Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a potentially reversible adverse event after aneurysmal subarachnoid hemorrhage (aSAH), when early detected and treated. Computer tomography perfusion (CTP) is used to identify the tissue at risk for DCI. In this study, the predictive power of early CTP was compared with that of blood distribution on initial CT for localization of tissue at risk for DCI. METHODS: A consecutive patient cohort with aSAH treated between 2012 and 2020 was retrospectively analyzed. Blood distribution on CT was semi-quantitatively assessed with the Hijdra-score. The vessel territory with the most surrounding blood and the one with perfusion deficits on CTP performed on day 3 after ictus were considered to be at risk for DCI, respectively. RESULTS: A total of 324 patients were included. Delayed infarction occurred in 17% (56/324) of patients. Early perfusion deficits were detected in 82% (46/56) of patients, 85% (39/46) of them developed infarction within the predicted vessel territory at risk. In 46% (25/56) a vessel territory at risk was reliably determined by the blood distribution. For the prediction of DCI, blood amount/distribution was inferior to CTP. Concerning the identification of "tissue at risk" for DCI, a combination of both methods resulted in an increase of sensitivity to 64%, positive predictive value to 58%, and negative predictive value to 92%. CONCLUSIONS: Regarding the DCI-prediction, early CTP was superior to blood amount/distribution, while a consideration of subarachnoid blood distribution may help identify the vessel territories at risk for DCI in patients without early perfusion deficits.

Spontaneous intracerebral hemorrhage - patients retrospectively consent to fibrinolytic surgery despite poor neurological outcome and reduced health-related quality of life.

Spontaneous intracerebral hemorrhage (ICH) might lead to devastating consequences. Nonetheless, subjective interpretation of life circumstances might vary. Recent data from ischemic stroke patients show that there might be a paradox between clinically rated neurological outcome and self-reported satisfaction with quality of life. Our hypothesis was that minimally invasive surgically treated ICH patients would still give their consent to stereotactic fibrinolysis despite experiencing relatively poor neurological outcome. In order to better understand the patients' perspective and to enhance insight beyond functional outcome, this is the first study assessing disease-specific health-related quality of life (hrQoL) in ICH after fibrinolytic therapy. We conducted a retrospective analysis of patients with spontaneous ICH treated minimally invasive by stereotactic fibrinolysis. Subsequently, using standardized telephone interviews, we evaluated functional outcome with the modified Rankin Scale (mRS), health-related Quality of Life with the Quality of life after Brain Injury Overall scale (QOLIBRI-OS), and assessed retrospectively if the patients would have given their consent to the treatment. To verify the primary hypothesis that fibrinolytic treated ICH patients would still retrospectively consent to fibrinolytic therapy despite a relatively poor neurological outcome, we conducted a chi-square test to compare good versus poor outcome (mRS) between consenters and non-consenters. To investigate the association between hrQoL (QOLIBRI-OS) and consent, we conducted a Mann-Whitney U-test. Moreover, we did a Spearman correlation to investigate the correlation between functional outcome (mRS) and hrQoL (QOLIBRI-OS). The analysis comprised 63 data sets (35 men, mean age: 66.9 ± 11.8 years, median Hemphill score: 3 [2-3]). Good neurological outcome (mRS 0-3) was achieved in 52% (33/63) of the patients. Patients would have given their consent to surgery retrospectively in 89.7% (52/58). These 52 consenting patients comprised all 33 patients (100%) who achieved good functional outcome and 19 of the 25 patients (76%) who achieved poor neurological outcome (mRS 4-6). The mean QOLIBRI-OS value was 49.55 ± 27.75. A significant association between hrQoL and retrospective consent was found (p = 0.004). This study supports fibrinolytic treatment of ICH even in cases when poor neurological outcome would have to be assumed since subjective perception of deficits could be in contrast with the objectively measured neurological outcome. HrQoL serves as a criterion for success of rtPa lysis therapy in ICH.

