Decompressive hemicraniectomy in the management of acute stroke in children with Moyamoya disease: the difficult balance between the spontaneous postoperative revascularization process and the need for cranial reconstruction.

BACKGROUND AND IMPORTANCE: The decompressive hemicraniectomy (DCH) after malignant middle cerebral artery infarction in children is a rare procedure, and the indication is discussed as being controversial. Etiological Moyamoya disease has some additional challenges concerning the therapeutic strategy that have not mentioned in the recent literature, as it is dependent on special pathophysiology. CLINICAL PRESENTATION: We report a case of a four-year-old patient with a decompressive hemicraniectomy after malignant middle cerebral artery infarction on the right hemisphere based on a Moyamoya syndrome with proximal MCA occlusions on both sides. After the decompression there was a good restitution of the hemiparesis, aphasia, and consciousness loss on admission. The bone flap replacement is usually done after three month in our department to ensure brain swelling has subsided. In this patient the cranioplasty was not arranged because of the development of collateral vessels to the right motor region through the craniotomy defect, to protect the supply of the eloquent cortex. CONCLUSION: We conclude that the indication of DCH and postoperative treatment should be discussed individually, especially when neovascularisation developments can occur like in Moyamoya disease. An important point is the right timing for bone flap replacement, which should be directly after cerebral edema has subsided prior to the evolution of collaterals through the craniotomy defect. Additionally, leaving the opportunity for neovascularization through smaller defects has to be taken into account.

Reliability of High-resolution Gadolinium-enhanced MR Cisternography and Gasket-seal Technique for Management of Anterior Skull Base Defects.

PURPOSE: Precise preoperative localization of anterior skull base defects is important to plan surgical access, increase the success rate and reduce complications. A stable closure of the defect is vital to prevent recurrence of cerebrospinal fluid (CSF) rhinorrhea. The purpose of this retrospective case series was to evaluate the reliability of a new high-resolution gadolinium-enhanced compressed-sensing SPACE technique (CS T1 SPACE) for magnetic resonance (MR) cisternography to detect cerebrospinal fluid leaks of the anterior skull base and to assess the long-term success rate of the gasket-seal technique for closure of skull base defects. METHOD: All patients with spontaneous or postoperative cerebrospinal fluid rhinorrhea and defects of the anterior skull base presenting to the Departments of Otorhinolaryngology and Neurosurgery between 2019 and 2020, receiving a computed tomography (CT) cisternography and MR cisternography (on a 3T whole-body MR scanner using a 64-channel head and neck coil) with CS T1 SPACE sequence and closure of the defect with the gasket-seal technique, were enrolled in the study. For the cisternography, iodinated contrast agent (15 ml Solutrast 250 M®), saline (4 mL) mixed with a 0.5 mL of gadoteridol was injected into the lumbar subarachnoid space. RESULTS: A total of four patients were included in the study and MR cisternography with CS T1 SPACE sequence was able to precisely localize CSF leaks in all patients. The imaging results correlated with intraoperative findings. All defects could be successfully closed with the gasket-seal technique. The mean follow-up was 35.25 months (range 33-37 months). CONCLUSION: MR cisternography with CS T1 SPACE sequence could be a promising technique for precise localization of CSF leaks and the gasket-seal technique resulted in good closure of the CSF fistula in this case series.

Multiomic spatial landscape of innate immune cells at human central nervous system borders.

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy.

PURPOSE: To analyze the safety profile of subdural and depth electrode implantation in a large monocentric cohort of patients of all ages undergoing intracranial EEG exploration because of drug resistant focal epilepsy diagnosed and implanted by a constant team of epileptologists and neurosurgeons. METHODS: We retrospectively analyzed data from 452 implantations in 420 patients undergoing invasive presurgical evaluation at the Freiburg Epilepsy Center from 1999 to 2019 (n = 160 subdural electrodes, n = 156 depth electrodes and n = 136 combination of both approaches). Complications were classified as hemorrhage with or without clinical manifestations, infection-associated and other complications. Furthermore, possible risk factors (age, duration of invasive monitoring, number of electrode contacts used) and changes in complication rates during the study period were analyzed. RESULTS: The most frequent complications in both implantation groups were hemorrhages. Subdural electrode explorations caused significantly more symptomatic hemorrhages and required more operative interventions (SDE 9.9%, DE 0.3%, p < 0.05). Hemorrhage risk was higher for grids with 64 contacts than for smaller grids (p < 0.05). The infection rate was very low (0,2%). A transient neurological deficit occurred in 8.8% of all implantations and persisted for at least 3 months in 1.3%. Transient, but not persistent neurological deficits were more common in patients with implanted subdural electrodes than in the depth electrode group. CONCLUSION: The use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms. However persistent deficits were rare with either approach, demonstrating that intracranial investigations using either subdural electrodes or depth electrodes carry acceptable risks in patients with drug-resistant focal epilepsy.

