Cerebral microdialysis can be used to detect mitochondrial dysfunction, a potential target of neuroprotective treatment. Cyclosporin A (CsA) is a mitochondrial stabiliser that in a recent clinical stroke trial showed protective potential in patients with successful recanalisation. To investigate specific metabolic effects of CsA during reperfusion, and hypothesising that microdialysis values can be used as a proxy outcome measure, we assessed the temporal patterns of cerebral energy substrates related to oxidative metabolism in a model of transient focal ischaemia. Transient ischaemia was induced by intracerebral microinjection of endothelin-1 (150 pmol/15 µL) through stereotaxically implanted guide cannulas in awake, freely moving rats. This was immediately followed by an intravenous injection of CsA (NeuroSTAT; 15 mg/kg) or placebo solution during continuous microdialysis monitoring. After reperfusion, the lactate/pyruvate ratio (LPR) was significantly lower in the CsA group vs placebo (n = 17, 60.6 ± 24.3%, p = 0.013). Total and striatal infarct volumes (mm³) were reduced in the treatment group (n = 31, 61.8 ± 6.0 vs 80.6 ± 6.7, p = 0.047 and 29.9 ± 3.5 vs 41.5 ± 3.9, p = 0.033). CsA treatment thus ameliorated cerebral reperfusion metabolism and infarct size. Cerebral microdialysis may be useful in evaluating putative neuroprotectants in ischaemic stroke.

Purpose: Intensive care for patients with traumatic brain injury (TBI) aims, among other tasks, at avoiding high intracranial pressure (ICP), which is perceived to worsen motor and cognitive deficits and increase mortality. International recommendations for threshold values for ICP were increased from 20 to 22 mmHg in 2016 following the findings in a study by Sorrentino et al., which were based on an observational study of patients with TBI of averaged ICP values. We aimed to reproduce their approach and validate the findings in a separate cohort. Methods: Three hundred thirty-one patients with TBI were included and categorised according to survival/death and favourable/unfavourable outcome at 6 months (based on Glasgow Outcome Score—Extended of 6–8 and 1—5, respectively). Repeated chi-square tests of survival and death (or favourable and unfavourable outcome) vs. high and low ICP were conducted with discrimination between high and low ICP sets at increasing values (integers) between 10 and 35 mmHg, using the average ICP for the entire monitoring period. The ICP limit returning the highest chi-square score was assumed to be the threshold with best discriminative ability. This approach was repeated after stratification by sex, age, and initial Glasgow Coma Score (GCS). Results: An ICP limit of 18 mmHg was found for both mortality and unfavourable outcome for the entire cohort. The female and the low GCS subgroups both had threshold values of 18 mmHg; for all other subgroups, the threshold varied between 16 and 30 mmHg. According to a multiple logistic regression analysis, age, initial GCS, and average ICP are independently associated with mortality and outcome. Conclusions: Using identical methods and closely comparable cohorts, the critical thresholds for ICP found in the study by Sorrentino et al. could not be reproduced.

To prospectively compare the diagnostic yields of standard EEG and continuous EEG (cEEG) monitoring for the diagnosis of non-convulsive status epilepticus (NCSE) in neurosurgical patients in the intensive care unit. We included 50 consecutive patients with clinical suspicion of NCSE due to unexplained coma or subtle clinical phenomena such as discrete myoclonus. The initial 30-minute EEG recording and the following cEEG were analyzed separately for seizure activity. Data were collected on neurosurgical diagnosis, previous diagnosis of epilepsy, current medication, level of consciousness, and outcome at discharge from the neurosurgical department. Recurrent electrographic seizure activity was detected in five patients. This was within the first 30 mins for three patients and on the following cEEG for two patients. Antiepileptic treatment had been initiated in three of these patients. Most of the 50 patients had severe newly acquired neurological disability at discharge. The prospective finding of a 10% seizure incidence was lower than reports from retrospective studies. Use of cEEG led to detection of seizure activity in 2 of 50 patients (4%) and was thus a low-yield method in neurosurgical patients with suspicion of NCSE. Specific markers for patient selection for cEEG are needed.

Cerebral micro-dialysis allows continuous sampling of extracellular metabolites, including glucose, lactate and pyruvate. Transient ischemic events cause a rapid drop in glucose and a rise in lactate levels. Following such events, the lactate/pyruvate (L/P) ratio may remain elevated for a prolonged period of time. In neurointensive care clinics, this ratio is considered a metabolic marker of ischemia and/or mitochondrial dysfunction. Here we propose a novel, sensitive microdialysis liquid chromatography-mass spectrometry (LC-MS) approach to monitor mitochondrial dysfunction in living brain using perfusion with ¹³C-labeled succinate and analysis of ¹³C-labeled tricarboxylic acid cycle (TCA) intermediates. This approach was evaluated in rat brain using malonate-perfusion (10–50 mM) and endothelin-1 (ET-1)-induced transient cerebral ischemia. In the malonate model, the expected changes upon inhibition of succinate dehydrogenase (SDH) were observed, i.e., an increase in endogenous succinate and decreases in fumaric acid and malic acid. The inhibition was further elaborated by incorporation of ¹³C into specific TCA intermediates from ¹³C-labeled succinate. In the ET-1 model, increases in non-labeled TCA metabolites (reflecting release of intracellular compounds) and decreases in ¹³C-labeled TCA metabolites (reflecting inhibition of de novo synthesis) were observed. The analysis of ¹³C incorporation provides further layers of information to identify metabolic disturbances in experimental models and neuro-intensive care patients.

Introduction: Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarniet alcreated the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis: The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination: The study is approved by appropriate ethics or patient safety boards in all participating countries. Trial registration number: NCT04773938; Pre-results.