperative motor deficit. The nTMS documented M1 invasion in all cases, and in eight patients, the lesions were embedded within the CST. Overall, 70% of patients underwent gross total resection; 20% of patients underwent near-total resection of the lesions. In only one patient was no surgical resection possible after both preoperative and intraoperative mapping. Overall, 70% of patients remained stable postoperatively, and previous motor weakness improved in 20%. CONCLUSION: The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) tests in patients with CST lesions provide a useful guide for resection. The inclusion of histologic information (smear with or without 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the center of the informed decision-making process.

Middle Frontal Gyrus and Area 55b: Perioperative Mapping and Language Outcomes.

Background: The simplistic approaches to language circuits are continuously challenged by new findings in brain structure and connectivity. The posterior middle frontal gyrus and area 55b (pFMG/area55b), in particular, has gained a renewed interest in the overall language network. Methods: This is a retrospective single-center cohort study of patients who have undergone awake craniotomy for tumor resection. Navigated transcranial magnetic simulation (nTMS), tractography, and intraoperative findings were correlated with language outcomes. Results: Sixty-five awake craniotomies were performed between 2012 and 2020, and 24 patients were included. nTMS elicited 42 positive responses, 76.2% in the inferior frontal gyrus (IFG), and hesitation was the most common error (71.4%). In the pMFG/area55b, there were seven positive errors (five hesitations and two phonemic errors). This area had the highest positive predictive value (43.0%), negative predictive value (98.3%), sensitivity (50.0%), and specificity (99.0%) among all the frontal gyri. Intraoperatively, there were 33 cortical positive responses-two (6.0%) in the superior frontal gyrus (SFG), 15 (45.5%) in the MFG, and 16 (48.5%) in the IFG. A total of 29 subcortical positive responses were elicited-21 in the deep IFG-MFG gyri and eight in the deep SFG-MFG gyri. The most common errors identified were speech arrest at the cortical level (20 responses-13 in the IFG and seven in the MFG) and anomia at the subcortical level (nine patients-eight in the deep IFG-MFG and one in the deep MFG-SFG). Moreover, 83.3% of patients had a transitory deterioration of language after surgery, mainly in the expressive component (p = 0.03). An increased number of gyri with intraoperative positive responses were related with better preoperative (p = 0.037) and worse postoperative (p = 0.029) outcomes. The involvement of the SFG-MFG subcortical area was related with worse language outcomes (p = 0.037). Positive nTMS mapping in the IFG was associated with a better preoperative language outcome (p = 0.017), relating to a better performance in the expressive component, while positive mapping in the MFG was related to a worse preoperative receptive component of language (p = 0.031). Conclusion: This case series suggests that the posterior middle frontal gyrus, including area 55b, is an important integration cortical hub for both dorsal and ventral streams of language.

Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading.

BACKGROUND: Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown. OBJECTIVE: To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS). METHODS: Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed. RESULTS: A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of the WHO grade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb. When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis-P = .0001; adjusted analysis-P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis-P = .020). CONCLUSION: An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.

Navigated Transcranial Magnetic Stimulation in Patient with Cranioplasty in Situ: Safe and Accurate Procedure.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a nonsurgical mapping technique used in mapping of motor and language eloquent areas within and/or surrounding brain tumors. Previous reports support this as a safe technique with minor side effects associated with minor headaches and discomfort around the stimulation area. Currently there are no published reports concerning the accuracy and safety of this procedure in patients with a titanium cranioplasty in situ. CASE PRESENTATION: A 59-year-old lady was diagnosed with a recurrent glioma in the context of increasing seizure frequency, left-sided numbness, and weakness. She was diagnosed with a World Health Organization grade 2 oligodendroglioma 10 years before her presentation, which was initially treated with radiotherapy and then surgical resection of this lesion 5 years later. The procedure was complicated with a wound infection, treated with a craniectomy and wound washout, followed by a titanium cranioplasty. Before proceeding with surgery for recurrence, nTMS was performed for motor mapping. No complications were identified. She underwent a craniotomy for tumor resection with aminolevulinic acid HCl (Gliolan), and the tumor was completely removed. Intraoperatively, the direct cortical stimulation correlated with the preoperative nTMS. The pathologic diagnosis on recurrence was an anaplastic oligodendroglioma grade III, and the patient is currently undergoing adjuvant chemotherapy. CONCLUSION: This report confirms that nTMS is a safe and accurate procedure in patients who have a titanium cranioplasty in situ.

First United Kingdom Experience of Navigated Transcranial Magnetic Stimulation in Preoperative Mapping of Brain Tumors.

BACKGROUND: Surgery for lesions in eloquent brain areas remains challenging owing to the risk of permanent neurological deficits. To date, direct electrical stimulation (DES) and intraoperative neuromonitoring represent the reference standard. Recently, navigated transcranial magnetic stimulation (nTMS) has emerged as a mapping tool to optimize surgical planning. Our aim was to correlate nTMS with the intraoperative findings and assess its effects on surgical decision-making. METHODS: We retrospectively reviewed our series of patients who had undergone craniotomy for removal of a brain tumor at our institution with preoperative nTMS, intraoperative neuromonitoring, and DES from February 2017 to February 2018. Demographic data, tumor entity and location, extent of resection, change in surgical approach, and neurological outcome were collected. RESULTS: Of 35 patients, 24 (68.6%) had undergone preoperative motor mapping and 11 (31.4%) had undergone mapping for language. Histopathological examination demonstrated glioma in 88.6% (high grade, n = 24; low grade, n = 6), metastasis (n = 2), epidermoid cyst (n = 1), and cavernoma (n = 1). nTMS resulted in change in the surgical strategy in 31.5% (craniotomy size, n = 7; access pathway, n = 3; surgical indication, n = 1). The specificity of nTMS for language was 66.7%, with a negative predictive value of 74.1%. nTMS motor mapping correlated with DES in all cases, with a mean abductor pollicis brevis hotspot distance of 3.50 ± 0.66 mm (n = 9). CONCLUSIONS: nTMS is a safe, noninvasive adjunctive tool for preoperative mapping of brain tumors in eloquent areas. Furthermore, nTMS can influence the surgical decisions in up to one third of patients in our experience.