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Abstract Background Microsurgical clipping is a delicate neurosurgical procedure used to treat complex Unruptured Intracranial Aneurysms (UIAs) whose outcome is dependent on surgeon’s experience. Simulations are emerging as excellent complements to standard training, but their adoption is limited by the realism they provide. The aim of this study was to develop and validate a microsurgical clipping simulator platform. Methods Physical and holographic simulators of UIA clipping have been developed. The physical phantom consisted of a 3D printed hard skull and five (n = 5) rapidly interchangeable, perfused and fluorescence compatible 3D printed aneurysm silicone phantoms. The holographic clipping simulation included a real-time finite-element-model of the aneurysm sac, allowing interaction with a virtual clip and its occlusion. Validity, usability, usefulness and applications of the simulators have been assessed through clinical scores for aneurysm occlusion and a questionnaire study involving 14 neurosurgical residents (R) and specialists (S) for both the physical (p) and holographic (h) simulators by scores going from 1 (very poor) to 5 (excellent). Results The physical simulator allowed to replicate successfully and accurately the patient-specific anatomy. UIA phantoms were manufactured with an average dimensional deviation from design of 0.096 mm and a dome thickness of 0.41 ± 0.11 mm. The holographic simulation executed at 25–50 fps allowing to gain unique insights on the anatomy and testing of the application of several clips without manufacturing costs. Aneurysm closure in the physical model evaluated by fluorescence simulation and post-operative CT revealed Raymond 1 (full) occlusion respectively in 68.89% and 73.33% of the cases. For both the simulators content validity, construct validity, usability and usefulness have been observed, with the highest scores observed in clip selection usefulness Rp=4.78, Sp=5.00 and Rh=4.00, Sh=5.00 for the printed and holographic simulators. Conclusions Both the physical and the holographic simulators were validated and resulted usable and useful in selecting valid clips and discarding unsuitable ones. Thus, they represent ideal platforms for realistic patient-specific simulation-based training of neurosurgical residents and hold the potential for further applications in preoperative planning.

Abstract Introduction With the application of high-resolution 3D 7 Tesla Magnetic Resonance Spectroscopy Imaging (MRSI) in high-grade gliomas, we previously identified intratumoral metabolic heterogeneities. In this study, we evaluated the potential of 3D 7 T-MRSI for the preoperative noninvasive classification of glioma grade and isocitrate dehydrogenase (IDH) status. We demonstrated that IDH mutation and glioma grade are detectable by ultra-high field (UHF) MRI. This technique might potentially optimize the perioperative management of glioma patients. Methods We prospectively included 36 patients with WHO 2021 grade 2–4 gliomas (20 IDH mutated, 16 IDH wildtype). Our 7 T 3D MRSI sequence provided high-resolution metabolic maps (e.g., choline, creatine, glutamine, and glycine) of these patients’ brains. We employed multivariate random forest and support vector machine models to voxels within a tumor segmentation, for classification of glioma grade and IDH mutation status. Results Random forest analysis yielded an area under the curve (AUC) of 0.86 for multivariate IDH classification based on metabolic ratios. We distinguished high- and low-grade tumors by total choline (tCho) / total N-acetyl-aspartate (tNAA) ratio difference, yielding an AUC of 0.99. Tumor categorization based on other measured metabolic ratios provided comparable accuracy. Conclusions We successfully classified IDH mutation status and high- versus low-grade gliomas preoperatively based on 7 T MRSI and clinical tumor segmentation. With this approach, we demonstrated imaging based tumor marker predictions at least as accurate as comparable studies, highlighting the potential application of MRSI for pre-operative tumor classifications.

Abstract Background So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). Methods Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. Results Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. Conclusion Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management.

Abstract Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype–phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin–eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype–phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration.

Abstract Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents’ opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

Introduction: Directional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads. Research question: The European Association of Neurosurgical Societies(EANS) functional neurosurgery Task Force on dLeads conducted a survey of DBS specialists in Europe to evaluate their use, applications, advantages, and disadvantages. Material and methods: EANS functional neurosurgery and European Society for Stereotactic and Functional Neurosurgery (ESSFN) members were asked to complete an online survey with 50 multiple-choice and open questions on their use of dLeads in clinical practice. Results: Forty-nine respondents from 16 countries participated in the survey (n = 38 neurosurgeons, n = 8 neurologists, n = 3 DBS nurses). Five had not used dLeads. All users reported that dLeads provided an advantage (n = 23 minor, n = 21 major). Most surgeons (n = 35) stated that trajectory planning does not differ when implanting dLeads or conventional leads. Most respondents selected dLeads for the ability to optimize stimulation parameters (n = 41). However, the majority (n = 24), regarded time-consuming programming as the main disadvantage of this technology. Innovations that were highly valued by most participants included full 3T MRI compatibility, remote programming, and closed loop technology. Discussion and conclusion: Directional leads are widely used by European DBS specialists. Despite challenges with programming time, users report that dLeads have had a positive impact and maintain an optimistic view of future technological advances.

