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Introduction: The role of low-pathogenic bacteria cultured from removed spinal implants is unclear and the efficacy of perioperative single-dose antibiotics against such bacteria remains underexplored. Research question: This study aims to investigate whether pedicle screw loosening is associated with pathogens and if the choice of perioperative antibiotics can prevent these bacteria. Methods: A retrospective analysis was conducted on 93 patients with implants removed between 01/01/2018 and 03/31/2020. Patients with both loosened and non-loosened implants were included. The latter group was subdivided into cases where implants were exchanged due to adjacent segment degeneration (ASD) and those with elective implant removal after fracture healing. Bacterial cultures from removed implants were analyzed for resistance profiles against the prophylactic single-shot antibiotics administered during implantation. Patients with acute infection, spondylodiscitis, deep wound infection, empyema, and carbon/polyetheretherketone spinal implants were excluded. Results: Bacterial isolates were detected in both loosened (41%) and non-loosened (27%) implants (p = 0.23). The most frequently cultivated bacteria were Cutibacterium acnes and Staphylococcus epidermidis. Sensitivity to the administered antibiotics was 75%. While Cutibacterium acnes was entirely sensitive, Staphylococcus epidermidis was completely resistant. Patients with loosened implants without bacteria had a significantly lower bone mineral density (BMD) than patients with implants removed due to ASD. However, patients with loosened implants and positive bacterial cultures had comparable BMD to ASD patients. Conclusions: The high rate of sensitive Cutibacterium acnes and resistant Staphylococcus epidermidis on removed spinal implants suggests a need to revisit current antimicrobial prophylaxis. Further research is required to determine the clinical significance of low-virulence bacteria, especially on non-loosened implants.

Introduction There are no guidelines or prospective studies defining the optimal surgical treatment for glioblastomas in older patients (≥70 years), for those with a limited functioning performance at presentation (Karnofsky Performance Scale ≤70) or for those with tumours in certain locations (midline, multifocal). Therefore, the decision between resection and biopsy is varied, among neurosurgeons internationally and at times even within an institution. This study aims to compare the effects of maximal tumour resection versus tissue biopsy on survival, functional, neurological and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximise the potential to undergo adjuvant treatment.Methods and analysis This study is an international, multicentre, prospective, two-arm cohort study of an observational nature. Consecutive patients with glioblastoma will be treated with resection or biopsy and matched with a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery; (2) progression-free survival (PFS); (3) quality of life at 6 weeks, 3 months and 6 months after surgery and (4) frequency and severity of serious adverse events. The total duration of the study is 5 years. Patient inclusion is 4 years; follow-up is 1 year.Ethics and dissemination The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.Trial registration number NCT06146725.

Abstract Background Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial was designed to test the clinical potential of perampanel to reduce tumor cell network connectivity and tumor growth with an extended window-of-opportunity concept. Methods PerSurge is a phase IIa clinical and translational treatment study around surgical resection of progressive or recurrent glioblastoma. In this multicenter, 2-arm parallel-group, double-blind superiority trial, patients are 1:1 randomized to either receive placebo or perampanel (n = 66 in total). It consists of a treatment and observation period of 60 days per patient, starting 30 days before a planned surgical resection, which itself is not part of the study interventions. Only patients with an expected safe waiting interval are included, and a safety MRI is performed. Tumor cell network connectivity from resected tumor tissue on single cell transcriptome level as well as AI-based assessment of tumor growth dynamics in T2/FLAIR MRI scans before resection will be analyzed as the co-primary endpoints. Secondary endpoints will include further imaging parameters such as pre- and postsurgical contrast enhanced MRI scans, postsurgical T2/FLAIR MRI scans, quality of life, cognitive testing, overall and progression-free survival as well as frequency of epileptic seizures. Further translational research will focus on additional biological aspects of neuron-tumor connectivity. Discussion This trial is set up to assess first indications of clinical efficacy and tolerability of perampanel in recurrent glioblastoma, a repurposed drug which inhibits neuron-glioma synapses and thereby glioblastoma growth in preclinical models. If perampanel proved to be successful in the clinical setting, it would provide the first evidence that interference with neuron-cancer interactions may indeed lead to a benefit for patients, which would lay the foundation for a larger confirmatory trial in the future. Trial registration EU-CT number: 2023-503938-52-00 30.11.2023.

Abstract This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals’ data. All models’ median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74–0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p

BackgroundAwake craniotomy is the standard of care for treating language eloquent gliomas. However, depending on preoperative functionality, it is not feasible in each patient and selection criteria are highly heterogeneous. Thus, this study aimed to identify broadly applicable predictor variables allowing for a more systematic and objective patient selection.MethodsWe performed post-hoc analyses of preoperative language status, patient and tumor characteristics including language eloquence of 96 glioma patients treated in a single neurosurgical center between 05/2018 and 01/2021. Multinomial logistic regression and stepwise variable selection were applied to identify significant predictors of awake surgery feasibility.ResultsStepwise backward selection confirmed that a higher number of paraphasias, lower age, and high language eloquence level were suitable indicators for an awake surgery in our cohort. Subsequent descriptive and ROC-analyses indicated a cut-off at ≤54 years and a language eloquence level of at least 6 for awake surgeries, which require further validation. A high language eloquence, lower age, preexisting semantic and phonological aphasic symptoms have shown to be suitable predictors.ConclusionThe combination of these factors may act as a basis for a systematic and standardized grading of patients’ suitability for an awake craniotomy which is easily integrable into the preoperative workflow across neurosurgical centers.

Introduction A greater extent of resection of the contrast-enhancing (CE) tumour part has been associated with improved outcomes in glioblastoma. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in high-grade glioma (HGG) patients in terms of survival, functional, neurological, cognitive and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively.Methods and analysis This study is an international, multicentre, prospective, two-arm cohort study of observational nature. Consecutive glioblastoma patients will be operated with SMR or maximal resection at a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months postoperatively. Secondary endpoints are (1) residual CE and NCE tumour volume on postoperative T1-contrast and FLAIR (Fluid-attenuated inversion recovery) MRI scans; (2) progression-free survival; (3) receipt of adjuvant therapy with chemotherapy and radiotherapy; and (4) quality of life at 6 weeks, 3 months and 6 months postoperatively. The total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.Ethics and dissemination The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

Summary: The preoperative distinction between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) can be difficult, even for experts, but is highly relevant. We aimed to develop an easy-to-use algorithm, based on a convolutional neural network (CNN) to preoperatively discern PCNSL from GBM and systematically compare its performance to experienced neurosurgeons and radiologists. To this end, a CNN-based on DenseNet169 was trained with the magnetic resonance (MR)-imaging data of 68 PCNSL and 69 GBM patients and its performance compared to six trained experts on an external test set of 10 PCNSL and 10 GBM. Our neural network predicted PCNSL with an accuracy of 80% and a negative predictive value (NPV) of 0.8, exceeding the accuracy achieved by clinicians (73%, NPV 0.77). Combining expert rating with automated diagnosis in those cases where experts dissented yielded an accuracy of 95%. Our approach has the potential to significantly augment the preoperative radiological diagnosis of PCNSL.

