Publications by authors named "Marek Czosnyka"

465 Publications

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 Apr 14. 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
April 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
January 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
January 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
January 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
January 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
January 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
January 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
January 2021

Cerebrovascular Impedance During Hemodynamic Change in Rabbits: A Pilot Study.

Acta Neurochir Suppl 2021 ;131:283-288

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

Introduction: Cerebrovascular impedance describes the relationship between pulsatile changes in arterial blood pressure (ABP) and cerebral blood flow (CBF). It is commonly defined by modulus and phase shift derived from Fourier spectra of ABP and CBF velocity (CBFV) signals under mostly steady-state conditions. The aim of this work was to assess heartbeat-to-heartbeat cerebrovascular impedance at heart rate frequency during controlled changes in mean ABP and intracranial pressure (ICP).

Material And Methods: Recordings of ABP in the femoral artery, transcranial Doppler CBFV in the basilar artery, and subarachnoid ICP were obtained from anesthetized rabbits with induced arterial hypotension (n = 8 rabbits), arterial hypertension (n = 5), or intracranial hypertension (n = 7). Modulus of cerebrovascular impedance (|Z|) was estimated from amplitudes of ABP and CBFV. Phase shift of cerebrovascular impedance (PS) was estimated from time-frequency (TF) representations of phase shift between ABP and CBFV overlaid with a time-variant mask based on the fundamental frequency of ABP.

Results: Both |Z| and PS increased with increasing mean ABP. |Z| decreased with increasing mean ICP, but no change was observed in PS.

Conclusions: The combined beat-to-beat and TF approach allows for the estimation of cerebrovascular impedance during transient hemodynamic changes. |Z| and PS follow the pattern of changes in CPP.
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http://dx.doi.org/10.1007/978-3-030-59436-7_53DOI Listing
January 2021

Analysis of Intracranial Pressure Pulse-Pressure Relationship: Experimental Validation.

Acta Neurochir Suppl 2021 ;131:279-282

Faculty of Electronics and Information Technology, Institute of Electronic Systems, Warsaw University of Technology, Warsaw, Poland.

The slope of linear relationship between the amplitude of pulsations in intracranial pressure (ICP) versus mean ICP has recently been suggested as a useful guide for selecting patients for shunt surgery in normal pressure hydrocephalus (NPH). To better understand how the pathophysiology of cerebral circulation influences this parameter, we aimed to study the relationship between mean pressure and pulsation amplitude in a wide range of conditions affecting cerebrovascular tone and ICP in experimental conditions.We retrospectively analysed experimental material collected previously. Three physiological manoeuvres were studied in 29 New Zealand white rabbits: lumbar infusion with an infusion rate ≤0.2 mL/min to induce mild intracranial hypertension (n = 43), sympathetic blockade to induce arterial hypotension (n = 19), and modulation of the ventilator tidal volume, simultaneously influencing arterial carbon dioxide partial pressure (PaCO) to induce hypocapnia or hypercapnia (n = 17). We investigated whether the slope of the pulse amplitude (AMP)-ICP line depended on PaCO and arterial blood pressure (ABP) changes.We found a linear correlation between AMP-ICP and ICP with positive slope. Regression of slope against mean ABP showed a negative dependence (p = 0.03). In contrast, the relationship between slope and PaCO was positive, although not reaching statistical significance (p = 0.18).The slope of amplitude-pressure line is strongly modulated by systemic vascular variables and therefore should be taken as a descriptor of cerebrospinal fluid dynamics with great care.
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http://dx.doi.org/10.1007/978-3-030-59436-7_52DOI Listing
January 2021

Lower Limit of Reactivity Assessed with PRx in an Experimental Setting.

