Author Correction: Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.

In this Letter, Dominic Grün and Sagar have been added to the author list (affiliated with Max-Planck-Institute of Immunology and Epigenetics (MPI-IE), Freiburg, Germany). The author list, 'Author contribution' and 'Acknowledgements' sections have been corrected online. See accompanying Amendment.

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.

Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system1-4. These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies.

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Structural connectivity of the ANT region based on human ex-vivo and HCP data. Relevance for DBS in ANT for epilepsy.

OBJECTIVE: Deep Brain Stimulation (DBS) in the Anterior Nucleus of the Thalamus (ANT) has been shown to be a safe and efficacious treatment option for patients with Drug-Resitant focal Epilepsy (DRE). The ANT has been selected frequently in open and controlled studies for bilateral DBS. There is a substantial variability in ANT-DBS outcomes which is not fully understood. These outcomes might not be explained by the target location alone but potentially depend on the connectivity of the mere stimulation site with the epilepsy onset-associated brain regions. The likely sub-components of this anatomy are fiber pathways which penetrate or touch the ANT region and constitute a complex and dense fiber network which has not been described so far. A detailed characterization of this ANT associated fiber anatomy may therefore help to identify which areas are associated with positive or negative outcomes of ANT-DBS. Furthermore, prediction properties in individual ANT-DBS cases might be tested. In this work we aim to generate an anatomically detailed map of candidate fiber structures which might in the future lead to a holistic image of structural connectivity of the ANT region. METHODS: To resolve the various components of the complex fiber network connected to the ANT we used a synthetic pathway reconstruction method that combines anatomical fiber tracking with dMRI-based tractography and iteratively created an anatomical high-resolution fiber map representing the most important bundles related to the ANT. RESULTS: The anatomically detailed 3D representation of the fibers in the ANT region generated with the synthetic pathway reconstruction method incorporates multiple anatomically defined fiber bundles with their course, orientation, connectivity and relative strength. Distinctive positions within the ANT region have a different hierarchical profile with respect to the stimulation-activated fiber bundles. This detailed connectivity map, which is embedded into the topographic map of the MNI brain, provides novel opportunities to analyze the outcomes of the ANT-DBS studies. CONCLUSION: Our synthetic reconstruction method provides the first anatomically realistic fiber pathway map in the human ANT region incorporating histological and structural MRI data. We propose that this complex ANT fiber network can be used for detailed analysis of the outcomes of DBS studies and potentially for visualization during the stimulation planning procedures. The connectivity map might also facilitate surgical planning and will help to simulate the complex ANT connectivity. Possible activation patterns that may be elicited by electrodes in different positions in the ANT region will help to understand clinically diverse outcomes based on this new dense fiber network map. As a consequence this work might in the future help to improve individual outcomes in ANT-DBS.

Quality of Life After Deep Brain Stimulation of Pediatric Patients with Dyskinetic Cerebral Palsy: A Prospective, Single-Arm, Multicenter Study with a Subsequent Randomized Double-Blind Crossover (STIM-CP).

BACKGROUND: Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. OBJECTIVE: The aim is to assess DBS effects in pediatric patients with pharmacorefractory dyskinetic cerebral palsy with focus on quality of life. METHODS: The method used is a prospective, single-arm, multicenter study. The primary endpoint is improvement in quality of life (CPCHILD [Caregiver Priorities & Child Health Index of Life with Disabilities]) from baseline to 12 months under therapeutic stimulation. The main key secondary outcomes are changes in Burke-Fahn-Marsden Dystonia Rating Scale, Dyskinesia Impairment Scale, Gross Motor Function Measure-66, Canadian Occupational Performance Measure (COPM), and Short-Form (SF)-36. After 12 months, patients were randomly assigned to a blinded crossover to receive active or sham stimulation for 24 hours each. Severity of dystonia and chorea were blindly rated. Safety was assessed throughout. The trial was registered at ClinicalTrials.gov, number NCT02097693. RESULTS: Sixteen patients (age: 13.4 ± 2.9 years) were recruited by seven clinical sites. Primary outcome at 12-month follow-up is as follows: mean CPCHILD increased by 4.2 ± 10.4 points (95% CI [confidence interval] -1.3 to 9.7; P = 0.125); among secondary outcomes: improvement in COPM performance measure of 1.1 ± 1.5 points (95% CI 0.2 to 1.9; P = 0.02) and in the SF-36 physical health component by 5.1 ± 6.2 points (95% CI 0.7 to 9.6; P = 0.028). Otherwise, there are no significant changes. CONCLUSION: Evidence to recommend DBS as routine treatment to improve quality of life in pediatric patients with dyskinetic cerebral palsy is not yet sufficient. Extended follow-up in larger cohorts will determine the impact of DBS further to guide treatment decisions in these often severely disabled patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neuropathological interpretation of stimulated Raman histology images of brain and spine tumors: part B.