ObjectiveThe purpose of this study was to present the first comprehensive analysis of perioperative quality indicators; length of hospital stay; readmission; reoperation; pre-, intra, and postoperative events; and mortality in a diverse neurosurgical patient cohort in Europe.MethodsElectronic medical records of all patients who were admitted to our institution between January 1 and December 31 of 2020, and underwent an index neurosurgical operation (n = 1142) were retrospectively reviewed.ResultsThe median length of hospital stay at the index admission and readmission was 8 days (range: 1-242 days) and 5 days (range: 0-94 days), respectively. Of the 1142 patients, 22.9% (n = 262) had an extended length of hospital stay of ≥14 days. The all-cause 7-, 15-, 30-, 60-, and 90-day readmission rates were 3.9% (n = 44), 5.7% (n = 65), 8.8% (n = 100), 12.3% (n = 141), and 16.5% (n = 188), respectively. The main reason for unplanned readmission was deterioration of medical and/or neurological condition. The all-cause 7-, 15-, 30-, 60-, and 90-day reoperation rates were 11.1% (n = 127), 13.8% (n = 158), 16.5% (n = 189), 18.7% (n = 213), and 19.4% (n = 221), respectively. Unplanned reoperations were due primarily to hydrocephalus. The rate of preoperative events was 1.1% (n = 13), one-third of which were associated with infection. The rate of intraoperative events was 11.0% (n = 126), of which 98 (64.47%) were surgical, 37 (24.34%) were anesthesiologic, and 17 (11.18%) were associated with technical equipment. The rate of postoperative events was 9.5% (n = 109). The most common postoperative event was malfunction, disconnection, or dislocation of an implanted device (n = 24, 17.91%). The mortality rates within 7, 15, 30, 60, and 90 days after the index operation were 0.9% (n = 10), 1.8% (n = 21), 2.5% (n = 29), 3.4% (n = 39), and 4.7% (n = 54), respectively. Several patient characteristics and perioperative factors were significantly associated with outcome parameters.ConclusionsThis study provides an in-depth analysis of quality indicators in neurosurgery, highlighting a variety of inherent and modifiable factors influencing patient outcomes.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Abstract We report the case of a 22-year-old woman presenting with an acute onset of dizziness, gait dysbalance and blurred vision. Magnetic resonance imaging included 3 Tesla and 7 Tesla imaging and revealed a T2-hyperintense, T1-hypointense, non-contrast-enhancing lesion strictly confined to the white matter affecting the right optic radiation. An extensive ophthalmologic examination yielded mild quadrantanopia but no signs of optic neuropathy. The lesion was biopsied. The neuropathological evaluation revealed a demyelinating lesion with marked tissue vacuolization and granular myelin disintegration accompanied by mild T cell infiltration and a notable absence of myelin uptake by macrophages. Oligodendrocytes were strikingly enlarged, displaying oncocytic characteristics and showed cytoplasmic accumulation of mitochondria, which had mildly abnormal morphology on electron microscopy. The diagnosis of multiple sclerosis was excluded. Harding's disease, a variant of Leber's hereditary optic neuropathy, was then suspected. However, neither PCR for relevant mutations nor whole exome sequencing yielded known pathogenetic mutations in the patient's genome. We present a pattern of demyelinating tissue injury of unknown etiology with an oncocytic change of oligodendrocytes and a lack of adequate phagocytic response by macrophages, which to the best of our knowledge, has not been described before.

Abstract Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th–April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017–2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017–2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag.