Introduction: Neuromodulation through deep brain stimulation (DBS) and spinal cord stimulation (SCS) has become a successful therapy for various neurological disorders, such as movement disorders and chronic pain. Implantable pulse generators (IPGs) are pivotal in these therapies, available as either rechargeable (r-IPGs) or non-rechargeable (nr-IPGs). Research question: To perform a meta-analysis on r-IPGs. Methods: A systematic literature search following PRISMA guidelines was conducted on PubMed, focusing on studies published from January 2005 to August 2023. Included studies comprised clinical trials, randomized controlled trials, and comparative studies involving human subjects. Data extraction focused on patient demographics, stimulation types, battery characteristics, and complications. Descriptive statistics and Pearson correlation analyses were performed using SPSS software. Results: Nine studies involving 288 patients with rechargeable IPGs (r-IPGs) for SCS and 257 patients with r-IPGs for DBS met the inclusion criteria. r-IPGs exhibited low rates of surgical revisions and infections, with surgical revision rates of 8.87% for SCS and 5.45% for DBS, and infection rates of 2.6% for SCS and 1.56% for DBS. Charge burden was comparable with 97.34 min and 93.41 min per week for SCS and DBS respectively. Correlation analyses indicated that longer battery recharge times were associated with an increased incidence of complications, including unintentional interruptions and hardware failures. Discussion: r-IPGs may offer substantial benefits in reducing re-operation rates and complications associated. Nonetheless, careful management of battery charging is crucial to maximize these benefits. Establishing international guidelines for the use of r-IPGs in specific patient populations and conditions is recommended to standardize and optimize outcomes.

Introduction: Neuroendoscopy has become a well-established procedure for treating various intracranial conditions. Research question: We evaluated the advantages of that technique, with focus on adverse events. Material and methods: Retrospective analysis included all patients who underwent neuroendoscopic procedures between January 2017 and December 2023. We conducted comparative analysis considering factors such as age, gender, follow-up duration, etiology, preoperative symptoms, clinical and radiological benefits, as well as surgical and nonsurgical adverse events rates. Results: Total of 318 neuroendoscopic procedures within 257 surgeries in 225 patients were included, with mean age of 18.8 ± 21.4 years. 170 cases (66.1%) were pediatric versus 87 cases adults (33.9%). Most common aetiologies were peri- and intraventricular cysts (27.2%), idiopathic aqueduct stenosis (24.9%), tumours (23.7%), and post-haemorrhagic hydrocephalus (17.1%). Procedures included endoscopic third ventriculostomy (51.0%), cyst fenestration (21.0%), and endoscopic-assisted ventricular catheter placements (19.5%). Headache was predominant preoperative symptom (42.0%). During follow-up, 84.8% and 82.5% of cases showed clinical and radiological improvement, respectively. Early surgical adverse events were observed in 5.4% of cases, while non-surgical adverse events occurred in 3.1%. There was no significant difference in the surgical adverse events rate between children and adults (4.7% vs. 6.9%, p = 0.563), compared to significant higher non-surgical adverse events in adults (6.9% vs 1.2%, p=0.020). Discussion and conclusion: Neuroendoscopy has demonstrated effectiveness and safety in treating intracranial diseases, boasting a low adverse events rate. Our study found no significant difference in the surgical adverse events rates between pediatric and adult groups.

Introduction: Many patients with high-grade gliomas (HGG) are of older age. Research question: We hypothesize that pre- and intraoperative mapping and monitoring preserve functional status in elderly patients while gross total resection (GTR) is the aim, resulting in overall survival (OS) rates comparable to the general population with HGG. Material and methods: We subdivided a prospective cohort of 168 patients above 65 years with eloquent high-grade gliomas into four groups ([years/cases] 1: 65–69/58; 2: 70–74/47; 3: 75–79/43; 4: >79/20). All patients underwent preoperative noninvasive mapping, which was also used for decision-making, intraoperative neuromonitoring in 138 cases, direct cortical and/or subcortical motor mapping in 66 and 50 cases, and awake language mapping in 11 cases. Results: GTR and subtotal resection (STR) could be achieved in 65% and 28%, respectively. Stereotactic biopsy was performed in 8% of cases. Postoperatively, we found transient and permanent functional deficits in 13% and 11% of cases. Postoperative Karnofsky Performance Scale (KPS) did not differ between subgroups. Patients with long-term follow-up (51%) had a progression-free survival of 5.5 (1–47) months and an overall survival of 10.5 (0–86) months. Discussion and conclusion: The interdisciplinary glioma treatment in the elderly is less age-dependent but must be adjusted to the functional status. Function-guided surgical resections could be performed as usual, with maximal tumor resection being the primary goal. However, less network capacity in the elderly to compensate for deficits might cause higher rates of permanent deficits in this group of patients with more fast-growing malignant gliomas.

Introduction: In light of an aging global population, understanding adverse events (AEs) in surgeries for older adults is crucial for optimal outcomes and patient safety. Research question: Our study compares surgical outcomes and AEs in patients aged 65–79 with those aged ≥80, focusing on clinical outcomes, morbidity and mortality rates, and age-related risk factors for AEs. Material and methods: Our study, from January 2019 to December 2022, involved patients aged 65–79 and ≥ 80 undergoing spinal surgery. Each patient was evaluated for AEs post-discharge, defined as negative clinical outcomes within 30 days post-surgery. Patients were categorized based on primary spinal diagnoses: degenerative, oncological, traumatic, and infectious. Results: We enrolled 546 patients aged 65–79 and 184 octogenarians. Degenerative diseases were most common in both groups, with higher infection and tumor rates in the younger cohort. Octogenarians had a higher Charlson Comorbidity Index and longer ICU/hospital stays. Surgery-related AE rates were 8.1% for 65-79-year-olds and 15.8% for octogenarians, with mortality around 2% in both groups. Discussion and conclusion: Our prospective analysis shows octogenarians are more susceptible to surgical AEs, linked to greater health complexities. Despite higher AEs in older patients, low mortality rates across both age groups highlight the safety of spinal surgery. Tracking AEs is crucial for patient communication and impacts healthcare accreditation and funding.

Objective: Stimulation-based language mapping relies on identifying stimulation-induced language disruptions, which preexisting speech disorders affecting the laryngeal and orofacial speech system can confound. This study ascertained the effects of preexisting stuttering on pre- and intraoperative language mapping to improve the reliability and specificity of established language mapping protocols in the context of speech fluency disorders. Method: Differentiation-ability of a speech therapist and two experienced nrTMS examiners between stuttering symptoms and stimulation-induced language errors during preoperative mappings were retrospectively compared (05/2018-01/2021). Subsequently, the impact of stuttering on intraoperative mappings was evaluated in all prospective patients (01/2021-12/2022). Results: In the first part, 4.85 % of 103 glioma patients stuttered. While both examiners had a significant agreement for misclassifying pauses in speech flow and prolongations (Κ ≥ 0.50, p ≤ 0.02, respectively), less experience resulted in more misclassified stuttering symptoms. In one awake surgery case within the second part, stuttering decreased the reliability of intraoperative language mapping.Comparison with Existing Method(s): By thoroughly differentiating speech fluency symptoms from stimulation-induced disruptions, the reliability and proportion of stuttering symptoms falsely attributed to stimulation-induced language network disruptions can be improved. This may increase the consistency and specificity of language mapping results in stuttering glioma patients. Conclusions: Preexisting stuttering negatively impacted language mapping specificity. Thus, surgical planning and the functional outcome may benefit substantially from thoroughly differentiating speech fluency symptoms from stimulation-induced disruptions by trained specialists.

