Ventricular Drainage Research Articles

Proteomic profile and predictive markers of outcome in patients with subarachnoid hemorrhage

BackgroundThe molecular mechanisms underlying development of posthemorrhagic hydrocephalus (PHH) following subarachnoid hemorrhage (SAH) remain incompletely understood. Consequently, treatment strategies tailored towards the individual patient remain limited. This study aimed to identify proteomic cerebrospinal fluid (CSF) biomarkers capable of predicting shunt dependency and functional outcome in patients with SAH in order to improve informed clinical decision making.MethodsVentricular CSF samples were collected twice from 23 patients with SAH who required external ventricular drain (EVD) insertion (12 patients with successful EVD weaning, 11 patients in need of permanent CSF shunting due to development of PHH). The paired CSF samples were collected acutely after ictus and later upon EVD removal. Cisternal CSF samples were collected from 10 healthy control subjects undergoing vascular clipping of an unruptured aneurysm. All CSF samples were subjected to mass spectrometry-based proteomics analysis. Proteomic biomarkers were quantified using area under the curve (AUC) estimates from a receiver operating curve (ROC).ResultsCSF from patients with SAH displayed a distinct proteomic profile in comparison to that of healthy control subjects. The CSF collected acutely after ictus from patients with SAH was moreover distinct from that collected weeks later but appeared similar in the weaned and shunted patient groups. Sixteen unique proteins were identified as potential predictors of shunt dependency, while three proteins were identified as potential predictors of functional outcome assessed six months after ictus with the modified Rankin Scale.ConclusionsWe here identified several potential proteomic biomarkers in CSF from patients with SAH capable of predicting (i) shunt dependency and thus development of PHH and (ii) the functional outcome assessed six months after ictus. These proteomic biomarkers may have the potential to aid clinical decision making by predicting shunt dependency and functional outcome following SAH.

Rotational Latissimus Dorsi Flap for Lateral Repair of Thoracic Cerebrospinal Fluid-Pleural Fistula: Case Report.

Giant calcified thoracic discs are challenging surgical pathologies that tend to be more centrally located and calcified. This complicates the removal process and potentiates the formation of dural defects, resulting in persistent cerebrospinal fluid (CSF) leaks and the formation of pleural fistulas. The typical intervention for this is CSF diversion through external ventricular drain or lumbar drain placement, followed by direct repair. However, if all these measures fail, subsequent salvage techniques have not been described previously. A 45-year-old man with past medical history of obesity (body mass index: 58), hypertension, and type 2 diabetes mellitus presented to the emergency department with thoracic myelopathy symptoms. MR demonstrated a giant calcified thoracic discs at T7-T8 with severe spinal cord compression. Intraoperatively, the disc was found fused to the dura and removal caused a large ventrolateral dural dehiscence. CSF diversion and direct repair were attempted unsuccessfully, so a salvage procedure with a rotational pedicled latissimus dorsi flap was performed. The patient's latissimus dorsi was exposed and resected from attachments, maintaining thoracodorsal blood supply, while removing thoracodorsal innervation. The flap was then rotated into the previous corpectomy site. The dural defect was repaired with a sealant patch, overlayed with a parietal pleural flap and the latissimus dorsi flap. By the patient's last follow-up, he had full functional independence at home. We present a surgical case highlighting the challenges of managing postoperative CSF-pleural fistula occurring after giant calcified thoracic disc removal and the successful use of a novel rotational latissimus dorsi flap to definitively repair the fistula after unsuccessful primary interventions.

Deriving Automated Device Metadata From Intracranial Pressure Waveforms: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury ICU Physiology Cohort Analysis.

