Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

OBJECTIVES: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. DESIGN: Observational cohort study. SETTING: Neurocritical care unit, Cambridge, United Kingdom. PATIENTS: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. CONCLUSIONS: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.

Long-term outcome in new onset refractory status epilepticus: a retrospective study.

BACKGROUND: New onset refractory status epilepticus (NORSE) is a neurologic emergency without an immediately identifiable cause. The complicated and long ICU stay of the patients can lead to perceiving a prolongation of therapies as futile. However, a recovery is possible even in severe cases. This retrospective study investigates ICU treatments, short- and long-term outcome and ethical decisions of a case series of patients with NORSE. METHODS: Overall, 283 adults were admitted with status epilepticus (SE) to the Neurocritical Care Unit of the University Hospital Zurich, Switzerland, between 01.2010 and 12.2022. Of them, 25 had a NORSE. We collected demographic, clinical, therapeutic and outcome data. Descriptive statistics was performed. RESULTS: Most patients were female (68%), previously healthy (Charlson comorbidity index 1 [0-4]) and relatively young (54 ± 17 years). 96% presented with super-refractory SE. Despite extensive workup, the majority (68%) of cases remained cryptogenic. Most patients had a long and complicated ICU stay. The in-hospital mortality was 36% (n = 9). The mortality at last available follow-up was 56% (n = 14) on average 30 months after ICU admission. The cause of in-hospital death for 89% (n = 8) of the patients was the withholding/withdrawing of therapies. Medical staff except for one patient triggered the decision. The end of life (EOL) decision was taken 29 [12-51] days after the ICU admission. Death occurred on day 6 [1-8.5] after the decision was taken. The functional outcome improved over time for 13/16 (81%) hospital survivors (median mRS at hospital discharge 4 [3.75-5] vs. median mRS at last available follow-up 2 [1.75-3], p < 0.001). CONCLUSIONS: Our data suggest that the long-term outcome can still be favorable in NORSE survivors, despite a prolonged and complicated ICU stay. Clinicians should be careful in taking EOL decisions to avoid the risk of a self-fulfilling prophecy. Our results encourage clinicians to continue treatment even in initially refractory cases.

Predicting outcome after aneurysmal subarachnoid hemorrhage by exploitation of signal complexity: a prospective two-center cohort study.

BACKGROUND: Signal complexity (i.e. entropy) describes the level of order within a system. Low physiological signal complexity predicts unfavorable outcome in a variety of diseases and is assumed to reflect increased rigidity of the cardio/cerebrovascular system leading to (or reflecting) autoregulation failure. Aneurysmal subarachnoid hemorrhage (aSAH) is followed by a cascade of complex systemic and cerebral sequelae. In aSAH, the value of entropy has not been established yet. METHODS: aSAH patients from 2 prospective cohorts (Zurich-derivation cohort, Aachen-validation cohort) were included. Multiscale Entropy (MSE) was estimated for arterial blood pressure, intracranial pressure, heart rate, and their derivatives, and compared to dichotomized (1-4 vs. 5-8) or ordinal outcome (GOSE-extended Glasgow Outcome Scale) at 12 months using uni- and multivariable (adjusted for age, World Federation of Neurological Surgeons grade, modified Fisher (mFisher) grade, delayed cerebral infarction), and ordinal methods (proportional odds logistic regression/sliding dichotomy). The multivariable logistic regression models were validated internally using bootstrapping and externally by assessing the calibration and discrimination. RESULTS: A total of 330 (derivation: 241, validation: 89) aSAH patients were analyzed. Decreasing MSE was associated with a higher likelihood of unfavorable outcome independent of covariates and analysis method. The multivariable adjusted logistic regression models were well calibrated and only showed a slight decrease in discrimination when assessed in the validation cohort. The ordinal analysis revealed its effect to be linear. MSE remained valid when adjusting the outcome definition against the initial severity. CONCLUSIONS: MSE metrics and thereby complexity of physiological signals are independent, internally and externally valid predictors of 12-month outcome. Incorporating high-frequency physiological data as part of clinical outcome prediction may enable precise, individualized outcome prediction. The results of this study warrant further investigation into the cause of the resulting complexity as well as its association to important and potentially preventable complications including vasospasm and delayed cerebral ischemia.

