Intraventricular Lavage vs External Ventricular Drainage for Intraventricular Hemorrhage: A Randomized Clinical Trial.

Importance: Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective: To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants: This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023. Interventions: Participants were randomized to receive either intraventricular lavage or standard drainage. Main Outcomes and Measures: The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency. Results: A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81; P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1; P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2]; P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control (P < .001). Conclusions and Relevance: This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety. Trial Registration: ClinicalTrials.gov Identifier: NCT05204849.

Focused ultrasound for the treatment of brain tumors.

This review investigates focused ultrasound for treating neuro-oncological diseases as an emerging treatment modality. The technique is based on focused ultrasound waves guided by MRI. By using high or low-frequency waves, thermoablation of smaller tissue volumes centrally in the brain or a safe, temporary opening of the blood-brain barrier can be carried out for better penetration of chemotherapy. Numerous studies on neuro-oncological treatments are ongoing, signaling increasing popularity for the technique in the near future.

The impact of short-course hypofractionated radiotherapy on multimodality treatment utilisation, compliance, and outcome in glioblastoma patients: a Danish patterns of care study.

BACKGROUND: The aim of this retrospective registry-based Danish patterns of care study was (1) to evaluate the real-world utilisation of short-course hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) patients over time, and (2) to evaluate the impact of short-course HFRT by assessing trends in multimodality treatment utilisation, compliance, and outcome. MATERIAL AND METHODS: Data of all adults with newly diagnosed pathology-confirmed GBM between 2011 and 2019 were extracted from the nationwide Danish Neuro-Oncology Registry. Short-course HFRT was defined as a fraction size of > 2 Gy to a planned dose of > 30 Gy. Patterns of care were assessed. To analyse trends in the assignment to short-course HFRT, and in radiotherapy (RT) compliance, multivariable logistic regression was applied. To analyse trends in survival, multivariable Cox regression was used. RESULTS: In this cohort of 2416 GBM patients, the utilisation of short-course HFRT significantly increased from ca. 10% in 2011 to 33% in recent years. This coincided with the discontinued use of palliative regimens and a decreased use of conventional fractionation. The proportion of patients proceeding to RT remained stable at ca. 85%. The proportion of patients assigned to chemoradiotherapy (CRT) remained stable at ca. 60%; the use of short-course hypofractionated CRT increased with ca. 10%, while the use of conventionally fractionated CRT decreased with ca. 10%. Compliance with conventionally fractionated and short-course HFRT was respective 92% and 93%, and significantly increasing in recent years. In the complete cohort, the median overall survival remained stable at ca. 11 months. Assignment to short-course HFRT was independently associated with shorter survival. CONCLUSION: In Denmark, the use of short-course HFRT significantly increased in recent years. Nonetheless, the overall utilisation of RT and chemotherapy did not increase on a population level. Nor did survival change. In contrast, compliance with both conventionally fractionated RT and short-course HFRT increased.

Treatment of Intraventricular Hemorrhage with External Ventricular Drainage and Fibrinolysis: A Comprehensive Systematic Review and Meta-Analysis of Complications and Outcome.

BACKGROUND: External ventricular drainage (EVD) is a key factor in the treatment of intraventricular hemorrhage (IVH) but associated with risks and complications. Intraventricular fibrinolysis (IVF) has been proposed to improve clinical outcome and reduce complications of EVD treatment. The following review and metaanalysis provides a comprehensive evaluation of IVH treatment with external ventricular drainage (EVD) and intraventricular fibrinolysis (IVF) with regards to complications and clinical outcomes. METHODS: The PRISMA guidelines were followed preparing this review. Studies included in the meta-analysis were compared using forest plots and the related odds ratios. RESULTS: After a literature search, 980 articles were identified and 65 and underwent full-text review. Forty-two articles were included in the review and meta-analysis. We found that bolted and antibiotic-coated catheters were superior to tunnelled/uncoated catheters (P < 0.001) and antibiotic- vs. silver-impregnated catheters (P < 0.001]) in preventing infection. Shunt dependency was related to the volume of blood in the ventricles but unaffected by IVF (P = 0.98). IVF promoted hematoma clearance, decreased mortality (22.4% vs. 40.9% with IVF vs. no IVF, respectively, P < 0.00001), improved good functional outcomes (47.2% [IVF] vs. 38.3% [no IVF], P = 0.03), and reduced the rate of catheter occlusion from 37.3% without IVF to 10.6% with IVF (P = 0.0003). CONCLUSIONS: We present evidence and best practice recommendations for the treatment of IVH with EVD and intraventricular fibrinolysis. Our analysis further provides a comprehensive quantitative reference of the most relevant clinical endpoints for future studies on novel IVH technologies and treatments.

