Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Semiautomated electric source imaging determines epileptogenicity of encephaloceles in temporal lobe epilepsy.

OBJECTIVE: We aimed to assess the ability of semiautomated electric source imaging (ESI) from long-term video-electroencephalographic (EEG) monitoring (LTM) to determine the epileptogenicity of temporopolar encephaloceles (TEs) in patients with temporal lobe epilepsy. METHODS: We conducted a retrospective study involving 32 temporal lobe epilepsy patients with TEs as potentially epileptogenic lesions in structural magnetic resonance imaging scans. Findings were validated through invasive intracerebral stereo-EEG in six of 32 patients and postsurgical outcome after tailored resection of the TE in 17 of 32 patients. LTM (mean duration = 6 days) was performed using the 10/20 system with additional T1/T2 for all patients and sphenoidal electrodes in 23 of 32 patients. Semiautomated detection and clustering of interictal epileptiform discharges (IEDs) were carried out to create IED types. ESI was performed on the averages of the two most frequent IED types per patient, utilizing individual head models, and two independent inverse methods (sLORETA [standardized low-resolution brain electromagnetic tomography], MUSIC [multiple signal classification]). ESI maxima concordance and propagation in spatial relation to TEs were quantified for sources with good signal quality (signal-to-noise ratio > 2, explained signal > 60%). RESULTS: ESI maxima correctly colocalized with a TE in 20 of 32 patients (62.5%) either at the onset or half-rising flank of at least one IED type per patient. ESI maxima showed propagation from the temporal pole to other temporal or extratemporal regions in 14 of 32 patients (44%), confirming propagation originating in the area of the TE. The findings from both inverse methods validated each other in 14 of 20 patients (70%), and sphenoidal electrodes exhibited the highest signal amplitudes in 17 of 23 patients (74%). The concordance of ESI with the TE predicted a seizure-free postsurgical outcome (Engel I vs. >I) with a diagnostic odds ratio of 2.1. SIGNIFICANCE: Semiautomated ESI from LTM often successfully identifies the epileptogenicity of TEs and the IED onset zone within the area of the TEs. Additionally, it shows potential predictive power for postsurgical outcomes in these patients.

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.

Development of a bleeding scale and hemostasis algorithm in cranial neurosurgery.

Effective hemostasis is crucial in neurosurgery as anatomical and functional considerations reduce tolerance for any bleeding. The classification of bleeding severities is a necessary step to enable neurosurgeons to counteract bleeding during surgery. Even though bleeding scales are used for a variety of surgical specialties, they cannot be transferred to cranial neurosurgery without adaption, and no consensus on the nature of such a classification exists to date. Moreover, there is plethora of topical hemostasis products with diverse mechanisms of action and application available. Clinical studies investigating those products used in neurosurgery did not define standardized procedures. This article demonstrates the systematic establishment of both a bleeding scale and a hemostasis algorithm to close this gap in the assessment of intracranial bleeding. The expert panel consisting of 7 members from different neurosurgical centers developed a qualitative bleeding scale with the peculiarities of neurosurgical procedures, based on the experience of each member in daily practice. The hemostasis algorithm is a recommendation for neurosurgeons to aid in the decision-making process to control any sort of bleeding, taking into account the rational use of available hemostatics, depending on type and location of bleeding, as well as the mechanism of action of such agents. Effectiveness of hemostasis, surgery times and economic costs can be optimized by applying the algorithm in daily practice.

Assessment of postoperative pain, dysesthesia, and weather sensitivity after pterional and temporal neurosurgical approaches.