Radiofrequency thermocoagulation under neuromonitoring guidance and general anesthesia for treatment of refractory trigeminal neuralgia.

OBJECTIVE: Radiofrequency thermocoagulation (RFT) for refractory trigeminal neuralgia is usually performed in awake patients to localize the involved trigeminal branches. It is often a painful experience. Here, we present RFT under neuromonitoring guidance and general anesthesia. METHOD: Stimulation of trigeminal branches at the foramen ovale with the tip of the RFT cannula is performed under short general anesthesia. Antidromic sensory-evoked potentials (aSEP) are recorded from the 3 trigeminal branches. The cannula is repositioned until the desired branch can be stimulated and lesioned. CONCLUSION: aSEP enable accurate localization of involved trigeminal branches during RFT and allow performing the procedure under general anesthesia.

Influence of cerebrospinal fluid drainage in the first days after aneurysm rupture on the severity of early brain injury following aneurysmal subarachnoid hemorrhage.

PURPOSE: Progressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH. METHODS: Patients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily. RESULTS: 90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02). CONCLUSION: A more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.

Establishing reliable selection criteria for performing fibrinolytic therapy in patients with intracerebral haemorrhage based on prognostic tools.

OBJECTIVES: Minimally invasive surgery combined with fibrinolytic therapy is a promising treatment option for patients with intracerebral haemorrhage (ICH), but a meticulous patient selection is required, because not every patient benefits from it. The ICH score facilitates a reliable patient selection for fibrinolytic therapy except for ICH-4. This study evaluated whether an additional use of other prognostic tools can overcome this limitation. MATERIALS AND METHODS: A consecutive ICH patient cohort treated with fibrinolytic therapy between 2010 and 2020 was retrospectively analysed. The following prognostic tools were calculated: APACHE II, ICH-GS, ICH-FUNC, and ICH score. The discrimination power of every score was determined by ROC-analysis. Primary outcome parameters regarding the benefit of fibrinolytic therapy were the in-hospital mortality and a poor outcome defined as modified Rankin scale (mRS) > 4. RESULTS: A total of 280 patients with a median age of 72 years were included. The mortality rates according to the ICH score were ICH-0 = 0 % (0/0), ICH-1 = 0 % (0/22), ICH-2 = 7.1 % (5/70), ICH-3 = 17.3 % (19/110), ICH-4 = 67.2 % (45/67), ICH-5 = 100 % (11/11). The APACHE II showed the best discrimination power for in-hospital mortality (AUC = 0.87, p < 0.0001) and for poor outcome (AUC = 0.79, p < 0.0001). In the subgroup with ICH-4, APACHE II with a cut-off of 24.5 showed a good discriminating power for in-hospital mortality (AUC = 0.83, p < 0.001) and for poor outcome (AUC = 0.87, p < 0.001). CONCLUSIONS: An additional application of APACHE II score increases the discriminating power of ICH score 4 enabling a more precise appraisal of in-hospital mortality and of functional outcome, which could support the patient selection for fibrinolytic therapy.

Cerebellar Stroke Score and Grading Scale for the Prediction of Mortality and Outcomes in Ischemic Cerebellar Stroke.