Treatment for intracranial pressure (ICP) has been increasingly informed by machine learning (ML)-derived ICP waveform characteristics. There are gaps, however, in understanding how ICP monitor type may bias waveform characteristics used for these predictive tools since differences between external ventricular drain (EVD) and intraparenchymal monitor (IPM)-derived waveforms have not been well accounted for. We sought to develop a proof-of-concept ML model differentiating ICP waveforms originating from an EVD or IPM. We examined raw ICP waveform data from the ICU physiology cohort within the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury multicenter study. Nested patient-wise five-fold cross-validation and group analysis with bagged decision trees (BDT) and linear discriminant analysis were used for feature selection and fair evaluation. Nine patients were kept as unseen hold-outs for further evaluation. ICP waveform data totaling 14,110 hours were included from 82 patients (EVD, 47; IPM, 26; both, 9). Mean age, Glasgow Coma Scale (GCS) total, and GCS motor score upon admission, as well as the presence and amount of midline shift, were similar between groups. The model mean area under the receiver operating characteristic curve (AU-ROC) exceeded 0.874 across all folds. In additional rigorous cluster-based subgroup analysis, targeted at testing the resilience of models to cross-validation with smaller subsets constructed to develop models in one confounder set and test them in another subset, AU-ROC exceeded 0.811. In a similar analysis using propensity score-based rather than cluster-based subgroup analysis, the mean AU-ROC exceeded 0.827. Of 842 extracted ICP features, 62 were invariant within every analysis, representing the most accurate and robust differences between ICP monitor types. For the nine patient hold-outs, an AU-ROC of 0.826 was obtained using BDT. The developed proof-of-concept ML model identified differences in EVD- and IPM-derived ICP signals, which can provide missing contextual data for large-scale retrospective datasets, prevent bias in computational models that ingest ICP data indiscriminately, and control for confounding using our model's output as a propensity score by to adjust for the monitoring method that was clinically indicated. Furthermore, the invariant features may be leveraged as ICP features for anomaly detection.

Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

BackgroundInsertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.MethodsDRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.ConclusionWe present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.Trial registrationClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

Development and Validation of a Novel Human-Fixed Cadaveric Model Reproducing Cerebrospinal Fluid Circulation for Simulation of Endoscopic Endonasal Skull Base Surgery.

Endoscopic endonasal surgery is a well-established surgical approach to the skull base. Surgeons need a reusable long-lasting tool to acquire the skills needed for skull base reconstruction. The aim of this study was to elaborate and validate a human formalin-fixed cadaveric model that reproduces a realistic cerebrospinal fluid (CSF) circulation and that adequately renders a CSF leak. An external ventricular drain that connects with a peristaltic pump is placed in the subarachnoid space, which allows a water circulation that reproduces CSF circulation. Intracranial pressure is measured in real time. Endoscopic endonasal skull base approaches are performed, to create different skull base openings and CSF leaks. Participants were tasked with reconstruction of the defects using a standardized multilayered approach, with the goal of obtaining a watertight closure under normal intracranial pressure ranges. Compiled data included time of reconstruction, years of experience of participants, and success/failure to achieve a watertight reconstruction. A Likert questionnaire was also used. The cadaveric model reproduced CSF circulation in 4 types of dural defects: sellar, suprasellar, transcribriform, and transclival. Intracranial pressures were similar to physiological conditions and were reproducible. Each model was tested multiple times, over several months. Success rates concurred with training levels (r = .8282 and P = .0017). A strong inverse correlation was also found between years of experience and time of reconstruction (r = .4977 and P < .0001). Participants agreed that the model was realistic (median Likert score of 4), and they strongly agreed that it allowed for the improvement of their surgical skills (median Likert score of 5). This novel human-fixed cadaveric model for CSF circulation is efficient and adequately reproduces surgical conditions for skull base approaches. The model is unique, easy to reproduce, and reusable. It can be used as a tool for teaching and for research purposes.

Occipital Interhemispheric Transtentorial Approach for Microsurgical Treatment of Posterior Midbrain Arteriovenous Malformation: 2-Dimensional Operative Video.

Arteriovenous malformations (AVMs) of the brain stem are very rare lesions accounting for 2% to 6% of the cerebral AVMs.1,2 They carry higher risk of hemorrhage3,4 and are associated with poor prognosis.5-7 This is a 27-year-old man who presented with intraventricular hemorrhage, hydrocephalus, and poor neurological status secondary to ruptured AVM. Deep branches from right triplicate superior cerebellar artery, left duplicate superior cerebellar artery, and right posterior cerebral artery were feeding the AVM. The drainage was directly to the vein of Galen. MRI brain showed the location of the AVM in the posterior midbrain area. The AVM was mostly exophytic to brain stem parenchyma which made it favorable for surgical resection.8 After cerebrospinal fluid diversion (initially with external ventricular drain that was then converted to ventriculoperitoneal shunt), the patient showed some neurological improvement over the next weeks. Thus, the decision was made to treat the AVM. The patient underwent preoperative embolization followed by an occipital interhemispheric transtentorial approach. This illustrative video outlines the steps and technical nuances of the right occipital interhemispheric transtentorial approach for microsurgical resection of this Spetzler-Martin grade 3 (S1, E1, V1)/supplementary Spetzler-Martin grade 2 (A2, B0, C0) AVM. Postoperative cerebral angiogram demonstrated no AVM residual. The patient was discharged to a rehabilitation institute and at 3 months of follow-up, he was alert and orientated to time, person, and place without focal deficits. The patient consented to the procedure and to the publication of his image. Institutional Review Board approval was deemed unnecessary.

