Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Navigated bedside implantation of external ventricular drains with mobile health guidance: technical note and case series.

PURPOSE: External ventricular drain (EVD) implantation is one of the fundamental procedures of emergency neurosurgery usually performed freehand at bedside or in the operating room using anatomical landmarks. However, this technique is frequently associated with malpositioning leading to complications or dysfunction. Here, we describe a novel navigated bedside EVD insertion technique, which is evaluated in a clinical case series with the aim of safety, accuracy, and efficiency in neurosurgical emergency settings. METHODS: From 2021 to 2022, a mobile health-assisted navigation instrument (Thomale Guide, Christoph Miethke, Potsdam, Germany) was used alongside a battery-powered single-use drill (Phasor Health, Houston, USA) for bedside EVD placement in representative neurosurgical pathologies in emergency situations requiring ventricular cerebrospinal fluid (CSF) relief and intracranial pressure (ICP) monitoring. RESULTS: In all 12 patients (8 female and 4 male), navigated bedside EVDs were placed around the foramen of Monro at the first ventriculostomy attempt. The most frequent indication was aneurysmal subarachnoid hemorrhage. Mean operating time was 25.8 ± 15.0 min. None of the EVDs had to be revised due to malpositioning or dysfunction. Two EVDs were converted into a ventriculoperitoneal shunt. Drainage volume was 41.3 ± 37.1 ml per day in mean. Mean length of stay of an EVD was 6.25 ± 2.8 days. Complications included one postoperative subdural hematoma and cerebrospinal fluid infection, respectively. CONCLUSION: Combining a mobile health-assisted navigation instrument with a battery-powered drill and an appropriate ventricular catheter may enable and enhance safety, accuracy, and efficiency in bedside EVD implantation in various pathologies of emergency neurosurgery without adding relevant efforts.

Human Taenia martis Neurocysticercosis, Switzerland.

Neurocysticercosis is almost exclusively caused by Taenia solium tapeworms. We describe a case of neurocysticercosis in Switzerland caused by infection with Taenia martis, the marten tapeworm, and review all 5 published cases of human infection with the marten tapeworm. In epidemiologically nonplausible cases of neurocysticercosis, zoonotic spillover infections should be suspected.

A minimally invasive tubular retractor-assisted retropleural approach for thoracic disc herniations - case series and technical note.

PURPOSE: Thoracic disc herniations are uncommon and carry a high risk for neurological deterioration. Traditional surgical approaches include thoracotomy, costotransversectomy or posterior approaches with considerable morbidity. In this technical note with case series, we describe a minimally invasive tubular retractor-assisted retropleural approach for simple and less invasive microsurgical exploration of thoracic disc herniations from a lateral angle. METHODS: Surgical technique consisted of partial rib resection and retropleural dissection followed by the placement of a tubular retractor (METRx Tubes, Medtronic) for an anterior-lateral exposure of the disc and neuroforamen. Epidemiological, clinical and surgical patient data were acquired. RESULTS: Between 2017 and 2020, six patients were surgically treated using the minimally invasive tubular retractor-assisted retropleural approach. Microsurgical exposure of the disc and neural structures was achieved from a lateral direction without requiring thoracotomy or lung deflation. Control imaging confirmed resection in all cases without relevant residuum. As postoperative complications, one dural injury and one postoperative pneumothorax occured. No neurologic deterioration or recurrence occurred during a median follow-up of 3 months. CONCLUSION: The described tubular retractor-assisted retropleural exposure serves as a feasible minimally invasive microsurgical approach to the anterior-lateral thoracic spine.

Resolution of Cerebral Inflammation Following Subarachnoid Hemorrhage.

