Publications by authors named "Marek Czosnyka"

485 Publications

Comparison of different metrics of cerebral autoregulation in association with major morbidity and mortality after cardiac surgery.

Br J Anaesth 2022 May 18. Epub 2022 May 18.

Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address:

Background: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery.

Methods: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. Regression models were used to examine associations of area under curve and duration of mean arterial pressure below thresholds with stroke, acute kidney injury (AKI), and major morbidity and mortality.

Results: Both mean flow index and cerebral oximetry index identified the cerebral lower limit of autoregulation below which MAP was associated with a higher incidence of AKI and major morbidity and mortality. Based on magnitude and significance of the estimates in adjusted models, the area under curve of MAP < lower limit of autoregulation had the strongest association with AKI and major morbidity and mortality. The odds ratio for area under the curve of MAP < lower limit of autoregulation was 1.05 (95% confidence interval, 1.01-1.09), meaning every 1 mm Hg h increase of area under the curve was associated with an average increase in the odds of AKI by 5%.

Conclusions: For cardiac surgery patients, area under curve of MAP < lower limit of autoregulation using mean flow index or cerebral oximetry index had the strongest association with AKI and major morbidity and mortality. Trials are necessary to evaluate this target for MAP management.
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http://dx.doi.org/10.1016/j.bja.2022.03.029DOI Listing
May 2022

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period.

Pediatr Res 2022 May 5. Epub 2022 May 5.

Neonatal Intensive Care Unit, IRCCS S. Orsola-Malpighi Hospital, Bologna, Italy.

Background: Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH).

Methods: Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed.

Results: Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH.

Conclusions: Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development.

Impact: The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.
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http://dx.doi.org/10.1038/s41390-022-02090-zDOI Listing
May 2022

Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.

Neurocrit Care 2022 Apr 6. Epub 2022 Apr 6.

Department of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant information in real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury.

Methods: Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetrating TBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indices such as the critical closing pressure, and the pressure reactivity index with the brain tissue oxygenation values obtained invasively.

Conclusions: The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.
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http://dx.doi.org/10.1007/s12028-022-01483-6DOI Listing
April 2022

Feasibility of non-invasive neuromonitoring in general intensive care patients using a multi-parameter transcranial Doppler approach.

J Clin Monit Comput 2022 Mar 1. Epub 2022 Mar 1.

Department of Neurology and Neurocritical Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation, Cambridge, United Kingdom.

Purpose: To assess the feasibility of Transcranial Doppler ultrasonography (TCD) neuromonitoring in a general intensive care environment, in the prognosis and outcome prediction of patients who are in coma due to a variety of critical conditions.

Methods: The prospective trial was performed between March 2017 and March 2019 Addenbrooke's Hospital, Cambridge, UK. Forty adult patients who failed to awake appropriately after resuscitation from cardiac arrest or were in coma due to conditions such as meningitis, seizures, sepsis, metabolic encephalopathies, overdose, multiorgan failure or transplant were eligible for inclusion. Gathered data included admission diagnosis, duration of ventilation, length of stay in the ICU, length of stay in hospital, discharge status using Cerebral Performance Categories (CPC). All patients received intermittent extended TCD monitoring following inclusion in the study. Parameters of interest included TCD-based indices of cerebral autoregulation, non-invasive intracranial pressure, autonomic system parameters (based on heart rate variability), critical closing pressure, the cerebrovascular time constant and indices describing the shape of the TCD pulse waveform.

Results: Thirty-seven patients were included in the final analysis, with 21 patients classified as good outcome (CPC 1-2) and 16 as poor neurological outcomes (CPC 3-5). Three patients were excluded due to inadequacies identified in the TCD acquisition. The results indicated that irrespective of the primary diagnosis, non-survivors had significantly disturbed cerebral autoregulation, a shorter cerebrovascular time constant and a more distorted TCD pulse waveform (all p<0.05).

Conclusions: Preliminary results from the trial indicate that multi-parameter TCD neuromonitoring increases outcome-predictive power and TCD-based indices can be applied to general intensive care monitoring.
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http://dx.doi.org/10.1007/s10877-022-00829-xDOI Listing
March 2022

Mathematical Modelling in Hydrocephalus.

Neurol India 2021 Nov-Dec;69(Supplement):S275-S282

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; Institute of Electronic Systems, Warsaw University of Technology, Warsaw, Poland.

Background: Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions.

Objective: This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus.