Epilepsy surgery in early infancy: A retrospective, multicenter study.

Although epilepsy surgery is the only curative therapeutic approach for lesional drug-resistant epilepsy (DRE), there is reluctance to operate on infants due to a fear of complications. A recent meta-analysis showed that epilepsy surgery in the first 6 months of life can achieve seizure control in about two thirds of children. However, robust data on surgical complications and postoperative cognitive development are lacking. We performed a retrospective multicenter study of infants who underwent epilepsy surgery in the first 6 months of life. 15 infants underwent epilepsy surgery at a median age of 134 days (IQR: 58) at four centers. The most common cause was malformation of cortical development, and 13 patients underwent a hemispherotomy. Two thirds required intraoperative red blood transfusions. Severe intraoperative complications occurred in two patients including death in one infant due to cardiovascular insufficiency. At a median follow-up of 1.5 years (IQR: 1.8), 57% of patients were seizure-free. Three patients where reoperated at a later age, resulting in 79% seizure freedom. Anti-seizure medication could be reduced in two thirds, and all patients improved in their development. Our findings suggest that early epilepsy surgery can result in good seizure control and developmental improvement. However, given the perioperative risks, it should be performed only in specialized centers.

Hydrocephalus Shunting in Supratentorial Glioblastoma: Functional Outcomes and Management.

BACKGROUND: Glioblastoma is the most common and the most challenging to treat adult primary central nervous system tumor. Although modern management strategies modestly improved the overall survival, the prognosis remains dismal associated with poor life quality and the clinical course often dotted by treatment side effects and cognitive decline. Functional deterioration might be caused by obstructive or communicating hydrocephalus but due to poor overall prognosis surgical treatment options are often limited and its optimal management strategies remain elusive. We aimed to investigate risk factors, treatment options and outcomes for tumor-associated hydrocephalus in a contemporary 10 years cohort of glioblastoma patients. METHODS: We reviewed electronic health records of 1800 glioblastoma patients operated at the Department of Neurosurgery, Medical Center - University of Freiburg from 2009 to 2019. Demographics, clinical characteristics and radiological features were analyzed. Univariate analysis for nominal variables was performed either by Fisher's exact test or Chi-square test, as appropriate. RESULTS: We identified 39 glioblastoma patients with symptomatic communicating hydrocephalus treated by ventricular shunting (incidence 2.1%). Opening of the ventricular system during a previous tumor resection was associated with symptomatic hydrocephalus (p<0.05). There was also a trend toward location (frontal and temporal) and larger tumor volume. Number of craniotomies before shunting was not considered as a risk factor. Shunting improved hydrocephalus symptoms in 95% of the patients and Karnofsky Performance Score (KPS) could be restored after shunting. Of note, 75% of the patients had a post-shunting oncological treatment such as radiotherapy or chemotherapy, most prevalently chemotherapy. Infection (7.7%) and over- or under drainage (17.9%) were the most common complications requiring shunt revision in ten patients (25.6%), No peritoneal metastasis was found. The median overall survival (OS) was 385 days and the median post shunting survival was 135 days. CONCLUSION: Ventricular system opening was identified as a risk factor for communicating hydrocephalus in glioblastoma patients. Although glioblastoma treatment remains challenging, shunting improved hydrocephalus-related functional status and may be considered even in a palliative setting for symptom relief.

Bedside Catheter Hematoma Evacuation in Vitamin K Antagonist-Related Intracerebral Hemorrhage: A Safe and Feasible Approach.