Study protocol for ACTIVE study: safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage-a phase 2, multi-center, randomized controlled trial.

BACKGROUND: Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73-82, 2010). Clearance of IVH might improve patient outcome. METHODS: The study is designed as an investigator-initiated, comparative, prospective, multi-center, 1:1 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm-IRRAflow) compared to passive external ventricular drainage (control arm-EVD). The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women. The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status-Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days-and mortality rates at 30 days and 90 days. DISCUSSION: With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19-47% of the cases. We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH. TRIAL REGISTRATION: ClicalTrials.gov NCT05204849. Registered 15 December 2021. Updated 24 January 2022.

Cerebral monitoring in a pig model of cardiac arrest with 48 h of intensive care.

BACKGROUND: Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting. METHODS: The aim of this study was to investigate temporal changes in measures of cerebral injury and metabolism in a cardiac arrest pig model with clinically relevant post-cardiac arrest intensive care. A cardiac arrest group (n = 11) underwent 7 min of no-flow and was compared with a sham group (n = 6). Pigs underwent intensive care with 24 h of hypothermia at 33 °C. Blood markers of cerebral injury, cerebral microdialysis, and intracranial pressure (ICP) were measured. After 48 h, pigs underwent a cerebral MRI scan. Data are presented as median [25th; 75th percentiles]. RESULTS: Return of spontaneous circulation was achieved in 7/11 pigs. Time to ROSC was 4.4 min [4.2; 10.9]. Both NSE and NfL increased over time (p < 0.001), and were higher in the cardiac arrest group at 48 h (NSE 4.2 µg/L [2.4; 6.1] vs 0.9 [0.7; 0.9], p < 0.001; NfL 63 ng/L [35; 232] vs 29 [21; 34], p = 0.02). There was no difference in ICP at 48 h (17 mmHg [14; 24] vs 18 [13; 20], p = 0.44). The cerebral lactate/pyruvate ratio had secondary surges in 3/7 cardiac arrest pigs after successful resuscitation. Apparent diffusion coefficient was lower in the cardiac arrest group in white matter cortex (689 × 10-6 mm2/s [524; 765] vs 800 [799; 815], p = 0.04) and hippocampus (854 [834; 910] vs 1049 [964; 1180], p = 0.03). N-Acetylaspartate was lower on MR spectroscopy in the cardiac arrest group (- 17.2 log [- 17.4; - 17.0] vs - 16.9 [- 16.9; - 16.9], p = 0.03). CONCLUSIONS: We have developed a clinically relevant cardiac arrest pig model that displays cerebral injury as marked by NSE and NfL elevations, signs of cerebral oedema, and reduced neuron viability. Overall, the burden of elevated ICP was low in the cardiac arrest group. A subset of pigs undergoing cardiac arrest had persisting metabolic disturbances after successful resuscitation.

[Intraoperative neuromonitoring during brain surgery].

Intraoperative neuromonitoring is a perioperative method, supplementary to stealth navigation and fluorescence microscopic imaging in brain surgery. It allows cortical and subcortical mapping, hence real time identification of eloquent brain areas through electrical stimulation of the cerebral cortex and subcortical areas. The method allows for functional guidance during both awake and asleep neurosurgery and aids in optimizing the extent of resection of the relevant pathology while preserving neurological function as summarised in this review.

[Cerebellar haemorrhage after lumbar surgery with intraoperative dural tear].

In this case report, a 71-year-old female developed headache and nausea and signs of brain stem involvement following lumbar surgery with intraoperative dural tear. A CT scan showed cerebellar haemorrhage and hydrocephalus, and the patient was transferred to a neurosurgical department and treated with an external ventricular drainage, haematoma evacuation, and posterior fossa decompression. This case highlights the importance of swift diagnostics in patients developing neurological symptoms following lumbar surgery, as well as limiting any cerebrospinal fluid leakage following intraoperative dural tear.

[Tumor treating fields in cancer treatment in Denmark].

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields is low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

[Tumor treating fields in cancer treatment in Denmark].

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.