Conclusions: Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.
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http://dx.doi.org/10.4103/0028-3886.332259DOI Listing
February 2022

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

Front Neurol 2021 12;12:740338. Epub 2022 Jan 12.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

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. 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. 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 ( = 0.001 and < 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 (r = 0.31; = 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 ( = -0.42; < 0.001). 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.
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http://dx.doi.org/10.3389/fneur.2021.740338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790510PMC
January 2022

The Use of Different Components of Brain Oxygenation for the Assessment of Cerebral Haemodynamics: A Prospective Observational Study on COVID-19 Patients.

Front Neurol 2021 20;12:735469. Epub 2021 Dec 20.

Neurocritical Care Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.

The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate the role of the integral components of regional cerebral oxygenation (rSO) measured by NIRS [i.e., arterial-oxyhemoglobin (OHbi) and venous-deoxyhemoglobin (HHbi)-components], as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD). Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO and its components [relative changes in OHbi, HHbi, and total haemoglobin (cHbi)] were compared with TCD (cerebral blood flow velocity, CBFV). Changes (Δ) in CBFV and rSO, ΔOHbi, ΔHHbi, and ΔcHbi after systemic arterial blood pressure (MAP) modifications induced by different manoeuvres (e.g., rescue therapies and haemodynamic manipulation) were assessed using mixed-effect linear regression analysis and repeated measures correlation coefficients. All values were normalised as percentage changes from the baseline (Δ%). One hundred and four measurements from 25 patients were included. Significant effects of Δ%MAP on Δ%CBF were observed after rescue manoeuvres for CBFV, ΔcHbi, and ΔOHbi. The highest correlation was found between ΔCBFV and ΔΔOHbi (R = 0.88, < 0.0001), and the poorest between ΔCBFV and ΔΔHHbi (R = 0.34, p = 0.002). ΔOHbi had the highest accuracy to assess CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. The use of indexes derived from the different components of rSO can be useful for the bedside evaluation of cerebral haemodynamics in mechanically ventilated patients with COVID-19.
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http://dx.doi.org/10.3389/fneur.2021.735469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722102PMC
December 2021

Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients.

PLoS One 2021 16;16(12):e0260291. Epub 2021 Dec 16.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p<0.05). Significant non-linear associations were observed between LPR and cerebral glucose, CPP, and PRx (p<0.001 to p<0.05). GAMM models suggested improved cerebral metabolism (i.e. reduced LPR with CPP >70mmHg, PRx <0.1, PbtO2 >18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260291PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675704PMC
January 2022

Cerebral Autoregulation in Non-Brain Injured Patients: A Systematic Review.

Front Neurol 2021 16;12:732176. Epub 2021 Nov 16.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.

Cerebral autoregulation (CA) plays a fundamental role in the maintenance of adequate cerebral blood flow (CBF). CA monitoring, through direct and indirect techniques, may guide an appropriate therapeutic approach aimed at improving CBF and reducing neurological complications; so far, the role of CA has been investigated mainly in brain-injured patients. The aim of this study is to investigate the role of CA in non-brain injured patients. A systematic consultation of literature was carried out. Search terms included: "CA and sepsis," "CA and surgery," and "CA and non-brain injury." Our research individualized 294 studies and after screening, 22 studies were analyzed in this study. Studies were divided in three groups: CA in sepsis and septic shock, CA during surgery, and CA in the pediatric population. Studies in sepsis and intraoperative setting highlighted a relationship between the incidence of sepsis-associated delirium and impaired CA. The most investigated setting in the pediatric population is cardiac surgery, but the role and measurement of CA need to be further elucidated. In non-brain injured patients, impaired CA may result in cognitive dysfunction, neurological damage, worst outcome, and increased mortality. Monitoring CA might be a useful tool for the bedside optimization and individualization of the clinical management in this group of patients.
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http://dx.doi.org/10.3389/fneur.2021.732176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660115PMC
November 2021

Author Correction: Comparison of wavelet and correlation indices of cerebral autoregulation in a pediatric swine model of cardiac arrest.

Sci Rep 2021 Nov 12;11(1):22514. Epub 2021 Nov 12.

Division of Pediatric Anesthesiology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

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http://dx.doi.org/10.1038/s41598-021-01918-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590060PMC
November 2021

Analysis of relative changes in pulse shapes of intracranial pressure and cerebral blood flow velocity.

Physiol Meas 2021 12 29;42(12). Epub 2021 Dec 29.

Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland.