BACKGROUND: Aneurismal subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke that, despite improvement through therapeutic interventions, remains a devastating cerebrovascular disorder that has a high mortality rate and causes long-term disability. Cerebral inflammation after SAH is promoted through microglial accumulation and phagocytosis. Furthermore, proinflammatory cytokine release and neuronal cell death play key roles in the development of brain injury. The termination of these inflammation processes and restoration of tissue homeostasis are of utmost importance regarding the possible chronicity of cerebral inflammation and the improvement of the clinical outcome for affected patients post SAH. Thus, we evaluated the inflammatory resolution phase post SAH and considered indications for potential tertiary brain damage in cases of incomplete resolution. METHODS: Subarachnoid hemorrhage was induced through endovascular filament perforation in mice. Animals were killed 1, 7 and 14 days and 1, 2 and 3 months after SAH. Brain cryosections were immunolabeled for ionized calcium-binding adaptor molecule-1 to detect microglia/macrophages. Neuronal nuclei and terminal deoxyuridine triphosphate-nick end labeling staining was used to visualize secondary cell death of neurons. The gene expression of various proinflammatory mediators in brain samples was analyzed by quantitative polymerase chain reaction. RESULTS: We observed restored tissue homeostasis due to decreased microglial/macrophage accumulation and neuronal cell death 1 month after insult. However, the messenger RNA expression levels of  interleukin 6  and  tumor necrosis factor α were still elevated at 1 and 2 months post SAH, respectively. The gene expression of interleukin 1ß reached its maximum on day 1, whereas at later time points, no significant differences between the groups were detected. CONCLUSIONS: By the herein presented molecular and histological data we provide an important indication for an incomplete resolution of inflammation within the brain parenchyma after SAH. Inflammatory resolution and the return to tissue homeostasis represent an important contribution to the disease's pathology influencing the impact on brain damage and outcome after SAH. Therefore, we consider a novel complementary or even superior therapeutic approach that should be carefully rethought in the management of cerebral inflammation after SAH. An acceleration of the resolution phase at the cellular and molecular levels could be a potential aim in this context.

Opportunities and challenges of supervised machine learning for the classification of motor evoked potentials according to muscles.

BACKGROUND: Even for an experienced neurophysiologist, it is challenging to look at a single graph of an unlabeled motor evoked potential (MEP) and identify the corresponding muscle. We demonstrate that supervised machine learning (ML) can successfully perform this task. METHODS: Intraoperative MEP data from supratentorial surgery on 36 patients was included for the classification task with 4 muscles: Extensor digitorum (EXT), abductor pollicis brevis (APB), tibialis anterior (TA) and abductor hallucis (AH). Three different supervised ML classifiers (random forest (RF), k-nearest neighbors (kNN) and logistic regression (LogReg)) were trained and tested on either raw or compressed data. Patient data was classified considering either all 4 muscles simultaneously, 2 muscles within the same extremity (EXT versus APB), or 2 muscles from different extremities (EXT versus TA). RESULTS: In all cases, RF classifiers performed best and kNN second best. The highest performances were achieved on raw data (4 muscles 83%, EXT versus APB 89%, EXT versus TA 97% accuracy). CONCLUSIONS: Standard ML methods show surprisingly high performance on a classification task with intraoperative MEP signals. This study illustrates the power and challenges of standard ML algorithms when handling intraoperative signals and may lead to intraoperative safety improvements.

Lithium inhibits tryptophan catabolism via the inflammation-induced kynurenine pathway in human microglia.

Despite its decades' long therapeutic use in psychiatry, the biological mechanisms underlying lithium's mood-stabilizing effects have remained largely elusive. Here, we investigated the effect of lithium on tryptophan breakdown via the kynurenine pathway using immortalized human microglia cells, primary human microglia isolated from surgical specimens, and microglia-like cells differentiated from human induced pluripotent stem cells. Interferon (IFN)-γ, but not lipopolysaccharide, was able to activate immortalized human microglia, inducing a robust increase in indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to the IDO1 promoter. Lithium counteracted these effects, increasing inhibitory GSK3ßS9 phosphorylation and reducing STAT1S727 and STAT3Y705 phosphorylation levels in IFN-γ treated cells. Studies in primary human microglia and hiPSC-derived microglia confirmed the anti-inflammatory effects of lithium, highlighting that IDO activity is reduced by GSK3 inhibitor SB-216763 and STAT inhibitor nifuroxazide via downregulation of P-STAT1S727 and P-STAT3Y705 . Primary human microglia differed from immortalized human microglia and hiPSC derived microglia-like cells in their strong sensitivity to LPS, resulting in robust upregulation of IDO1 and anti-inflammatory cytokine IL-10. While lithium again decreased IDO1 activity in primary cells, it further increased release of IL-10 in response to LPS. Taken together, our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.