BACKGROUND: Several individual predictors for outcomes in patients with cerebellar stroke (CS) have been previously identified. There is, however, no established clinical score for CS. Therefore, the aim of this study was to develop simple and accurate grading scales for patients with CS in an effort to better estimate mortality and outcomes. METHODS: This multicentric retrospective study included 531 patients with ischemic CS presenting to 5 different academic neurosurgical and neurological departments throughout Germany between 2008 and 2021. Logistic regression analysis was performed to determine independent predictors related to 30-day mortality and unfavorable outcome (modified Rankin Scale score of 4-6). By weighing each parameter via calculation of regression coefficients, an ischemic CS-score and CS-grading scale (CS-GS) were developed and internally validated. RESULTS: Independent predictors for 30-day mortality were aged ≥70 years (odds ratio, 5.2), Glasgow Coma Scale score 3 to 4 at admission (odds ratio, 2.6), stroke volume ≥25 cm3 (odds ratio, 2.7), and involvement of the brain stem (odds ratio, 3.9). When integrating each parameter into the CS-score, age≥70 years and brain stem stroke were assigned 2 points, Glasgow Coma Scale score 3 to 4, and stroke volume≥25 cm3 1 point resulting in a score ranging from 0 to 6. CS-score of 0, 1, 2, 3, 4, 5, and 6 points resulted in 30-day mortality of 1%, 6%, 6%, 17%, 21%, 55%, and 67%, respectively. Independent predictors for 30-day unfavorable outcomes consisted of all components of the CS-score with an additional variable focused on comorbidities (CS-GS). Except for Glasgow Coma Scale score 3 to 4 at admission, which was assigned 3 points, all other parameters were assigned 1 point resulting in an overall score ranging from 0 to 7. CS-GS of 0, 1, 2, 3, 4, 5, 6, and 7 points resulted in 30-day unfavorable outcome of 1%, 17%, 33%, 40%, 50%, 80%, 77%, and 100%, respectively. Both 30-day mortality and unfavorable outcomes increased with increasing CS-score and CS-GS (P<0.001). CONCLUSIONS: The CS-score and CS-GS are simple and accurate grading scales for the prediction of 30-day mortality and unfavorable outcome in patients with CS. While the score systems proposed here may not directly impact treatment decisions, it may help discuss mortality and outcome with patients and caregivers.

Mini review: Current status and perspective of S100B protein as a biomarker in daily clinical practice for diagnosis and prognosticating of clinical outcome in patients with neurological diseases with focus on acute brain injury.

Prognosticating the clinical outcome of neurological diseases is essential to guide treatment and facilitate decision-making. It usually depends on clinical and radiological findings. Biomarkers have been suggested to support this process, as they are deemed objective measures and can express the extent of tissue damage or reflect the degree of inflammation. Some of them are specific, and some are not. Few of them, however, reached the stage of daily application in clinical practice. This mini review covers available applications of the S100B protein in prognosticating clinical outcome in patients with various neurological disorders, particularly in those with traumatic brain injury, spontaneous subarachnoid hemorrhage and ischemic stroke. The aim is to provide an understandable picture of the clinical use of the S100B protein and give a brief overview of the current limitations that require future solutions.

Positioning of epidural electrode for motor cortex stimulation in general anesthesia based on intraoperative electrophysiological monitoring to treat refractory trigeminal neuropathic pain.

BACKGROUND: Motor cortex stimulation (MCS) represents a treatment option for refractory trigeminal neuralgia (TGN). Usually, patients need to be awake during surgery to confirm a correct position of the epidural electrode above the motor cortex, reducing patient's comfort. METHOD: Epidural cortical mapping (ECM) and motor evoked potentials (MEPs) were intraoperatively performed for correct localization of motor cortex under general anesthesia that provided comparable results to test stimulation after letting the patient to be awake during the operation. CONCLUSION: Intraoperative ECM and MEPs facilitate a confirmation of correct MCS-electrode position above the motor cortex allowing the MCS-procedure to be performed under general anesthesia.

Surgical timing and indications for decompressive craniectomy in malignant stroke: results from a single-center retrospective analysis.