Acta Neurochir Suppl 2021 ;131:275-278

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

In traumatic brain injury, longer time spent with a cerebral perfusion pressure (CPP) below the pressure reactivity index (PRx)-derived lower limit of reactivity (LLR) has been shown to be statistically associated with higher mortality. We set out to scrutinise the behaviour of LLR and the methods of its estimation in individual cases by performing retrospective analysis of intracranial pressure (ICP), arterial blood pressure (ABP) and laser Doppler flow (LDF) signals recorded in nine piglets undergoing controlled, terminal hypotension. We focused on the sections of the recordings with stable experimental conditions where a clear breakpoint of LDF/CPP characteristic (LLA) could be identified.In eight of the nine experiments, when CPP underwent a monotonous decrease, the relationship PRx/CPP showed two breakpoints (1 - when PRx starts to rise; 2 - when PRx saturates at PRx > 0.3), with LDF-based LLA sitting between them. LLR (CPP at PRx reaching 0.3 in the error bar chart) was close to the lower LLR breakpoint.In conclusion, when CPP has a monotonous decrease, PRx starts worsening before CPP crosses the LLA. A further decrease in CPP below LLA would cause a decrease in CBF, even if the pressure reactivity is not completely lost. This pattern should be taken into account when PRx is used to detect LLA continuously.
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http://dx.doi.org/10.1007/978-3-030-59436-7_51DOI Listing
January 2021

DeepClean: Self-Supervised Artefact Rejection for Intensive Care Waveform Data Using Deep Generative Learning.

Acta Neurochir Suppl 2021 ;131:235-241

Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.

Waveform physiological data are important in the treatment of critically ill patients in the intensive care unit. Such recordings are susceptible to artefacts, which must be removed before the data can be reused for alerting or reprocessed for other clinical or research purposes. Accurate removal of artefacts reduces bias and uncertainty in clinical assessment, as well as the false positive rate of ICU alarms, and is therefore a key component in providing optimal clinical care. In this work, we present DeepClean, a prototype self-supervised artefact detection system using a convolutional variational autoencoder deep neural network that avoids costly and painstaking manual annotation, requiring only easily obtained 'good' data for training. For a test case with invasive arterial blood pressure, we demonstrate that our algorithm can detect the presence of an artefact within a 10s sample of data with sensitivity and specificity around 90%. Furthermore, DeepClean was able to identify regions of artefacts within such samples with high accuracy, and we show that it significantly outperforms a baseline principal component analysis approach in both signal reconstruction and artefact detection. DeepClean learns a generative model and therefore may also be used for imputation of missing data.
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http://dx.doi.org/10.1007/978-3-030-59436-7_45DOI Listing
January 2021

Methodological Consideration on Monitoring Refractory Intracranial Hypertension and Autonomic Nervous System Activity.

Acta Neurochir Suppl 2021 ;131:211-215

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

Refractory intracranial hypertension (RIH) refers to a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment and leads to patient death. Detrimental sequelae of raised ICP in acute brain injury (ABI) are unclear because the underlying physiopathological mechanisms of raised ICP have not been sufficiently investigated. Recent reports have shown that autonomic activity is altered during changes in ICP. The aim of our study was to evaluate the feasibility of assessing autonomic activity during RIH with our adopted methodology. We selected 24 ABI patients for retrospective review who developed RIH. They were monitored based on ICP, arterial blood pressure, and electrocardiogram using ICM+ software. Secondary parameters reflecting autonomic activity were computed in time and frequency domains through the continuous measurement of heart rate variability and baroreflex sensitivity. The results of the analysis will be presented later in a full paper. This preliminary analysis shows the feasibility of the adopted methodology.
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http://dx.doi.org/10.1007/978-3-030-59436-7_41DOI Listing
January 2021

Spectral Cerebral Blood Volume Accounting for Noninvasive Estimation of Changes in Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:193-199

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

We present the application of a new method for non-invasive cerebral perfusion pressure estimation (spectral nCPP or nCPP) accounting for changes in transcranial Doppler-derived pulsatile cerebral blood volume. Primarily, we analysed cases in which CPP was changing (delta [∆],magnitude of changes]): (1) rise during vasopressor-induced augmentation of ABP (N = 16); and (2) spontaneous changes in intracranial pressure (ICP) during plateau waves (N = 14). Secondarily, we assessed nCPP in a larger cohort in which CPP presented a wider range of values. The average correlation in the time domain between CPP and nCPP for patients undergoing an induced rise in arterial blood pressure (ABP) was 0.95 ± 0.07. For the greater traumatic brain injury (TBI) cohort, this correlation was 0.63 ± 0.37. ∆ correlations between mean values of CPP and nCPP were 0.73 (p = 0.002) and 0.78 (p < 0.001) respectively for induced rise in ABP and ICP plateau wave cohorts. The area under the curve (AUC) for ∆CPP was of 0.71 with a 95% confidence interval of 0.54-0.88. To detect low CPP, AUC was 0.817 with a 95% confidence interval of 0.79-0.85. nCPP can reliably identify changes in direct CPP across time and the magnitude of these changes in absolute values. The ability to detect changes in CPP is reasonable but stronger for detecting low CPP, ≤70 mmHg.
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http://dx.doi.org/10.1007/978-3-030-59436-7_38DOI Listing
January 2021

