Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain-Heart Interrelationship for Improved Patient Outcomes.

The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain-heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as well as cardiac-specific biomarkers. The secondary category encompasses parameters associated with cerebral autoregulation and the autonomic nervous system. A group of 15 aSAH patients were included in the analysis. Severe cardiac complications were diagnosed in seven (47%) of patients. In the whole population, a significant correlation was observed between CSF S100 calcium-binding protein B (S100B) and brain natriuretic peptide (BNP) (rS = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (rS = 0.57; p = 0.025) and BNP (rS = 0.66; p = 0.029), as well as between CSF tau protein and BNP (rS = 0.78; p = 0.039). Patients experiencing severe cardiac complications exhibited notably higher levels of serum tau protein at day 1 (0.21 ± 0.23 [ng/mL]) compared to those without severe cardiac complications (0.03 ± 0.04 [ng/mL]); p = 0.009. Impaired cerebral autoregulation was noted in patients both with and without severe cardiac complications. Elevated serum NSE at day 1 was related to impaired cerebral autoregulation (rS = 0.90; p = 0.037). On the first day, a substantial, reciprocal correlation between heart rate variability low-to-high frequency ratio (HRV LF/HF) and both GFAP (rS = -0.83; p = 0.004) and S100B (rS = -0.83; p = 0.004) was observed. Cardiac and brain-specific biomarkers hold the potential to assist clinicians in providing timely insights into cardiac complications, and therefore they contribute to the prognosis of outcomes.

The Role of Early Serum Biomarkers and Clinical Rating Scales in the Prediction of Delayed Cerebral Ischaemia and Short-Term Outcome after Aneurysmal Subarachnoid Haemorrhage: Single Centre Experience.

Considering the variety of complications that arise after aneurysmal subarachnoid haemorrhage (aSAH) and the complex pathomechanism of delayed cerebral ischaemia (DCI), the task of predicting the outcome assumes a profound complexity. Therefore, there is a need to develop early predictive and decision-making models. This study explores the effect of serum biomarkers and clinical scales on patients' outcomes and their interrelationship with DCI and systemic complications in aSAH. This was a retrospective analysis including aSAH patients admitted to the Wroclaw University Hospital (Wroclaw, Poland) from 2011 to 2020. A good outcome was defined as a modified Rankin Scale (mRS) score of 0-2. The prediction of the development of DCI and poor outcome was conducted using logistic regression as a standard model (SM) and random forest as a machine learning method (ML). A cohort of 174 aSAH patients were included in the analysis. DCI was diagnosed in 79 (45%) patients. Significant differences between patients with poor vs. good outcome were determined from their levels of albumin (31 ± 7 vs. 35 ± 5 (g/L); p < 0.001), D-dimer (3.0 ± 4.5 vs. 1.5 ± 2.8 (ng/mL); p < 0.001), procalcitonin (0.2 ± 0.4 vs. 0.1 ± 0.1 (ng/mL); p < 0.001), and glucose (169 ± 69 vs. 137 ± 48 (nmol/L); p < 0.001). SM for DCI prediction included the Apache II scale (odds ratio [OD] 1.05; 95% confidence interval [CI] 1.00-1.09) and albumin level (OD 0.88; CI 0.82-0.95). ML demonstrated that low albumin level, high Apache II scale, increased D-dimer and procalcitonin levels had the highest predictive values for DCI. The integration of clinical parameters and scales with a panel of biomarkers may effectively facilitate the stratification of aSAH patients, identifying those at high risk of secondary complications and poor outcome.

Applying video motion magnification to reveal spontaneous tympanic membrane displacement as an indirect measure of intracranial pressure in patients with brain pathologies.