OBJECTIVE: Many neurosurgical approaches require incision of the temporal muscle (TM). Consequently, patients often report reduced opening of the mouth, facial asymmetry, numbness, and pain after lateral craniotomies. A systematic assessment of these postoperative subjective complaints is lacking in the literature. Therefore, in this study, the authors evaluate subjective complaints after pterional, frontolateral-extended pterional, or temporal craniotomy using a 6-item questionnaire. They examine the association of these subjective complaints with the extent of the mobilization of the TM. METHODS: The questionnaire assessed complaints about limited opening of the mouth, pain in the mastication muscles, facial asymmetry, sensory deficits in the temporal region, weather sensitivity, and headache. Eligible patients with benign intracranial processes operated on using lateral cranial approaches between 2016 and 2019 were included. The questionnaire was answered before surgery (baseline) and 3 and 15 months after surgery. Surgeons documented the extent of TM incision. RESULTS: Among the 55 patients in this study, all complaints apart from headache showed an increase at a statistically significant rate at 3 months postoperatively, that is, limited mouth opening (p < 0.0001), pain in the mastication muscles (p < 0.0001), an impression of asymmetry in the mastication muscles (p = 0.0002), sensory disturbances in the temporal region (p < 0.0001), and weather sensitivity (p < 0.001). Only pain in the mastication muscles showed a relevant decrease at 15 months postsurgery (p = 0.058). The extent of the mobilized TM was associated with pain in the mastication muscles at 3 months (p = 0.0193). CONCLUSIONS: Subjective complaints in patients following lateral craniotomy can be detected. As the extent of the mobilized TM relevantly influenced pain in the mastication muscles, the authors conclude that one should sparsely mobilize the TM. Furthermore, a neurosurgeon should be aware and warn the patient of subjective postoperative complaints and inform the patient about their natural course.

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.

Diagnostic Accuracy of Epilepsy-dedicated MRI with Post-processing.

PURPOSE: To evaluate the diagnostic accuracy of epilepsy-dedicated 3 Tesla MRI including post-processing by correlating MRI, histopathology, and postsurgical seizure outcomes. METHODS: 3 Tesla-MRI including a magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence for post-processing using the morphometric analysis program MAP was acquired in 116 consecutive patients with drug-resistant focal epilepsy undergoing resection surgery. The MRI, histopathology reports and postsurgical seizure outcomes were recorded from the patient's charts. RESULTS: The MRI and histopathology were concordant in 101 and discordant in 15 patients, 3 no hippocampal sclerosis/gliosis only lesions were missed on MRI and 1 of 28 focal cortical dysplasia (FCD) type II associated with a glial scar was considered a glial scar only on MRI. In another five patients, MRI was suggestive of FCD, the histopathology was uneventful but patients were seizure-free following surgery. The MRI and histopathology were concordant in 20 of 21 glioneuronal tumors, 6 cavernomas, and 7 glial scars. Histopathology was negative in 10 patients with temporal lobe epilepsy, 4 of them had anteroinferior meningoencephaloceles. Engel class IA outcome was reached in 71% of patients. CONCLUSION: The proposed MRI protocol is highly accurate. No hippocampal sclerosis/gliosis only lesions are typically MRI negative. Small MRI positive FCD can be histopathologically missed, most likely due to sampling errors resulting from insufficient harvesting of tissue.

Quality of Life After Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

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 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.

A Retrospective Evaluation of the Retrosigmoidal Approach for Petroclival Meningioma Surgery and Prognostic Factors Affecting Clinical Outcome.

Introduction: Petroclival meningioma (PCM) remains a major neurosurgical challenge. There are still controversial strategic treatment concepts about surgical approach, the extent of resection, and postoperative radiotherapy. We aimed to evaluate prognostic factors influencing the progression-free survival (PFS) rates of PCM, with a particular focus on the retrosigmoidal approach, the role of the extent of resection, and postoperative radiotherapy. Methods: Eighty-nine patients with complete follow-up data were included. All patients were operated on via a retrosigmoidal approach, of whom 19 underwent gross total resection (GTR) and 70 underwent subtotal resection (STR). In the subgroups of tumors with infiltration of the cavernous sinus, 41 patients received near total resection (NTR) and 24 STR. Thirty-one patients received postoperative radiotherapy of the residual tumor and 58 were treated with surgery alone. Kaplan-Meier analyses and Cox regression were used to identify significant factors associated with treatment. Results: GTR (p=0.0107) and postoperative radiotherapy (p=0.014) were associated with significantly improved PFS. Even the subgroup analysis of extended PCM with infiltration of the cavernous sinus (CS) showed an advantage for PFS after near total resection (NTR) (p=0.0017). The additional radiotherapy of the residual tumor in the CS in this subgroup also showed a beneficial effect on PFS (p=0.012). Conclusion: The extension of surgical resection remains the most important prognostic factor in relation to oncological outcomes. However, the GTR of extended PCM with infiltration of the CS is associated with significant neurological morbidity and requires additional adjuvant therapy concepts. Postoperative radiotherapy is an important element in the treatment of the residual tumor after surgery.