Optimal Cerebral Perfusion Pressure Assessed with a Multi-Window Weighted Approach Adapted for Prospective Use: A Validation Study.

Acta Neurochir Suppl 2021 ;131:181-185

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

Background: Pressure reactivity index (PRx)-cerebral perfusion pressure (CPP) relationships over a given time period can be used to detect a value of CPP at which PRx shows the best autoregulation (optimal CPP, or CPPopt). Algorithms for continuous assessment of CPPopt in traumatic brain injury (TBI) patients reached the desired high yield with a multi-window approach (CPPopt_MA). However, the calculations were tested on retrospective manually cleaned datasets. Moreover, CPPopt false-positive values can be generated from non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP). Therefore, the algorithm robustness was improved, making it suitable for prospective bedside application (COGiTATE trial).

Objective: To validate the CPPopt revised algorithm in a large single-centre retrospective cohort of TBI patients.

Methods: 840 TBI patients were included. CPPopt yield, stability and ability to discriminate outcome groups were compared to CPPopt_MA and the Brain Trauma Foundation (BTF) guideline reference.

Results: CPPopt yield was lower than CPPopt_MA yield (85% and 90%, p < 0.001), but, importantly, with increased stability (p < 0.0001). The ∆(CPP-CPPopt) could distinguish the mortality and survival outcome (t = -6.7, p < 0.0001) with a statistical significance higher than the ∆CPP calculated with the guideline reference (CPP-60) (t = -4.5, p < 0.0001).

Conclusion: This study validates, on a large cohort of patients, the new algorithm proposed for prospective use of CPPopt as a CPP target at bedside.
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http://dx.doi.org/10.1007/978-3-030-59436-7_36DOI Listing
January 2021

Optimal Cerebral Perfusion Pressure Based on Intracranial Pressure-Derived Indices of Cerebrovascular Reactivity: Which One Is Better for Outcome Prediction in Moderate/Severe Traumatic Brain Injury?

Acta Neurochir Suppl 2021 ;131:173-179

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

Intracranial pressure (ICP)-derived indices of cerebrovascular reactivity (e.g., PRx, PAx, and RAC) have been developed to improve understanding of brain status from available neuromonitoring variables. These indices are moving correlation coefficients between slow-wave vasogenic fluctuations in ICP and arterial blood pressure. In this retrospective analysis of neuromonitoring data from 200 patients admitted with moderate/severe traumatic brain injury (TBI), we evaluate the predictive value of CPPopt based on these ICP-derived indices of cerebrovascular reactivity. Valid CPPopt values were obtained in 92.3% (PRx), 86.7% (PAX), and 84.6% (RAC) of the monitoring periods, respectively. In multivariate logistic analysis, a baseline model that includes age, sex, and admission Glasgow Coma Score had an area under the receiver operating curve of 0.762 (P < 0.0001) for dichotomous outcome prediction (dead vs. good recovery). When adding time/dose of CPP below CPPopt, all multivariate models (based on PRx, PAx, and RAC) predicted the dichotomous outcome measure, but additional value of the prediction was only significantly added by the PRx-based calculations of time spent with CPP below CPPopt and dose of CPP below CPPopt.
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http://dx.doi.org/10.1007/978-3-030-59436-7_35DOI Listing
January 2021

Patient's Clinical Presentation and CPPopt Availability: Any Association?