BACKGROUND: The observation of tympanic membrane displacement (TMD) opens up the possibility of indirect intracranial pressure (ICP) estimation. In this study, we applied a phase-based video motion magnification (VMM) algorithm to reveal spontaneous pulse TMD waveforms (spTMD) and compare them with invasively measured ICP in patients with intracranial pathologies. METHODS: Nine adults (six traumatic brain injury and three aneurysmal subarachnoid haemorrhage; median age 44 (29-53) years admitted to the intensive care unit of Wroclaw Medical University between October 2021 and October 2022 with implanted ICP sensors were included in this retrospective study. Video recordings of the tympanic membrane were performed using a portable otoscope with a video camera and analysed by a custom-written VMM algorithm. ICP was monitored using intraparenchymal sensors and arterial blood pressure (ABP) was measured in the radial arterial lines. ICP, ABP, and spTMD videos were captured simultaneously. The pulse amplitudes of ICP (Amp_ICP), ABP (Amp_ABP) and spTMD (Amp_spTMD) were estimated using fast Fourier transform within the heart rate (HR)-related frequency range. RESULTS: Amp_spTMD was significantly correlated with mean ICP (rS = 0.73; p = 0.025) and with Amp_ICP (rS = 0.88; p = 0.002). Age was not a significant moderator of this association. There were no significant relationships between Amp_spTMD and either mean ABP, HR, or Amp_ABP. CONCLUSIONS: The study suggests that Amp_spTMD increases with the increase in mean ICP and Amp_ICP. Estimation of Amp_spTMD using the VMM algorithm has the potential to allow for non-invasive detection of the risk of elevated ICP; however, further investigation in a larger group of patients is required.

Cerebral Autoregulation, Cerebral Hemodynamics, and Injury Biomarkers, in Patients with COVID-19 Treated with Veno-Venous Extracorporeal Membrane Oxygenation.

BACKGROUND: This study aimed to describe the cerebrovascular dynamics, in particular cerebral autoregulation (CA), and cerebral biomarkers as neuron-specific enolase (NSE) in patients with a diagnosis of coronavirus disease 2019 and acute respiratory distress syndrome as well as undergoing veno-venous extracorporeal membrane treatment. METHODS: This was a single center, observational study conducted in the intensive care unit of the University Hospital in Wroclaw from October 2020 to February 2022. Transcranial Doppler recordings of the middle cerebral artery conducted for at least 20 min were performed. Cerebral autoregulation (CA) was estimated by using the mean velocity index (Mxa), calculated as the moving correlation coefficient between slow-wave oscillations in cerebral blood flow velocity and arterial blood pressure. Altered CA was defined as a positive Mxa. Blood samples for the measurement of NSE were obtained at the same time as transcranial Doppler measurements. RESULTS: A total of 16 patients fulfilled the inclusion criteria and were enrolled in the study. The median age was 39 (34-56) years. Altered CA was found in 12 patients, and six out of seven patients who died had altered CA. A positive Mxa was a significant predictor of mortality, with a sensitivity of 85.7%. We found that three out of five patients with pathological changes in brain computed tomography and six out of ten patients with neurological complications had altered CA. NSE was a significant predictor of mortality (cutoff value: 28.9 µg/L); area under the curve = 0.83, p = 0.006), with a strong relationship between increased level of NSE and altered CA, χ2 = 6.24; p = 0.035; φ = 0.69. CONCLUSIONS: Patients with coronavirus disease 2019-related acute respiratory distress syndrome, requiring veno-venous extracorporeal membrane treatment, are likely to have elevated NSE levels and altered CA. The CA was associated with NSE values in this group. This preliminary analysis suggests that advanced neuromonitoring and evaluation of biomarkers should be considered in this population.

Association between temporal patterns of baroreflex sensitivity after traumatic brain injury and prognosis: a preliminary study.

