Intracranial Pressure Pulse Amplitude Research Articles

Continuous monitoring methods of cerebral compliance and compensatory reserve: a scoping review of human literature.

Continuous monitoring of cerebrospinal compliance (CC)/ cerebrospinal compensatory reserve (CCR) is crucial for timely interventions and preventing more substantial deterioration in the context of acute neural injury, as it enables the early detection of abnormalities in intracranial pressure (ICP). However, to date, the literature on continuous CC/CCR monitoring is scattered and occasionally challenging to consolidate. 
Approach: 
We subsequently conducted a systematic scoping review of the human literature to highlight the available continuous CC/CCR monitoring methods.
Main Results:
This systematic review incorporated a total number of 76 studies, covering diverse patient types and focusing on three primary continuous CC or CCR monitoring metrics and methods - Moving Pearson's correlation between ICP pulse amplitude waveform (AMP) and ICP, referred to as RAP, the Spiegelberg Compliance Monitor, changes in cerebral blood velocity (CBV) with respect to the alternation of ICP measured through Transcranial Doppler (TCD), changes in centroid metric, high frequency centroid (HFC) or higher harmonics centroid (HHC), and the P2/P1 ratio which are the distinct peaks of ICP pulse wave (ICPW). The majority of the studies in this review encompassed RAP metric analysis (n=43), followed by Spiegelberg Compliance Monitor (n=11), TCD studies (n=9), studies on the HFC/HHC (n=5), and studies on the P2/P1 ratio studies (n=6). These studies predominantly involved acute traumatic neural injury (i.e. Traumatic Brain Injury (TBI)) patients and those with hydrocephalus. RAP is the most extensively studied of the five focused methods and exhibits diverse applications. However, most papers lack clarification on its clinical applicability, a circumstance that is similarly observed for the other methods.
Significance: Future directions involve exploring RAP patterns and identifying characteristics and artifacts, investigating neuroimaging correlations with continuous CC/CCR and integrating machine learning, holding promise for simplifying CC/CCR determination. These approaches should aim to enhance the precision and accuracy of the metric, making it applicable in clinical practice.&#xD.

Relationship between the shape of intracranial pressure pulse waveform and computed tomography characteristics in patients after traumatic brain injury

BackgroundMidline shift and mass lesions may occur with traumatic brain injury (TBI) and are associated with higher mortality and morbidity. The shape of intracranial pressure (ICP) pulse waveform reflects the state of cerebrospinal pressure–volume compensation which may be disturbed by brain injury. We aimed to investigate the link between ICP pulse shape and pathological computed tomography (CT) features.MethodsICP recordings and CT scans from 130 TBI patients from the CENTER-TBI high-resolution sub-study were analyzed retrospectively. Midline shift, lesion volume, Marshall and Rotterdam scores were assessed in the first CT scan after admission and compared with indices derived from the first 24 h of ICP recording: mean ICP, pulse amplitude of ICP (AmpICP) and pulse shape index (PSI). A neural network model was applied to automatically group ICP pulses into four classes ranging from 1 (normal) to 4 (pathological), with PSI calculated as the weighted sum of class numbers. The relationship between each metric and CT measures was assessed using Mann–Whitney U test (groups with midline shift > 5 mm or lesions > 25 cm3 present/absent) and the Spearman correlation coefficient. Performance of ICP-derived metrics in identifying patients with pathological CT findings was assessed using the area under the receiver operating characteristic curve (AUC).ResultsPSI was significantly higher in patients with mass lesions (with lesions: 2.4 [1.9–3.1] vs. 1.8 [1.1–2.3] in those without; p << 0.001) and those with midline shift (2.5 [1.9–3.4] vs. 1.8 [1.2–2.4]; p < 0.001), whereas mean ICP and AmpICP were comparable. PSI was significantly correlated with the extent of midline shift, total lesion volume and the Marshall and Rotterdam scores. PSI showed AUCs > 0.7 in classification of patients as presenting pathological CT features compared to AUCs ≤ 0.6 for mean ICP and AmpICP.ConclusionsICP pulse shape reflects the reduction in cerebrospinal compensatory reserve related to space-occupying lesions despite comparable mean ICP and AmpICP levels. Future validation of PSI is necessary to explore its association with volume imbalance in the intracranial space and a potential complementary role to the existing monitoring strategies.

Analysis of intracranial pressure pulse waveform in traumatic brain injury patients: a CENTER-TBI study.