Modified ventriculoperitoneal shunt applied to temporary external ventricular drainage

External ventricular drainage (EVD) is a common procedure in neurosurgical practice. Presently, the three methods used most often include direct EVD (dEVD), long-tunneled external ventricular drains (LTEVDs), and EVD via the Ommaya reservoir (EVDvOR). But they possess drawbacks such as limited duration of retention, vulnerability to iatrogenic secondary infections, and challenges in regulating drainage flow. This study aimed to explore the use of a modified ventriculoperitoneal shunt (mVPS)—the abdominal end of the VPS device was placed externally—as a means of temporary EVD to address the aforementioned limitations. This retrospective cohort study, included 120 cases requiring EVD. dEVD was performed for 31 cases, EVDvOR for 54 cases (including 8 cases with previously performed dEVD), and mVPS for 35 cases (including 6 cases with previously performed EVDvOR). The one-time success rate (no need for further other EVD intervention) for dEVD, EVDvOR, and mVPS were 70.97%, 88.89%, and 91.42%, dEVD vs EVDvOR (P < 0.05), dEVD vs mVPS (P < 0.05), EVDvOR vs mVPS (P > 0.05). Puncture needle displacement or detachment was observed in nearly all cases of EVDvOR, while no such complications have been observed with mVPS. Apart from this complication, the incidence of postoperative complications was 35.48%, 14.81%, and 8.5%, dEVD vs EVDvOR (P < 0.05), dEVD vs mVPS (P < 0.05), EVDvOR vs mVPS (P > 0.05). Mean postoperative retention for EVD was 14.68 ± 9.50 days, 25.96 ± 15.14 days, and 82.43 ± 64.45 days, respectively (P < 0.001). In conclusion, mVPS significantly extends the duration of EVD, which is particularly beneficial for patients requiring long-term EVD.

Use of intensive care, intracranial pressure monitoring, and external ventricular drainage devises in patients with bacterial meningitis, a cohort study

BackgroundBacterial meningitis can cause a life-threatening increase in intracranial pressure (ICP). ICP-targeted treatment including an ICP monitoring device and external ventricular drainage (EVD) may improve outcomes but is also associated with the risk of complications. The frequency of use and complications related to ICP monitoring devices and EVDs among patients with bacterial meningitis remain unknown. We aimed to investigate the use of ICP monitoring devices and EVDs in patients with bacterial meningitis including frequency of increased ICP, drainage of cerebrospinal fluid (CSF), and complications associated with the insertion of ICP monitoring and external ventricular drain (EVD) in patients with bacterial meningitis.MethodIn a single-center prospective cohort study (2017–2021), we examined the frequency of use and complications of ICP-monitoring devices and EVDs in adult patients with bacterial meningitis.ResultsWe identified 108 patients with bacterial meningitis admitted during the study period. Of these, 60 were admitted to the intensive care unit (ICU), and 47 received an intracranial device (only ICP monitoring device N = 16; EVD N = 31). An ICP > 20 mmHg was observed in 8 patients at insertion, and in 21 patients (44%) at any time in the ICU. Cerebrospinal fluid (CSF) was drained in 24 cases (51%). Severe complications (intracranial hemorrhage) related to the device occurred in two patients, but one had a relative contraindication to receiving a device.ConclusionsApproximately half of the patients with bacterial meningitis needed intensive care and 47 had an intracranial device inserted. While some had conservatively correctable ICP, the majority needed CSF drainage. However, two patients experienced serious adverse events related to the device, potentially contributing to death. Our study highlights that the incremental value of ICP measurement and EVD in managing of bacterial meningitis requires further research.

Acute Stroke in the Emergency Department: Profiles of Patients and Obstacles to Acute Intervention.