Intraoperative histopathological examinations are routinely performed to provide neurosurgeons with information about the entity of tumor tissue. Here, we quantified the neuropathological interpretability of stimulated Raman histology (SRH) acquired using a Raman laser imaging system in a routine clinical setting without any specialized training or prior experience. Stimulated Raman scattering microscopy was performed on 117 samples of pathological tissue from 73 cases of brain and spine tumor surgeries. A board-certified neuropathologist - novice in the interpretation of SRH - assessed image quality by scoring subjective tumor infiltration and stated a diagnosis based on the SRH images. The diagnostic accuracy was determined by comparison to frozen hematoxylin-eosin (H&E)-stained sections and the ground truth defined as the definitive neuropathological diagnosis. The overall SRH imaging quality was rated high with the detection of tumor cells classified as inconclusive in only 4.2% of all images. The accuracy of neuropathological diagnosis based on SRH images was 87.7% and was non-inferior to the current standard of fast frozen H&E-stained sections (87.3 vs. 88.9%, p = 0.783). We found a substantial diagnostic correlation between SRH-based neuropathological diagnosis and H&E-stained frozen sections (κ = 0.8). The interpretability of intraoperative SRH imaging was demonstrated to be equivalent to the current standard method of H&E-stained frozen sections. Further research using this label-free innovative alternative vs. conventional staining is required to determine to which extent SRH-based intraoperative decision-making can be streamlined in order to facilitate the advancement of surgical neurooncology.

Stimulated Raman histology in the neurosurgical workflow of a major European neurosurgical center - part A.

Histopathological diagnosis is the current standard for the classification of brain and spine tumors. Raman spectroscopy has been reported to allow fast and easy intraoperative tissue analysis. Here, we report data on the intraoperative implementation of a stimulated Raman histology (SRH) as an innovative strategy offering intraoperative near real-time histopathological analysis. A total of 429 SRH images from 108 patients were generated and analyzed by using a Raman imaging system (Invenio Imaging Inc.). We aimed at establishing a dedicated workflow for SRH serving as an intraoperative diagnostic, research, and quality control tool in the neurosurgical operating room (OR). First experiences with this novel imaging modality were reported and analyzed suggesting process optimization regarding tissue collection, preparation, and imaging. The Raman imaging system was rapidly integrated into the surgical workflow of a large neurosurgical center. Within a few minutes of connecting the device, the first high-quality images could be acquired in a "plug-and-play" manner. We did not encounter relevant obstacles and the learning curve was steep. However, certain prerequisites regarding quality and acquisition of tissue samples, data processing and interpretation, and high throughput adaptions must be considered. Intraoperative SRH can easily be integrated into the workflow of neurosurgical tumor resection. Considering few process optimizations that can be implemented rapidly, high-quality images can be obtained near real time. Hence, we propose SRH as a complementary tool for the diagnosis of tumor entity, analysis of tumor infiltration zones, online quality and safety control and as a research tool in the neurosurgical OR.

Stereotactic cysto-ventricular catheters in craniopharyngiomas: an effective minimally invasive method to improve visual impairment and achieve long-term cyst volume reduction.

Craniopharyngiomas are typically located in the sellar region and frequently contain space-occupying cysts. They usually cause visual impairment and endocrine disorders. Due to the high potential morbidity associated with radical resection, several less invasive surgical approaches have been developed. This study investigated stereotactic-guided implantation of cysto-ventricular catheters (CVC) as a new method to reduce and control cystic components. Twelve patients with cystic craniopharyngiomas were treated with CVC in our hospital between 04/2013 and 05/2017. The clinical and radiological data were retrospectively analysed to evaluate safety aspects as well as ophthalmological and endocrine symptoms. The long-term development of tumour and cyst volumes was assessed by volumetry. The median age of our patients was 69.0 years and the median follow-up period was 41.0 months. Volumetric analyses demonstrated a mean reduction of cyst volume of 64.2% after CVC implantation. At last follow-up assessment, there was a mean reduction of cyst volume of 92.0% and total tumour volume of 85.8% after completion of radiotherapy. Visual acuity improved in 90% of affected patients, and visual field defects improved in 70% of affected patients. No patient showed ophthalmological deterioration after surgery, and endocrine disorders remained stable. Stereotactic implantation of CVC proved to be a safe minimally invasive method for the long-term reduction of cystic components with improved ophthalmological symptoms. The consequential decrease of total tumour volumes optimised conditions for adjuvant radiotherapy. Given the low surgical morbidity and the effective drainage of tumour cysts, this technique should be considered for the treatment of selected cystic craniopharyngiomas.