Intracranial pressure (ICP) pulse waveform analysis may provide valuable information about cerebrospinal pressure-volume compensation in patients with traumatic brain injury (TBI). The authors applied spectral methods to analyze ICP waveforms in terms of the pulse amplitude of ICP (AMP), high frequency centroid (HFC), and higher harmonics centroid (HHC) and also used a morphological classification approach to assess changes in the shape of ICP pulse waveforms using the pulse shape index (PSI). The authors included 184 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Sub-Study in the analysis. HFC was calculated as the average power-weighted frequency within the 4- to 15-Hz frequency range of the ICP power density spectrum. HHC was defined as the center of mass of the ICP pulse waveform harmonics from the 2nd to the 10th. PSI was defined as the weighted sum of artificial intelligence-based ICP pulse class numbers from 1 (normal pulse waveform) to 4 (pathological waveform). AMP and PSI increased linearly with mean ICP. HFC increased proportionally to ICP until the upper breakpoint (average ICP of 31 mm Hg), whereas HHC slightly increased with ICP and then decreased significantly when ICP exceeded 25 mm Hg. AMP (p < 0.001), HFC (p = 0.003), and PSI (p < 0.001) were significantly greater in patients who died than in patients who survived. Among those patients with low ICP (< 15 mm Hg), AMP, PSI, and HFC were greater in those with poor outcome than in those with good outcome (all p < 0.001). Whereas HFC, AMP, and PSI could be used as predictors of mortality, HHC may potentially serve as an early warning sign of intracranial hypertension. Elevated HFC, AMP, and PSI were associated with poor outcome in TBI patients with low ICP.

Cerebrovascular Reactivity Is Not Associated With Therapeutic Intensity in Adult Traumatic Brain Injury: A Validation Study.

Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal-derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required.

Interpretation of telemetric intracranial pressure recordings in people with idiopathic intracranial hypertension after shunt implantation.

The M.scio telesensor (Aesculap-Miethke, Germany) is a device integrated within a ventriculoperitoneal (VP) shunt for non-invasive measurement of the intracranial pressure (ICP). The purpose of this study was to analyze the telemetric recordings with the M.scio system in shunted patients with idiopathic intracranial hypertension (IIH), in order to determine reference values and assist the interpretation of telemetric data. This was a cohort study of consecutive patients with fulminant IIH who underwent primary VP shunt insertion between July 2019 and June 2022. The first telemetric measurements after surgery in the sitting and supine positions were analyzed. Telemetric ICP values, wave morphology, and pulse amplitude were determined for functioning and malfunctioning shunts. Fifty-seven out of 64 patients had available telemetric recordings. The mean ICP was - 3.8mmHg (standard deviation (SD) = 5.9) in the sitting and 16.4mmHg (SD = 6.3) in the supine position. The ICP curve demonstrated pulsatility in 49 (86%) patients. A pulsatile curve with mean ICP in the above ranges indicated a functioning shunt, whereas the lack of pulsatility was challenging to interpret. There was a significant positive correlation between ICP versus amplitude, ICP versus body mass index (BMI), and amplitude versus BMI. This clinical study defined ICP values and curves in IIH patients with a shunt. The results will assist the interpretation of telemetric ICP recordings in clinical decision making. More research is required to model longitudinal recordings and explore the link between telemetric measurements with clinical outcomes.

Spindle wave in intracranial pressure signal analysis for patients with traumatic brain injury: A single-center prospective observational cohort study.

Objective: Intracranial pressure (ICP) monitoring is an integral part of the multimodality monitoring system in the neural intensive care unit. The present study aimed to describe the morphology of the spindle wave (a shuttle shape with wide middle and narrow ends) during ICP signal monitoring in TBI patients and to investigate its clinical significance. Methods: Sixty patients who received ICP sensor placement and admitted to the neurosurgical intensive care unit between January 2021 and September 2021 were prospectively enrolled. The patient's Glasgow Coma Scale (GCS) score on admission and at discharge and length of stay in hospital were recorded. ICP monitoring data were monitored continuously. The primary endpoint was 6-month Glasgow Outcome Scale-Extended (GOSE) score. Patients with ICP spindle waves were assigned to the spindle wave group and those without were assigned to the control group. The correlation between the spindle wave and 6-month GOSE was analyzed. Meanwhile, the mean ICP and two ICP waveform-derived indices, ICP pulse amplitude (AMP) and correlation coefficient between AMP and ICP (RAP) were comparatively analyzed. Results: There were no statistically significant differences between groups in terms of age (p = 0.89), gender composition (p = 0.62), and GCS score on admission (p = 0.73). Patients with spindle waves tended to have a higher GCS score at discharge (12.75 vs. 10.90, p = 0.01), a higher increment in GCS score during hospitalization (ΔGCS, the difference between discharge GCS score and admission GCS score) (4.95 vs. 2.80, p = 0.01), and a better 6-month GOSE score (4.90 vs. 3.68, p = 0.04) compared with the control group. And the total duration of the spindle wave was positively correlated with 6-month GOSE (r = 0.62, p = 0.004). Furthermore, the parameters evaluated during spindle waves, including mean ICP, AMP, and RAP, demonstrated significant decreases compared with the parameters before the occurrence of the spindle wave (all p < 0.025). Conclusion: The ICP spindle wave was associated with a better prognosis in TBI patients. Physiological parameters such as ICP, AMP, and RAP were significantly improved when spindle waves occurred, which may explain the enhancement of clinical outcomes. Further studies are needed to investigate the pathophysiological mechanisms behind this wave.