Association between EEG metrics and continuous cerebrovascular autoregulation assessment: a scoping review.

OBJECTIVE: Cerebrovascular autoregulation is defined as the capacity of cerebral blood vessels to maintain stable cerebral blood flow despite changing blood pressure. It is assessed using the pressure reactivity index (the correlation coefficient between mean arterial blood pressure and intracranial pressure). The objective of this scoping review is to describe the existing evidence concerning the association of EEG and cerebrovascular autoregulation in order to identify key concepts and detect gaps in the current knowledge. METHODS: Embase, MEDLINE, SCOPUS, and Web of Science were searched considering articles between their inception up to September 2023. Inclusion criteria were human (paediatric and adult) and animal studies describing correlations between continuous EEG and cerebrovascular autoregulation assessments. RESULTS: Ten studies describing 481 human subjects (67% adult, 59% critically ill) were identified. Seven studies assessed qualitative (e.g. seizures, epileptiform potentials) and five evaluated quantitative (e.g. bispectral index, alpha-delta ratio) EEG metrics. Cerebrovascular autoregulation was evaluated based on intracranial pressure, transcranial Doppler, or near infrared spectroscopy. Specific combinations of cerebrovascular autoregulation and EEG metrics were evaluated by a maximum of two studies. Seizures, highly malignant patterns or burst suppression, alpha peak frequency, and bispectral index were associated with cerebrovascular autoregulation. The other metrics showed either no or inconsistent associations. CONCLUSION: There is a paucity of studies evaluating the link between EEG and cerebrovascular autoregulation. The studies identified included a variety of EEG and cerebrovascular autoregulation acquisition methods, age groups, and diseases allowing for few overarching conclusions. However, the preliminary evidence for the presence of an association between EEG metrics and cerebrovascular autoregulation prompts further in-depth investigations.

Sex differences in the use of mechanical ventilation in a neurointensive care population: a retrospective study.

BACKGROUND: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. METHODS: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. RESULTS: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. CONCLUSION: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm.

Delirium in Neurocritical Care: Uncovering Undisclosed Psychotropic Substance and Medication Use and Stress Exposure by Hair Analysis.

OBJECTIVE: In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids. METHODS: Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium. RESULTS: Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium. CONCLUSIONS: Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures.

Nonconvulsive status epilepticus in neurocritical care: A critical reappraisal of outcome prediction scores.

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) is a frequent condition in the neurocritical care unit (NCCU) patient population, with high morbidity and mortality. We aimed to assess the validity of available outcome prediction scores for prognostication in an NCCU patient population in relation to their admission reason (NCSE vs. non-NCSE related). METHODS: All 196 consecutive patients diagnosed with NCSE during the NCCU stay between January 2010 and December 2020 were included. Demographics, Simplified Acute Physiology Score II (SAPS II), NCSE characteristics, and in-hospital and 3-month outcome were extracted from the electronic charts. Status Epilepticus Severity Score (STESS), Epidemiology-Based Mortality Score in Status Epilepticus (EMSE), and encephalitis, NCSE, diazepam resistance, imaging features, and tracheal intubation score (END-IT) were evaluated as previously described. Univariable and multivariable analysis and comparison of sensitivity/specificity/positive and negative predictive values/accuracy were performed. RESULTS: A total of 30.1% died during the hospital stay, and 63.5% of survivors did not achieve favorable outcome at 3 months after onset of NCSE. Patients admitted primarily due to NCSE had longer NCSE duration and were more likely to be intubated at diagnosis. The receiver operating characteristic (ROC) for SAPS II, EMSE, and STESS when predicting mortality was between .683 and .762. The ROC for SAPS II, EMSE, STESS, and END-IT when predicting 3-month outcome was between .649 and .710. The accuracy in predicting mortality/outcome was low, when considering both proposed cutoffs and optimized cutoffs (estimated using the Youden Index) as well as when adjusting for admission reason. SIGNIFICANCE: The scores EMSE, STESS, and END-IT perform poorly when predicting outcome of patients with NCSE in an NCCU environment. They should be interpreted cautiously and only in conjunction with other clinical data in this particular patient group.