INTRODUCTION: Traumatic brain injury (TBI) may lead to an increase in intracranial pressure (ICP) as well as impairment of cerebral vascular reactivity and the autonomic nervous system. This study aimed to investigate individual patterns of changes in baroreflex sensitivity (BRS) along with the assessment of pressure reactivity index (PRx) and ICP after TBI. MATERIALS AND METHODS: Twenty-nine TBI patients with continuous arterial blood pressure (ABP) and ICP monitoring were included. BRS was calculated using the sequential cross-correlation method. PRx was estimated using slow-wave oscillations of ABP and ICP. Outcome was assessed using the Glasgow Outcome Scale. RESULTS: Pooled data analysis of the lower breakpoint during the week that followed TBI revealed that BRS reached a minimum about 2 days after TBI. In patients with good outcome, there was a significant increase in BRS during the 7 days following TBI: rp = 0.21; p = 0.008 and the temporal changes in BRS showed either a "U-shaped" pattern or a gradual increase over time. The BRS value after 1.5 days was found to be a significant predictor of mortality (cut-off BRS = 1.8 ms/mm Hg; AUC = 0.83). In patients with poor outcome, ICP and PRx increased while BRS remained low. CONCLUSIONS: We found an association between temporal patterns of BRS and prognosis in the early days following TBI. Further research in a larger cohort of patients is needed to confirm the weight of these preliminary observations for prediction of prognosis in TBI patients.

Changes in autonomic nervous system during cerebral desaturation episodes in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Little evidence is available on the effect of regional cerebral desaturation (rCD) episodes that occur in the first days after aneurysm subarachnoid haemorrhage (aSAH) on the autonomic nervous system activity and on cardiovascular hemodynamics. In this study, we aimed to determine the impact of rCD episodes, developed within 5 days of aSAH, on the autonomic nervous system based on the assessment of baroreflex sensitivity (BRS) and on cardiac output (CO) and cardiac index (CI), and on cerebral autoregulation (CA). MATERIALS AND METHODS: Of 96 patients with aSAH, 36 patients (aged 57 (48-69)) met the inclusion criteria and were included in the study. Regional cerebral oxygen saturation and rCD episodes were evaluated using near-infrared spectroscopy. CA was quantified by the correlation coefficient (TOxa). Cardiac output (CO) and cardiac index (CI) were monitored using the FloTrack®/EV1000. Baroreflex sensitivity (BRS) was assessed using the cross-correlation method. Scores of 1 to 3 in Glasgow Outcome Scale were classified as a poor outcome. RESULTS: During episodes of rCD, BRS decreased significantly compared to baseline (p = 0.027) in patients who had a total duration of rCD episodes of more than 10 hours. During rCD episodes, CA improved slightly in comparison to baseline (p = 0.027). The threshold associated with poor outcome was: rSO2 < 62% (p = 0.002). CONCLUSIONS: BRS decreased in patients who had a total duration rCD episodes of more than 10 hours within the 5 days of aSAH. These results might partly explain the relationship between lower BRS and worse prognosis.

End-to-End Automatic Morphological Classification of Intracranial Pressure Pulse Waveforms Using Deep Learning.

OBJECTIVE: Mean intracranial pressure (ICP) is commonly used in the management of patients with intracranial pathologies. However, the shape of the ICP signal over a single cardiac cycle, called ICP pulse waveform, also contains information on the state of the craniospinal space. In this study we aimed to propose an end-to-end approach to classification of ICP waveforms and assess its potential clinical applicability. METHODS: ICP pulse waveforms obtained from long-term ICP recordings of 50 neurointensive care unit (NICU) patients were manually classified into four classes ranging from normal to pathological. An additional class was introduced to simultaneously identify artifacts. Several deep learning models and data representations were evaluated. An independent testing dataset was used to assess the performance of final models. Occurrence of different waveform types was compared with the patients' clinical outcome. RESULTS: Residual Neural Network using 1-D ICP signal as input was identified as the best performing model with accuracy of 93% in the validation and 82% in the testing dataset. Patients with unfavorable outcome exhibited significantly lower incidence of normal waveforms compared to the favorable outcome group even at ICP levels below 20 mm Hg (median [first-third quartile]: 9 [1-36]% vs. 63 [52-88] %, p = 0.002). CONCLUSIONS: Results of this study confirm the possibility of analyzing ICP pulse waveform morphology in long-term recordings of NICU patients. Proposed approach could potentially be used to provide additional information on the state of patients with intracranial pathologies beyond mean ICP.

Endoscopic third ventriculostomy before surgery of third ventricle and posterior fossa tumours decreases the risk of secondary hydrocephalus and early postoperative complications.

Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus (HCP) at the level of third or fourth ventricle. To date, there is no consensus regarding its role as intervention preceding the operation of tumour removal. The aim of this prospective open-label controlled study is to assess if ETV prevents secondary HCP after tumour removal and if ETV influences the early results of tumour surgery. The study was performed on 68 patients operated for tumours of the third ventricle and posterior fossa. In 30 patients, ETV was performed several days before tumour removal, while in 38 patients, the tumour was removed during a one-stage procedure without ETV. Patients who did not receive ETV before the tumour removal procedure had a higher probability of developing postoperative HCP (n = 12, p = 0.03). They also demonstrated a substantially higher rate of early postoperative complications (n = 20, p = 0.002) and a lower Karnofsky score (p = 0.004) than patients in whom ETV was performed before tumour removal. The performance of external ventricular drainage in the non-ETV group did not prevent secondary HCP (p = 0.68). Postoperative cerebellar swelling (p = 0.01), haematoma (p = 0.04), cerebrospinal fluid leak (p = 0.04) and neuroinfection (p = 0.04) were the main risk factors of persistent HCP. Performance of ETV before tumour removal is not only beneficial for control of acute HCP but also prevents the occurrence of secondary postoperative HCP and may also minimize early postoperative complications.

Awake craniotomy with dexmedetomidine during resection of brain tumours located in eloquent regions.

INTRODUCTION: An awake craniotomy (AC) is the gold standard for the resection of supra-tentorial brain tumours in eloquent areas. Intraoperative monitoring "on-demand" of essential eloquent brain functions and the increasing need to preserve higher intellectual functions during surgery requires a unique anaesthetic approach during AC. Dexmedetomidine is considered the first-choice pharmacological agent for sedation during AC. MATERIAL AND METHODS: Twenty-six patients with a single brain tumour located in areas of eloquent brain function were enrolled in this prospective study. The patients underwent AC under conscious sedation. Motor-evoked potentials and brainstem-evoked auditory potentials were measured using neurophysiological tests during surgery to assess brain potentials. Intraoperative brain relaxation was reached using a modified Bristow scale. Neuromonitoring and psychological tests were maintained until meningeal closure. RESULTS: All operations were carried out successfully, and no reoperations were needed. No significant impact on circulatory and respiratory parameters was observed during conscious sedation based on dexmedetomidine. Neither instrumental airway support nor conversion to general anaesthesia was necessary. Brain relaxation was good in 84% of cases. Intraoperative epileptic episodes were observed in 15% of the patients. Neuro-logical and psychological monitoring was satisfactory. Unaltered muscle force was observed postoperatively in 88% of the patients. CONCLUSIONS: AC performed under conscious sedation, and dexmedetomidine infusion without instrumental airway support, was safe and well-tolerated by patients with comfortable physiological sleep for most of the procedure. This approach to AC was associated with minimal risk of perioperative adverse events and may be particularly beneficial in patients with severe comorbidities.

Analysis of the Shape of Intracranial Pressure Pulse Waveform in Traumatic Brain Injury Patients.

Intracranial pressure (ICP) pulse waveform, i.e., the shape of the ICP signal over a single cardiac cycle, is regarded as a potential source of information about intracranial compliance. In this study we aimed to compare the results of automatic classification of ICP pulse shapes on a scale from normal to pathological with other ICP pulse-derived metrics. Additionally, identification of artifacts was performed simultaneously with pulse classification to assess the effect of artifact removal on the results. Data from 35 traumatic brain injury (TBI) patients were analyzed retrospectively in terms of dominant waveform shape, mean ICP, mean amplitude of ICP (AmpICP), mean index of compensatory reserve (RAP index), and their association with the patient's clinical outcome. Our results show that patients with poor outcome exhibit more pathological waveform shape than patients with good outcome. More pathological ICP pulse shape is associated with higher mean ICP, mean AmpICP, and RAP.Clinical relevance- In the clinical setting, ICP pulse waveform analysis could potentially be used to complement the commonly monitored mean ICP and improve the assessment of intracranial compliance in TBI patients. Artifact removal from the ICP signal could reduce the frequency of false positive detection of clinically adverse events.