Background and Purpose: Although outcome in intracerebral hemorrhage (ICH) patients is generally not improved by surgical intervention, the use of minimally invasive surgery (MIS) has shown promising results. However, vitamin K antagonist (VKA)-related ICH patients are underrepresented in surgical treatment trials. We therefore assessed the safety and efficacy of a bedside MIS approach including local application of urokinase in VKA-related ICH. Methods: Patients with a VKA-related ICH > 20 ml who received bedside hematoma evacuation treatment (n = 21) at the University Medical Center Freiburg were retrospectively included for analysis and compared to a historical control group (n = 35) selected from an institutional database (University Medical Center Erlangen) according to identical inclusion criteria. Propensity score matching was performed to obtain comparable cohorts. The evolution of hematoma and peri-hemorrhagic edema (PHE) volumes, midline shift, and the occurrence of adverse events were analyzed. Furthermore, we assessed the modified Rankin Scale and NIHSS scores recorded at discharge. Results: Propensity score matching resulted in 16 patients per group with well-balanced characteristics. Median ICH volume at admission was 45.7 (IQR: 24.2-56.7) ml in the control group and 48.4 (IQR: 28.7-59.6) ml in the treatment group (p = 0.327). ICH volume at day 7 was less pronounced in the treatment group [MIS: 23.2 ml (IQR: 15.8-32.3) vs. control: 43.2 ml (IQR: 27.5-52.4); p = 0.013], as was the increase in midline shift up to day 7 [MIS: -3.75 mM (IQR: -4.25 to -2) vs. control: 1 mM (IQR: 0-2); p < 0.001]. No group differences were observed in PHE volume on day 7 [MIS: 42.4 ml (IQR: 25.0-72.3) vs. control: 31.0 ml (IQR: 18.8-53.8); p = 0.274] or mRS at discharge [MIS: 5 (IQR: 4-5) and 5 (IQR: 4-5); p = 0.949]. No hematoma expansion was observed. The catheter had to be replaced in 1 patient (6%). Conclusions: Bedside catheter-based hematoma evacuation followed by local thrombolysis with urokinase appears to be feasible and safe in cases of large VKA-related ICH. Further studies that assess the functional outcome associated with this technique are warranted. Clinical Trial Registration: DRKS00007908 (German Clinical Trial Register; www.drks.de).

Corrigendum: Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

[This corrects the article DOI: 10.3389/fneur.2019.01113.].

Mapping microglia states in the human brain through the integration of high-dimensional techniques.

Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.

Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

Temporary middle cerebral artery occlusion (MCAO) in sheep allows modeling of acute large vessel occlusion stroke and subsequent vessel recanalization. However, rapid and precise imaging-based assessment of vessel occlusion and the resulting perfusion deficit during MCAO still represents an experimental challenge. Here, we tested feasibility and suitability of a strategy for MCAO verification and perfusion deficit assessment. We also compared the extent of the initial perfusion deficit and subsequent lesion size for different MCAO durations. The rete mirabile prevents reliable vascular imaging investigation of middle cerebral artery filling status. Hence, computed tomography perfusion imaging was chosen for indirect confirmation of MCAO. Follow-up infarct size evaluation by diffusion-weighted magnetic resonance imaging revealed fluctuating results, with no apparent relationship of lesion size with MCAO at occlusion times below 4 h, potentially related to the variable collateralization of the MCA territory. This underlines the need for intra-ischemic perfusion assessment and future studies focusing on the correlation between perfusion deficit, MCAO duration, and final infarct volume. Temporary MCAO and intra-ischemic perfusion imaging nevertheless has the potential to be applied for the simulation of novel recanalization therapies, particularly those that aim for a fast reperfusion effect in combination with mechanical thrombectomy in a clinically realistic scenario.

Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology.

When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry, genetic expression, and electrophysiology. This method was then used to assess glioblastoma (GBM) progression in its natural environment by microinjection of patient-derived tumor cells into cultured sections. The result closely resembles the pattern of de novo tumor growth and invasion, drug therapy response, and cytokine environment. Reactive transformation of astrocytes, as an example of the cellular nonmalignant tumor environment, can be accurately simulated with transcriptional differences similar to those of astrocytes isolated from acute GBM specimens. In a nutshell, we present a simple method to study GBM in its physiological environment, from which valuable insights can be gained. This technique can lead to further advancements in neuroscience, neuro-oncology, and pharmacotherapy.