Analysis of relative changes in the shapes of pulse waveforms of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the ratio of pulse slopes (RPS) that is based on inclinations of the ascending parts of the ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: a value of 1 indicates good compliance and a value less than 1, reduced compliance. Here, we investigated the usefulness of RPS for assessment of intracranial compliance.ICP and CBFV signals recorded simultaneously in 30 normal-pressure hydrocephalus patients during infusion tests were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared with changes in the height ratio of the first and second peak of the ICP pulse (P1/P2) and the shape of the ICP pulse was classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles).There was a significant correlation between baseline RPS and intracranial elasticity ( = -0.55, = 0.0018). During the infusion tests, both RPS and P1/P2 decreased with rising ICP [RPS, 0.80 (0.56, 0.92) versus 0.63 (0.44, 0.80), = 0.00015; P1/P2, 0.58 (0.50, 0.91) versus 0.52 (0.36, 0.71), = 0.00009] while the ICP pulses became more pathological in shape [class: 3 (2, 3) versus 3 (3, 4), = 0.04]. The magnitude of the decrease in RPS during infusion was inversely correlated with baseline P1/P2 ( = -0.40, < 0.03).During infusion, the slopes of the ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems to be a promising methodological tool for monitoring intracranial compliance with no additional volumetric manipulation required.
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http://dx.doi.org/10.1088/1361-6579/ac38bfDOI Listing
December 2021

Causal relationship between slow waves of arterial, intracranial pressures and blood velocity in brain.

Comput Biol Med 2021 12 27;139:104970. Epub 2021 Oct 27.

University of Cambridge, Brain Physics Laboratory, Division of Neurosurgery, Box 167, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom.

Purpose: Slow vasogenic waves in arterial blood pressure (ABP), intracranial pressure (ICP) and cerebral blood flow velocity (FV) carry information on multiple brain homeostatic control mechanisms. This work presents an approach to evaluate causal relation between oscillatory modes of these signals as an alternative to time or frequency domain Granger analysis.

Methods: Forty-five patients with simultaneous recordings of ICP, ABP and FV during CSF infusion studies were examined retrospectively. Each time series was decomposed into ten intrinsic mode functions (IMFs) via Ensemble Empirical Mode Decomposition (EEMD) and, afterwards, Granger causality (GC) was computed.

Results: Slow waves of ICP, ABP and FV were reconstructed from mode functions IMF of each time series, covering a frequency range between 0.013 and 0.155 Hz. Most significant connections were from FV to ICP, being stronger during elevation of mean ICP during infusion study. No G-causality was found between any of the IMFs during the baseline phase.

Conclusion: Nonlinearity and nonstationarity of the cerebral and systemic signals can be addressed using EEMD decomposition There is a causal influence of slow waves of FV on slow waves on ICP during the plateau phase of the infusion study for a frequency band between 0.095 and 0.155 Hz. This relationship is magnified during mild intracranial hypertension.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104970DOI Listing
December 2021

Modeling Brain-Heart Crosstalk Information in Patients with Traumatic Brain Injury.

Neurocrit Care 2022 06 12;36(3):738-750. Epub 2021 Oct 12.

Computer Laboratory, University of Cambridge, Cambridge, UK.

Background: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality..

Methods: In our previous work, we introduced a novel measure of brain-heart interaction termed brain-heart crosstalks (ct), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ω)] obtained through a complex network modeling of the brain-heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package.

Results: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain-heart crosstalks varied (mean 58, standard deviation 57). The Kruskal-Wallis test comparing brain-heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for [Formula: see text], 0.005 for ct and 0.006 for ω). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ct (p value 0.04), - 0.19 for ω (p value 0.002969) and - 0.09 for [Formula: see text] (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16-29, 30-49, 50-65, and 65-85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16-29, 50-65, and 65-85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain-heart crosstalks and mortality was also confirmed.

Conclusions: The presence of a negative relationship between mortality and brain-heart crosstalks indicators suggests that a healthy brain-cardiovascular interaction plays a role in TBI.
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http://dx.doi.org/10.1007/s12028-021-01353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110542PMC
June 2022

Is Lumbar Puncture Needed? - Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension.

Ultraschall Med 2021 Sep 8. Epub 2021 Sep 8.

Neurology, Klinikum Chemnitz gGmbH, Chemnitz, Germany.

Purpose:  Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH.

Materials And Methods:  nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ± 11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmHO, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed.

Results:  In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ± 4.93 cmHO. The capability of nICP to diagnose increased LPP (LPP > 20 cmHO) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmHO with both a sensitivity and specificity of 0.92. Presuming 20 cmHO as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases.