Platelet Receptor Activity for Predicting Survival in Patients with Intracranial Bleeding.

Blood coagulation disorders in patients with intracranial bleeding as a result of head injuries or ruptured aneurysms are a diagnostic and therapeutic problem and appropriate assessments are needed to limit CNS damage and to implement preventive measures. The aim of the study was to monitor changes in platelet aggregation and to assess the importance of platelet dysfunction for predicting survival. Platelet receptor function analysis was performed using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating protein (TRAP), ristocetin (RISTO) upon admission to the ICU and on days 2, 3, and 5. On admission, the ASPI, ADP, COL, TRAP, and RISTO tests indicated there was reduced platelet aggregation, despite there being a normal platelet count. In 'Non-survivors', the platelet response to all agonists was suppressed throughout the study period, while in 'Survivors' it improved. Measuring platelet function in ICU patients with intracranial bleeding is a strong predictor related to outcome: patients with impaired platelet aggregation had a lower 28-day survival rate compared to patients with normal platelet aggregation (log-rank test p = 0.014). The results indicated that measuring platelet aggregation can be helpful in the early detection, diagnosis, and treatment of bleeding disorders.

Serum biomarkers and cerebral autoregulation as early warnings of delayed cerebral ischemia risk in patients after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Identifying patients at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) remains challenging. This study aimed to evaluate the concentration of serum biomarkers along with cerebral autoregulation impairment on DCI. METHODS: 55 patients suffering from aSAH were enrolled in the study. Serum S100protein B (S100B) was tested both on the day of admission and over three consecutive days following the occurrence of aSAH. Cerebral autoregulation was assessed using a tissue oxygenation index (TOxa) based on near-infrared spectroscopy. RESULTS: Changes in serum S100B levels interacted with DCI status (presence vs. absence): F = 3.84, p = 0.016. Patients with DCI had higher S100B concentration level on day 3 than those without DCI (3.54 ± 0.50 ng/ml vs. 0.58 ± 0.43 ng/ml, p = 0.001). S100B concentration on day 3 following aSAH predicted DCI (AUC = 0.77, p = 0.006). Raised level of serum S100B on day 3 was related with higher TOxa, thus with impaired cerebral autoregulation (rS = 0.52,p = 0.031). Multivariate logistic regression analysis showed thatimpaired cerebral autoregulation andelevatedS100B concentration on day 3 increasethe likelihood of DCI. CONCLUSIONS: Tracking changes in the serum biomarkers concentration along with monitoring of cerebral autoregulation, may play a role in early detection of patients at risk of DCI after aSAH. These results need to be validated in larger prospective cohorts.

Biomarkers of Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage as Early Predictors at Discharge from an Intensive Care Unit.