The role of neuronal antibodies in cryptogenic new onset refractory status epilepticus.

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt-Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other-especially T-cell- and cytokine-mediated-mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far.

Brain tissue oxygen monitoring in traumatic brain injury-part II: isolated and combined insults in relation to outcome.

BACKGROUND: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO2) in relation to outcome in traumatic brain injury (TBI). METHODS: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO2 monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO2 was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. RESULTS: Median pbtO2 was slightly, but not significantly, associated with outcome. A pbtO2 threshold at 25 and 20 mmHg, respectively, yielded the highest x2 when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO2 below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO2 went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO2 under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO2 < 15 mmHg was associated with a higher rate of unfavourable outcome. CONCLUSIONS: Low pbtO2, under 25 mmHg and particularly below 15 mmHg, for longer durations and in combination with disturbances in global cerebral physiological variables were associated with poor outcome and may indicate detrimental ischaemic hypoxia. Prospective trials are needed to determine if pbtO2-directed therapy is beneficial, at what individualised pbtO2 threshold therapies are warranted, and how this may depend on the presence/absence of concurrent cerebral physiological disturbances.

Brain tissue oxygen monitoring in traumatic brain injury: part I-To what extent does PbtO2 reflect global cerebral physiology?

BACKGROUND: The primary aim was to explore the association of global cerebral physiological variables including intracranial pressure (ICP), cerebrovascular reactivity (PRx), cerebral perfusion pressure (CPP), and deviation from the PRx-based optimal CPP value (∆CPPopt; actual CPP-CPPopt) in relation to brain tissue oxygenation (pbtO2) in traumatic brain injury (TBI). METHODS: A total of 425 TBI patients with ICP- and pbtO2 monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Generalized additive models (GAMs) and linear mixed effect models were used to explore the association of ICP, PRx, CPP, and CPPopt in relation to pbtO2. PbtO2 < 20 mmHg, ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, and ∆CPPopt < - 5 mmHg were considered as cerebral insults. RESULTS: PbtO2 < 20 mmHg occurred in median during 17% of the monitoring time and in less than 5% in combination with ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, or ∆CPPopt < - 5 mmHg. In GAM analyses, pbtO2 remained around 25 mmHg over a large range of ICP ([0;50] mmHg) and PRx [- 1;1], but deteriorated below 20 mmHg for extremely low CPP below 30 mmHg and ∆CPPopt below - 30 mmHg. In linear mixed effect models, ICP, CPP, PRx, and ∆CPPopt were significantly associated with pbtO2, but the fixed effects could only explain a very small extent of the pbtO2 variation. CONCLUSIONS: PbtO2 below 20 mmHg was relatively frequent and often occurred in the absence of disturbances in ICP, PRx, CPP, and ∆CPPopt. There were significant, but weak associations between the global cerebral physiological variables and pbtO2, suggesting that hypoxic pbtO2 is often a complex and independent pathophysiological event. Thus, other variables may be more crucial to explain pbtO2 and, likewise, pbtO2 may not be a suitable outcome measure to determine whether global cerebral blood flow optimization such as CPPopt therapy is successful.

Broad Range Eubacterial Polymerase Chain Reaction of Cerebrospinal Fluid Reduces the Time to Exclusion of and Costs Associated with Ventriculostomy-Related Infection in Hemorrhagic Stroke.