PURPOSE: Acute ischemic stroke induces rapid neuronal death and time is a key factor in its treatment. Despite timely recanalization, malignant cerebral infarction can ensue, requiring decompressive surgery (DC). The ideal timing of surgery is still a matter of debate; in this study, we attempt to establish the ideal time to perform surgery in this population. METHODS: We conducted a retrospective study of patients undergoing DC for stroke at our department. The indication for DC was based on drop in level of consciousness and standard imaging parameters. Patients were stratified according to the timing of DC in four groups: (a) "ultra-early" ≤12 h, (b) "early" >12≤24 h, (c) "timely" >24≤48 h, and (d) "late" >48 h. The primary endpoint of this study was in-house mortality, as a dependent variable from surgical timing. Secondary endpoint was modified Rankin scale at discharge. RESULTS: In a cohort of 110 patients, the timing of surgery did not influence mortality or functional outcome (p=0.060). Patients undergoing late DC were however significantly older (p=0.008), and those undergoing ultra-early DC showed a trend towards a lower GCS at admission. CONCLUSIONS: Our results add to the evidence supporting an extension of the time window for DC in stroke beyond 48 h. Further criteria beyond clinical and imaging signs of herniation should be considered when selecting patients for DC after stroke to identify patients who would benefit from the procedure.

Surgery for brain metastases: radiooncology scores predict survival-score index for radiosurgery, graded prognostic assessment, recursive partitioning analysis.

BACKGROUND: Radiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease. METHODS: We performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems. RESULTS: All scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21-24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR. CONCLUSIONS: All scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling.

Endoscope-enhanced fluorescence-guided microsurgery increases survival in patients with glioblastoma.

PURPOSE: Extent of resection (EOR) predicts progression-free survival (PFS) and may impact overall survival (OS) in patients with glioblastoma. We recently demonstrated that 5-aminolevulinic acid-(5-ALA)-fluorescence-enhanced endoscopic surgery increase the rate of gross total resection. However, it is hitherto unknown whether fluorescence-enhanced endoscopic resection affects survival. METHODS: We conducted a retrospective single-center analysis of a consecutive series of patients who underwent surgery for non-eloquently located glioblastoma between 2011 and 2018. All patients underwent fluorescence-guided microscopic or fluorescence-guided combined microscopic and endoscopic resection. PFS, OS, EOR as well as clinical and demographic parameters, adjuvant treatment modalities, and molecular characteristics were compared between microscopy-only vs. endoscopy-assisted microsurgical resection. RESULTS: Out of 114 patients, 73 (65%) were male, and 57 (50%) were older than 65 years. Twenty patients (18%) were operated on using additional endoscopic assistance. Both cohorts were equally distributed in terms of age, performance status, lesion location, adjuvant treatment modalities, and molecular status. Gross total resection was achieved in all endoscopy-assisted patients compared to about three-quarters of microscope-only patients (100% vs. 75.9%, p=0.003). The PFS in the endoscope-assisted cohort was 19.3 months (CI95% 10.8-27.7) vs. 10.8 months (CI95% 8.2-13.4; p=0.012) in the microscope-only cohort. OS in the endoscope-assisted group was 28.9 months (CI95% 20.4-34.1) compared to 16.8 months (CI95% 14.0-20.9), in the microscope-only group (p=0.001). CONCLUSION: Endoscope-assisted fluorescence-guided resection of glioblastoma appears to substantially enhance gross total resection and OS. The strong effect size observed herein is contrasted by the limitations in study design. Therefore, prospective validation is required before we can generalize our findings.