Microglia/macrophages express alternative proangiogenic factors depending on granulocyte content in human glioblastoma.

Myeloid cells are an inherent part of the microenvironment of glioblastoma multiforme (GBM). There is growing evidence for their participation in mechanisms of tumor escape, especially in the development of resistance following initially promising anti-VEGF/VEGFR treatment. Thus, we sought to define the capability of myeloid cells to contribute to the expression of proangiogenic molecules in human GBM. We investigated GBM specimens in comparison with anaplastic astrocytoma (WHO grade III) and epilepsy patient samples freshly obtained from surgery. Flow cytometric analyses revealed two distinct CD11b+ CD45+ cell populations in GBM tissues, which were identified as microglia/macrophages and granulocytes. Due to varied granulocyte influx, GBM samples were subdivided into groups with low (GBM-lPMNL) and high (GBM-hPMNL) numbers of granulocytes (polymorphonuclear leukocytes; PMNL), which were related to activation of the microglia/macrophage population. Microglia/macrophages of the GBM-lPMNL group were similar to those of astrocytoma specimens, but those of GBM-hPMNL tissues revealed an altered phenotype by expressing high levels of CD163, TIE2, HIF1α, VEGF, CXCL2 and CD13. Although microglia/macrophages represented the main source of alternative proangiogenic factors, additionally granulocytes participated by production of IL8 and CD13. Moreover, microglia/macrophages of the GBM-hPMNL specimens were highly associated with tumor blood vessels, accompanied by remodeling of the vascular structure. Our data emphasize that tumor-infiltrating myeloid cells might play a crucial role for limited efficacy of anti-angiogenic therapy bypassing VEGF-mediated pathways through expression of alternative proangiogenic factors. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery.

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

Minocycline Attenuates Microglia/Macrophage Phagocytic Activity and Inhibits SAH-Induced Neuronal Cell Death and Inflammation.

BACKGROUND: Neuroprotective treatment strategies aiming at interfering with either inflammation or cell death indicate the importance of these mechanisms in the development of brain injury after subarachnoid hemorrhage (SAH). This study was undertaken to evaluate the influence of minocycline on microglia/macrophage cell activity and its neuroprotective and anti-inflammatory impact 14 days after aneurismal SAH in mice. METHODS: Endovascular filament perforation was used to induce SAH in mice. SAH + vehicle-operated mice were used as controls for SAH vehicle-treated mice and SAH + minocycline-treated mice. The drug administration started 4 h after SAH induction and was daily repeated until day 7 post SAH and continued until day 14 every second day. Brain cryosections were immunolabeled for Iba1 to detect microglia/macrophages and NeuN to visualize neurons. Phagocytosis assay was performed to determine the microglia/macrophage activity status. Apoptotic cells were stained using terminal deoxyuridine triphosphate nick end labeling. Real-time quantitative polymerase chain reaction was used to estimate cytokine gene expression. RESULTS: We observed a significantly reduced phagocytic activity of microglia/macrophages accompanied by a lowered spatial interaction with neurons and reduced neuronal apoptosis achieved by minocycline administration after SAH. Moreover, the SAH-induced overexpression of pro-inflammatory cytokines and neuronal cell death was markedly attenuated by the compound. CONCLUSIONS: Minocycline treatment may be implicated as a therapeutic approach with long-term benefits in the management of secondary brain injury after SAH in a clinically relevant time window.

Outlines to Initiate Epilepsy Surgery in Low- and Middle-Income Countries.

