Papers by Christian Scheiwe
Epileptic disorders, May 24, 2024
Clinical Neurophysiology, Aug 1, 2020
Hippocampus, Mar 15, 2021
Hippocampal sclerosis (HS) in Temporal Lobe Epilepsy (TLE) shows neuronal death in cornu ammonis ... more Hippocampal sclerosis (HS) in Temporal Lobe Epilepsy (TLE) shows neuronal death in cornu ammonis (CA)1, CA3, and CA4. It is known that granule cells and CA2 neurons survive and their axons, the mossy fibers (MF), lose their target cells in CA3 and CA4 and sprout to the granule cell layer and molecular layer. We examined in TLE patients and in a mouse epilepsy model, whether MF sprouting is directed to the dentate gyrus or extends to distant CA regions and whether sprouting is associated with death of target neurons in CA3 and CA4. In 319 TLE patients, HS was evaluated by Wyler grade and International League against Epilepsy (ILAE) types using immunohistochemistry against neuronal nuclei (NeuN). Synaptoporin was used to colocalize MF. In addition, transgenic Thy1-eGFP mice were intrahippocampally injected with kainate and sprouting of eGFP-positive MFs was analyzed together with immunocytochemistry for regulator of G-protein signaling 14 (RGS14). In human HS Wyler III and IV as well as in ILAE 1, 2, and 3 specimens, we found synaptoporin-positive axon terminals in CA2 and even in CA1, associated with the extent of granule cell dispersion. Sprouting was seen in cases with cell death of target neurons in CA3 and CA4 (classical severe HS ILAE type 1) but also without this cell death (atypical HS ILAE type 2). Similarly, in epileptic mice eGFP-positive MFs sprouted to CA2 and beyond. The presence of MF terminals in the CA2 pyramidal cell layer and in CA1 was also correlated with the extent of granule cell dispersion. The similarity of our findings in human specimens and in the mouse model highlights the importance and opens up new chances of using translational approaches to determine mechanisms underlying TLE.
Neurosurgery, Mar 30, 2018
BACKGROUND Surgery is a widely accepted option for the treatment of pharmacoresistant epilepsies ... more BACKGROUND Surgery is a widely accepted option for the treatment of pharmacoresistant epilepsies of extratemporal origin. OBJECTIVE To analyze clinical and epileptological results and to provide prognostic factors influencing seizure outcome. METHODS This retrospective single-center study comprises a consecutive series of 383 patients, most of whom had an identifiable lesion on MRI, who underwent resective surgery for extratemporal epilepsy. Data including diagnostic modalities, surgical treatment, histopathology, prognostic factors, and epileptological outcome were analyzed. RESULTS Resective procedures were located as follows: frontal (n = 183), parietal (n = 44), occipital (n = 24), and insular (n = 24). In 108 cases resection included more than 1 lobe. Histopatholological evaluation revealed focal cortical dysplasias (n = 178), tumors (n = 110), cavernomas (n = 27), gliosis (n = 42), and nonspecific findings (n = 36). A distinct epileptogenic lesion was detected in 338 (88.7%) patients. After a mean follow-up of 54 mo, 227 (62.5%) patients remained free from disabling seizures (Engel class I), and 178 (49%) were completely seizure free (Engel class Ia). There was no perioperative mortality. Permanent morbidity was encountered in 46 cases (11.8%). The following predictors were significantly associated with excellent seizure outcome (Engel I): lesion visible on magnetic resonance imaging (MRI; P = .02), noneloquent location (P = .01), complete resection of the lesion (P = .001), absence of epileptic activity postoperatively (P = .001), circumscribed histological findings (P = .001), lower age at surgery (P = .008), and shorter duration of epilepsy (P = .02). CONCLUSION Surgical treatment of extratemporal epilepsy provides satisfying epileptological results with an acceptable morbidity. Best results can be achieved in younger patients with circumscribed MRI lesions, which can be resected completely.