Intracranial Pressure Monitoring for Acute Brain Injured Patients: When, How, What Should We Monitor.

While there is no level I recommendation for intracranial pressure (ICP) monitoring, it is typically indicated for patients with severe traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score of 3-8 (class II). Even for moderate TBI patients with GCS 9-12, ICP monitoring should be considered for risk of increased ICP. The impact of ICP monitoring on patient outcomes is still not well-established, but recent studies reported a reduction of early mortality (class III) in TBI patients. There is no standard protocol for the application of ICP monitoring. In cases where cerebrospinal fluid drainage is required, an external ventricular drain is commonly used. In other cases, parenchymal ICP monitoring devices are generally employed. Subdural or non-invasive forms are not suitable for ICP monitoring. The mean value of ICP is the parameter recommended for observation in many guidelines. In TBI, values above 22 mmHg are associated with increased mortality. However, recent studies proposed various parameters including cumulative time with ICP above 20 mmHg (pressure-time dose), pressure reactivity index, ICP waveform characteristics (pulse amplitude of ICP, mean ICP wave amplitude), and the compensatory reserve of the brain (reserve-amplitude-pressure), which are useful in predicting patient outcomes and guiding treatment. Further research is required for validation of these parameters compared to simple ICP monitoring.

Head Elevation, Cerebral Venous System, and Intracranial Pressure: Review and Hypothesis

Background Facilitation of venous outflow from the brain is largely believed to be responsible for the beneficial effect of head elevation on intracranial pressure (ICP). However, the impact on cerebral perfusion pressure can be deleterious. Although the adverse effect of obstructing venous outflow in the setting of intracranial hypertension is well documented, the converse (improvement with augmented drainage) has not been demonstrated. Our hypothesis is that the effect of active augmentation of cerebral venous outflow on ICP, although unknown, could be potentially beneficial under conditions of intracranial hypertension. Methods Published literature was perused to ascertain known relationships between head elevation, ICP, cerebral perfusion pressure, and the cerebral venous system. Results Head elevation benefits ICP control in intracranial hypertension from improved venous outflow via various networks and craniospinal cerebrospinal fluid displacement; but patients on the severe spectrum have a high likelihood of experiencing cerebral perfusion pressure decline especially beyond 30°. In addition, the interaction between autoregulation, compliance, head elevation, ICP pulse amplitude, cerebral perfusion pressure, and ICP becomes increasingly dyssynchronous in the severely affected brain. Although the detrimental effects of obstructing venous drainage are well documented, the possibility of augmenting venous outflow by withdrawal of sagittal sinus blood has not been described previously. Conclusion There could exist a potential role for targeted sagittal sinus venous aspiration in favorably influencing control of increased ICP conditions, without significant risk to cerebral perfusion.

Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study.

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury.

We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2years of age or 8years of ageor more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2years or younger to less than 8years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

Epidural Oscillating Cardiac-Gated Intracranial Implant Modulates Cerebral Blood Flow.