BACKGROUND: Subarachnoid bleeding is associated with brain injuries and ranges from almost negligible to acute and life threatening. The main objectives were to study changes in brain-specific biomarker levels in patients after an aneurysmal subarachnoid hemorrhage (aSAH) in relation to early clinical findings, severity scores, and intensive care unit (ICU) outcome. Analysis was done to identify specific biomarkers as predictors of a bad outcome in the acute treatment phase. METHODS: Analysis was performed for the proteins of neurofilament, neuron-specific enolase (NSE), microtubule-associated protein tau (MAPT), and for the proteins of glial cells, S100B, and glial fibrillary acidic protein (GFAP). Outcomes were assessed at discharge from the ICU and analyzed based on the grade in the Glasgow Outcome Scale (GOS). Patients were classified into two groups: with a good outcome (Group 1: GOS IV-V, n = 24) and with a bad outcome (Group 2: GOS I-III, n = 31). Blood samples were taken upon admission to the ICU and afterward daily for up to 6 days. RESULTS: In Group 1, the level of S100B (1.0, 0.9, 0.7, 2.0, 1.0, 0.3 ng/mL) and NSE (1.5, 2.0, 1.6, 1.2, 16.6, 2.2 ng/mL) was significantly lower than in Group 2 (S100B: 4.7, 4.8, 4.4, 4.5, 6.6, 6.8 ng/mL; NSE: 4.0, 4.1, 4.3, 3.8, 4.4, 2.5 1.1 ng/mL) on day 1-6, respectively. MAPT was significantly lower only on the first and second day (83.2 ± 25.1, 132.7 ± 88.1 pg/mL in Group 1 vs. 625.0 ± 250.7, 616.4 ± 391.6 pg/mL in Group 2). GFAP was elevated in both groups from day 1 to 6. In the ROC analysis, S100B showed the highest ability to predict bad ICU outcome of the four biomarkers measured on admission [area under the curve (AUC) 0.81; 95% CI 0.67-0.94, p < 0.001]. NSE and MAPT also had significant predictive value (AUC 0.71; 95% CI 0.54-0.87, p = 0.01; AUC 0.74; 95% CI 0.55-0.92, p = 0.01, respectively). A strong negative correlation between the GOS and S100B and the GOS and NSE was recorded on days 1-5, and between the GOS and MAPT on day 1. CONCLUSION: Our findings provide evidence that brain biomarkers such as S100B, NSE, GFAP, and MAPT increase significantly in patients following aSAH. There is a direct relationship between the neurological outcome in the acute treatment phase and the levels of S100B, NSE, and MAPT. The detection of brain-specific biomarkers in conjunction with clinical data may constitute a valuable diagnostic and prognostic tool in the early phase of aSAH treatment.

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH. Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal. Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50-67). WFNS scale was 2 (1-4) and the modified Fisher scale was 3 (1-3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (R p = -0.42; p < 0.001). Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

A comparison of the time constant of the cerebral arterial bed using invasive and non-invasive arterial blood pressure measurements.

OBJECTIVE: The time constant of the cerebral arterial bed (τ), which is an index of brain haemodynamics, can be estimated in patients using continuous monitoring of arterial blood pressure (ABP), transcranial Doppler cerebral blood flow velocity (CBFV) and intracranial pressure (ICP) if these measures are available. But, in some clinical scenarios invasive measurement of ABP is not feasible. Therefore, in this study we aimed to investigate whether invasive ABP can be replaced with non-invasive ABP, monitored using the Finapres photoplethysmograph (fABP). APPROACH: Forty-six recordings of ICP, ABP, fABP, and CBFV in the right and left middle cerebral arteries were performed daily for approximately 30 min in 10 head injury patients. Two modelling approaches (constant flow forward [CFF, pulsatile blood inflow and steady blood outflow] and pulsatile flow forward [PFF, where both blood inflow and outflow are pulsatile]) were applied to estimate τ using either invasive ABP (τCFF, τPFF) or non-invasive ABP (fτCFF, fτPFF). MAIN RESULTS: Bland-Altman analysis showed quite poor agreement between the fτ and τ methods of estimation. The fτ method produced significantly higher values than the τ method when calculated using both the CFF and PFF models (p < .001 for both). The correlation between fτCFF and τCFF was moderately high (r s = 0.63; p < .001), whereas that between fτPFF and τPFF was weaker (r s = 0.40; p = .009). SIGNIFICANCE: Our results suggest that using non-invasive ABP for estimation of τ is inaccurate in head injury patients.

Brain-Specific Biomarkers as Mortality Predictors after Aneurysmal Subarachnoid Haemorrhage.

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality predictors after aSAH. In patients with an external ventricular drain, enolase, S100B, and GFAP levels were measured in the blood and cerebrospinal fluid (CSF) on days 1, 2, and 3 after aSAH. Compared to survivors, non-survivors showed a significantly higher peak of S100B and enolase levels in the blood (S100B: 5.7 vs. 1.5 ng/mL, p = 0.031; enolase: 6.1 vs. 1.4 ng/mL, p = 0.011) and the CSF (S100B: 18.3 vs. 0.9 ng/mL, p = 0.042; enolase: 109.2 vs. 6.1 ng/mL, p = 0.015). Enolase showed the highest level of predictability at 1.8 ng/mL in the blood (AUC of 0.873) and 80.0 ng/mL in the CSF (AUC of 0.889). The predictive ability of S100B was also very good with a threshold of 5.7 ng/mL in the blood (AUC 0.825) and 4.5 ng/mL in the CSF (AUC 0.810). In conclusion, enolase and S100B, but not GFAP, might be suitable as biomarkers for the early prediction of in-hospital mortality after aSAH.