Basic Surveillance Parameters Improve the Prediction of Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Background: To establish a practical risk chart for prediction of delayed cerebral infarction (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) by using information that is available until day 5 after ictus. Methods: We assessed all consecutive patients with aSAH admitted to our service between September 2008 and September 2015 (n = 417). The data set was randomly split into thirds. Two-thirds were used for model development and one-third was used for validation. Characteristics that were present between the bleeding event and day 5 (i.e., prior to >95% of DCI diagnoses) were assessed to predict DCI by using logistic regression models. A simple risk chart was established and validated. Results: The amount of cisternal and ventricular blood on admission CT (Hijdra sum score), early sonographic vasospasm (i.e., mean flow velocity of either intracranial artery >160 cm/s until day 5), and a simplified binary level of consciousness score until day 5 were the strongest predictors of DCI. A model combining these predictors delivered a high predictive accuracy [the area under the receiver operating characteristic (AUC) curve of 0.82, Nagelkerke's R 2 0.34 in the development cohort]. Validation of the model demonstrated a high discriminative capacity with the AUC of 0.82, Nagelkerke's R 2 0.30 in the validation cohort. Conclusion: Adding level of consciousness and sonographic vasospasm between admission and postbleed day 5 to the initial blood amount allows for simple and precise prediction of DCI. The suggested risk chart may prove useful for selection of appropriate candidates for interventions to prevent DCI.

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Mitigation of Blood Load Impact in Patients with Subarachnoid Hemorrhage by Cisternal Lavage.

OBJECT: The initial amount of subarachnoid and ventricular blood is an important prognostic factor for outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this comparative study of an unselected aSAH-population, we assess the modifiability of these factors by implementation of blood clearance by cisternal lavage. METHODS: All patients with aSAH treated in our department between October 2011 and October 2019 (8 years, n = 458) were included in our study. In the first 4-year period (BEFORE, n = 237), patients were treated according to international guidelines. In the second 4-year period (AFTER, n = 221), cisternal lavage methods were available and applied in 72 high-risk patients (32.5%). The cisternal and ventricular blood load was recorded by the Hijdra score. Multivariable regression models were used to assess the prognostic significance of risk factors, including blood load, in relation to common aSAH characteristics in both study groups. RESULTS: Worse neurological outcomes (mRS > 3) occurred in the BEFORE population with 41.45% versus 30.77% in the AFTER cohort, 6 months after aSAH (HR: 1.59, 95% CI 1.08-2.34, p = 0.01). Admission WFNS grade, comorbidities (Charlson Comorbidity Index), herniation signs, concomitant intracerebral hemorrhage, and the development of delayed cerebral infarction were strongly associated with poor outcome in both study groups. Intraventricular and cisternal blood load and, particularly, a cast fourth ventricle (Cast 4) represented strong prognosticators of poor neurological outcome in the BEFORE cohort. This effect was lost after implementation of cisternal lavage (AFTER cohort). CONCLUSION: Cisternal and ventricular blood load - in particular: a Cast 4 - represent important prognosticators in patients with aSAH. They are, however, amenable to modification by blood clearing therapies.

Mastication after craniotomy: pilot assessment of postoperative oral health-related quality of life.

BACKGROUND: Neurosurgical approaches to the brain often require the mobilization of the temporal muscle. Many patients complain of postoperative pain, atrophy, reduced mouth opening, and masticatory problems. Although the pterional, frontolateral-extended-pterional, and temporal craniotomies are the most frequently used approaches in neurosurgery, a systematic assessment of the postoperative oral health-related quality of life has never been performed so far. This study evaluates the oral health-related quality of life of patients after pterional, frontolateral-extended-pterional, or temporal craniotomy using a validated and standardized dental questionnaire, compares the results with the normal values of the general population, and investigates whether this questionnaire is sensitive to changes caused by surgical manipulation of the temporal muscle. METHODS: The "Oral Health Impact Profile" (OHIP14) is a validated questionnaire to assess the oral health-related quality of life. It asks the patients to assess their oral health situation within the past 7 days in 14 questions. Possible answers range from 0 (never) to 4 (very often). Sixty patients with benign intracranial processes operated through a lateral cranial approach were included. The questionnaire was answered before surgery (baseline) and 3 months and 15 months after surgery. RESULTS: Overall, postoperative OHIP scores increase significantly after 3 months and decrease after 15 months, but not to preoperative values. No factors can be identified which show a considerable relationship with the postoperative OHIP score. CONCLUSIONS: Postoperative impairment of mouth opening and pain during mastication can be observed 3 to 15 months after surgery and sometimes cause feedback from patients and their dentists. However, in line with existing literature, these complaints decrease with time. The study shows that the OHIP questionnaire is sensitive to changes caused by surgical manipulation of the temporal muscle and can therefore be used to investigate the influence of surgical techniques on postoperative complaints. Postoperatively, patients show worse OHIP scores than the general population, demonstrating that neurosurgical cranial approaches negatively influence the patient's oral health-related wellbeing. Larger studies using the OHIP questionnaire should evaluate if postoperative physical therapy, speech therapy, or specialized rehabilitation devices can improve the masticatory impairment after craniotomy. TRIAL REGISTRATION: Clinical trial register: DRKS00011096.