BACKGROUND: Patients with hemorrhagic stroke and an external ventricular drain in situ are at risk for ventriculostomy-related-infections (VRI). Because of the contamination of the cerebrospinal fluid (CSF) with blood and the high frequency of false negative CSF culture, the diagnosis of VRI remains challenging. This study investigated the introduction of CSF broad range eubacterial polymerase chain reaction (ePCR) and its effect on frequency and duration of antibiotic therapy for VRI, neurocritical care unit (NCCU) length of stay, related costs, and outcome. METHODS: Between 2020 and 2022, we prospectively included 193 patients admitted to the NCCU of the University Hospital of Zürich with hemorrhagic stroke and an external ventricular drain for more than 48 h. Patient characteristics, serum inflammatory markers, white blood cell count in CSF, use and duration of antibiotic treatment for VRI, microbiological findings (CSF cultures and ePCR tests), and NCCU length of stay were compared in patients with no infection, noncerebral infection, suspected VRI, and confirmed VRI. Data of patients with suspected VRI of this cohort were compared with a retrospective cohort of patients with suspected VRI treated at our NCCU before the introduction of CSF ePCR testing (2013-2019). RESULTS: Out of 193 patients, 12 (6%) were diagnosed with a confirmed VRI, 66 (34%) with suspected VRI, 90 (47%) with a noncerebral infection, and 25 (13%) had no infection at all. Compared with the retrospective cohort of patients, the use of CSF ePCR resulted in a reduction of patients treated for suspected VRI for the whole duration of 14 days (from 51 to 11%). Furthermore, compared with the retrospective group of patients with suspected VRI (n = 67), after the introduction of CSF ePCR, patients with suspected VRI had shorter antibiotic treatment duration of almost 10 days and, hence, lower related costs with comparable outcome at 3 months. CONCLUSIONS: The use of CSF ePCR to identify VRI resulted in shorter antibiotic treatment duration without changing the outcome, as compared with a retrospective cohort of patients with suspected VRI.

Dizziness and benign paroxysmal positional vertigo among retirement home residents: a cross-sectional descriptive and interventional study.

BACKGROUND: The prevalence of dizziness increases with age. We aimed to determine the point prevalence of dizziness and, in particular, of benign paroxysmal positional vertigo (BPPV) among retirement home residents. Furthermore, we aimed to evaluate the efficacy of a 2-axis turntable based BPPV treatment. METHODS: We contacted all large retirement homes in or around the city of Zurich (Switzerland). 10 retirement homes (with a total of 536 residents) agreed to participate in this study. 83 rejected inquiries by residents led to a potential study population of 453 residents. After a structured interview evaluating the presence and characteristics of dizziness, all willing patients were tested for positional vertigo and nystagmus on a portable and manually operated 2-axis turntable that was transported to the retirement home. Testing consisted of the Dix-Hallpike and supine roll maneuvers to both sides. Participants were immediately treated with the appropriate liberation maneuver whenever BPPV was diagnosed. Otherwise, taking the resident's medical history, a neuro-otological bedside examination, and a review of the available medical documentation was used to identify other causes of dizziness. RESULTS: Out of the 453 residents, 75 (16.6%; average age: 87.0 years; 68% female) were suffering from dizziness presently or in the recent past and gave their consent to participate in this study. Among the participants tested on the turntable (n = 71), BPPV was present in 11.3% (point prevalence). Time-related properties, triggering factors and qualitative attributes of vertigo or dizziness were not significantly different between the dizzy participants with and those without BPPV. In all BPPV patients, appropriate liberation maneuvers were successful. CONCLUSIONS: BPPV could be demonstrated in about one tenth of retirement home residents with dizziness or recent dizziness. Such point prevalence of BPPV translates to a much higher yearly prevalence if one assumes that BPPV is not present on every day. Our finding suggests that retirement home residents suffering from dizziness should be regularly tested for BPPV and treated with appropriate liberation maneuvers, ideally on turntable to reduce strain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03643354 .