The relationship between the time of cerebral desaturation episodes and outcome in aneurysmal subarachnoid haemorrhage: a preliminary study.

In this preliminary study we investigated the relationship between the time of cerebral desaturation episodes (CDEs), the severity of the haemorrhage, and the short-term outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH). Thirty eight patents diagnosed with aneurysmal subarachnoid haemorrhage were analysed in this study. Regional cerebral oxygenation (rSO2) was assessed using near infrared spectroscopy (NIRS). A CDE was defined as rSO2 < 60% with a duration of at least 30 min. The severity of the aSAH was assessed using the Hunt and Hess scale and the short-term outcome was evaluated utilizing the Glasgow Outcome Scale. CDEs were found in 44% of the group. The total time of the CDEs and the time of the longest CDE on the contralateral side were longer in patients with severe versus moderate aSAH [h:min]: 8:15 (6:26-8:55) versus 1:24 (1:18-4:18), p = 0.038 and 2:05 (2:00-5:19) versus 0:48 (0:44-2:12), p = 0.038. The time of the longest CDE on the ipsilateral side was longer in patients with poor versus good short-term outcome [h:min]: 5:43 (3:05-9:36) versus 1:47 (0:42-2:10), p = 0.018. The logistic regression model for poor short-term outcome included median ABP, the extent of the haemorrhage in the Fisher scale and the time of the longest CDE. We have demonstrated that the time of a CDE is associated with the severity of haemorrhage and short-term outcome in aSAH patients. A NIRS measurement may provide valuable predictive information and could be considered as additional method of neuromonitoring of patients with aSAH.

Assessment of Baroreflex Sensitivity Using Time-Frequency Analysis during Postural Change and Hypercapnia.

Baroreflex is a mechanism of short-term neural control responsible for maintaining stable levels of arterial blood pressure (ABP) in an ABP-heart rate negative feedback loop. Its function is assessed by baroreflex sensitivity (BRS)-a parameter which quantifies the relationship between changes in ABP and corresponding changes in heart rate (HR). The effect of postural change as well as the effect of changes in blood O2 and CO2 have been the focus of multiple previous studies on BRS. However, little is known about the influence of the combination of these two factors on dynamic baroreflex response. Furthermore, classical methods used for BRS assessment are based on the assumption of stationarity that may lead to unreliable results in the case of mostly nonstationary cardiovascular signals. Therefore, we aimed to investigate BRS during repeated transitions between squatting and standing in normal end-tidal CO2 (EtCO2) conditions (normocapnia) and conditions of progressively increasing EtCO2 with a decreasing level of O2 (hypercapnia with hypoxia) using joint time and frequency domain (TF) approach to BRS estimation that overcomes the limitation of classical methods. Noninvasive continuous measurements of ABP and EtCO2 were conducted in a group of 40 healthy young volunteers. The time course of BRS was estimated from TF representations of pulse interval variability and systolic pressure variability, their coherence, and phase spectra. The relationship between time-variant BRS and indices of ABP and HR was analyzed during postural change in normocapnia and hypercapnia with hypoxia. In normocapnia, observed trends in all measures were in accordance with previous studies, supporting the validity of presented TF method. Similar but slightly attenuated response to postural change was observed in hypercapnia with hypoxia. Our results show the merits of the nonstationary methods as a tool to study the cardiovascular system during short-term hemodynamic changes.

Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects.

The cerebral arterial blood volume changes (∆CaBV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of Ca and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using a non-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher Ca of the MCA than that of the PCA. Our results demonstrate MCA-PCA differences in the τ, but only when the PFF model was applied.