Nature, Feb 1, 2019
Microglia play critical roles in neural development and homeostasis. They are also implicated in ... more Microglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses in up to six different regions during development and disease. Single-cell analysis of mouse CNS tissues revealed specific time-and region-dependent microglia subtypes, which were transcriptionally distinct from perivascular macrophages, during homeostasis. Demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Diverse microglia clusters were also identified in normal and diseased human brains. Our data provide new insights into the endogenous immune system of the CNS during development, health and disease.
Clinical neuroradiology, Jan 28, 2014
Acta neurochirurgica, May 6, 2023
Background The study of the distinct structure and function of the human central nervous system, ... more Background The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. Methods In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. Results The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. Conclusion The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.
Operative Neurosurgery, Jun 3, 2017
BACKGROUND Cerebral vasospasm leading to delayed cerebral infarction (DCI) is a central source of... more BACKGROUND Cerebral vasospasm leading to delayed cerebral infarction (DCI) is a central source of poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Current treatments of cerebral vasospasm are insufficient. Cisternal blood clearance is a promising treatment option. However, a generally applicable, safe, and effective method to access the cisterns of the brain is lacking. OBJECTIVE To report on stereotactic catheter ventriculocisternostomy (STX-VCS) as a method to access the cisterns of the brain for clearance of subarachnoid hemorrhage in patients with aSAH and coiled aneurysms. METHODS In 9 aSAH patients at high risk for DCI (Hunt and Hess grade ≥3, modified Fisher grade ≥3), access to the basal cisterns of the brain was created by STX-VCS. Fibrinolytic and/or spasmolytic lavage therapy was administered. RESULTS STX-VCS was feasible and safe in all patients. Subarachnoid blood was rapidly cleared by irrigation with urokinase. Vasospasm occurred in 2 patients and was interrupted by irrigation with nimodipine. There was 1 fatality due to pneumogenic sepsis. Minor DCI occurred in 1 patient. Eight survived without DCI and are independent (modified Rankin score [mRS] ≤ 3) at 6 mo after aSAH. CONCLUSION STX-VCS allows for rapid clearance of subarachnoid hemorrhage in patients with coiled aneurysms.
Clinical Neurophysiology, Aug 1, 2015
bioRxiv (Cold Spring Harbor Laboratory), Jun 2, 2020
The diversity of molecular states and cellular plasticity of immune cells in the glioblastoma env... more The diversity of molecular states and cellular plasticity of immune cells in the glioblastoma environment is still poorly understood. Here, we performed scRNA sequencing of the immune compartment and mapped potential cellular interactions leading to an immunosuppressive microenvironment and dysfunction of T cells. Through inferring the dynamic adaptation during T cell activation, we identified three different terminal states with unique transcriptional programs. Modeling of driver genes for terminal T cell fate identified IL-10 signaling alterations in a subpopulation of HAVCR2(+) T cells. To explore in depth cellular interactions, we established an in-silico model by the integration of spatial transcriptomic and scRNA-sequencing, and identified a subset of HMOX1 + myeloid cells defined by IL10 release leading to T cell exhaustion. We found a spatial overlap between HMOX(+) myeloid and HAVCR2(+) T cells, suggesting that myeloid-lymphoid interaction causes immunosuppression present in tumor regions with enriched mesenchymal gene expression. Using human neocortical GBM model, coupled with patient-derived T cells, we confirmed that the functional interaction between myeloid and lymphoid cells, leads to a dysfunctional state of T cells. This IL-10 driven T cell exhaustion was found to be rescued by JAK/STAT inhibition. A comprehensive understanding of the cellular states and plasticity of lymphoid cells in GBM will aid towards successful immunotherapeutic approaches. .