Sex-Related Differences in Patients' Characteristics, Provided Care, and Outcomes Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Sex-related differences in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) are poorly investigated so far. This study elucidates whether sex-related differences in ICH care in a neurocritical care setting exist, particularly regarding provided care, while also taking patient characteristics, and outcomes into account. METHODS: This retrospective single center study includes all consecutive patients with spontaneous ICH admitted to the neurocritical care unit in a 10-year period. Patients' demographics, comorbidities, symptoms at presentation, radiological findings, surgical and medical provided care, intensive care unit mortality and 12 month-mortality, and functional outcome at discharge were compared among men and women. RESULTS: Overall, 398 patients were included (male = 198 and female = 200). No differences in demographics, Charlson Comorbidity Index (CCI), symptoms at presentation, radiological findings, intensive care unit mortality and 12-month mortality were observed among men and women. Men received an external ventricular drain (EVD) for hydrocephalus-therapy significantly more often than women, despite similar location of the ICH and radiographic parameters. In the multivariate analysis, EVD insertion was independently associated with male sex (odds ratio 2.82, 95% confidence interval 1.61-4.95, P < 0.001) irrespective of demographic or radiological features. Functional outcome after ICH as assessed by the modified Rankin scale, was more favorable for women (P = 0.044). CONCLUSIONS: Sex-related differences in patients with ICH regarding to provided neurosurgical care exist. We provide evidence that insertion of EVD is associated with male sex, disregarding clear reasoning. A sex-bias as well as social factors may play a significant role in decision-making for the insertion of an EVD.

Blood Pressure Variability Indices for Outcome Prediction After Thrombectomy in Stroke by Using High-Resolution Data.

BACKGROUND: Blood pressure variability (BPV) is associated with outcome after endovascular thrombectomy in acute large vessel occlusion stroke. We aimed to provide the optimal sampling frequency and BPV index for outcome prediction by using high-resolution blood pressure (BP) data. METHODS: Patient characteristics, 3-month outcome, and BP values measured intraarterially at 1 Hz for up to 24 h were extracted from 34 patients treated at a tertiary care center neurocritical care unit. Outcome was dichotomized (modified Rankin Scale 0-2, favorable, and 3-6, unfavorable) and associated with systolic BPV (as calculated by using standard deviation, coefficient of variation, averaged real variability, successive variation, number of trend changes, and a spectral approach using the power of specific BP frequencies). BP values were downsampled by either averaging or omitting all BP values within each prespecified time bin to compare the different sampling rates. RESULTS: Out of 34 patients (age 72 ± 12.7 years, 67.6% men), 10 (29.4%) achieved a favorable functional outcome and 24 (70.6%) had an unfavorable functional outcome at 3 months. No group differences were found in mean absolute systolic BP (SBP) (130 ± 18 mm Hg, p = 0.82) and diastolic BP (DBP) (59 ± 10 mm Hg, p = 1.00) during the monitoring time. BPV only reached predictive significance when using successive variation extracted from downsampled (averaged over 5 min) SBP data (median 4.8 mm Hg [range 3.8-7.1]) in patients with favorable versus 7.1 mmHg [range 5.5-9.7] in those with unfavorable outcome, area under the curve = 0.74 [confidence interval (CI) 0.57-0.85; p = 0.031], or the power of midrange frequencies between 1/20 and 1/5 min [area under the curve = 0.75 (CI 0.59-0.86), p = 0.020]. CONCLUSIONS: Using high-resolution BP data of 1 Hz, downsampling by averaging all BP values within 5-min intervals is essential to find relevant differences in systolic BPV, as noise can be avoided (confirmed by the significance of the power of midrange frequencies). These results demonstrate how high-resolution BP data can be processed for effective outcome prediction.