Summary: There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.

ObjectiveTreatment strategies of patients suffering from pyogenic spondylodiscitis are a controverse topic. Percutaneous dorsal instrumentation followed by surgical debridement and fusion of the infectious vertebral disc spaces is a common approach for surgical treatment. Technical advances enable spinal navigation for dorsal and lateral instrumentation. This report investigates combined navigated dorsal and lateral instrumentation in a single surgery and positioning for lumbar spondylodiscitis in a pilot series.MethodsPatients diagnosed with 1- or 2-level discitis were prospectively enrolled. To enable posterior navigated pedicle screw placement and lateral interbody fusion (LLIF) patients were positioned semi-prone in 45-degree fashion. For spinal referencing, a registration array was attached to the pelvic or spinal process. 3D scans were acquired intraoperatively for registration and implant control.Results27 patients suffering from 1- or 2-level spondylodiscitis with a median ASA of 3 (1–4) and a mean BMI of 27.9 ± 4.9 kg/m2 were included. Mean duration of surgery was 146 ± 49 min. Mean blood loss was 367 ± 307 ml. A median of 4 (4–8) pedicle screws were placed for dorsal percutaneous instrumentation with an intraoperative revision rate of 4.0%. LLIF was performed on 31 levels with an intraoperative cage revision rate of 9.7%.ConclusionsNavigated lumbar dorsal and lateral instrumentation in a single operation and positioning is feasible and safe. It enables rapid 360-degree instrumentation in these critically ill patients and potentially reduces overall intraoperative radiation exposure for patient and staff. Compared to purely dorsal approaches it allows for optimal discectomy and fusion while overall incisions and wound size are minimized. Compared to prone LLIF procedures, semi-prone in 45-degree positioning allows for a steep learning curve due to minor changes of familiar anatomy.

Abstract Over the past years navigated repetitive transcranial magnetic stimulation (nrTMS) had become increasingly important for the preoperative examination and mapping of eloquent brain areas. Among other applications it was demonstrated that the detection of neuropsychological function, such as arithmetic processing or face recognition, is feasible with nrTMS. In order to investigate the mapping of further brain functions, this study aims to investigate the cortical mapping of categorization function via nrTMS. 20 healthy volunteers purely right-handed, with German as mother tongue underwent nrTMS mapping using 5 Hz/10 pulses. 52 cortical spots spread over each hemisphere were stimulated. The task consisted of 80 pictures of living and non-living images, which the volunteers were instructed to categorize while the simulation pulses were applied. The highest error rates for all errors of all subjects were observed in the left hemisphere’s posterior middle frontal gyrus (pMFG) with an error rate of 60%, as well as in the right pMFG and posterior supra marginal gyrus (pSMG) (45%). In total the task processing of non-living objects elicited more errors in total, than the recognition of living objects. nrTMS is able to detect cortical categorization function. Moreover, the observed bihemispheric representation, as well as the higher error incidence for the recognition of non-living objects is well in accordance with current literature. Clinical applicability for preoperative mapping in brain tumor patients but also in general neuroscience has to be evaluated as the next step.

Introduction: Intraoperative neuromonitoring (IOM) of motor/somatosensory evoked potentials is a well-established approach for reducing ischemic complications after aneurysm clipping. Research question: To determine the predictive validity of IOM for postoperative functional outcome and its perceived added value for intraoperative real-time feedback of functional impairment in the surgical treatment of unruptured intracranial aneurysms (UIAs). Material and methods: Prospective study of patients scheduled for elective clipping of UIAs between 02/2019–02/2021. Transcranial motor evoked potentials (tcMEP) were used in all cases, a significant decline was defined as loss of ≥50% in amplitude or 50% latency increase. Clinical data were correlated to postoperative deficits. A surgeon's questionnaire was conceived. Results: 47 patients were included, median age 57 years (range 26–76). IOM was successful in all cases. In 87.2%, IOM was stable throughout surgery, although 1 patient (2.4%) demonstrated a permanent postoperative neurological deficit. All patients with an intraoperatively reversible tcMEP-decline (12.7%) showed no surgery-related deficit, regardless of the decline duration (range 0.5–40.0 ​min; mean: 13.8). Temporary clipping (TC) was performed in 12 cases (25.5%), with a decline in amplitude in 4 patients. After clip-removal, all amplitudes returned to baseline. IOM provided the surgeon with a higher sense of security in 63.8%. Discussion and conclusion: IOM remains invaluable during elective microsurgical clipping, particularly during TC of MCA and AcomA-aneurysms. It alerts the surgeon of impending ischemic injury and offers a way of maximizing the time frame for TC. IOM has highly increased surgeons’ subjective feeling of security during the procedure.

Introduction: Lateral lumbar interbody fusion (LLIF) and lateral thoracic interbody fusion (LTIF), supported by intraoperative neuromonitoring (IONM), gained popularity as a mini-invasive alternatives for standard interbody fusion. The objective of this study was to investigate the clinical outcome in a large elderly patient cohort who underwent LTIF/LLIF without IONM. Methods: This retrospective, single-center study enrolled elderly patients (≥70 years old) operated during the period from 2010 to 2016. Anterior lumbar interbody fusion (ALIF) in the L5/S1 segment was excluded from the analysis. Results: The study enrolled 108 patients (63 males, 58.3%) with a mean age of 76.5 ​y/o. The mean follow-up was 14.4 ​± ​11.3 months. The mean time of the surgery was 92 ​± ​34.2 ​min. The mean blood loss was 62.2 ​ml. There were no vascular or visceral surgical complications. 39 medical complications were encountered in 24 (22%) patients. Less than 5% of patients presented with a new onset of motor weakness and less than 2% of the patients developed a new sensory deficit at the discharge. 46% of patients were lost in follow-up at 12 months. Conclusions: IONM is not mandatory for LLIF/LTIF surgery in geriatric patients and has a low frequency of approach-related complications as well as neurological deterioration. Our results are comparable to the available literature. Regardless of the utilization of these mini-invasive, anterior approaches, in patients of advanced aged, the risk for major medical complications is high and is responsible for contributing to prolonged hospitalization.