Clinical spine surgery, Jul 1, 2017
Study Design: A radiation exposure study in vitro. Objective: This study aimed to compare the rad... more Study Design: A radiation exposure study in vitro. Objective: This study aimed to compare the radiation exposure of 2 different 3-dimensional (3D) C-arm devices on an anthropomorphic phantom. Summary of Background Data: Minimally invasive pedicle screw placement requires intraoperative imaging techniques for visualization of the unexposed spine. Mobile 3D C-arms compose a 3D image data set out of multiple successive fluoroscopic images. Methods: We compared the 3D C-arm devices Siremobil Iso-C 3D (Siemens Sector Healthcare, Erlangen, Germany) and Vision FD Vario 3D (Ziehm Imaging, Nuremberg, Germany) regarding their radiation exposure. For this purpose, dosimeters were attached on an anthropomorphic phantom at various sites (eye lenses, thyroid gland, female, and male gonads). With each C-arm, 10 automated 3D scans as well as 400 fluoroscopic images were performed on the cervical and lumbar spine, respectively. Results: The Vision FD Vario 3D generally causes higher radiation exposures than the Siremobil Iso-C 3D. Significantly higher radiation exposures were assessed at the eye lenses performing cervical (294.1 vs. 84.6 μSv) and lumbar 3D scans (22.5 vs. 11.2 μSv) as well as at the thyroid gland performing cervical 3D scans (4405.2 vs. 2761.9 μSv). Moreover, the Vision FD Vario 3D caused significantly higher radiation exposure at the eye lenses for standard cervical fluoroscopic images (3.2 vs. 0.4 μSv). Conclusions: 3D C-arms facilitate minimally invasive and accurate pedicle screw placement by providing 3D image datasets for intraoperative 3D imaging and navigation. However, the hereby potentially increased radiation exposure has to be considered. In particular, the Vision FD Vario 3D appears to generally evoke higher radiation exposures than the Siremobil Iso-C 3D. Well-indicated application of ionizing radiation and compliance with radiation protection principles remain mandatory to keep radiation exposure to patient and staff as low as reasonably achievable.
Neurosurgery, Jan 4, 2023
BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortalit... more BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH. OBJECTIVE: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives. METHODS: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 &amp; 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Rankin Scale. RESULTS: Two hundred-fifty patients were enrolled, of whom 237 were included in the analysis after 6 months and 223 after 12 months. After 6 months, 118 (49.8%) patients were alive, and after 12 months, 104 (46.6%) patients were alive. Of those, 95 (80.5%) and 89 (85.6%) reached a favorable outcome with mean EQ-5D-3L index values of 0.85 (±0.18) and 0.86 (±0.18). After 6 and 12 months, 23 (19.5%) and 15 (14.4%) of those alive had an unfavorable outcome with mean EQ-5D-3L index values of 0.27 (±0.25) and 0.19 (±0.14). CONCLUSION: Despite high initial mortality, the proportion of poor-grade aSAH survivors with good QoL is reasonably large. Only a minority of survivors reports poor QoL and requires permanent care.
The number of implantable bidirectional neural interfaces available for neuroscientific research ... more The number of implantable bidirectional neural interfaces available for neuroscientific research applications is still limited, despite the rapidly increasing number of customized components. We previously reported on how to translate available components into ”ready-to-use” wireless implantable systems utilizing components off-the-shelf (COTS). The aim of the present study was to verify the viability of a micro-electrocorticographic ($\mu $ECoG) device built by this approach. Functionality for both neural recording and stimulation was evaluated in an ovine animal model using acoustic stimuli and cortical electrical stimulation, respectively. We show that auditory evoked responses were reliably recorded in both time and frequency domain and present data that demonstrates the cortical electrical stimulation functionality. The successful recording of neuronal activity suggests that the device can compete with existing implantable systems as a neurotechnological research tool.