Conclusion:  The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.
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http://dx.doi.org/10.1055/a-1586-6487DOI Listing
September 2021

Change in Blood Flow Velocity Pulse Waveform during Plateau Waves of Intracranial Pressure.

Brain Sci 2021 Jul 29;11(8). Epub 2021 Jul 29.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.

A reliable method for non-invasive detection of dangerous intracranial pressure (ICP) elevations is still unavailable. In this preliminary study, we investigate quantitatively our observation that superimposing waveforms of transcranial Doppler blood flow velocity (FV) and arterial blood pressure (ABP) may help in non-invasive identification of ICP plateau waves. Recordings of FV, ABP and ICP in 160 patients with severe head injury (treated in the Neurocritical Care Unit at Addenbrookes Hospital, Cambridge, UK) were reviewed retrospectively. From that cohort, we identified 18 plateau waves registered in eight patients. A "measure of dissimilarity" (Dissimilarity/Difference Index, DI) between ABP and FV waveforms was calculated in three following steps: 1. fragmentation of ABP and FV signal according to cardiac cycle; 2. obtaining the normalised representative ABP and FV cycles; and finally; 3. assessing their difference, represented by the area between both curves. DI appeared to discriminate ICP plateau waves from baseline episodes slightly better than conventional pulsatility index did: area under ROC curve 0.92 vs. 0.90, sensitivity 0.81 vs. 0.69, accuracy 0.88 vs. 0.84, respectively. The concept of DI, if further tested and improved, might be used for non-invasive detection of ICP plateau waves.
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http://dx.doi.org/10.3390/brainsci11081000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391497PMC
July 2021

Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

J Neurotrauma 2021 10 16;38(20):2790-2800. Epub 2021 Aug 16.

Department of Intensive Care Medicine, University Maastricht (KEMTA), Maastricht University Medical Center+, Maastricht, The Netherlands.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%;  < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.
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http://dx.doi.org/10.1089/neu.2021.0197DOI Listing
October 2021

Intracranial pulse pressure waveform analysis using the higher harmonics centroid.

Acta Neurochir (Wien) 2021 12 13;163(12):3249-3258. Epub 2021 Aug 13.

Neurosurgical Associates, Red Cross Hospital, Kassel, Germany.

Background: The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves.

Material And Methods: Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline.

Results: For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10).

Conclusions: The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.
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http://dx.doi.org/10.1007/s00701-021-04958-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599247PMC
December 2021

Early Effects of Passive Leg-Raising Test, Fluid Challenge, and Norepinephrine on Cerebral Autoregulation and Oxygenation in COVID-19 Critically Ill Patients.

Front Neurol 2021 16;12:674466. Epub 2021 Jun 16.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.

Coronavirus disease 2019 (COVID-19) patients are at high risk of neurological complications consequent to several factors including persistent hypotension. There is a paucity of data on the effects of therapeutic interventions designed to optimize systemic hemodynamics on cerebral autoregulation (CA) in this group of patients. Single-center, observational prospective study conducted at San Martino Policlinico Hospital, Genoa, Italy, from October 1 to December 15, 2020. Mechanically ventilated COVID-19 patients, who had at least one episode of hypotension and received a passive leg raising (PLR) test, were included. They were then treated with fluid challenge (FC) and/or norepinephrine (NE), according to patients' clinical conditions, at different moments. The primary outcome was to assess the early effects of PLR test and of FC and NE [when clinically indicated to maintain adequate mean arterial pressure (MAP)] on CA (CA index) measured by transcranial Doppler (TCD). Secondary outcomes were to evaluate the effects of PLR test, FC, and NE on systemic hemodynamic variables, cerebral oxygenation (rSo), and non-invasive intracranial pressure (nICP). Twenty-three patients were included and underwent PLR test. Of these, 22 patients received FC and 14 were treated with NE. The median age was 62 years (interquartile range = 57-68.5 years), and 78% were male. PLR test led to a low CA index [58% (44-76.3%)]. FC and NE administration resulted in a CA index of 90.8% (74.2-100%) and 100% (100-100%), respectively. After PLR test, nICP based on pulsatility index and nICP based on flow velocity diastolic formula was increased [18.6 (17.7-19.6) vs. 19.3 (18.2-19.8) mm Hg, = 0.009, and 12.9 (8.5-18) vs. 15 (10.5-19.7) mm Hg, = 0.001, respectively]. PLR test, FC, and NE resulted in a significant increase in MAP and rSo. In mechanically ventilated severe COVID-19 patients, PLR test adversely affects CA. An individualized strategy aimed at assessing both the hemodynamic and cerebral needs is warranted in patients at high risk of neurological complications.
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http://dx.doi.org/10.3389/fneur.2021.674466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242251PMC
June 2021

Monitoring cerebrovascular reactivity in pediatric traumatic brain injury: comparison of three methods.