Acta Neurochir Suppl 2021 ;131:167-172

Department of Intensive Care, University Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: The 'optimal' CPP (CPPopt) concept is based on the vascular pressure reactivity index (PRx). The feasibility and effectiveness of CPPopt guided therapy in severe traumatic brain injury (TBI) patients is currently being investigated prospectively in the COGiTATE trial. At the moment there is no clear evidence that certain admission and treatment characteristics are associated with CPPopt availability (yield).

Objective: To test the relation between patients' admission and treatment characteristics and the average CPPopt yield.

Methods: Retrospective analysis of 230 patients from the CENTER-TBI high-resolution database with intracranial pressure (ICP) measured using an intraparenchymal probe. CPPopt was calculated using the algorithm set for the COGiTATE study. CPPopt yield was defined as the percentage of CPP monitored time (%) when CPPopt is available. The variables in the statistical model included age, admission Glasgow Coma Scale (GCS), gender, pupil response, hypoxia and hypotension at the scene, Marshall computed tomography (CT) score, decompressive craniectomy, injury severity score score and 24-h therapeutic intensity level (TIL) score.

Results: The median CPPopt yield was 80.7% (interquartile range 70.9-87.4%). None of the selected variables showed a significant statistical correlation with the CPPopt yield.

Conclusion: In this retrospective multicenter study, none of the selected admission and treatment variables were related to the CPPopt yield.
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http://dx.doi.org/10.1007/978-3-030-59436-7_34DOI Listing
January 2021

Usability of Noninvasive Counterparts of Traditional Autoregulation Indices in Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:163-166

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

The pressure reactivity index (PRx) and the pulse amplitude index (PAx) are invasively determined parameters that are commonly used to describe autoregulation following traumatic brain injury (TBI). Using a transcranial Doppler ultrasound (TCD) technique, it is possible to approximate cerebral arterial blood volume (CaBV) solely from cerebral blood flow velocities, and further, to calculate non-invasive markers of autoregulation. In this brief study, we aimed to investigate whether the estimation of relative CaBV with different models could describe the cerebrovascular reactivity of TBI patients. PRx, PAx and their non-invasive counterparts (nPRx and nPAx) were calculated retrospectively from data collected during the monitoring of TBI patients. CaBV, an essential parameter for the calculation of nPRx and nPAx, was determined with both a continuous flow forward (CFF) model-considering a non-pulsatile blood outflow from the brain-and a pulsatile flow forward (PFF) model, presuming a pulsatile outflow. We found that the estimated CaBV demonstrates good coherence with ICP and that nPRx and nPAx can describe cerebrovascular reactivity similarly to PRx and PAx. Continuous monitoring with TCD is difficult, so the usability of PRx and PAx is limited. However, they might become useful for clinicians in the near future owing to rapid advances in these technologies.
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http://dx.doi.org/10.1007/978-3-030-59436-7_33DOI Listing
January 2021

An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:143-147

Department of Intensive Care Medicine, University of Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.

Introduction: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy.

Methods: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used.

Results: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021.

Conclusion: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_29DOI Listing
January 2021

Arterial and Venous Cerebral Blood Flow Velocities in Healthy Volunteers.

Acta Neurochir Suppl 2021 ;131:131-134

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

Transcranial Doppler ultrasound (TCD) enables assessment of brain hemodynamics through insonation of cerebral arteries and veins. Few studies have investigated whether the normal ranges of flow velocities in both arterial and venous compartments may be affected by age and sex.The purpose of this study was to determine the normal blood flow velocities across different sex and age subgroups in a cohort of healthy volunteers by studying the middle cerebral arteries (MCAs) and the straight sinus (SS).A total of 122 healthy volunteers undergoing preanesthetic assessment were recruited at Galliera Hospital in Genoa, Italy. The cohort was stratified for sex (males and females) and for age (18-44 years, 45-64 years, and ≥65 years). Data on systolic, diastolic, and mean flow velocities (FVs, FVd, and FVm, respectively) in the MCA and peak venous flow velocity in the SS (FVVs) were collected from each volunteer.The arterial FVs and FVm were significantly higher in males than in females; FVs, FVm, FVd, and FVVs increased across the age spectrum, especially in the elderly female population.Our findings suggest that there are differences in cerebrovascular flow velocities due to age and sex, which may be correlated to hormonal variations during the lifespan.
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http://dx.doi.org/10.1007/978-3-030-59436-7_27DOI Listing
January 2021

Variability of the Optic Nerve Sheath Diameter on the Basis of Sex and Age in a Cohort of Healthy Volunteers.