Introduction: Decompressive craniectomy (DC) is the ultimate intervention to lower intracranial pressure (ICP) following severe traumatic brain injury (TBI). However, this intervention is associated with considerable adverse events and a higher proportion of survivors with poor functional outcomes. Research question: In a multicompartment system ICP is associated with intraabdominal pressure (IAP) due to cerebral venous outflow from the brain. This is the rationale for decompressive laparotomy (DL) to control ICP after TBI as reported by experimental and retrospective clinical data. The safety profile of DL is superior to DC. This study aims to randomly assign patients with intractable high ICP after severe TBI to DL or DC. Material and methods: Among other inclusion criteria, ICP must be above 20 mmHg (1–12 h) despite sedation and all other measures according to current guidelines. The primary outcome is the Extended Glasgow Outcome Scale assessed after twelve months. Further secondary outcome measures are compartmental pressure values, complications, etc. After 20 initial patients, results will be reviewed by the ethics committees and safety monitoring board to decide on the enrolment of 80 additional patients. Results: The study is designed to provide not only high-quality prospective data for the first time on this treatment approach, its two-stage design (20 + 80 pts) also provides maximum patient safety. This protocol conforms with the SPIRIT 2013 Statement. Ethics approval was granted by our but also 5 other university ethics committees (registration 473/18S). Conclusion: Registration was performed prior to study initiation in November 2021 (registration number NCT 05115929).

Introduction: The resection of brainstem cerebral cavernous malformations (CCM) harbors the risk of damaging the corticospinal tract (CST) and other major tracts. Hence, visualization of eloquent fiber tracts supports pre- and intraoperative planning. However, diffusion tensor imaging fiber tracking at brainstem level suffers from distortion due to field inhomogeneities and eddy currents by steep diffusion gradients. Research question: This study aims to analyze the effect of distortion correction for CST tractography in brainstem CCM patients. Material and methods: 25 patients who underwent resection of brainstem CCM were enrolled, 24 suffered from hemorrhage. We performed an anatomically based tractography of the CST with a mean minimal fractional anisotropy of 0.22 ± 0.04 before and after cranial distortion correction (CDC). Accuracy was measured by anatomical plausibility and aberrant fibers. Results: CDC led to a more precise CST tractography, further approximating its assumed anatomical localization in all cases. CDC resulted in a significantly more ventral location of the CST of 1.5 ± 0.6 mm (6.1 ± 2.7 mm before CDC vs. 4.6 ± 2.1 mm after CDC; p

Background: Navigated repetitive transcranial magnetic stimulation (nrTMS) is effective therapy for stroke patients. Neurorehabilitation could be supported by low-frequency stimulation of the non-damaged hemisphere to reduce transcallosal inhibition. Objective: The present study examines the effect of postoperative nrTMS therapy of the unaffected hemisphere in glioma patients suffering from acute surgery-related paresis of the upper extremity (UE) due to subcortical ischemia. Methods: We performed a randomized, sham-controlled, double-blinded trial on patients suffering from acute surgery-related paresis of the UE after glioma resection. Patients were randomly assigned to receive either low frequency nrTMS (1 Hz, 15 min) or sham stimulation directly before physical therapy for 7 consecutive days. We performed primary and secondary outcome measures on day 1, on day 7, and at a 3-month follow-up (FU). The primary endpoint was the change in Fugl-Meyer Assessment (FMA) at FU compared to day 1 after surgery. Results: Compared to the sham stimulation, nrTMS significantly improved outcomes between day 1 and FU based on the FMA (mean [95% CI] +31.9 [22.6, 41.3] vs. +4.2 [-4.1, 12.5]; P = .001) and the National Institutes of Health Stroke Scale (NIHSS) (−5.6 [-7.5, −3.6] vs. −2.4 [-3.6, −1.2]; P = .02). To achieve a minimal clinically important difference of 10 points on the FMA scale, the number needed to treat is 2.19. Conclusion: The present results show that patients suffering from acute surgery-related paresis of the UE due to subcortical ischemia after glioma resection significantly benefit from low-frequency nrTMS stimulation therapy of the unaffected hemisphere. Clinical trial registration: Local institutional registration: 12/15; ClinicalTrials.gov number: NCT03982329

The neural representation of language can be identified cortically using navigated repetitive transcranial magnetic stimulation and subcortically using the fiber tracking of diffusion tensor imaging. We investigated how cortical locations of language and language-eloquent white matter pathways differ in 40 brain lesion patients speaking various languages. Error rates related to stimulations at single sites in the frontal and parietal lobe differed significantly between Balto-Slavic and Indo-European languages. Error rates related to stimulations at single sites in the temporal lobe differed significantly between bilingual individuals. No differences were found in the white matter language pathway volumes between Balto-Slavic and Indo-European languages nor between bilingual patients. These original and exploratory data indicate that the underlying subcortical structure might be similar across languages, with initially observed differences in the cortical location of language depending on the semantic processing, but these could not be confirmed using detailed statistical analyses pointing at a similar cortical and subcortical network.

BackgroundRepetitive neuromuscular magnetic stimulation (rNMS) of the trapezius muscles showed beneficial effects in preventing episodic migraine. However, clinical characteristics that predict a favorable response to rNMS are unknown. The objective of this analysis is to identify such predictors.MethodsThirty participants with a diagnosis of episodic migraine (mean age: 24.8 ± 4.0 years, 29 females), who were prospectively enrolled in two non-sham-controlled studies evaluating the effects of rNMS were analyzed. In these studies, the interventional stimulation of the bilateral trapezius muscles was applied in six sessions and distributed over two consecutive weeks. Baseline and follow-up assessments included the continuous documentation of a headache calendar over 30 days before and after the stimulation period, the Migraine Disability Assessment Score (MIDAS) questionnaire (before stimulation and 90 days after stimulation), and measurements of pain pressure thresholds (PPTs) above the trapezius muscles by algometry (before and after each stimulation session). Participants were classified as responders based on a ≥25% reduction in the variable of interest (headache frequency, headache intensity, days with analgesic intake, MIDAS score, left-sided PPTs, right-sided PPTs). Post-hoc univariate and multivariate binary logistic regression analyses were performed.ResultsLower headache frequency (P = 0.016) and intensity at baseline (P = 0.015) and a migraine diagnosis without a concurrent tension-type headache component (P = 0.011) were significantly related to a ≥25% reduction in headache frequency. Higher headache frequency (P = 0.052) and intensity at baseline (P = 0.014) were significantly associated with a ≥25% reduction in monthly days with analgesic intake. Lower right-sided PPTs at baseline were significantly related to a ≥25% increase in right-sided PPTs (P = 0.015) and left-sided PPTs (P =0.030). Performance of rNMS with higher stimulation intensities was significantly associated with a ≥25% reduction in headache intensity (P = 0.046).ConclusionsClinical headache characteristics at baseline, the level of muscular hyperalgesia, and stimulation intensity may inform about how well an individual patient responds to rNMS. These factors may allow an early identification of patients that would most likely benefit from rNMS.