DBS dysfunction mimicking transient ischemic attacks-a case report.

We report on a patient with thalamic deep brain stimulation (DBS) for essential tremor who was admitted to a stroke unit with transient vertigo, dysarthria, and gait disturbance. Transient ischemic attacks were assumed but fluctuating neurological symptoms persisted until presentation to a DBS center. Here, unstable high monopolar impedances of the right-hemispheric electrode contacts were detected. Surgical revision revealed a fracture of the pocket adaptor connecting this electrode to the impulse generator. Replacement resulted in stable impedances and remitted the transient neurological symptoms. Emergency and stroke doctors should be aware of neurological symptoms induced by technical dysfunctions in DBS.

The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series.

INTRODUCTION: Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance. METHODS: A total of 36 patients were enrolled (essential tremor (17), Parkinson's tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1W and T2W sequences. The DRT was individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio). RESULTS: Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis. DISCUSSION: Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.

Rapid battery depletion and loss of therapy due to a short circuit in bipolar DBS for essential tremor.

Technical dysfunctions have been reported reducing efficacy of deep brain stimulation (DBS). Here, we report on an essential-tremor patient in whom a short circuit in bipolar DBS resulted not only in unilateral loss of therapy but also in high current flow and thereby rapid decline of the impulse-generator battery voltage from 2.83 V a week before the event to 2.54 V, indicating the need for an impulse-generator replacement. Immediate re-programming restored therapeutic efficacy. Moreover, the reduction in current flow allowed the battery voltage to recover without immediate surgical intervention to 2.81 V a week later.

Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor.

BACKGROUND: We report a patient who received conventional bilateral deep brain stimulation of the ventral intermediate nucleus of thalamus (Vim) for the treatment of medication refractory essential tremor (ET). After initial beneficial effects, therapeutic efficacy was lost due to a loss of control of his proximal trunkal and extremity tremor. The patient received successful diffusion tensor magnetic resonance imaging fiber tractographic (DTI FT)-assisted DBS revision surgery targeting the dentato-rubro-thalamic tract (DRT) in the subthalamic region (STR). OBJECTIVE: To report the concept of DTI FT-assisted DRT DBS revision surgery for ET and to show sophisticated postoperative neuroimaging analysis explaining improved symptom control. METHODS: Analysis was based on preoperative DTI sequences and postoperative helical computed tomography (hCT). Leads, stimulation fields, and fibers were reconstructed using commercial software systems (Elements, Brainlab AG, Feldkirchen, Germany; GUIDE XT, Boston Scientific Corp., Boston, MA, USA). RESULTS: The patient showed immediate and sustained tremor improvement after DTI FT-assisted revision surgery. Analysis of the two implantations (electrode positions in both instances) revealed a lateral and posterior shift in the pattern of modulation of the cortical fiber pathway projection after revision surgery as compared to initial implantation, explaining a more efficacious stimulation. CONCLUSIONS: Our work underpins a possible superiority of direct targeting approaches using advanced neuroimaging technologies to perform personalized DBS surgery. The evaluation of DBS electrode positions with the herein-described neuroimaging simulation technologies will likely improve targeting and revision strategies. Direct targeting with DTI FT-assisted approaches in a variety of indications is the focus of our ongoing research.

One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease.

BACKGROUND: Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. METHODS: Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. RESULTS: Both patients showed immediate and sustained improvement of their tremor, bilaterally. CONCLUSIONS: The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( OPINION: www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research.

Brain alterations with deep brain stimulation: New insight from a neuropathological case series.

BACKGROUND: Previous studies on human brain tissue alterations caused by deep brain stimulation described glial and reactive inflammatory changes. In the current pathoanatomical study, we extended the analysis to signs of axonal changes and the influence of concomitant disease. METHODS: Brains of 10 patients with Parkinson's disease or essential tremor and a total of 18 electrodes were systematically examined up to 7.5 y after surgery. RESULTS: In general, tissue that had long-term contact with the electrode material exhibited astrogliosis in all, T-lymphocytes in 93%, and multinucleated giant cells in 68% of patients. Immunohistochemistry showed an increase in amyloid precursor protein immunoreactive axonal swellings in the brain at the electrically active parts of the electrodes. Patients who died of septicemia showed a more severe astrogliosis and giant cell reaction than patients who died of cardiovascular events. Parkinson's disease or essential tremor did not differentially produce histopathological changes around the electrodes. CONCLUSION: Long-term electrical stimulation by deep brain stimulation causes minor axonal changes. The cause of death, but not the underlying neurological disease, affects the histopathological changes around the electrode. The findings need to be reproduced by examining larger patient subgroups.