Acta Neurochir Suppl 2021 ;131:121-124

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

Many studies have demonstrated that the optic nerve sheath diameter (ONSD) is a good indicator of intracranial pressure (ICP). There are uncertainties regarding the optimal ONSD threshold, considering age and sex differences in the healthy population, and these differences could lead to uncertainties in evaluation of ONSD in pathological conditions.The aim of this prospective observational study was to investigate if age and sex could influence ONSD in a cohort of healthy Italian volunteers recruited during preanesthetic assessment for low-risk surgical procedures.The population was stratified for sex (males versus females) and for age (18-44 years, 45-64 years, and ≥65 years). The axial and longitudinal ONSD diameters were measured by two trained investigators.A significant difference in ONSD between males and females was found (median 4.2 (interquartile range 3.9-4.6) versus 4.1 (interquartile range 3.6-4.2) mm, P = 0.01), and a positive correlation between ONSD and age was found (R = 0.50, P < 0.0001).It was concluded that ONSD increases with age and is significantly larger in the healthy male population. These discrepancies should be taken into consideration when ONSD measurement is performed.
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http://dx.doi.org/10.1007/978-3-030-59436-7_25DOI Listing
January 2021

Brain Multimodal Monitoring in Severe Acute Brain Injury: Is It Relevant to Patient Outcome and Mortality?

Acta Neurochir Suppl 2021 ;131:83-86

Department of Intensive Care Medicine, Centro Hospitalar e Universitário São João, Porto, Portugal.

Introduction: Advanced multimodal monitoring (MMM) of the brain is recommended as a tool to manage severe acute brain injury in intensive care units (ICUs) and prevent secondary lesions. The aim of this study was to determine if MMM has implications for patient outcome and mortality.

Methods: We analyzed data on 389 patients admitted with a subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI) to two general ICUs and one neurocritical care ICU (NCCU) between March 2014 and October 2016, and their subsequent outcomes.

Results: The study population consisted of 259 males and 130 females. Group 1, which comprised 69 patients with MMM admitted to the NCCU, was compared with group 2, which comprised patients managed without MMM. With the exceptions of the Simplified Acute Physiology Score (SAPS II) and Glasgow Coma Scale (GCS) scores, there were no differences between the two groups. Group 1 had significantly better outcomes at ICU discharge, at 28 days, and at 3 months, and also had a lower mortality rate (P < 0.05). When outcomes were adjusted for SAPS II scores, patients who had MMM had better outcomes (odds ratios 0.215 at ICU discharge, 0.234 at 28 days, 0.338 at 3 months, and 0.474 at 6 months) but no difference in mortality.

Conclusion: Use of MMM in patients with SAH or TBI is associated with better outcomes and should be considered in the management of these patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_18DOI Listing
January 2021

Effects of Cranioplasty After Decompressive Craniectomy on Neurological Function and Cerebral Hemodynamics in Traumatic Versus Nontraumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:79-82

Graduate Program in Medical Science, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

After decompressive craniectomy (DC), cranioplasty (CP) can help to normalize vascular and cerebrospinal fluid circulation besides improving the patient's neurological status. The aim of this study was to investigate the effects of CP on cerebral hemodynamics and on cognitive and functional outcomes in patients with and without a traumatic brain injury (TBI). Over a period of 3 years, 51 patients were included in the study: 37 TBI patients and 14 non-TBI patients. The TBI group was younger (28.86 ± 9.71 versus 45.64 ± 9.55 years, P = 0.0001), with a greater proportion of men than the non-TBI group (31 versus 6, P = 0.011). Both groups had improved cognitive outcomes (as assessed by the Mini-Mental State Examination) and functional outcomes (as assessed by the Barthel Index and Modified Rankin Scale) 90 days after CP. In the TBI group, the mean velocity of blood flow in the middle cerebral artery ipsilateral to the cranial defect increased between the time point before CP and 90 days after CP (34.24 ± 11.02 versus 42.14 ± 10.19 cm/s, P = 0.0001). In conclusion, CP improved the neurological status in TBI and non-TBI patients, but an increment in cerebral blood flow velocity after CP occurred only in TBI patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_17DOI Listing
January 2021

A Comparative Study of the Effects of Early Versus Late Cranioplasty on Cognitive Function.