Abstract Radiolucent carbon-fiber-reinforced (CFR) polyethyl-ether-ether-ketone (PEEK) has been established in spinal instrumentation for oncological reasons. Laboratory data reported comparable bacterial adhesion as titanium. Thus, using of CFR-PEEK spinal instrumentation for spondylodiscitis bases on artifact-free imaging to evaluate therapeutic success. Studies comparing the rate of pedicle screw loosening and relapse of spondylodiscitis following titanium versus CFR-PEEK instrumentation do not exist so far. This study evaluates the rate of pedicle screw loosening and recurrence of spondylodiscitis after CFR-PEEK instrumentation for spondylodiscitis compared to titanium. We conducted a prospective single center study between June 2018 and March 2019 on consecutive 23 patients with thoracolumbar spondylodiscitis. Imaging data was evaluated for screw loosening at a minimum of three months after surgery. A matched-pair analysis was performed using spondylodiscitis cases between 2014 and 2016 using titanium instrumentation for equal localization, surgery, and microorganism class. Among 17 cases with follow-up imaging, six cases (35%) showed screw loosening while only 14% (two patients) with titanium instrumentation were loosened (p = 0.004). In both groups the most frequent bacterium was Staphylococcus aureus, followed by Staphylococcus epidermidis. From the S. aureus cases, one infection in both groups was caused by methicillin resistant species (MRSA). No difference was found in the rate of 360° fusion in either group due to matching criteria. As opposed to other indications CFR-PEEK screws show more loosening than titanium in this series with two potentially underlying reasons: a probably stronger bacterial adhesion on CFR-PEEK in vivo as shown by a statistical trend in vitro and instrumentation of spondylytic vertebrae. Until these factors are validated, we advise caution when implanting CFR-PEEK screws in infectious cases.

We present three cases fulfilling diagnostic criteria of hemorrhagic variants of acute disseminated encephalomyelitis (acute hemorrhagic encephalomyelitis, AHEM) occurring within 9 days after the first shot of ChAdOx1 nCoV-19. AHEM was diagnosed using magnetic resonance imaging, cerebrospinal fluid analysis and brain biopsy in one case. The close temporal association with the vaccination, the immune-related nature of the disease as well as the lack of other canonical precipitating factors suggested that AHEM was a vaccine-related adverse effect. We believe that AHEM might reflect a novel COVID-19 vaccine-related adverse event for which physicians should be vigilant and sensitized.

BackgroundPerioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions.Materials and MethodsSeven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change.ResultsWe observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity.ConclusionUsing a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill.

Introduction: To achieve a maximum extent of resection, intraoperative MRI (ioMRI) scan is frequently performed. Intraoperative diffusion-weighted imaging (DWI) is not standardly performed and has been described to be inferior to early postoperative MRI regarding the detection of ischemia. Research question: This feasibility study evaluates the detection of ischemia by ioMRI and its clinical relevance in patients with motor-eloquent gliomas. Material and methods: Of 262 glioma patients, eight patients (3.1%) showed an amplitude loss of continuous motor evoked potential (MEP) monitoring during resection before the ioMRI scan (group loss of MEP ​= ​LOM). In these patients and a matched-pair cohort (MPC) of glioma resections without MEP loss, we performed additional ioMRI sequences including turbo-spin-echo (TSE)- and echo-planar-imaging (EPI)-DWI and perfusion-weighted imaging (PWI). The clinical outcome was measured 5 days and 3 months after surgery. Results: The mean ​± ​standard time between loss of MEPs and ioMRI was 63.0 ​± ​8.7 ​min (range: 40–84). Ischemia within the motor system could be detected by ioMRI in group LOM in 100% EPI-DWIs, 75% TSE-DWIs, and 66.7% PWIs. No sequence showed motor ischemia in the MPC group. All patients of group LOM and no patient of group MPC suffered from permanent motor deficit. Discussion and conclusion: The current results provide data on the time sequence of ischemia apparent in MRI sequences which is superior to previous data on symptomatic stroke patients on this topic. The early detection of ischemia adds an additional predictor for the long-term outcome of patients and shows the reason of an intraoperative loss of MEPs. Thereby the performance of intraoperative EPI-DWI might be justified after confirmation of the present data in a larger cohort.Subcortical ischemia can be detected by ioMRI after MEP loss during the resection of motor-eloquent gliomas and was clinically relevant in all cases.

Introduction: Surgical treatment for CCS in patients with an underlying cervical stenosis without instability remains controversial. Research question: The aim was to assess the incidence of concomitant discoligamentous injury (DLI) in patients with CCS and underlying degenerative cervical spinal stenosis and to determine the sensitivity of MRI by comparing intraoperative site inspection to preoperative imaging findings. Material and methods: We performed a retrospective analysis of our clinical prospective database. Fifty-one patients (39 male, 12 female) between January 2010 and June 2019 were included. Age, sex, neurological deficits, preoperative MRI, and surgical treatment were recorded. Sensitivity was determined by the quotient of patients in whom all levels of DLI were correctly identified on MRI and the total number of patients with intraoperatively confirmed DLI. Results: Mean age at surgery was 64.1 ​± ​11.3 (range 41–86). DLI was suspected in 33 (62.1%) patients based on MRI findings, which could be confirmed intraoperatively in 29 patients (56.9%). In 2 patients, DLI was detected intraoperatively that was not suspected in preoperative MRI; in 5 patients, another level was affected intraoperatively than was indicated by MRI. The overall specificity and sensitivity of preoperative MRI imaging to identify discoligamentous lesions of the cervical spine was 73% and 79%, respectively. Discussion and conclusion: The incidence of DLI in patients with traumatic CCS based on preexisting spinal stenosis was 60.78%, which is higher than previously reported. The sensitivity of MRI imaging to detect DLI of 79% suggests that these patients are at risk of missing traumatic DLI on imaging.

While the diagnosis of high-grade glioma (HGG) is still associated with a considerably poor prognosis, neurosurgical tumor resection provides an opportunity for prolonged survival and improved quality of life for affected patients. However, successful tumor resection is dependent on a proper surgical planning to avoid surgery-induced functional deficits whilst achieving a maximum extent of resection (EOR). With diffusion magnetic resonance imaging (MRI) providing insight into individual white matter neuroanatomy, the challenge remains to disentangle that information as correctly and as completely as possible. In particular, due to the lack of sensitivity and accuracy, the clinical value of widely used diffusion tensor imaging (DTI)-based tractography is increasingly questioned. We evaluated whether the recently developed multi-level fiber tracking (MLFT) technique can improve tractography of the corticospinal tract (CST) in patients with motor-eloquent HGGs. Forty patients with therapy-naïve HGGs (mean age: 62.6 ± 13.4 years, 57.5% males) and preoperative diffusion MRI [repetition time (TR)/echo time (TE): 5000/78 ms, voxel size: 2x2x2 mm3, one volume at b=0 s/mm2, 32 volumes at b=1000 s/mm2] underwent reconstruction of the CST of the tumor-affected and unaffected hemispheres using MLFT in addition to deterministic DTI-based and deterministic constrained spherical deconvolution (CSD)-based fiber tractography. The brain stem was used as a seeding region, with a motor cortex mask serving as a target region for MLFT and a region of interest (ROI) for the other two algorithms. Application of the MLFT method substantially improved bundle reconstruction, leading to CST bundles with higher radial extent compared to the two other algorithms (delineation of CST fanning with a wider range; median radial extent for tumor-affected vs. unaffected hemisphere – DTI: 19.46° vs. 18.99°, p=0.8931; CSD: 30.54° vs. 27.63°, p=0.0546; MLFT: 81.17° vs. 74.59°, p=0.0134). In addition, reconstructions by MLFT and CSD-based tractography nearly completely included respective bundles derived from DTI-based tractography, which was however favorable for MLFT compared to CSD-based tractography (median coverage of the DTI-based CST for affected vs. unaffected hemispheres – CSD: 68.16% vs. 77.59%, p=0.0075; MLFT: 93.09% vs. 95.49%; p=0.0046). Thus, a more complete picture of the CST in patients with motor-eloquent HGGs might be achieved based on routinely acquired diffusion MRI data using MLFT.