Termination of seizures by ictal transcranial focal cortex stimulation.

Whereas high-level evidence exists on chronic neuromodulatory effects of different brain stimulation approaches in reducing seizure frequency, evidence for acute antiseizure effects of electrical brain stimulation during seizures is sparse. As part of an ongoing trial, we implanted a patient with a novel focal cortex stimulation (FCS) device with a Laplacian electrode placed over a precentral focal cortical dysplasia. The baseline seizure frequency was 125 per month, consisting of (i) focal aware sensory seizures that invariably progressed to uni- or bilateral tonic contraction and clonic jerking, and (ii) primary motor seizures. Besides an overall reduction in seizure frequency, on-demand stimulation had an immediate effect on seizures with a sensory phase, whereby 63%-86% of these seizures were terminated by ictal stimulation. These observations provide the first evidence that ictal self-triggered transcranial focal cortex stimulation can significantly interfere with the progression of seizure semiology.

Accuracy of augmented reality-guided drainage versus stereotactic and conventional puncture in an intracerebral hemorrhage phantom model.

BACKGROUND: Minimally invasive intracranial drain placement is a common neurosurgical emergency procedure in patients with intracerebral hemorrhage (ICH). We aimed to retrospectively investigate the accuracy of conventional freehand (bedside) hemorrhage drain placement and to prospectively compare the accuracy of augmented/mixed reality-guided (AR) versus frame-based stereotaxy-guided (STX) and freehand drain placement in a phantom model. METHODS: A retrospective, single-center analysis evaluated the accuracy of drain placement in 73 consecutive ICH with a visual rating of postinterventional CT data. In a head phantom with a simulated deep ICH, five neurosurgeons performed four punctures for each technique: STX, AR, and the freehand technique. The Euclidean distance to the target point and the lateral deviation of the achieved trajectory from the planned trajectory at target point level were compared between the three methods. RESULTS: Analysis of the clinical cases revealed an optimal drainage position in only 46/73 (63%). Correction of the drain was necessary in 23/73 cases (32%). In the phantom study, accuracy of AR was significantly higher than the freehand method (P<0.001 for both Euclidean and lateral distances). The Euclidean distance using AR (median 3 mm) was close to that using STX (median 1.95 mm; P=0.023). CONCLUSIONS: We demonstrated that the accuracy of the freehand technique was low and that subsequent position correction was common. In a phantom model, AR drainage placement was significantly more precise than the freehand method. AR has great potential to increase precision of emergency intracranial punctures in a bedside setting.

Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials.

Importance: For the large population of people with drug-refractory epilepsy, alternative treatment approaches are needed. Clinical trial outcomes of a novel stimulation device, which is newly available in Europe for the treatment of patients with a predominant seizure focus, are reported for the first time. Objective: To perform a pooled analysis of the results of 2 prospective, multicenter, single-arm trials, A Pilot Study to Assess the Feasibility of Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (EASEE II) and A Pilot Study to Assess the Feasibility of Patient-Controlled Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (PIMIDES I), assessing the safety and efficacy of epicranial focal cortex stimulation (FCS) with a novel implantable device (EASEE [Precisis]) as adjunctive treatment for adult patients with drug-refractory focal epilepsy. Design, Setting, and Participants: This study was a pooled analysis of 2 nonrandomized uncontrolled trials, EASEE II and PIMIDES I, which began on January 15, 2019, and January 14, 2020, respectively, and ended on July 28, 2021. EASEE II and PIMIDES I were the first in-human, prospective, single-arm trials with an 8-month evaluation period. Patients were recruited at 7 European epilepsy centers. Consecutive participants with drug-refractory focal epilepsy were enrolled. Study data were analyzed from September 29, 2021, to February 2, 2022. Interventions: After a 1-month prospective baseline period, patients were implanted with the neurostimulation device. After a 1-month postimplantation recovery period, unblinded FCS was activated using both high-frequency and direct current (DC)-like components performed via electrode arrays placed epicranially above the individual epileptic focus region. Main Outcomes and Measures: Efficacy was prospectively assessed by the responder rate in the sixth month of stimulation compared with baseline; safety and additional end points were assessed after device implantation and during the stimulation period. Results: Of the 34 adult patients enrolled at 6 German and 1 Belgian investigational site, 33 (mean [SD] age, 34.6 [13.5] years; 18 male patients [54.5%]) received the neurostimulation device implant. A total of 32 patients underwent combined high-frequency direct current-like stimulation at least until the 8-month postimplant follow-up visit. After 6 months of stimulation, 17 of 32 patients (53.1%) were responders to treatment with at least a 50% reduction in seizure frequency compared with baseline, corresponding to a significant median seizure reduction by 52% (95% CI, 0.37%-0.76%; P < .001). No device- or procedure-related serious adverse events were reported (0; 95% CI, 0%-10.58%). There were no significant alterations in cognition, mood, or overall quality of life. Conclusions and Relevance: Results of this pooled analysis of 2 nonrandomized uncontrolled trials suggest that FCS with a novel neurostimulation device was associated with an effective reduction in seizure frequency in patients with drug-refractory focal epilepsy and may offer a promising treatment option for patients with a predominant epileptic focus. Trial Registration: German Clinical Trials Register: DRKS00015918 and DRKS00017833, respectively, and jointly under PROSPERO: CRD42021266440.