Surgery is an essential treatment option for patients with drug-resistant epilepsy. While most epilepsy patients worldwide live in low- and middle-income countries (LMIC), most of these countries do not have epilepsy surgery, and those that do have surgical epilepsy services lack capacities. The rapidly growing population in LMIC further widens the gap between the number of patients who can potentially benefit from surgery and those who can actually receive it. This makes the initiation of new surgical epilepsy centers in those countries an urgent issue. Epilepsy surgery is feasible in LMIC, even in resource-poor settings, but lack of local expertise is a major obstacle to the introduction of new surgical services. Importantly, expertise deficits can be compensated by collaborating with a well-established epilepsy center for knowledge transfer, skill building and mentoring. Such projects need to be organized in a multidisciplinary team, should focus on the given circumstances, and should use technologies and personnel that are reasonably available and can function sustainably. Local cultural factors and improvement of patients' quality of life are further spotlights reflected by an increasing number of studies. As a general outline for a new surgical epilepsy program in LMIC, it is recommended to initially focus on patients with mesial temporal lobe epilepsy due to hippocampal sclerosis or other well defined pathologies. These constellations have an excellent surgical outcome in terms of seizure control, can be diagnosed by non-invasive methods, and can be reliably identified even under low-resource conditions. Moreover, surgery can be performed with a highly standardized approach and at reasonable costs, and the vast majority of patients will benefit from surgical intervention. The range of services can then be gradually expanded, depending on growing expertise, local needs, prospects and constraints. Although the introduction of surgical epilepsy services in LMIC can face several challenges, none of them should be a permanent barrier for further establishments.

TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies.

Subarachnoid hemorrhage is associated with severe neurological deficits for survivors. Among survivors of the initial bleeding, secondary brain injury leads to additional brain damage. Apart from cerebral vasospasm, secondary brain injury mainly results from cerebral inflammation taking place in the brain parenchyma after bleeding. The brain's innate immune system is activated, which leads to disturbances in brain homeostasis, cleavage of inflammatory cytokines and, subsequently, neuronal cell death. The toll-like receptor (TLR)4 signaling pathway has been found to play an essential role in the pathophysiology of acute brain injuries such as subarachnoid hemorrhage (SAH). TLR4 is expressed on the cell surface of microglia, which are key players in the cellular immune responses of the brain. The participants in the signaling pathway, such as TLR4-pathway-like ligands, the receptor itself, and inflammatory cytokines, can act as biomarkers, serving as clues regarding the inflammatory status after SAH. Moreover, protein complexes such as the NLRP3 inflammasome or receptors such as TREM1 frame the TLR4 pathway and are indicative of inflammation. In this review, we focus on the activity of the TLR4 pathway and its contributors, which can act as biomarkers of neuroinflammation or even offer potential new treatment targets for secondary neuronal cell death after SAH.

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH).

BACKGROUND: Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. METHODS: 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. RESULTS: Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. CONCLUSIONS: Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

Initiating a new national epilepsy surgery program: Experiences gathered in Georgia.

Surgery is the most effective therapeutic approach for medically refractory epilepsies and a safe and cost-efficient treatment in terms of long-term expenses of direct, indirect, and intangible costs. Georgia is a Caucasian low- to middle-income country with a remarkable effort to deal with epileptic diseases, but without an appropriate epilepsy surgery program. To address the needs for such a service in this country, two joint German-Georgian projects were initiated in 2017 and 2019. In the framework of these projects, a productive exchange program involving German and Georgian experts was undertaken in the past two years. This program included training and mentoring for Georgian clinical colleagues, as well as joint case conferences and workshops with the aim of optimizing presurgical diagnostics and preparing for an epilepsy surgery program in Georgia. Finally, a postsurgical medium- and long-term follow-up scheme was organized as the third component of this comprehensive approach. As a result of our efforts, the first patients underwent anterior temporal lobectomy and all of them remain seizure-free up to the present day. Hence, epilepsy surgery is not only feasible, but also already available in Georgia. In this report, we aim to share our experiences in the initiation and implementation of surgical epilepsy intervention in Georgia and illustrate our recent endeavor and achievements.

Need for ensuring care for neuro-emergencies-lessons learned from the COVID-19 pandemic.

BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

Diagnostic reliability of the Berlin classification for complex MCA aneurysms-usability in a series of only giant aneurysms.

BACKGROUND AND OBJECTIVE: The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. METHODS: We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. RESULTS: We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. CONCLUSION: The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.

Craniotomy Size for Subdural Grid Electrode Placement in Invasive Epilepsy Diagnostics.

BACKGROUND: Traditionally, for subdural grid electrode placement, large craniotomies have been applied for optimal electrode placement. Nowadays, microneurosurgeons prefer patient-tailored minimally invasive approaches. Absolute figures on craniotomy size have never been reported. To elucidate the craniotomy size necessary for successful diagnostics, we reviewed our single-center experience. METHODS: Within 3 years, 58 patients with focal epilepsies underwent subdural grid implantation using patient-tailored navigation-based craniotomies. Craniotomy sizes were measured retrospectively. The number of electrodes and the feasibility of the resection were evaluated. Sixteen historical patients served as controls. RESULTS: In all 58 patients, subdural electrodes were implanted as planned through tailored craniotomies. The mean craniotomy size was 28 ± 15 cm2 via which 55 ± 16 electrodes were implanted. In temporal lobe diagnostics, even smaller craniotomies were applied (21 ± 11 cm2). Craniotomies were significantly smaller than in historical controls (65 ± 23 cm2, p < 0.05), while the mean number of electrodes was comparable. The mean operation time was shorter and complications were reduced in tailored craniotomies. CONCLUSION: Craniotomy size for subdural electrode implantation is controversial. Some surgeons favor large craniotomies, while others strive for minimally invasive approaches. For the first time, we measured the actual craniotomy size for subdural grid electrode implantation. All procedures were straightforward. We therefore advocate for patient-tailored minimally invasive approaches - standard in modern microneurosurgery - in epilepsy surgery as well.

Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus.

Human mesial temporal lobe epilepsy (MTLE) features subregion-specific hippocampal neurodegeneration and reactive astrogliosis, including up-regulation of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine synthetase (GS). However, the regional astrocytic expression pattern of GFAP and GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP and GS expression in strict correlation with the local neuronal number in cortical and hippocampal surgical specimens from 16 MTLE patients using immunohistochemistry, stereology and high-resolution image analysis for digital pathology and whole-slide imaging. In the cortex, GS-positive (GS+) astrocytes are dominant in all neuronal layers, with a neuron to GS+ cell ratio of 2:1. GFAP-positive (GFAP+) cells are widely spaced, with a GS+ to GFAP+ cell ratio of 3:1-5:1. White matter astrocytes, on the contrary, express mainly GFAP and, to a lesser extent, GS. In the hippocampus, the neuron to GS+ cell ratio is approximately 1:1. Hippocampal degeneration is associated with a reduction of GS+ astrocytes, which is proportional to the degree of neuronal loss and primarily present in the hilus. Up-regulation of GFAP as a classical hallmark of reactive astrogliosis does not follow the GS-pattern and is prominent in the CA1. Reactive alterations were proportional to the neuronal loss in the neuronal somatic layers (stratum pyramidale and hilus), while observed to a lesser extent in the axonal/dendritic layers (stratum radiatum, molecular layer). We conclude that astrocytic GS is expressed in the neuronal somatic layers and, upon neurodegeneration, is down-regulated proportionally to the degree of neuronal loss.

Adenosine A1 receptor-mediated suppression of carbamazepine-resistant seizure-like events in human neocortical slices.

OBJECTIVE: The need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy (TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug-resistant seizure-like events (SLEs) in human temporal cortex slices. METHODS: Layer V/VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K(+) ] and 50 µm bicuculline. RESULTS: Activating A1 receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A1 agonist, in slices insensitive to a high dose of carbamazepine (50 µm). Also in these cases the A1 agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A1 receptors. SIGNIFICANCE: Selective activation of A1 receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure-like activity is a feasible option for future studies investigating new antiepileptic drug (AED) candidates.