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions.

Navigated Transcranial Magnetic Stimulation (nTMS) is used to understand the cortical organization of language in preparation for the surgical removal of a brain tumor. Action naming with finite verbs can be employed for that purpose, providing additional information to object naming. However, little research has focused on the properties of the verbs that are used in action naming tasks, such as their status as transitive (taking an object; e.g., to read) or intransitive (not taking an object; e.g., to wink). Previous neuroimaging data show higher activation for transitive compared to intransitive verbs in posterior perisylvian regions bilaterally. In the present study, we employed nTMS and production of finite verbs to investigate the cortical underpinnings of transitivity. Twenty neurologically healthy native speakers of German participated in the study. They underwent language mapping in both hemispheres with nTMS. The action naming task with finite verbs consisted of transitive (e.g., The man reads the book) and intransitive verbs (e.g., The woman winks) and was controlled for relevant psycholinguistic variables. Errors were classified in four different error categories (i.e., non-linguistic errors, grammatical errors, lexico-semantic errors and, errors at the sound level) and were analyzed quantitatively. We found more nTMS-positive points in the left hemisphere, particularly in the left parietal lobe for the production of transitive compared to intransitive verbs. These positive points most commonly corresponded to lexico-semantic errors. Our findings are in line with previous aphasia and neuroimaging studies, suggesting that a more widespread network is used for the production of verbs with a larger number of arguments (i.e., transitives). The higher number of lexico-semantic errors with transitive compared to intransitive verbs in the left parietal lobe supports previous claims for the role of left posterior areas in the retrieval of argument structure information.

Abstract Background It is difficult to set up a balanced higher-order full-factorial experiment that can capture multiple intricate interactions between cognitive and psycholinguistic factors underlying bilingual speech production. To capture interactions more fully in one study, we analyzed object-naming reaction times (RTs) by using mixed-effects multiple regression. Methods Ten healthy bilinguals (median age: 23 years, seven females) were asked to name 131 colored pictures of common objects in each of their languages. RTs were analyzed based on language status, proficiency, word choice, word frequency, word duration, initial phoneme, time series, and participant’s gender. Results Among five significant interactions, new findings include a facilitating effect of a cross-language shared initial phoneme (mean RT for shared phoneme: 974 ms vs. mean RT for different phoneme: 1020 ms), which profited males less (mean profit: 10 ms) than females (mean profit: 47 ms). Conclusions Our data support language-independent phonological activation and a gender difference in inhibitory cognitive language control. Single word production process in healthy adult bilinguals is affected by interactions among cognitive, phonological, and semantic factors.

Introduction The main surgical dilemma during glioma resections is the surgeon’s inability to accurately identify eloquent areas when the patient is under general anaesthesia without mapping techniques. Intraoperative stimulation mapping (ISM) techniques can be used to maximise extent of resection in eloquent areas yet simultaneously minimise the risk of postoperative neurological deficits. ISM has been widely implemented for low-grade glioma resections backed with ample scientific evidence, but this is not yet the case for high-grade glioma (HGG) resections. Therefore, ISM could thus be of important value in HGG surgery to improve both surgical and clinical outcomes.Methods and analysis This study is an international, multicenter, prospective three-arm cohort study of observational nature. Consecutive HGG patients will be operated with awake mapping, asleep mapping or no mapping with a 1:1:1 ratio. Primary endpoints are: (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery and (2) residual tumour volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: (1) overall survival and (2) progression-free survival at 12 months after surgery; (3) oncofunctional outcome and (4) frequency and severity of serious adverse events in each arm. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.Ethics and dissemination The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020–0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.Trial registration number ClinicalTrials.gov ID number NCT04708171 (PROGRAM-study), NCT03861299 (SAFE-trial)

Introduction: Spinal cord herniation (SCH) is a rare cause of progressive myelopathy and Brown-Séquard-Syndrome. Research question: Evaluation of functional outcome after SCH treatment compared to conservatively treated patients. Material and methods: We retrospectively analysed functional outcome in SCH patients treated between 2009 and 2020. We conducted a systematic search using PubMed, MEDLINE and EMBASE to perform a pooled analysis in SCH patients. Results: Our hospital cohort included 17 patients of which 9 were treated surgically. Mean age was 51.9 years, 58.8% of the patients were female. In 4/9 patients (44.4%) the neurological state remained stable after surgery. Four patients improved (44.4%) and one deteriorated after surgery (11.1%). Conservatively treated patients had a higher deterioration rate on follow-up with 3/8 patients deteriorating (37.5%). In our pooled analysis, 109/145 (75.2%) of patients improved, 32/145 (22.1%) remained stable and 4/145 patients deteriorated (2.8%). Among the available data of nine cohorts, mean recovery rate measured by the JOA score was 36.6% (SD 14.4). In our pooled multivariable model lower preoperative JOA score was associated with worse functional outcome (OR 0.86, 95%CI 0.74–0.99, p ​= ​.04). Discussion and conclusion: Our data shows that patients who are treated surgically have a higher improvement rate and acceptable perioperative morbidity compared to conservatively treated patients. Lower preoperative JOA score decreases chances of improved functional outcome on follow-up. We therefore advocate early surgery for symptomatic patients. Wait and see appears outdated due to progressive impairment and decreased chances of recovery. However, it is still an option in asymptomatic incidental SCH patients.