Childs Nerv Syst 2021 10 1;37(10):3057-3065. Epub 2021 Jul 1.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

Purpose: To study three different methods of monitoring cerebral autoregulation in children with severe traumatic brain injury.

Methods: Prospective cohort study of all children admitted to the pediatric intensive care unit at a university-affiliated hospital with severe TBI over a 4-year period to study three different methods of monitoring cerebral autoregulation: pressure-reactivity index (PRx), transcranial Doppler derived mean flow velocity index (Mx), and near-infrared spectroscopy derived cerebral oximetry index (COx).

Results: Twelve patients were included in the study, aged 5 months to 17 years old. An empirical regression analyzing dependence of PRx on cerebral perfusion pressure (CPP) displayed the classic U-shaped distribution, with low PRx values (< 0.3) reflecting intact auto-regulation, within the CPP range of 50-100 mmHg. The optimal CPP was 75-80 mmHg for PRx and COx. The correlation coefficients between the three indices were as follows: PRx vs Mx, r = 0.56; p < 0.0001; PRx vs COx, r = 0.16; p < 0.0001; and COx vs Mx, r = 0.15; p = 0.022. The mean PRx with a cutoff value of 0.3 predicted correctly long-term outcome (p = 0.015).

Conclusions: PRx seems to be the most robust index to access cerebrovascular reactivity in children with TBI and has promising prognostic value. Optimal CPP calculation is feasible with PRx and COx.
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http://dx.doi.org/10.1007/s00381-021-05263-zDOI Listing
October 2021

Prediction of Life-Threatening Intracranial Hypertension During the Acute Phase of Traumatic Brain Injury Using Machine Learning.

IEEE J Biomed Health Inform 2021 10 5;25(10):3967-3976. Epub 2021 Oct 5.

Intracranial hypertension (IH) following acute phase traumatic brain injury (TBI) is associated with high mortality. Objective: This study proposes a novel parameter that may identify a potentially life-threatening IH (LTH) event and designs a machine learning model to predict LTH. Continuous recordings of intracranial pressure (ICP) and arterial blood pressure (ABP) from 273 TBI patients were used as the development dataset. The pressure-time dose (PTD) and pressure reactivity index (PRx) were calculated for each IH event, and an IH event with PRx > 0 and PTD > 5 was considered an LTH event. The association between the LTH parameters accumulated over five days and mortality was analyzed. A categorical boosting (CatBoost) model was employed to predict the occurrence of a future LTH event from the onset of IH using the ABP- and ICP-related parameters. Training and validation were performed on a total of 5,938 IH events. External performance evaluation was performed in 307 IH events included in the Cerebral Haemodynamic Autoregulatory Information System (CHARIS) database. The performance of the proposed model was evaluated through the area under the receiver operating characteristic curve (AUROC). The LTH parameters were able to distinguish between the deceased and surviving patients (AUROC > 0.7, p < 0.001). The CatBoost model predicted LTH with an AUROC = 0.7 on the external test dataset. This study demonstrated that the proposed LTH prediction model has a reasonable predictive capacity for mortality. The CatBoost model anticipates whether an IH event will develop into an LTH event. The findings of this study support the usefulness of ICP monitoring.
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http://dx.doi.org/10.1109/JBHI.2021.3085881DOI Listing
October 2021

CSF Dynamics for Shunt Prognostication and Revision in Normal Pressure Hydrocephalus.

J Clin Med 2021 Apr 15;10(8). Epub 2021 Apr 15.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.

Background: Despite the quantitative information derived from testing of the CSF circulation, there is still no consensus on what the best approach could be in defining criteria for shunting and predicting response to CSF diversion in normal pressure hydrocephalus (NPH).

Objective: We aimed to review the lessons learned from assessment of CSF dynamics in our center and summarize our findings to date. We have focused on reporting the objective perspective of CSF dynamics testing, without further inferences to individual patient management.