Impact of Seizures and Status Epilepticus on Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: We aimed to evaluate the association between seizures as divided by timing and type (seizures or status epilepticus) and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: All consecutive patients with aSAH admitted to the neurocritical care unit of the University Hospital Zurich between 2016 and 2020 were included. Seizure type and frequency were extracted from electronic patient files. RESULTS: Out of 245 patients, 76 experienced acute symptomatic seizures, with 39 experiencing seizures at onset, 18 experiencing acute seizures, and 19 experiencing acute nonconvulsive status epilepticus (NCSE). Multivariate analysis revealed that acute symptomatic NCSE was an independent predictor of unfavorable outcome (odds ratio 14.20, 95% confidence interval 1.74-116.17, p = 0.013) after correction for age, Hunt-Hess grade, Fisher grade, and delayed cerebral ischemia. Subgroup analysis showed a significant association of all seizures/NCSE with higher Fisher grade (p < 0.001 for acute symptomatic seizures/NCSE, p = 0.031 for remote symptomatic seizures). However, although acute seizures/NCSE (p = 0.750 and 0.060 for acute seizures/NCSE respectively) were not associated with unfavorable outcome in patients with a high Hunt-Hess grade, they were significantly associated with unfavorable outcome in patients with a low Hunt-Hess grade (p = 0.019 and p < 0.001 for acute seizures/NCSE, respectively). CONCLUSIONS: Acute symptomatic NCSE independently predicts unfavorable outcome after aSAH. Seizures and NCSE are associated with unfavorable outcome, particularly in patients with a low Hunt-Hess grade. We propose that NCSE and the ictal or postictal reduction of Glasgow Coma Scale may hamper close clinical evaluation for signs of delayed cerebral ischemia, and thus possibly leading to delayed diagnosis and therapy thereof in patients with a low Hunt-Hess grade.

Cerebellar Rebound Nystagmus Explained as Gaze-Evoked Nystagmus Relative to an Eccentric Set Point: Implications for the Clinical Examination.

A brain stem/cerebellar neural integrator enables stable eccentric gaze. Cerebellar loss-of-function can cause an inability to maintain gaze eccentrically (gaze-evoked nystagmus). Moreover, after returning gaze to straight ahead, the eyes may drift toward the prior eye position (rebound nystagmus). Typically, gaze-evoked nystagmus decays during continuously held eccentric gaze. We hypothesized this adaptive behavior to be prerequisite for rebound nystagmus and thus predicted a correlation between the velocity decay of gaze-evoked nystagmus and the initial velocity of rebound nystagmus. Using video-oculography, eye position was measured in 11 patients with cerebellar degeneration at nine horizontal gaze angles (15° nasal to 25° temporal) before (baseline), during, and after attempted eccentric gaze at ± 30° for 20 s. We determined the decrease of slow-phase velocity at eccentric gaze and the slow-phase velocity of the subsequent rebound nystagmus relative to the baseline. During sustained eccentric gaze, eye drift velocity of gaze-evoked nystagmus decreased by 2.40 ± 1.47°/s. Thereafter, a uniform change of initial eye drift velocity relative to the baseline (2.40 ± 1.35°/s) occurred at all gaze eccentricities. The velocity decrease during eccentric gaze and the subsequent uniform change of eye drift were highly correlated (R2 = 0.80, p < 0.001, slope = 1.09). Rebound nystagmus can be explained as gaze-evoked nystagmus relative to a set point (position with least eye drift) away from straight-ahead eye position. To improve detection at the bedside, we suggest testing rebound nystagmus not at straight-ahead eye position but at an eccentric position opposite of prior eccentric gaze (e.g., 10°), ideally using quantitative video-oculography to facilitate diagnosis of cerebellar loss-of-function.

Spontaneous alternation behavior in larval zebrafish.