Interaction of Optimal Cerebral Perfusion Pressure with Early Brain Injury and its Impact on Ischemic Complications and Outcome Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral autoregulation is impaired early on after aneurysmal subarachnoid hemorrhage (aSAH). The study objective was to explore the pressure reactivity index (PRx) and cerebral perfusion pressure (CPP) in the earliest phase after aneurysm rupture and to address the question of whether an optimal CPP (CPPopt)-targeted management is associated with less severe early brain injury (EBI). METHODS: Patients with aSAH admitted between 2012 and 2020 were retrospectively included in this observational cohort study. The PRx was calculated as a correlation coefficient between intracranial pressure and mean arterial pressure. By plotting the PRx versus CPP, CPP correlating the lowest PRx value was identified as CPPopt. EBI was assessed by applying the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) on day 3 after ictus. An SEBES ≥ 3 was considered severe EBI. RESULTS: In 90 of 324 consecutive patients with aSAH, intracranial pressure monitoring was performed ≥ 7 days, allowing for PRx calculation and CPPopt determination. Severe EBI was associated with larger mean deviation of CPP from CPPopt 72 h after ictus (r = 0.22, p = 0.03). Progressive edema requiring decompressive hemicraniectomy was associated with larger deviation of CPP from CPPopt on day 2 (r = 0.23, p = 0.02). The higher the difference of CPP from CPPopt on day 3 the higher the mortality rate (r = 0.31, p = 0.04). CONCLUSIONS: Patients with CPP near to the calculated CPPopt in the early phase after aSAH experienced less severe EBI, less frequently received decompressive hemicraniectomy, and exhibited a lower mortality rate. A prospective evaluation of CPPopt-guided management starting in the first days after ictus is needed to confirm the clinical validity of this concept.

Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid.

In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue. How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical. Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen availability and tissue damage.

False-positive results in transcranial motor evoked potentials for outcome prognostication during surgery for supratentorial lesions.

During monitoring of motor evoked potentials (MEP) elicited by transcranial electrical stimulation (TES) for prognostication of postoperative motor deficit, significant MEP changes without postoperative deterioration of motor function represent false-positive results. We aimed to investigate this phenomenon in a large series of patients who underwent resection of supratentorial lesions. TES was applied in 264 patients during resection of motor-eloquent supratentorial lesions. MEP were recorded bilaterally from arm, leg, and/ or facial muscles. The threshold criterion was applied assessing percentage increase in threshold level, which was considered significant if being > 20% higher on affected side than on the unaffected side. Subcortical stimulation was additionally applied to estimate the distance to corticospinal tract. Motor function was evaluated at 24 h after surgery and at 3-month follow-up. Patients with false-positive results were analyzed regarding tumor location, tumor volume, and characteristics of the monitoring. MEP were recorded from 399 muscles (264 arm muscles, 75 leg muscles, and 60 facial muscles). Motor function was unchanged postoperatively in 359 muscles in 228 patients. Among these cases, the threshold level did not change significantly in 354 muscles in 224 patients, while it increased significantly in the remaining 5 muscles in 4 patients (abductor pollicis brevis in all four patients and orbicularis oris in one patient), leading to a false-positive rate of 1.1%. Tumor volume, opening the ventricle, and negative subcortical stimulation did not significantly correlate with false-positive results, while the tumor location in the parietal lobe dorsal to the postcentral gyrus correlated significantly (p = 0.012, odds ratio 11.2, 95% CI 1.8 to 69.8). False-negative results took place in 1.1% of cases in a large series of TES-MEP monitoring using the threshold criterion. Tumor location in the parietal lobe dorsal to the postcentral gyrus was the only predictor of false-positive results.

Microsurgical clipping vs Woven EndoBridge (WEB) device for the management of unruptured wide-neck bifurcation aneurysms.

The Woven EndoBridge device (WEB) was introduced in 2010 to treat wide-neck bifurcation aneurysms (WNBAs). Three landmark studies have been conducted to assess its safety and efficacy: WEBCAST, WEBCAST 2, and French Observatory Study. However, these studies have not compared its safety and efficacy to other treatment modalities. In this study, we compare WEB versus microsurgical clipping in the management of unruptured WNBA. We conducted a retrospective study of unruptured WNBA meeting the morphological criteria to be amenable for WEB treatment operated on at our institution. Surgical morbidity, mortality, and occlusion rates were assessed. We compared our results to those reported in the cumulative population of the three WEB landmark studies at 1 year. A total of 84 patients with 89 WNBA were included. The most common aneurysm location was the middle cerebral artery bifurcation (n = 67/89, 75%). No operative mortality was observed. Morbidity comprised small-vessel vasospasm (n = 1/89, 1%) resulting in hemiparesis vs. 3% morbidity for WEB (p = .324). All but one (n = 1/89, 1%) WNBA were completely occluded vs WEB occlusion rate of 53% at 1 year, statistically significantly worse (p < .001). In our analysis, we were not able to show superiority of WEB in terms of procedural morbidity in comparison to microsurgical clipping, defined as worsening in mRS. Microsurgical clipping achieves statistically significantly higher rates of complete aneurysm occlusion, thus posing the question of whether the WEB should be presented as a viable, comparable alternative to patients amenable to surgical treatment.