Discussion: No single parameter from the CSF infusion study has so far been able to serve as an unquestionable outcome predictor. Resistance to CSF outflow (Rout) is an important biological marker of CSF circulation. It should not, however, be used as a single predictor for improvement after shunting. Testing of CSF dynamics provides information on hydrodynamic properties of the cerebrospinal compartment: the system which is being modified by a shunt. Our experience of nearly 30 years of studying CSF dynamics in patients requiring shunting and/or shunt revision, combined with all the recent progress made in producing evidence on the clinical utility of CSF dynamics, has led to reconsidering the relationship between CSF circulation testing and clinical improvement.

Conclusions: Despite many open questions and limitations, testing of CSF dynamics provides unique perspectives for the clinician. We have found value in understanding shunt function and potentially shunt response through shunt testing in vivo. In the absence of infusion tests, further methods that provide a clear description of the pre and post-shunting CSF circulation, and potentially cerebral blood flow, should be developed and adapted to the bed-space.
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http://dx.doi.org/10.3390/jcm10081711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071572PMC
April 2021

Compliance of the cerebrospinal space: comparison of three methods.

Acta Neurochir (Wien) 2021 07 14;163(7):1979-1989. Epub 2021 Apr 14.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

Background: Cerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance.

Methods: ICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou's model of cerebrospinal fluid dynamics (C), (b) based on the evaluation of changes in cerebral arterial blood volume (C), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (C).

Results: Increase in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88-0.97] for C vs. C, 0.77 [0.63-0.91] for C vs. C, and 0.68 [0.48-0.91] for C vs. C).

Conclusions: Indirect methods, C and C, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.
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http://dx.doi.org/10.1007/s00701-021-04834-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195969PMC
July 2021

Reference values for intracranial pressure and lumbar cerebrospinal fluid pressure: a systematic review.

Fluids Barriers CNS 2021 Apr 13;18(1):19. Epub 2021 Apr 13.

Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark.

Background: Although widely used in the evaluation of the diseased, normal intracranial pressure and lumbar cerebrospinal fluid pressure remain sparsely documented. Intracranial pressure is different from lumbar cerebrospinal fluid pressure. In addition, intracranial pressure differs considerably according to the body position of the patient. Despite this, the current reference values do not distinguish between intracranial and lumbar cerebrospinal fluid pressures, and body position-dependent reference values do not exist. In this study, we aim to establish these reference values.

Method: A systematic search was conducted in MEDLINE, EMBASE, CENTRAL, and Web of Sciences. Methodological quality was assessed using an amended version of the Joanna Briggs Quality Appraisal Checklist. Intracranial pressure and lumbar cerebrospinal fluid pressure were independently evaluated and subdivided into body positions. Quantitative data were presented with mean ± SD, and 90% reference intervals.

Results: Thirty-six studies were included. Nine studies reported values for intracranial pressure, while 27 reported values for the lumbar cerebrospinal fluid pressure. Reference values for intracranial pressure were -  5.9 to 8.3 mmHg in the upright position and 0.9 to 16.3 mmHg in the supine position. Reference values for lumbar cerebrospinal fluid pressure were 7.2 to 16.8 mmHg and 5.7 to 15.5 mmHg in the lateral recumbent position and supine position, respectively.

Conclusions: This systematic review is the first to provide position-dependent reference values for intracranial pressure and lumbar cerebrospinal fluid pressure. Clinically applicable reference values for normal lumbar cerebrospinal fluid pressure were established, and are in accordance with previously used reference values. For intracranial pressure, this study strongly emphasizes the scarcity of normal pressure measures, and highlights the need for further research on the matter.
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http://dx.doi.org/10.1186/s12987-021-00253-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045192PMC
April 2021

The Role of Cerebrospinal Fluid Dynamics in Normal Pressure Hydrocephalus Diagnosis and Shunt Prognostication.

Acta Neurochir Suppl 2021 ;131:359-363

Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Background: Over the years, there have been several reports and trials of the resistance to cerebrospinal fluid (CSF) outflow (Rout) in normal pressure hydrocephalus (NPH). This work aimed to revisit the utility of testing CSF circulation in a large population of patients clinically presenting with NPH.

Materials And Methods: We retrospectively analyzed the data of 369 NPH patients-either shunted or with endoscopic third ventriculostomy (ETV)-in Cambridge between 1992 and 2018. We determined the patients' outcomes (improvement versus no improvement at 6 months) by applying a threshold on R values and compared our results with those of existing literature. We also conducted a correlation analysis between all variables and calculated Chi-Statistics (as a measure of separability between improvement and no improvement outcomes) to determine a subset of variables which achieved the highest accuracy in prediction of outcome.