To build a demographic profile of patients presenting to the emergency department (ED) with stroke, determine the proportion who successfully undergo thrombolysis and active interventions, and study their outcomes up to discharge or death in the hospital. A sample size of 215 was calculated and patients were recruited consecutively on presentation to the ED after obtaining consent. Data was collected and they were followed up till the outcome. Data was tabulated and analyzed both as a whole and after further categorization into infarction, hemorrhagic stroke, and cerebral venous thrombosis (CVT). Mean and standard deviation were used for continuous variables and chi-square for categorical variables. A total of 216 patients were recruited, 156 (72%) male and 60 (28%) female. There were 135 (63%) ischemic strokes, 67 (31%) hemorrhagic, and 14 (6%) CVT. The mean age was 56.57 years (SD 14.22 years). A total of 12 patients (5.5%) presented within the 'golden hour' and 28 ischemic strokes presented within the thrombolysis window, of which nine were thrombolyzed. In total, 39 patients were intubated in the ED, of which 10 (7.41%) had ischemic strokes, 27 (40.3%) had hemorrhagic strokes and two(14.29%) had CVTs. There were 192 patients admitted to in-patient care, while 24 (11%) were discharged against medical advice. A further 14 patients were intubated during admission. Nine patients (13.43%) with hemorrhagic strokes underwent surgical decompression, five (7.46%) had an external ventricular drain (EVD) placed, six (8.96%) underwent aneurysm clipping, and two (2.99%) underwent aneurysm coiling. One case of CVT underwent surgical decompression. Stroke is a highly heterogeneous clinical entity with nuanced differences between the different subtypes. There appear to be significant obstacles regarding the early presentation of strokes to hospitals and the initiation of thrombolysis in the case of acute interventions.

Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid

Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Management of external ventricular drain: to wean or not to wean?

PurposeExternal ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD.MethodsThis was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome.ResultsOut of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039).ConclusionGradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

Effectiveness of a multimodal strategy to reduce external ventricular drain–associated infection: A quasi-experimental study

Infection is a serious complication in neurosurgical patients who undergo external ventricular drain (EVD) insertion. We conducted a quasi-experimental study in patients who underwent EVD insertion to evaluate the impact of a multi-modal strategy to reduce the incidence of external ventricular drain associated infections (EVDAIs). The study was divided into 2 periods; (1) the pre-intervention period when techniques for EVD insertion and maintenance were up to the discretion of the neurosurgeons and (2) the post-intervention after implementation of a multi-modal strategy (cefazolin antibiotic prophylaxis, preoperative chlorhexidine showers, application of postoperative chlorhexidine-impregnated dressing, limited manipulation of the EVD, and meticulous EVD management). The primary outcome was the incidence rate of EVDAIs; secondary outcomes included in-hospital mortality rate, the hospital length of stay. In total, 135 patients were included. The incidence rate of EVDAIs was significantly reduced in the post-intervention period (5.6 cases/1,000 EVD-days) compared with the pre-intervention period (18.2 cases/1,000 EVD-days; P=0.026). There were no differences in all secondary outcomes analyzed. This multi-modal strategy was associated with high satisfaction among health care personnel. Implementation of a multi-modal strategy was associated with a reduction in the incidence of EVDAIs. This was in line with our goal of promoting a new culture of safety despite being in a resource-limited setting.

FilmArray Meningitis/Encephalitis Panel Impact on Antibiotic Usage in Patients with Suspected Community-Acquired Meningitis