Clinical neuroradiology, Jul 16, 2013
a 61-year-old woman developed progressive exophthalmos of the left ocular bulb over a period of s... more a 61-year-old woman developed progressive exophthalmos of the left ocular bulb over a period of several weeks. she complained of conjunctival irritation, increased lacrimation, and associated gait disturbance. Ophthalmologic examination showed no visual field deficit and a visus of 0.8 versus 1.0 on her right eye. These findings remained stable at follow-up 4 weeks later. at clinical examination no neurological deficit was observed. Magnetic resonance imaging (MRI) revealed a left-sided orbital, intra-conal lesion. Lateral orbital decompression (according to Kronlein) was performed with resection of the lateral orbital wall and the orbital roof. Opening the periorbita, the capsulated tumour was situated in the intra-conal fat tissue. The tumour capsule was mostly of a white colour with some vascular injections and also adherent veins. after coagulation and opening of the capsule, the tumour was of a tough and adherent consistence, appearing white-greyish. intra-capsular tumour reduction without manipulation of the optic nerve could be achieved. The post-operative course was uneventful without visual impairment. Mild ptosis and diplopia resolved completely within several days. Imaging
Zeitschrift Für Epileptologie, Jan 27, 2021
Kallosotomien bei Sturzanfällen und epileptischen Spasmen Die Kallosotomie ist ein palliativer ep... more Kallosotomien bei Sturzanfällen und epileptischen Spasmen Die Kallosotomie ist ein palliativer epilepsiechirurgischer Eingriff für Patienten mit pharmakorefraktären bilateral-manifestiertenAnfällen,beideneneinresektives Verfahren nicht möglich ist. Die Reduktion von Sturzanfällen durch eine Kallosotomie wurde in vielen Fallserien belegt, auch für epileptische Spasmen scheint eine Verbesserung erreicht werden zu können. Dennoch bleiben viele Fragen offen, z. B. das Ausmaß der Diskonnektion. Dieser Artikel beschreibt die unterschiedlichen chirurgischen Methoden und fasst die Datenlage zu Anfallsreduktion, neurokognitiven Veränderungen und Nebenwirkungen zusammen.
Journal of Clinical Neuroscience, Jul 1, 2021
Intradural petrous bone drilling has become a widespread practice, providing extended exposure in... more Intradural petrous bone drilling has become a widespread practice, providing extended exposure in the removal of cerebellopontine angle (CPA) or petroclival tumors. Adjacent neurovascular structures are at risk, however, when drilling is performed in this deep and narrow area. Hence, this study evaluates the use of Piezosurgery (PS) as a non-rotating tool for selective bone cutting in CPA surgery. A Piezosurgery® device was used in 36 patients who underwent microsurgery for extra-axial CPA or petroclival tumors in our Neurosurgical Department between 2013 and 2019. The clinical and radiological data were retrospectively analyzed. The use of PS was evaluated with respect to the intraoperative applicability and limitations as well as efficacy and safety of the procedure. Piezosurgical petrous bone cutting was successfully performed in the removal of meningiomas or extra-axial metastases arising from the dura of the petroclival region (21 patients) or petrous bone (15 patients). PS proved to be very helpful in the deep and narrow CPA region, considerably reducing the surgeon's distress toward bone removal in close proximity to cranial nerves and vessels in comparison to common rotating drills. The use of PS was safe without injuries to neurovascular structures. Gross total resection was achieved in 67% of petroclival and 100% of petrous bone tumors. Piezosurgery proved to be an effective and safe method for selective petrous bone cutting in CPA surgery avoiding rotating power and associated risks. This technique can particularly be recommended for bone cutting in close vicinity to critical neurovascular structures.
Seizure: European Journal of Epilepsy
Neurosurgery
BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortalit... more BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH. OBJECTIVE: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives. METHODS: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 & 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Ra...
SummaryThe diversity of molecular states and cellular plasticity of immune cells in the glioblast... more SummaryThe diversity of molecular states and cellular plasticity of immune cells in the glioblastoma environment is still poorly understood. Here, we performed scRNA sequencing of the immune compartment and mapped potential cellular interactions leading to an immunosuppressive microenvironment and dysfunction of T cells. Through inferring the dynamic adaptation during T cell activation, we identified three different terminal states with unique transcriptional programs. Modeling of driver genes for terminal T cell fate identified IL-10 signaling alterations in a subpopulation of HAVCR2(+) T cells. To explore in depth cellular interactions, we established an in-silico model by the integration of spatial transcriptomic and scRNA-sequencing, and identified a subset of HMOX1+ myeloid cells defined by IL10 release leading to T cell exhaustion. We found a spatial overlap between HMOX(+) myeloid and HAVCR2(+) T cells, suggesting that myeloid-lymphoid interaction causes immunosuppression pre...
Uploads
Papers by Christian Scheiwe