We have previously reported a method and device capable of manipulating ICP pulsatility while minimally effecting mean ICP. To test the hypothesis that different modulations of the intracranial pressure (ICP) pulse waveform will have a differential effect on cerebral blood flow (CBF). Using an epidural balloon catheter attached to a cardiac-gated oscillating pump, 13 canine subjects underwent ICP waveform manipulation comparing different sequences of oscillation in successive animals. The epidural balloon was implanted unilaterally superior to the Sylvian sulcus. Subjects underwent ICP pulse augmentation, reduction and inversion protocols, directly comparing time segments of system activation and deactivation. ICP and CBF were measured bilaterally along with systemic pressure and heart rate. CBF was measured using both thermal diffusion, and laser doppler probes. The activation of the cardiac-gate balloon implant resulted in an ipsilateral/contralateral ICP pulse amplitude increase with augmentation (217%/202% respectively, P<.0005) and inversion (139%/120%, P<.0005). The observed changes associated with the ICP mean values were smaller, increasing with augmentation (23%/31%, P<.0001) while decreasing with inversion (7%/11%, P=.006/.0003) and reduction (4%/5%, P<.0005). CBF increase was observed for both inversion and reduction protocols (28%/7.4%, P<.0001/P=.006 and 2.4%/1.3%, P<.0001/P=.003), but not the augmentation protocol. The change in CBF was correlated with ICP pulse amplitude and systolic peak changes and not with change in mean ICP or systemic variables (heart rate, arterial blood pressure). Cardiac-gated manipulation of ICP pulsatility allows the study of intracranial pulsatile dynamics and provides a potential means of altering CBF.

The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis.

BackgroundIntravenous hypertonic saline is utilized commonly in critical care for treatment of acute or refractory elevations of intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Though there is a clear understanding of the general physiological effects of a hypertonic saline solution over long periods of time, smaller epoch effects of hypertonic saline (HTS) have not been thoroughly analyzed. The aim of this study was to perform a direct evaluation of the high-frequency response of HTS on the cerebrovascular physiological responses in TBI.MethodsWe retrospectively reviewed our prospectively maintained adult TBI database for those with archived high-frequency cerebral physiology and available HTS treatment information. We evaluated different epochs of physiology around HTS bolus dosing, comparing pre- with post-HTS. We assessed for changes in slow fluctuations in ICP, pulse amplitude of ICP (AMP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), cerebrovascular reactivity (as measured through pressure reactivity index (PRx)), and cerebral compensatory reserve (correlation (R) between AMP (A) and ICP (P)). Comparisons of mean measures and percentage time above clinically relevant thresholds for the physiological parameters were compared pre- and post-HTS using descriptive statistics and Mann-Whitney U testing. We assessed for subgroups of physiological responses using latent profile analysis (LPA).ResultsFifteen patients underwent 69 distinct bolus infusions of hypertonic saline. Apart from the well-documented decrease in ICP, there was also a reduction in AMP. The analysis of cerebrovascular reactivity response to HTS solution had two main effects. For patients with grossly impaired cerebrovascular reactivity pre-HTS (PRx > + 0.30), HTS bolus led to improved reactivity. However, for those with intact cerebrovascular reactivity pre-HTS (PRx < 0), HTS bolus demonstrated a trend towards more impaired reactivity. This indicates that HTS has different impacts, dependent on pre-bolus cerebrovascular status. There was no significant change in metrics of cerebral compensatory reserve. LPA failed to demonstrate any subgroups of physiological responses to HTS administration.ConclusionsThe direct decrease in ICP and AMP confirms that a bolus dose of a HTS solution is an effective therapeutic agent for intracranial hypertension. However, in patients with intact autoregulation, hypertonic saline may impair cerebral hemodynamics. These findings regarding cerebrovascular reactivity remain preliminary and require further investigation.Electronic supplementary materialThe online version of this article (10.1007/s00701-020-04579-0) contains supplementary material, which is available to authorized users.

Descriptive analysis of low versus elevated intracranial pressure on cerebral physiology in adult traumatic brain injury: a CENTER-TBI exploratory study

BackgroundTo date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP.MethodsThe Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP < 15 mmHg versus those with mean ICP > 20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts.Results185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p < 0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score.ConclusionsLow versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture.

Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. Multimodal neurologic monitoring data from the initial 3days after cerebral AVM rupture were retrospectively analyzed in children (< 18years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support.