Background: Cerebrospinal fluid (CSF) cultures are commonly performed to evaluate patients with suspected bacterial meningitis. These cultures, however, can take up to 72 hours, leading to delays in antibiotic de-escalation and increased antimicrobial utilization. The turnaround for the BioFire® FilmArray® Meningitis/Encephalitis(FA/ME) panel is less than an hour, which may facilitate early de-escalation. Our study aimed to assess whether the use of FA/ME panels in combination with CSF cultures could impact antimicrobial therapy compared to cultures alone in patients treated for suspected bacterial meningitis. Methods: Our retrospective study included patients from five hospitals in Texas (2017-2023) who received empiric antibiotics for suspected community-acquired meningitis and underwent a lumbar puncture within 96 hours of admission. Patients with ventricular drains, traumatic brain injury, and non-central nervous system infections were excluded. Cases comprised patients who had an FA/ME panel performed, while controls included patients without the panel. Outcomes were defined as the empiric duration of antimicrobial therapy (days) and total days of antibiotic therapy (DOT). Wilcoxon Rank Sum test and multiple linear regression models were applied to assess the relationship between the use of the FA/ME panel and study outcomes. Independent variables comprised demographics, institution type, acuity, clinical presentation, CSF values, and FA/ME panel use. Imputation was performed using multiple imputation by chained equations. Results: A total of 193 patients were included in our study. Seventy-one patients received the FA/ME panel (along with the CSF culture), while 122 patients received the CSF culture alone (controls). The median empiric duration of antibiotic therapy in the cases and controls were 1.71 days and 1.18 days, respectively (p = .160). The median DOT in the cases and controls were eight days and six days, respectively (p = .045). After adjusting for confounders, the FA/ME panel was not significantly associated with changes in the empiric duration of antibiotic therapy (B= 0.18, p = .669, Figure 1) or DOT (B= 1.28, p = .170, Figure 2).Conclusion: Providing FA/ME panel testing without active antimicrobial stewardship interventions did not result in a change in antimicrobial prescribing patterns. The difference from prior literature could be explained by the smaller sample size, limiting the power of the study. Further prospective antimicrobial stewardship efforts should focus on training providers on interpreting FA/ME panel results and providing prospective audits and feedback.

ИСПОЛЬЗОВАНИЕ AR-НАВИГАЦИИ ПРИ ПОСТАНОВКЕ ВЕНТРИКУЛЯРНЫХ ДРЕНАЖЕЙ НА КАДАВЕРНОМ МАТЕРИАЛЕ

Augmented reality (AR) technologies are being actively introduced into medicine. AR can be used as a navigation tool in neurosurgery. The purpose of our study is to evaluate the accuracy of placement of external ventricular drainage, the size of the incision and the duration of this manipulation in an animal model using AR navigation and without its use. A CT scan of an animal model (ram's head) was performed, the results were segmented and loaded into AR-glasses. Participants in the experiment are divided into 2 groups of 5 people each. In the main group, ventricular drainage was placed using AR navigation, in the control group without its use. The average incision size in the non-AR group was 29.58 ± 1.566 mm. In the AR group 29.42 ± 1.279 mm. The differences in the two groups are statistically insignificant (p=0.797). In the AR group, the mean operative time was 10.26 ± 1.121 min. In the group without AR use 13.64 ± 1.588 min. The differences between the groups are statistically significant (p&lt;0.05). In the AR group, drainage was inserted into the ventricle in 47 of 50 cases (94%). In the group without the use of AR in 40 cases out of 50 (80%). These differences are statistically significant (p=0.037). AR navigation does not affect the size of the incision, but increases the accuracy of drainage placement and reduces the duration of the procedure. This shows the possibility of using this technology in clinical practice, however, additional research on the use of AR in phantom models is required.

Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off-label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High-performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two-compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <-.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine.

Cerebrospinal fluid diversion prior to posterior fossa tumor resection in adults: A systematic review

Abstract Background Posterior fossa tumors (PFTs) comprise 15%–20% of adult brain tumors, with the reported frequency of hydrocephalus (HCP) ranging between 3.7% and 58%. Most HCP resolves after resection of PFTs, but studies report persistent or new-onset HCP occurring in between 2% and 7% of cases. Preoperative cerebrospinal fluid (CSF) diversion with a ventriculoperitoneal shunt (VPS), external ventricular drain (EVD), or endoscopic third ventriculostomy (ETV) has been shown to improve outcomes. Evidence regarding the efficacy of these techniques is limited. Methods A systematic literature search was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data points were extracted from individual patient cohort data. A failure rate was determined by the number of patients requiring further postoperative CSF diversion. Results In total, 8863 records were identified. Thirteen studies consisting of 17 patient cohorts met our inclusion criteria. Across all individual cohort studies, 2976 patients underwent surgical resection of a PFT in whom the frequency of hydrocephalus at presentation was 22.98% (1.92%–100%), and persistent hydrocephalus following preoperative CSF diversion was 13.63% (0%–18%). Of the 684 hydrocephalic patients, 83.63% underwent CSF diversion in the form of ETV, EVD, or VPS. Between years 1992 and 2020, 1986 and 2021, and 1981and 2013, the pre-resection ETV, EVD, and VPS failure rates were 14.66% (17/116), 16.26% (60/369), and 0% (0/87), respectively. Conclusions This systematic review highlights that VPS has a better failure rate profile in minimizing postoperative hydrocephalus in adult patients with PFTs.