The value of comorbidities and illness severity scores as prognostic tools for early outcome estimation in patients with aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe cerebrovascular disease not only causing brain injury but also frequently inducing a significant systemic reaction affecting multiple organ systems. In addition to hemorrhage severity, comorbidities and acute extracerebral organ dysfunction may impact the prognosis after aSAH as well. The study objective was to assess the value of illness severity scores for early outcome estimation after aSAH. A retrospective analysis of consecutive aSAH patients treated from 2012 to 2020 was performed. Comorbidities were evaluated applying the Charlson comorbidity index (CCI) and the American Society of Anesthesiologists (ASA) classification. Organ dysfunction was assessed by calculating the simplified acute physiology score (SAPS II) 24 h after admission. Modified Rankin scale (mRS) at 3 months was documented. The outcome discrimination power was evaluated. A total of 315 patients were analyzed. Significant comorbidities (CCI > 3) and physical performance impairment (ASA > 3) were found in 15% and 12% of all patients, respectively. The best outcome discrimination power showed SAPS II (AUC 0.76), whereas ASA (AUC 0.65) and CCI (AUC 0.64) exhibited lower discrimination power. A SAPS II cutoff of 40 could reliably discriminate patients with good (mRS ≤ 3) from those with poor outcome (p < 0.0001). Calculation of SAPS II allowed a comprehensive depiction of acute organ dysfunctions and facilitated a reliable early prognosis estimation in our study. In direct comparison to CCI and ASA, SAPS II demonstrated the highest discrimination power and deserves a consideration as a prognostic tool after aSAH.

Regorafenib for recurrent high-grade glioma: a unicentric retrospective analysis of feasibility, efficacy, and toxicity.

We describe here 11 consecutive patients with recurrence of high-grade glioma treated with regorafenib at our university medical center. The majority of patients had MGMT promoter methylation (9/11 cases). Regorafenib was given as 2nd line systemic treatment in 6/11 patients and 3rd or higher line treatment in 5/11 patients. The median number of applied cycles was 2 with dosage reductions in 5/11. Response to treatment was observed in 4/11 (PR in 1/11, and SD in 3/11). Median overall survival for the cohort was 16.1 months, median progression-free survival 9.0 months, and median time to treatment failure 3.3 months. Side effects of any CTCAE grade were noted in all patients, hereby 6/11 with CTCAE °III-IV reactions. High-grade side effects were of dermatologic, cardiovascular, and hematologic nature. A mean treatment delay of 57.5 days (range 23-119) was noted between tumor board recommendation and treatment initiation due to the application process for off-label use in this indication. In conclusion, treatment with regorafenib in relapsed high-grade glioma is a feasible treatment option but has to be considered carefully due to the significant side effect profile.

Infratentorial ganglioglioma mimicking a cerebellar metastasis.

We report a case of an infratentorial ganglioglioma in a 56-year-old male, who underwent magnetic resonance imaging (MRI) during the diagnostic workup for a suspected lung cancer. The MRI scan revealed a space-occupying lesion of the left lobulus semilunaris superior cerebelli, which was assumed being a metastasis. The asymptomatic lesion was resected to establish the diagnosis. Histologic and immunohistochemical studies showed a ganglioglioma with World Health Organization grade I characteristics. Although ganglioglioma typically exhibits a supratentorial predilection, it should be included in the differential diagnosis of lesions occurring in the cerebellum.