Early cisternal fibrinolysis is more effective than rescue spasmolysis for the prevention of delayed infarction after subarachnoid haemorrhage.

BACKGROUND: To compare the efficacy of two different concepts of cisternal therapy-PREVENTIVE fibrinolysis plus on-demand spasmolysis versus RESCUE spasmolysis-for the prevention of cerebral vasospasm (CVS) and delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid haemorrhage (aSAH). METHODS: Retrospective analysis of 84 aSAH patients selected for cisternal therapy for DCI prevention. 66 high-risk patients received PREVENTIVE cisternal therapy to enhance blood clearance. Either stereotactic catheter ventriculocisternostomy (STX-VCS) or intraoperative placement of a cisterno-ventriculostomy catheter (CVC), followed by fibrinolytic cisternal lavage using urokinase was performed. In case of vasospasm, nimodipine was applied intrathecally. 22 low-risk patients who developed CVS against expectations were selected for STX-VCS as RESCUE intervention for cisternal spasmolysis with nimodipine. Rates of DCI and mean flow velocities of daily transcranial Doppler (TCD) ultrasonographies were evaluated. RESULTS: Despite a higher prespecified DCI risk, patients selected for PREVENTIVE intervention primarily aiming at blood clearance had a lower DCI rate compared with patients selected for intrathecal spasmolysis as a RESCUE therapy (11.3% vs 18.2%). After intrathecal treatment onset, CVS (TCD>160 cm/s) occurred in 45% of patients with PREVENTIVE and 77% of patients with RESCUE therapy (p=0.013). A stronger response of CVS to intrathecal nimodipine was observed in patients with PREVENTIVE intervention as the mean CVS duration after start of intrathecal nimodipine was 3.2 days compared with 5.8 days in patients with RESCUE therapy (p=0.026). CONCLUSIONS: PREVENTIVE cisternal therapy directed at blood clearance is more effective for the prevention of CVS and delayed infarction compared with cisternal RESCUE spasmolysis. TRIAL REGISTRATION NUMBER: DRKS00016532.

Application of Augmented Reality in Percutaneous Procedures-Rhizotomy of the Gasserian Ganglion.

BACKGROUND: Percutaneous rhizotomy of the Gasserian ganglion for trigeminal neuralgia is an effective therapeutic procedure. Yet, landmark-guided cannulation of the foramen ovale is manually challenging and difficult to learn. OBJECTIVE: To overcome these limitations, we assessed the feasibility and accuracy of an augmented reality (AR)-guided puncture of the foramen ovale. METHODS: A head phantom with soft tissue structures of the facial area was built. A three-dimensional (3D)-dataset of the phantom was generated using a stereotactic planning workstation. An optimal trajectory to the foramen ovale was created and then transferred to an AR headset. A total of 2 neurosurgeons and 2 neuroradiologists independently performed 8 AR-guided and 8 landmark-guided cannulations of the foramen ovale, respectively. For each AR-guided cannulation, the hologram was manually aligned with the phantom. Accuracy of the cannulation was evaluated using the Euclidean distance to the target point as well as the lateral deviation of the achieved trajectory from the planned trajectory at target point level. RESULTS: With the help of AR guidance, a successful cannulation of the foramen ovale was achieved in 90.6% compared to the purely landmark-based method with 18.8%. Euclidean distance and lateral deviation were significantly lower with AR guidance than landmark guidance (P < .01). CONCLUSION: AR greatly improved accuracy of simulated percutaneous rhizotomy of the Gasserian ganglion.