PATH-08. PRE-OPERATIVE TUMOUR CLASSIFICATION USING NANOPORE SEQUENCING OF CEREBROSPINAL FLUID

Abstract BACKGROUND The introduction of tumour classification by analysis of DNA methylation has changed the landscape of paediatric neuro-oncology. With the launch of Oxford Nanopore sequencing, generation of sequencing data is possible in real-time, including information on base-modifications. Diverse classification tools for tumour tissue have been developed recently. While this is an important step towards optimization of surgical treatment, pre-operative knowledge on tumour entity would further facilitate surgical planning. Therefore, we investigated the possibility of liquid biopsy for rapid pre-operative tumour classification. METHODS CSF samples from patients with pre-operative extra-ventricular drain (EVD) (n = 5) as well as samples obtained via Ommaya reservoirs in cases of suspected recurrence (n = 3) were analysed. Additionally, samples from non-tumour patients (epilepsy, inflammation) who had lumbar puncture were available as controls. Samples were sequenced on MinIon devices (Oxford Nanopore) and subsequently classified with previously published tumour tissue classification pipelines (NanoDx, crossNN, Sturgeon). RESULTS Even though CSF derived from EVD has been stored on room temperature for up to 72 hours before processing, cfDNA isolation was possible with the advantage of higher CSF input amounts. DNA fragments showed a distribution characteristic for cell-free DNA, with a maximum peak at 170bp. The amount of total input DNA ranged from 0.35ng to 12ng, with higher input amounts generating more sequencing data but not resulting in better classification. Classification by sturgeon and crossNN/nanoDx using CSF derived cfDNA was possible in exemplary cases, such as a medulloblastoma patient with a new inoperable lesion, where CSF analysis resulted in medulloblastoma Group 4 within the first hour of sequencing. In total, 38% of samples were correctly classified. CONCLUSION Liquid biopsy as a method to pre-operatively classify tumours and thereby enable risk-adjusted surgery is feasible. Ongoing efforts focus on optimisation of ctDNA based tumour classification by extension of the cohort.

EPEN-05. SURGERY FOR CHILDHOOD EPENDYMOMA: THE EPENDYMOMA MULTIDISCIPLINARY ADVISORY GROUP (EMAG) CLINICAL TRIAL EXPERIENCE

Abstract INTRODUCTION The National Ependymoma Multidisciplinary Advisory Group (EMAG) is the central review mechanism for the SIOP Ependymoma II clinical trial in the UK. EMAG is a multiprofessional group which meets weekly to support decision making. We report detailed surgical outcomes for children with confirmed intracranial ependymoma, discussed through EMAG between January 2020 and November 2022. METHODS Data was collected on resection status, surgical outcomes, reasons for not achieving Gross Total Resection (GTR), number of surgeries and adjuvant therapies. Data was analysed descriptively. RESULTS After first surgery, GTR or near total resection (NTR) rate was 69/105 (66%) rising to 83/105 (79%) following repeated surgeries. 17 patients underwent second-look surgery prior to further therapy, whilst 9 underwent second-look surgery after chemotherapy but before radiotherapy. Eight (17%) posterior fossa (PF) surgeries were not completed due to factors including patient instability and tumour attachments. Most post-operative problems were seen in PF tumours with 26/60 (43%) bulbar palsy, 13/60 (22%) focal weakness and 12/60 (20%) cerebellar mutism. Incomplete PF resections were associated with increased bulbar palsy risk (p=0.02, Chi-Square test). 73% of PF patients required hydrocephalus management with external ventricular drainage, endoscopic third ventriculostomy (ETV) or shunt. Longer term hydrocephalus management with ETV or shunt was required in 29% and was more common in those with subtotal resection (R3-RX, 8/16, 50%) compared to GTR or NTR (R0-R2, 9/43, 21%, p=0.03). 27/60 (45%) received post-op NG feeding and 2/60 (3%) needed tracheostomies. Second surgery was associated with lower complication rates. DISCUSSION Our National MDT approach supports collaborative surgical decision making without a need for centralisation of the surgery itself. There was no evidence of increased complication rates compared to historical trials despite a more aggressive surgical approach. We argue for continued centralisation of EPN evaluation to support optimal care for children with this devastating disease.