BackgroundThroughout the last years, the coronavirus disease 2019 (COVID-19) pandemic posed a major challenge to the optimal and timely treatment of neurooncological patients around the world. While the importance of prompt surgical treatment in high-grade gliomas is widely accepted, there is sparse data on the impact of the pandemic on patients suffering from this malignant disease.MethodsWe performed a retrospective analysis of patients undergoing surgical high-grade glioma treatment at the Medical University of Vienna between March 2020 and February 2021, as well as a control cohort of patients who received treatment between January and December 2019. Time lag between referral for surgical treatment to actual surgery, preoperative tumor volume and overall patient survival were compared between groups.ResultsA total of 118 patients, including 62 cases treated during the first year of the COVID-19 pandemic, as well as 56 control patients, were investigated in this study. Median interval to surgery was significantly shorter in patients treated during COVID-19 compared with the control group (4.00 versus 7.00 days; p = 0.0005). In contrast, patients treated during COVID-19 exhibited marginally larger preoperative tumor volumes, while overall patient survival was comparable between groups.ConclusionsThe COVID-19 pandemic did not negatively affect the overall survival of patients undergoing surgical high-grade glioma treatment at our institution. The significantly shorter treatment delay in patients treated during the pandemic likely reflects increased resource allocation for this critical patient population.

Summary: Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain.

Abstract The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th–April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

Summary: Objective: To determine patients’ characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. Methods: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. Results: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8− 14.4%) and fusiform gyrus (decline range: 12.1−18.4%). Significance: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy.Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded.Outcomes: The collected data will be used for establishing standardized reference values (“benchmarks”) for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications.Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials.Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).

Objectives: Successful neurosurgical intervention in gliomas depends on the precision of the preoperative definition of the tumor and its margins since a safe maximum resection translates into a better patient outcome. Metabolic high-resolution imaging might result in improved presurgical tumor characterization, and thus optimized glioma resection. To this end, we validated the performance of a fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in a patient cohort of 23 high-grade gliomas (HGG). Materials and methods: We preoperatively measured 23 patients with histologically verified HGGs (17 male, 8 female, age 53 ± 15) with an MRSI sequence based on concentric ring trajectories with a 64 × 64 × 39 measurement matrix, and a 3.4 × 3.4 × 3.4 mm3 nominal voxel volume in 15 min. Quantification used a basis-set of 17 components including N-acetyl-aspartate (NAA), total choline (tCho), total creatine (tCr), glutamate (Glu), glutamine (Gln), glycine (Gly) and 2-hydroxyglutarate (2HG). The resultant metabolic images were evaluated for their reliability as well as their quality and compared to spatially segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast enhanced + edema, peritumoral) based on clinical data and also compared to histopathology (e.g., grade, IDH-status). Results: Eighteen of the patient measurements were considered usable. In these patients, ten metabolites were quantified with acceptable quality. Gln, Gly, and tCho were increased and NAA and tCr decreased in nearly all tumor regions, with other metabolites such as serine, showing mixed trends. Overall, there was a reliable characterization of metabolic tumor areas. We also found heterogeneity in the metabolic images often continued into the peritumoral region. While 2HG could not be satisfyingly quantified, we found an increase of Glu in the contrast-enhancing region of IDH-wildtype HGGs and a decrease of Glu in IDH1-mutant HGGs. Conclusions: We successfully demonstrated high-resolution 7T 3D-MRSI in HGG patients, showing metabolic differences between tumor regions and peritumoral tissue for multiple metabolites. Increases of tCho, Gln (related to tumor metabolism), Gly (related to tumor proliferation), as well as decreases in NAA, tCr, and others, corresponded very well to clinical tumor segmentation, but were more heterogeneous and often extended into the peritumoral region.

Background: Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals. Methods: We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes. Results: FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 ± 8,1 mm to the MRI-lesion. After a mean follow up of >3 years, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033). Conclusion: We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy. Keywords: Focal cortical dysplasia, Magnetic source imaging, epilepsy surgery

Drug-resistant epilepsy can be most limiting for patients, and surgery represents a viable therapy option. With the growing research on the human connectome and the evidence of epilepsy being a network disorder, connectivity analysis may be able to contribute to our understanding of epilepsy and may be potentially developed into clinical applications. In this magnetoencephalographic study, we determined the whole-brain node degree of connectivity levels in patients and controls. Resting-state activity was measured at five frequency bands in 15 healthy controls and 15 patients with focal epilepsy of different etiologies. The whole-brain all-to-all imaginary part of coherence in source space was then calculated. Node degree was determined and parcellated and was used for further statistical evaluation. In comparison to controls, we found a significantly higher overall node degree in patients with lesional and non-lesional epilepsy. Furthermore, we examined the conditions of high/reduced vigilance and open/closed eyes in controls, to analyze whether patient node degree levels can be achieved. We evaluated intraclass-correlation statistics (ICC) to evaluate the reproducibility. Connectivity and specifically node degree analysis could present new tools for one of the most common neurological diseases, with potential applications in epilepsy diagnostics.