Results: In our dataset, R of 18 mmHg*min/mL achieved the highest Chi-statistics of 9.7 with p-value <0.01 when adjusted for age. In addition to R , intracranial pressure (ICP) values at the baseline and plateau, CSF production rate and ICP amplitude to slope ratio showed significant Chi-Statistics values (more than 5). Using these variables, an overall accuracy of 0.70 ± 0.09 was achieved for prediction of the shunt outcome.

Conclusion: Rout can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Critical, multivariable approaches are required to comprehend CSF dynamics and pressure-volume compensation in NPH. Outcome definition and assessment could also be brought to question.
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http://dx.doi.org/10.1007/978-3-030-59436-7_69DOI Listing
June 2021

Comparison of Assessment for Shunting with Infusion Studies Versus Extended Lumbar Drainage in Suspected Normal Pressure Hydrocephalus.

Acta Neurochir Suppl 2021 ;131:355-358

Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Introduction: Tools available for diagnosis of normal pressure hydrocephalus (NPH) and prediction of shunt-response are overnight ICP monitoring, infusion studies, and extended lumbar drainage (ELD). We investigated the shunt-response predictive value by infusion tests versus ELD.

Material And Methods: We retrospectively recruited 83 patients who had undergone both infusion study and ELD assessments and compared infusion study hydrodynamics with improvement at clinic follow-up after ELD and after shunting.

Results: 62 patients had Rout >11 mmHg/mL/min. 28 Showed physiotherapy-documented improvement following ELD, and were selected for shunting, of which 21 were shunted. Of these, 19 showed improvement. Eight patients with Rout >20 mmHg/mL/min showed no response to ELD and were not shunted.There were 21 patients with Rout <11 mmHg/mL/min: five were shunted, showed improvement at follow-up, and had Rout >6 mmHg/mL/min. ICP amplitude did not differ at baseline or plateau between responders and non-responders.

Conclusions: ELD response and CSF dynamics differed remarkably. All patients with Rout <6 mmHg/mL/min showed no improvement with ELD, indicating that ELD and shunting might be contraindicated in these subjects. High Rout patients with no response to ELD could merit further consideration.
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http://dx.doi.org/10.1007/978-3-030-59436-7_68DOI Listing
June 2021

Global Cerebral Autoregulation, Resistance to Cerebrospinal Fluid Outflow and Cerebrovascular Burden in Normal Pressure Hydrocephalus.

Acta Neurochir Suppl 2021 ;131:349-353

Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Introduction: We previously examined the relationship between global autoregulation pressure reactivity index (PRx), mean arterial blood pressure (ABP), Resistance to cerebral spinal fluid (CSF) outflow (Rout) and their possible effects on outcome after surgery on 83 shunted patients. In this study, we aimed to quantify the relationship between all parameters that influence Rout, their interaction with the cerebral vasculature, and their role in shunt prognostication.

Methods: From 423 patients having undergone infusion tests for possible NPH, we selected those with monitored ABP and calculated its mean and PRx. After shunting, 6 months patients' outcome was marked using a simple scale (improvement, temporary improvement, and no improvement). We explored the relationship between age, different CSF dynamics variables, and vascular parameters using multivariable models.

Results: Rout had a weaker predictive value than ABP (Fisher Discrimination Ratio of 0.02 versus 0.42). ABP > 98 was an independent predictor of shunt outcome with odd ratio 6.4, 95% CI: 1.8-23.4 and p-value = 0.004. There was a strong and significant relationship between the interaction of age, PRx, ABP, and Rout (R = 0.53 with p = 7.28 × 10). Using our linear model, we achieved an AUC 86.4% (95% CI: 80.5-92.3%) in detecting shunt respondents. The overall sensitivity was 94%, specificity 75%, positive predictive value (PPV) of 54%, and negative predictive value of 97%.

Conclusion: In patients with low Rout and high cerebrovascular burden, as described by high ABP and disturbed global autoregulation, response to shunting is less likely. The low PPV of high resistance, preserved autoregulation and absence of hypertension could merit further exploration.
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http://dx.doi.org/10.1007/978-3-030-59436-7_67DOI Listing
June 2021

Differences in Cerebrospinal Fluid Dynamics in Posttraumatic Hydrocephalus Versus Atrophy, Including Effect of Decompression and Cranioplasty.