Abstract Background Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. Methods Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. Results The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. Conclusions Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Objective: The adult brain’s potential for plastic reorganization is an important mechanism for the preservation and restoration of function in patients with primary glial neoplasm. Patients with recurrent brain tumors requiring multiple interventions over time present an opportunity to examine brain reorganization. Magnetoencephalography (MEG) is a noninvasive imaging modality that can be used for motor cortical network mapping which, when performed at regular intervals, offers insight into this process of reorganization. Utilizing MEG-based motor mapping, we sought to characterize the reorganization of motor cortical networks over time in a cohort of 78 patients with recurrent glioma.Methods: MEG-based motor cortical maps were obtained by measuring event-related desynchronization (ERD) in ß-band frequency during unilateral index finger flexion. Each patient presented at our Department at least on two occasions for tumor resection due to tumor recurrence, and MEG-based motor mapping was performed as part of preoperative assessment before each surgical resection. Whole-brain activation patterns from first to second MEG scan (obtained before first and second surgery) were compared. Additionally, we calculated distances of activation peaks, which represent the location of the primary motor cortex (MC), to determine the magnitude of movement in motor eloquent areas between the first and second MEG scan. We also explored which demographic, anatomic, and pathological factors influence these shifts.Results: The whole-brain activation motor maps showed a subtle movement of the primary MC from first to second timepoint, as was confirmed by the determination of motor activation peaks. The shift of ipsilesional MC was directly correlated with a frontal-parietal tumor location (p < 0.001), presence of motor deficits (p = 0.021), and with a longer period between MEG scans (p = 0.048). Also, a disengagement of wide areas in the contralesional (ipsilateral to finger movement) hemisphere at the second time point was observed.Conclusions: MEG imaging is a sensitive method for depicting the plasticity of the motor cortical network. Although the location of the primary MC undergoes only subtle changes, appreciable shifts can occur in the setting of a stronger and longer impairment of the tumor on the MC. The ipsilateral hemisphere may serve as a reservoir for functional recovery.

Abstract Background The treatment recommendations for Low-grade Gliomas (LGG) underwent profound changes due to results from RTOG 9802 published in April 2016. This work aims to investigate whether the results from the trial were already incorporated into the treatment recommendations at German oncology centers before an update of the official guidelines. Methods An online based questionnaire with questions covering all aspects of adjuvant treatments of LGGs was generated, including three cases with distinct clinical situations. We contacted all members of the neuro-oncologic working group (NOA) of the German Cancer Society (DKG) as well as all German-speaking members of the European Low-Grade Glioma Network via E-mail. Results We collected 38 responses. All responders were at least specialists; they predominantly worked at tertiary hospitals with a high volume of LGGs treated annually (75% with more than 10 cases per year). All responders stated to consent treatment recommendation for LGGs within interdisciplinary oncologic boards. The treatment recommendations for LGGs changed profoundly between 2015 and 12/2016. There is a trend towards PCV-based multimodal treatments, especially for oligodendroglial LGGs, as well as a trend away from watchful-waiting-policies for astrocytic LGGs. Conclusion Neurooncologists do adapt results from clinical trials quickly. None the less, there is still an immense heterogeneity within the treatment recommendations, predominantly for astrocytic LGGs. Well planned clinical trials and concise treatment recommendations are warranted; additionally, individual counseling of patients is essential.

Abstract Background Visuospatial attention is executed by the frontoparietal cortical areas of the brain. Damage to these areas can result in visual neglect. We therefore aimed to assess a combination of the greyscales task and repetitive navigated transcranial magnetic stimulation (rTMS) to identify cortical regions involved in visuospatial attention processes. This pilot study was designed to evaluate an approach in a cohort of healthy volunteers, with the future aim of using this technique to map brain tumor patients before surgery. Ten healthy, right-handed subjects underwent rTMS mapping of 52 cortical spots in both hemispheres. The greyscales task was presented tachistoscopically and was time-locked to rTMS pulses. The task pictures showed pairs of horizontal rectangles shaded continuously from black at one end to white at the other, mirror-reversed. On each picture the subject was asked to report which of the two greyscales appeared darker overall. The responses were categorized into “leftward” and “rightward,” depending on whether the subject had chosen the rectangle with the darker end on the left or the right. rTMS applied to cortical areas involved in visuospatial attention is supposed to affect lateral shifts in spatial bias. These shifts result in an altered performance on the greyscales task compared to the baseline performance without rTMS stimulation. Results In baseline conditions, 9/10 subjects showed classic pseudoneglect to the left. Leftward effects also occurred more often in mapping conditions. Yet, calculated rightward deviations were strikingly greater in magnitude (p

Argon has shown neuroprotective effects after traumatic brain injury (TBI) and cerebral ischemia in vitro and in focal cerebral ischemia in vivo. The purpose of this study is to show whether argon beneficially impacts brain contusion volume (BCV) as the primary outcome parameter, as well as secondary outcome parameters, such as brain edema, intracranial pressure (ICP), neurological outcome, and cerebral blood flow (CBF) in an in-vivo model. Subjects were randomly assigned to either argon treatment or room air. After applying controlled cortical impact (CCI) onto the dura with 8 m/s (displacement 1 mm, impact duration 150 ms), treatment was administered by a recovery chamber with 25%, 50%, or 75% argon and the rest being oxygen for 4 h after trauma. Two control groups received room air for 15 min and 24 h, respectively. Neurological testing and ICP measurements were performed 24 h after trauma, and brains were removed to measure secondary brain damage. The primary outcome parameter, BCV, and the secondary outcome parameter, brain edema, were not significantly reduced by argon treatment at any concentration. There was a highly significant decrease in ICP at 50% argon (p = 0.001), and significant neurological improvement (beamwalk missteps) at 25% and 50% argon (p = 0.01; p = 0.049 respectively) compared to control.

Background: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. Methods: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. Discussion: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming.

Introduction Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting.Methods and analysis Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan.Ethics and dissemination The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal.Trial registration number Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage.

Purpose: Repetitive peripheral magnetic stimulation (rPMS) has been successfully applied recently in migraineurs to alleviate migraine symptoms. Symptom relief has been achieved by stimulating myofascial trigger points (mTrPs) of the trapezius muscles, which are considered part of the trigemino-cervical complex (TCC). However, effects on musculature have not been assessed in detail, and the specificity of effects to muscles considered part of the TCC yet has to be elucidated. Against this background, this study presents the setup of rPMS in migraine and evaluates effects on skeletal musculature.Materials and Methods: Thirty-seven adults (mean age: 25.0 ± 4.1 years, 36 females) suffering from migraine and presenting mTrPs according to physical examination underwent rPMS either to mTrPs in the trapezius muscles (considered part of the TCC; n = 19) or deltoid muscles (considered not part of the TCC; n = 18) during six sessions over the course of 2 weeks. Standardized questionnaires were filled in to assess any adverse events and experience with rPMS as well as satisfaction and benefits from stimulation. Algometry was performed to evaluate changes in pressure pain thresholds (PPTs).Results: All stimulation sessions were successfully performed without adverse events, with 84.2% of subjects of the trapezius group and 94.4% of subjects of the deltoid group describing rPMS as comfortable (p = 0.736). Muscular pain or tension improved in 73.7% of subjects of the trapezius group and in 61.1% of subjects of the deltoid group (p = 0.077). PPTs of the trapezius muscles clearly increased from the first to the last stimulation sessions—regardless of the stimulated muscle (rPMS to the trapezius or deltoid muscles). However, depending on the examined muscles the increase of PPTs differed significantly (subjects with stimulation of trapezius muscles: p = 0.021; subjects with stimulation of deltoid muscles: p = 0.080).Conclusion: rPMS is a comfortable method in migraineurs that can improve local muscular pain or tension. Furthermore, it is able to increase directly and indirectly the PPTs of the trapezius muscles (considered part of the TCC) when applied over mTrPs, supporting the role of the TCC in migraineurs.