Treatment of Recurrent, Twice Coiled, Previously Ruptured Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Aneurysm With Excision and End-to-End Anastomosis: 2-Dimensional Operative Video.

Anterior inferior cerebellar artery-posterior inferior cerebellar artery (AICA-PICA) variant is a well-established variant of the vertebrobasilar system. AICA-PICA aneurysms are extremely rare.1-3 There are only 12 cases reported in the literature.1-3 Here, we are presenting a case of a previously ruptured AICA-PICA dissecting aneurysm which had undergone coil embolization twice at an outside institution. The aneurysm continued to grow, and therefore, the patient was transferred to our institution for definitive treatment. Placement of a flow diverter was felt not to be feasible because of the acute bend of the vessel at the neck of the aneurysm. After a retrosigmoid craniotomy, the aneurysm sac was opened to untether the coil mass from the neck of the aneurysm. Clip reconstruction was attempted but intraoperative blood flow measurements demonstrated no flow in the distal outflow artery, indicating that the clip was occluding the parent vessel at the neck because of the challenging geometry and atherosclerosis. We then proceeded with an excision and end-to-end anastomosis of the AICA-PICA. The details of vascular reconstruction while the inflow and outflow arteries are at acute angle are described. Intraoperative indocyanine video angiography demonstrated complete exclusion of the aneurysm from the circulation and patency of the bypass. Postoperative computed tomography angiography demonstrated bypass patency. Postoperatively, the patient required a temporary external ventricular drain for hydrocephalus; however, she was eventually discharged home without any neurological deficits. The patient gave informed consent for the surgery and video recording. Institutional Review Board approval was deemed unnecessary.

Concurrent Extraparenchymal and Spinal Neurocysticercosis in an Immunocompetent Patient Treated for Obstructive Hydrocephalus and Spinal Cord Compression

Introduction: Neurocysticercosis (NCC) is a condition caused by infection of the central nervous system (CNS) by Taenia solium, or pork tapeworm, larvae. Despite commonly infecting the CNS, it may be easily misdiagnosed for more common pathologies, such as arachnoid cysts or tumors. Though most frequently seen in endemic areas, immigration patterns are altering its traditional distribution. Extraparenchymal neurocysticercosis (including ventricular, spinal, and subarachnoid types) carries a poorer prognosis Objective: We present a case of NCC presenting in a young immunocompetent patient which was initially thought to be an arachnoid cyst due to non-pathognomonic imaging results and symptoms. This case illustrates a challenging NCC diagnosis. Case Report: A 24-year-old male without known past medical history presented with 2 years of chronic headache, 2 months of blurry vision in the left eye, and 1 week of progressive nausea and vomiting found to have aqueductal stenosis with obstructive hydrocephalus and bilateral 1.5 cm, peripherally-enhancing cystic lesions of the cerebellopontine angle with associated mass effect, initially described as arachnoid cysts, as well as a left sided foramen magnum cyst. He had an external ventricular drain placed and later underwent ventriculoperitoneal shunt (VPS) insertion. He presented 10 days later with sepsis symptoms and the initial workup was concerning for tuberculosis-associated meningitis and he underwent shunt externalization and re-internalization after clinical improvement, though he was lost to follow up. Two months later he presented with acute urinary retention and right sided weakness. He had spinal cord compression of the cervicothoracic and thoracolumbar spine due to cystic lesion and underwent right C7-T1 and T10-T11 hemilaminotomies for cyst resection, with pathology consistent with NCC. Conclusion: Neurocysticercosis (NCC) is a complex disease which is largely overlooked and is increasing in prevalence in non-endemic areas such as the United States. NCC has various symptoms and presentations depending on location and progression of larval development, which may mimic more common pathologies. The clinical manifestations depend on the parasite load and the host’s immune response regarding their location in CNS and their evolutionary stage. There are two types of NCC, the parenchymal and the extraparenchymal form. The extraparenchymal racemose NCC has the worst prognosis among all forms of NCC with mortality ranging between 30% and 80%. This reinforces the need for a broad differential diagnosis in these scenarios, as well as the importance of close Infectious Disease follow up for patients diagnosed with concurrent cranial and spinal NCC.