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.

Progression-Free Survival, Prognostic Factors, and Surgical Outcome of Spheno-Orbital Meningiomas.

OBJECTIVE: Spheno-orbital meningiomas (SOM) are rare intracranial tumors that arise at the sphenoid wing. These tumors can invade important neurovascular structures making radical resection difficult, while residual tumors often lead to recurrence. The purpose of this study was to evaluate prognostic factors influencing the recurrence and progression-free survival (PFS) rates of spheno-orbital meningiomas, with a particular focus on the role of surgery and postoperative radiotherapy. METHODS: Between 2000 and March 2020, 65 cases of spheno-orbital meningioma were included, of which 50 cases underwent surgical treatment alone, and 15 cases underwent resection and radiotherapy. A Kaplan-Meier analysis was performed to provide median point estimates and PFS rates; further, Cox regression analysis was used to identify significant factors associated with treatment. RESULTS: Gross total resection significantly reduced the risk of recurrence (p-value = 0.0062). There was no significant benefit for progression-free survival after postoperative radiotherapy (p-value = 0.42). Additionally, spheno-orbital meningiomas with an invasion of the cavernous sinus and intraconal invasion showed significantly worse PFS compared to other locations (p-value = 0.017). CONCLUSION: The maximal safe resection remains the most important prognostic factor associated with lower recurrence rates and longer PFS in patients with spheno-orbital meningioma. The invasion of the cavernous sinus and intraconal invasion was an independent factor associated with worse PFS. Patients with postoperative high-precision radiotherapy did not show significantly better PFS due to the small number of patients.

Patterns of intracerebral hemorrhage that result in unfavorable outcomes in patients with subarachnoid hemorrhage.

OBJECTIVE(S): Intracerebral hemorrhage (ICH) contributes considerably to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Specific patterns of aSAH-associated ICH that are not compatible with favorable outcome remain unknown. The main objective of this study is to report patterns of aSAH-associated ICH that result in unfavorable outcomes. METHODS: This is a retrospective analysis of 1036 consecutive aSAH patients admitted to an academic neurosurgical center in a 15-year period (01/2005-12/2019). Admission imaging was investigated for presence, location and size of intracerebral hemorrhage. The rates of favorable outcome at 6 months (modified Rankin Scale) relative to ICH location and volume were analyzed to identify patterns of ICH which were incompatible with favorable outcome. RESULTS: 284 of 1036 patients (27.4%) suffered from aSAH-related ICH. The median ICH volume was 14.0 ml. Outcome of patients with ICH < 10 ml was comparable to patients without ICH. ICH volumes > 10 ml were associated with worse outcomes. We identified the fronto-basal brain to tolerate even larger ICH without compromise of neurological outcomes. ICH located in the frontal, fronto-insular, temporo-insular and temporal regions were associated with intermediate prognoses as outcome declined with larger ICH volumes. ICH located in the basal ganglia, cerebellum, corpus callosum and bifrontal ICH were associated with particularly poor outcomes irrespective of ICH volumes. CONCLUSION: aSAH-associated ICH of the basal ganglia, cerebellum, corpus callosum and bifrontal brain are associated with exceptionally poor outcomes. ICH volume alone is insufficient for prognostic considerations.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

BACKGROUND: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. METHODS: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. DISCUSSION: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.