Objective: In this study, we use a novel automated method for localization and quantitative comparison of magnetoencephalographic (MEG) delta activity in patients with and without recurrent seizures after epilepsy surgery as well as healthy controls. Methods: We identified the generators of delta activity by source location in frequency domain between 1 and 4 Hz in spontaneous MEG data. Comparison with healthy control subjects by z-transform emphasized relative changes of activation in patients. The individual results were compared to spike localizations and statistical group analysis was performed. Additionally, MEG results were compared to 1–4 Hz activity in invasive EEG (iEEG) in two patients, in whom this data was available. Results: Patients with recurrent seizures exhibited significantly increased focal MEG delta activity both in comparison to healthy controls and seizure free patients. This slow activity showed a correlation to interictal epileptic activity and was not explained by consequences of the resection alone. In two patients with iEEG, iEEG analysis was concordant with the MEG findings. Significance: The quantity of delta activity could be used as a diagnostic marker for recurrent seizures. The close relation to epileptic spike localizations and the resection volume of patients with successful second surgery imply involvement in seizure recurrence. This initial evidence suggests a potential application in the planning of second epilepsy surgery.

IntroductionPreoperative functional mapping in the vicinity of brain lesion is of high importance for avoiding complications in surgical management. However, space-occupying lesions may lead to functional reorganization or decreased BOLD activity.MethodsTherefore in 13 patients with cerebral gliomas or brain arterio-venous malformations/ hemangioma fMRI- and MEG-based cortical localizations of motor and somatosensory cortical activation pattern were compared in order to investigate their congruency.ResultsLocalization of cortical sensorimotor areas with fMRI and MEG showed good congruency with a mean spatial distance of around 10 mm, with differences depending on the localization method. The smallest mean differences for the centroids were found for MEF with MNE 8 mm and SEF with sLORETA 8 mm. Primary motor area (M1) reorganization was found in 5 of 12 patients in fMRI and confirmed with MEG data. In these 5 patients with M1-reorganization the distance between the border of the fMRI-based cortical M1-localization and the tumor border on T1w MR images varied between 0-4 mm, which was significant (P = 0.025) different to the distance in glioma patients without M1-reorganization (5-26 mm).ConclusionOur multimodal preoperative mapping approach combining fMRI and MEG reveals a high degree of spatial congruence and provided high evidence for the presence of motor cortex reorganization.

The aim of the present study is to differentiate subtypes of hippocampal sclerosis (HS) using ex vivo ultra-high field magnetic resonance imaging (MRI). Included were 14 surgically resected hippocampi of patients with medically intractable temporal lobe epilepsy. The resected hippocampi were histologically categorized into subtypes of hippocampal sclerosis (HS type 1 (n = 10), HS type 2 (n = 2) and no-HS (n = 2)) and subsequently scanned on a preclinical 7T MRI acquiring T2-weighted morphology, relaxometry and diffusion tensor imaging. On the morphological images, the pyramidal cell layer (PCL) of the hippocampus was segmented and the following parameters were derived: T2 signal intensity, T1-, T2- and T2*-relaxation times, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and mean diffusivity (MD). Furthermore, the area of the PCL was determined, as well as the parameter product which refers to the widths of the PCL parallel and perpendicular to the stratum moleculare. Spearman correlation coefficient was used to demonstrate relationships between MR-parameters and type of sclerosis. In comparison to no-HS specimens, the PCL was significantly narrower in HS type 1 and HS type 2 hippocampi. This narrowing affected the entire cornu ammonis sector (CA) 1 in HS type 1, while it was limited to the upper half of CA1 in direction to CA2 in HS type 2. The parameter product median increased from 0.43 to 1.67 and 2.91 mm2 for HS type 1, HS type 2 and no-HS, respectively. Correlation coefficients were significant for the PCL parameters product (0.73), area (0.71), T2*-time (-0.67), FA (0.65) and ADC (0.55). Our initial results suggest that HS type 1, HS type 2 and no-HS subtypes can be distinguished from each other using ex vivo UHF MRI based on T2-weighted morphologic images and the assessment of the parameter product. Upon clinical translation, UHF-MRI may provide a promising technique for the preoperative differentiation of HS subtypes in patients.