Acta Neurochir Suppl 2021 ;131:343-347

Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Introduction: Challenges in diagnosing post-traumatic hydrocephalus (PTH) have created a need for an accurate diagnostic tool. We aim to report CSF dynamics in PTH and atrophy, along with differences before and after cranioplasty.

Methods: We retrospectively analyzed traumatic brain injury patients with ventriculomegaly who had infusion studies. We divided patients depending on CSF dynamics into two groups: 'likely PTH' (A) and 'likely atrophy' (B). A group of idiopathic normal pressure hydrocephalus shunt-responsive patients was used for comparison (C).

Results: Group A consisted of 36 patients who were non-decompressed or had a cranioplasty in situ for over 1 month. Group B included 16 patients with low Rout, AMP, and dAMP, 9 of whom were decompressed. Rout and dAMP were significantly higher in Group A than B, but significantly lower than Group C (45 iNPH patients). RAP change during infusion in group A indicated depleted compensatory reserve compared to ample reserve in group B. Repeat studies in five decompressed patients post-cranioplasty showed all parameters increased.

Conclusions: Infusion tests are not useful in decompressed patients, whilst cranioplasty allowed differentiation between possible PTH and atrophy. Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus reported on imaging.
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http://dx.doi.org/10.1007/978-3-030-59436-7_66DOI Listing
June 2021

Noninvasive Intracranial Pressure Assessment in Patients with Suspected Idiopathic Intracranial Hypertension.

Acta Neurochir Suppl 2021 ;131:325-327

Department of Neurology, Chemnitz Medical Centre, Chemnitz, Germany.

Introduction: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight disorders. Besides ophthalmoscopy, lumbar puncture is used for both diagnosis and therapy of IIH. In this study, noninvasively-assessed intracranial pressure (nICP) was compared to lumbar pressure (LP) to clarify its suitability for diagnosis of IIH.

Methods: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity, a method previously introduced by the authors. In thirteen patients (f = 11, m = 2; age: 36 ± 10 years), nICP was assessed 1 h prior to LP. If LP was >20 cmHO (~15 mmHg), lumbar drainage was performed, LP was measured again, and nICP was reassessed.

Results: In six patients, LP and nICP were compared after lumbar drainage. In three patients, assessment of nICP versus LP was repeated. In total, LP and nICP correlated with R = 0.82 (p < 0.001; N = 22). Mean difference of ICP-nICP was 0.8 ± 3.7 mmHg. Presuming 15 mmHg as critical threshold for indication of lumbar drainage in 20 of 22 cases, the clinical implications would have been the same in both methods.

Conclusion: TCD-based ICP assessment seems to be a promising method for pre-diagnosis of increased LP and might prevent the need for lumbar puncture if nICP is low.
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http://dx.doi.org/10.1007/978-3-030-59436-7_62DOI Listing
June 2021

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Acta Neurochir Suppl 2021 ;131:311-313

Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25 years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p < 0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p < 0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.
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http://dx.doi.org/10.1007/978-3-030-59436-7_58DOI Listing
June 2021

Lower Breakpoint of Intracranial Amplitude-Pressure Relationship in Normal Pressure Hydrocephalus.

Acta Neurochir Suppl 2021 ;131:307-309

Academic Neurosurgery, Cambridge University Hospital, Cambridge, UK.

The relationship between intracranial pulse amplitude (AMP) and mean intracranial pressure (ICP) has been previously described. Generally, AMP increases proportionally to rises in ICP. However, at low ICP a lower breakpoint (LB) of amplitude-pressure relationship can be observed, below which pulse amplitude stays constant when ICP varies. Theoretically, below this breakpoint, the pressure-volume relationship is linear (good compensatory reserve, brain compliance stays constant); above the breakpoint, it is exponential (brain compliance decreases with rising ICP).Infusion tests performed in 169 patients diagnosed for idiopathic normal pressure hydrocephalus (iNPH) during the period 2004-2013 were available for analysis. A lower breakpoint was observed in 62 patients diagnosed for iNPH. Improvement after shunt surgery in patients in whom LB was recorded was 77% versus 90% in patients where LB was absent (p < 0.02). There was no correlation between improvement and slope of amplitude-pressure line above LB.The detection of a lower breakpoint is associated with less frequent improvement after shunting in NPH. It may be interpreted that cerebrospinal fluid dynamics of patients working on the flat part of the pressure-volume curve and having a 'luxurious' compensatory reserve, are more frequently caused by brain atrophy, which is obviously not responding to shunting.
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http://dx.doi.org/10.1007/978-3-030-59436-7_57DOI Listing
June 2021
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