Background: Functional reorganization (FR) was shown in glioma patients by direct electrical stimulation (DES) during awake craniotomy. This option for repeated mapping is available in cases of tumor recurrence and after decision for a second surgery. Navigated repetitive transcranial magnetic stimulation (nrTMS) has shown a high correlation with results of DES during awake craniotomy for language-negative sites (LNS) and allows for a non-invasive evaluation of language function. This preliminary study aims to examine FR in glioma patients by nrTMS.Methods: A cohort of eighteen patients with left-sided perisylvian gliomas underwent preoperative nrTMS language mapping twice. The mean time between mappings was 17 ± 12 months. The cortex was separated into anterior and posterior language-eloquent regions. We defined a tumor area and an area without tumor (WOT). Error rates (ER = number of errors per number of stimulations) and hemispheric dominance ratios (HDR) were calculated as the quotient of the left- and right-sided ER.Results: In cases in which most language function was located near the tumor during the first mapping, we found significantly more LNS in the tumor area during the second mapping as compared to cases in which function was not located near the tumor (p = 0.049). Patients with seizures showed fewer LNS during the second mapping. We found more changes of cortical language function in patients with a follow-up time of more than 13 months and lower WHO-graded tumors.Conclusion: Present results confirm that nrTMS can show FR of LNS in glioma patients. Its extent, clinical impact and correlation with DES requires further evaluation but could have a considerable impact in neuro-oncology.

Screw placement in the correct angular trajectory is one of the most intricate tasks during spinal fusion surgery. Due to the crucial role of pedicle screw placement for the outcome of the operation, spinal navigation has been introduced into the clinical routine. Despite its positive effects on the precision and safety of the surgical procedure, local separation of the navigation information and the surgical site, combined with intricate visualizations, limit the benefits of the navigation systems. Instead of a tech-driven design, a focus on usability is required in new research approaches to enable advanced and effective visualizations. This work presents a new tool-mounted interface (TMI) for pedicle screw placement. By fixing a TMI onto the surgical instrument, physical de-coupling of the anatomical target and navigation information is resolved. A total of 18 surgeons participated in a usability study comparing the TMI to the state-of-the-art visualization on an external screen. With the usage of the TMI, significant improvements in system usability (Kruskal–Wallis test p < 0.05) were achieved. A significant reduction in mental demand and overall cognitive load, measured using a NASA-TLX (p < 0.05), were observed. Moreover, a general improvement in performance was shown by means of the surgical task time (one-way ANOVA p < 0.001).

Navigated transcranial magnetic stimulation (nTMS) has developed into a reliable non-invasive clinical and scientific tool over the past decade. Specifically, it has undergone several validating clinical trials that demonstrated high agreement with intraoperative direct electrical stimulation (DES), which paved the way for increasing application for the purpose of motor mapping in patients harboring motor-eloquent intracranial neoplasms. Based on this clinical use case of the technique, in this article we review the evidence for the feasibility of motor mapping and derived models (risk stratification and prediction, nTMS-based fiber tracking, improvement of clinical outcome, and assessment of functional plasticity), and provide collected sets of evidence for the applicability of quantitative mapping with nTMS. In addition, we provide evidence-based demonstrations on factors that ensure methodological feasibility and accuracy of the motor mapping procedure. We demonstrate that selection of the stimulation intensity (SI) for nTMS and spatial density of stimuli are crucial factors for applying motor mapping accurately, while also demonstrating the effect on the motor maps. We conclude that while the application of nTMS motor mapping has been impressively spread over the past decade, there are still variations in the applied protocols and parameters, which could be optimized for the purpose of reliable quantitative mapping.

Navigated transcranial magnetic stimulation (nTMS) is a modality for noninvasive cortical mapping. Specifically, nTMS motor mapping is an objective measure of motor function, offering quantitative diagnostic information regardless of subject cooperation or consciousness. Thus far, it has mostly been restricted to the outpatient setting. This study evaluates the feasibility of nTMS motor mapping in the intensive care unit (ICU) setting and solves the challenges encountered in this special environment. We compared neuronavigation based on computed tomography (CT) and magnetic resonance imaging (MRI). We performed motor mappings in neurocritical patients under varying conditions (e.g., sedation or hemicraniectomy). Furthermore, we identified ways of minimizing electromyography (EMG) noise in the interference-rich ICU environment. Motor mapping was performed in 21 patients (six females, median age: 69 years). In 18 patients, motor evoked potentials (MEPs) were obtained. In three patients, MEPs could not be evoked. No adverse reactions occurred. We found CT to offer a comparable neuronavigation to MRI (CT maximum e-field 52 ± 14 V/m vs. MRI maximum e-field 52 ± 11 V/m; p = 0.6574). We detailed EMG noise reduction methods and found that propofol sedation of up to 80 mcg/kg/h did not inhibit MEPs. Yet, nTMS equipment interfered with exposed pulse oximetry. nTMS motor mapping application and use was illustrated in three clinical cases. In conclusion, we present an approach for the safe and reliable use of nTMS motor mapping in the ICU setting and outline possible benefits. Our findings support further studies regarding the clinical value of nTMS in critical care settings.

To date, the structural characteristics that distinguish language-involved from non-involved cortical areas are largely unclear. Particularly in patients suffering from language-eloquent brain tumors, reliable mapping of the cortico-subcortical language network is of high clinical importance to prepare and guide safe tumor resection. To investigate differences in structural characteristics between language-positive and language-negative areas, 20 patients (mean age: 63.2 ± 12.9 years, 16 males) diagnosed with language-eloquent left-hemispheric glioblastoma multiforme (GBM) underwent preoperative language mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT). The number of language-positive and language-negative points as well as the gray matter intensity (GMI), normalized volumes of U-fibers, interhemispheric fibers, and fibers projecting to the cerebellum were assessed and compared between language-positive and language-negative nTMS mappings and set in correlation with aphasia grades. We found significantly lower GMI for language-positive nTMS points (5.7 ± 1.7 versus 7.1 ± 1.6, p = 0.0121). Furthermore, language-positive nTMS points were characterized by an enhanced connectivity profile, i.e., these points showed a significantly higher ratio in volumes for U-fibers (p ≤ 0.0056), interhemispheric fibers (p = 0.0494), and fibers projecting to the cerebellum (p = 0.0094). The number of language-positive nTMS points (R ≥ 0.4854, p ≤ 0.0300) as well as the ratio in volumes for U-fibers (R ≤ −0.4899, p ≤ 0.0283) were significantly associated with aphasia grades, as assessed pre- or postoperatively and during follow-up examinations. In conclusion, this study provides evidence for structural differences on cortical and subcortical levels between language-positive and language-negative areas, as detected by nTMS language mapping. The results may further increase confidence in the technique of nTMS language mapping and nTMS-based tractography in the direct clinical setting. Future studies may confirm our results in larger cohorts and may expand the findings to patients with other tumor entities than GBM.