Acta Neurochir Suppl 2021 ;131:75-78

Graduate Program in Medical Science, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Cranioplasty (CP) after decompressive craniectomy (DC) is associated with neurological improvement. We evaluated neurological recovery in patients who underwent late CP (more than 6 months after DC) in comparison with early CP. This prospective study of 51 patients investigated neurological function using the Addenbrooke's Cognitive Examination Revised (ACE-R), Mini-Mental State Examination (MMSE), Barthel Index (BI), and Modified Rankin Scale (mRS) prior to and after CP. Most patients with traumatic brain injury (74%) were young (mean age 33.4 ± 12.2 years) and male (33/51; 66%). There were general improvements in the patients' cognition and functional status, especially in the late-CP group. The ACE-R score increased from the time point before CP to 3 days after CP (51 ± 28.94 versus 53.1 ± 30.39, P = 0.016) and 90 days after CP (51 ± 28.94 versus 58.10 ± 30.43, P = 0.0001). In the late-CP group, increments also occurred from the time point before CP to 90 days after CP in terms of the MMSE score (18.54 ± 1.51 versus 20.34 ± 1.50, P = 0.003), BI score (79.84 ± 4.66 versus 85.62 ± 4.10, P = 0.028), and mRS score (2.07 ± 0.22 versus 1.74 ± 0.20, P = 0.015). CP is able to improve neurological outcomes even more than 6 months after DC.
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http://dx.doi.org/10.1007/978-3-030-59436-7_16DOI Listing
January 2021

Cerebrovascular Consequences of Elevated Intracranial Pressure After Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:43-48

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

We compared various descriptors of cerebral hemodynamics in 517 patients with traumatic brain injury (TBI) who had, on average, elevated (>23 mmHg) or normal (<15 mmHg) intracranial pressure (ICP). In a subsample of 193 of those patients, transcranial Doppler ultrasound (TCD) recordings were made. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), cerebral autoregulation indices based on TCD (the mean flow index (Mx; the coefficient of correlation between the the cerebral perfusion pressure CPP and flow velocity) and the autoregulation index (ARI)), and the pressure reactivity index (PRx) were compared between groups. We also analyzed the TCD-based cerebral blood flow (CBF) index (diastolic CBFV/mean CBFV), the spectral pulsatility index (sPI), and the critical closing pressure (CrCP). Finally, we also looked at brain tissue oxygenation (cerebral oxygen partial tension (PbtO)) in 109 patients. The mean cerebral perfusion pressure (CPP) was lower in the group with elevated ICP (p < 0.01), despite a higher mean arterial pressure (MAP) (p < 0.005) and worse autoregulation (as assessed with the Mx, ARI, and PRx indices), greater CrCP, a lower CBF index, and a higher sPI (all with p values of <0.001). Neither the mean CBFV nor PbtO reached significant differences between groups. Mortality in the group with elevated ICP was almost three times greater than that in the group with normal ICP (45% versus 17%). Elevated ICP affects cerebral autoregulation. When autoregulation is not working properly, the brain is exposed to ischemic insults whenever CPP falls.
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http://dx.doi.org/10.1007/978-3-030-59436-7_10DOI Listing
January 2021

Analysis of Cardio-Cerebral Crosstalk Events in an Adult Cohort from the CENTER-TBI Study.

Acta Neurochir Suppl 2021 ;131:39-42

Computer Laboratory, University of Cambridge, Cambridge, UK.

Objective: In a previous study, we observed the presence of simultaneous increases in intracranial pressure (ICP) and the heart rate (HR), which we denominated cardio-cerebral crosstalk (CC), and we related the number of such events to patient outcomes in a paediatric cohort. In this chapter, we present an extension of this work to an adult cohort from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study.