Spontaneous alternation behavior (SAB) describes the tendency of animals to alternate their turn direction in consecutive turns. SAB, unlike other mnestic tasks, does not require any prior training or reinforcement. Because of its close correlation with the development and function of the hippocampus in mice, it is thought to reflect a type of memory. Adult zebrafish possess a hippocampus-like structure utilizing the same neurotransmitters as in human brains, and have thus been used to study memory. In the current study, we established SAB in zebrafish larvae at 6 days post-fertilization using a custom-made forced-turn maze with a rate of 57%. Our demonstration of the presence of SAB in larval zebrafish at a very early developmental stage not only provides evidence for early cognition in this species but also suggests its future usefulness as a high-throughput model for mnestic studies.

Limitation of life sustaining measures in neurocritical care: sex, timing, and advance directive.

BACKGROUND: The limitation of life sustaining treatments (LLST) causes ethical dilemmas even in patients faced with poor prognosis, which applies to many patients admitted to a Neurocritical Care Unit (NCCU). The effects of social and cultural aspects on LLST in an NCCU population remain poorly studied. METHODS: All NCCU patients between 01.2018 and 08.2021 were included. Medical records were reviewed for: demographics, diagnosis, severity of disease, and outcome. Advance directives (AD) and LLST discussions were reviewed evaluating timing, degree, and reason for LLST. Social/cultural factors (nationality, language spoken, religion, marital status, relationship to/sex of legal representative) were noted. Associations between these factors and the patients' sex, LLST timing, and presence of AD were evaluated. RESULTS: Out of 2975 patients, 12% of men and 10.5% of women underwent LLST (p = 0.30). Women, compared to men, more commonly received withdrawal instead of withholding of life sustaining treatments (57.5 vs. 45.1%, p = 0.028) despite comparable disease severity. Women receiving LLST were older (73 ± 11.7 vs. 69 ± 14.9 years, p = 0.005) and often without a partner (43.8 vs. 25.8%, p = 0.001) compared to men. AD were associated with female sex and early LLST, but not with an increased in-hospital mortality (57.1 vs. 75.2% of patients with and without AD respectively). CONCLUSIONS: In patients receiving LLST, the presence of an AD was associated with an increase of early LLST, but not with an increased in-hospital mortality. This supports the notion that the presence of an AD is primarily an expression of the patients' will but does not per se predestine the patient for an unfavorable outcome.

Feasibility and Safety of Integrating Extended TCD Assessments in a Full Multimodal Neuromonitoring Protocol After Traumatic Brain Injury.

OBJECTIVE: Targeting single monitoring modalities such as intracranial pressure (ICP) or cerebral perfusion pressure alone has shown to be insufficient in improving outcome after traumatic brain injury (TBI). Multimodality monitoring (MMM) allows for a more complete description of brain function and for individualized management. Transcranial Doppler (TCD) represents the gold standard for continuous cerebral blood flow velocity assessment, but requires high levels skill and time. In TBI, the practical aspects of conducting extended TCD monitoring sessions have yet to be evaluated. METHODS: Patients with acute moderate-to-severe TBI admitted to the neurocritical care unit between March 2022 and December 2023 receiving invasive ICP measurements were evaluated for inclusion. Exclusion criteria included trauma incompatible with TCD monitoring and if MMM was unwarranted. Daily MMM sessions (in addition to regular monitoring) were performed using TCD (Delica EMS 9D System or the DWL Doppler Box) for ≤5 d. Quantitative and qualitative feasibility, safety, and quality metrics were assessed. RESULTS: Of 74 patients, 36 (75% male; mean age, 44 ± 17 y) were included. Common reasons for exclusion were skull fractures (n = 12) and decompressive craniectomy (n = 9). We acquired 88 recordings (mean, 275 ± 88 min). Overall monitoring times increased, and set-up times decreased. Physiologic variables (including ICP/brain temperature) did not change with TCD application. A single adverse event (dislodging of a microdialysis catheter) occurred. CONCLUSION: Implementing extended TCD monitoring in MMM protocols is feasible and safe. Considering these results, inclusion of long-term TCD as part of the MMM is strongly encouraged to allow for in-depth description and direct evaluation of hemodynamic changes after TBI.