Methods: We implemented a sliding window algorithm to detect CC events. We considered subwindows of 10-min observations. If simultaneous increases of at least 20% in ICP and HR occurred with respect to the minimum ICP and HR values in the time windows, a CC event was detected. Correlation between the number of CC events and mortality was then obtained.

Results: The cohort consisted of 226 adults (aged 16-85 years). The number of CC events that were detected varied (mean 50, standard deviation 58). A point biserial correlation coefficient of -0.13 between mortality and CC was found. Although the correlation was weaker than that seen in the paediatric cohort (-0.30), the negative direction was replicated.

Conclusion: In this work, we first extracted CC events from ICP and HR observations of adult patients with traumatic brain injury and related the number of CC events to patient outcomes. Consistency with the previous results in the paediatric cohort was observed. The more crosstalk events occurred, the better the patient outcome was.
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http://dx.doi.org/10.1007/978-3-030-59436-7_9DOI Listing
January 2021

External Hydrocephalus After Traumatic Brain Injury: Retrospective Study of 102 Patients.

Acta Neurochir Suppl 2021 ;131:35-38

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

Introduction: External hydrocephalus (EH) refers to impairment of extra-axial cerebrospinal fluid flow with enlargement of the subarachnoid space (SAS) and concomitant raised intracranial pressure (ICP). It is often confused with a subdural hygroma and overlooked, particularly when there is no ventricular enlargement. In this study, we aimed to describe the epidemiology of EH in a large population of adults with traumatic brain injury (TBI).

Methods: This observational, retrospective cohort study was conducted in adult patients who were admitted with TBI to the Department of Clinical Neuroscience at Addenbrooke's Hospital (Cambridge, UK) over a period of 3 years (2014-2017). Patients were included in the study if they had ICP monitoring and at least three CT scans within the first 21 days to assess SAS evolution. Patients who underwent a decompressive craniectomy were excluded. SAS was assessed individually on each CT scan by two independent investigators. ICP data were analysed with ICM+ software (Cambridge Enterprise Ltd., Cambridge, UK). Short-term and 6-month outcomes were examined. The groups of patients with and without EH were compared.

Results: Of the 102 patients included in the study, 30.4% developed EH after a delay of 2.98 ± 2.4 days. The initial Glasgow Coma Scale (GCS) scores did not differ between patients with and without EH. Subarachnoid haemorrhage was found to be the main risk factor for EH. Patients with EH required a significantly longer period of mechanical ventilation (+6.9 days), were more likely to have a tracheostomy (55% versus 33%), and had a longer stay in the intensive care unit (+8.5 days). ICP was higher during the 48 h after diagnosis of EH than during the previous 48 h. EH survivors had a lower mean Glasgow Outcome Scale Extended (GOS-E) score (4.6 versus 5.9, P = 0.031) and were more likely to receive a permanent shunt for secondary hydrocephalus (17.4% versus 1.8%, odds ratio 7.1).

Conclusion: In adults with TBI, EH remains insufficiently understood and probably underdiagnosed. This study showed that it is a frequent complication of TBI, with significant clinical consequences.
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http://dx.doi.org/10.1007/978-3-030-59436-7_8DOI Listing
January 2021

Comparison of Two Intracranial Pressure Calculation Methods and Their Effects on the Mean Intracranial Pressure and Intracranial Pressure Dose.

Acta Neurochir Suppl 2021 ;131:31-33

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

This study compared two methods of calculating the intracranial pressure (ICP) in a patient: end-hour ICP and hour-averaged ICP. A total of 1060 patients with traumatic brain injury and a known clinical outcome were studied. For each patient, the end-hour ICP and hour-averaged ICP were calculated. The mean ICP and the ICP dose above 20 mmHg were evaluated using both calculation methods. The results for patients who survived and those who died were compared using a Student's t test. The average correlation between the end-hour and hour-averaged mean ICP was 0.747, indicating that the end-hour ICP method agrees moderately with the hour-averaged method. However, the comparison between surviving and dead patients did not present significant differences between ICP values averaged with these two different methods. The Student's t test gave similar results for both the mean ICP and ICP dose. The results suggest that the end-hour and hour-averaged methods have similar predictive power for patients' clinical outcome.
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http://dx.doi.org/10.1007/978-3-030-59436-7_7DOI Listing
January 2021