Mechanisms behind altered pulsatile intracranial pressure in idiopathic normal pressure hydrocephalus: role of vascular pulsatility and systemic hemodynamic variables

BackgroundThe dementia subtype idiopathic normal pressure hydrocephalus (iNPH) has unknown etiology, but one characteristic is elevated intracranial pressure (ICP) wave amplitudes in those individuals who respond with clinical improvement following cerebrospinal fluid (CSF) diversion. To explore the mechanisms behind altered ICP wave amplitudes, we correlated central aortic blood pressure (BP) and ICP waveform amplitudes (intracranial aortic amplitude correlation) and examined how this correlation relates to ICP wave amplitude levels and systemic hemodynamic parameters.MethodsThe study included 29 patients with probable iNPH who underwent continuous multi-hour measurement of ICP, radial artery BP, and systemic hemodynamic parameters. The radial artery BP waveforms were used to estimate central aortic BP waveforms, and the intracranial aortic amplitude correlation was determined over consecutive 4-min periods.ResultsThe average intracranial aortic amplitude correlation was 0.28 ± 0.16 at the group level. In the majority of iNPH patients, the intracranial aortic amplitude correlation was low, while in about 1/5 patients, the correlation was rather high (average Pearson correlation coefficient > 0.4). The degree of correlation was hardly influenced by systemic hemodynamic parameters.ConclusionsIn about 1/5 iNPH patients of this study, the intracranial aortic amplitude correlation (IAACAORTIC) was rather high (average Pearson correlation coefficient > 0.4), suggesting that cerebrovascular factors to some extent may affect the ICP wave amplitudes in a subset of patients. However, in 14/19 (74%) iNPH patients with elevated ICP wave amplitudes, the intracranial aortic amplitude correlation was low, indicating that the ICP pulse amplitude in most iNPH patients is independent of central vascular excitation, ergo it is modulated by local cerebrospinal physiology. In support of this assumption, the intracranial aortic amplitude correlation was not related to most systemic hemodynamic variables. An exception was found for a subgroup of the patients with high systemic vascular resistance, where there was a correlation.

Alternative continuous intracranial pressure-derived cerebrovascular reactivity metrics in traumatic brain injury: a scoping overview.

Pressure reactivity index (PRx) has emerged as a means to continuously monitor cerebrovascular reactivity in traumatic brain injury (TBI). However, other intracranial pressure (ICP)-based continuous metrics exist, and may have advantages over PRx. The goal of this study was to perform a scoping overview of the literature on non-PRx ICP-based continuous cerebrovascular reactivity metrics in adult TBI. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2019. Using a two-stage filtering of title/abstract, and then full manuscript, we identified pertinent articles. Data was abstracted to tables and each technique summarized, including pulse amplitude index (PAx), correlation between pulse amplitude of ICP and cerebral perfusion pressure (RAC), PRx55-15, and low-resolution metrics LAx and L-PRx. A total of 23 articles met the inclusion criteria, with the vast majority being retrospective in nature and based out of European centers. Sixteen articles focused on high-resolution metrics PAx, RAC, and PRx55-15, with 6 articles focusing on LAx and L-PRx. PAx may have a role in low ICP situations, where it appears to perform superior to PRx. RAC displays similar behavior to PRx, with a trend to stronger associations with favorable/unfavorable outcome at 6months, and stronger parabolic relationship with CPP. PRx55-15 provides a focused assessment on the vasogenic frequency range associated with cerebral autoregulation, with preliminary data supporting a strong association with outcome in TBI. LAx and L-PRx display varying associations with 6-month outcome in TBI, depending on the window length of calculation, with shorter windows demonstrating stronger correlations with classical PRx. Non-PRx continuous ICP-based cerebrovascular reactivity metrics can be split into high-resolution and low-resolution measures. High-resolution indices include PAx, RAC, and PRx55-15, while low-resolution indices include L-PRx and LAx. The true role for these metrics beyond classic PRx remains unclear. Each displays situations where it may prove superior over PRx, given limitations with this currently widely accepted measure. Much future investigation into each of these alternative metrics is required prior to adoption into the clinical monitoring armamentarium in adult TBI.

Cerebrospinal fluid dynamics in non-acute post-traumatic ventriculomegaly

BackgroundPost-traumatic hydrocephalus (PTH) is potentially under-diagnosed and under-treated, generating the need for a more efficient diagnostic tool. We aim to report CSF dynamics of patients with post-traumatic ventriculomegaly.Materials and methodsWe retrospectively analysed post-traumatic brain injury (TBI) patients with ventriculomegaly who had undergone a CSF infusion test. We calculated the resistance to CSF outflow (Rout), AMP (pulse amplitude of intracranial pressure, ICP), dAMP (AMPplateau-AMPbaseline) and compensatory reserve index correlation coefficient between ICP and AMP (RAP). To avoid confounding factors, included patients had to be non-decompressed or with cranioplasty > 1 month previously and Rout > 6 mmHg/min/ml. Compliance was assessed using the elasticity coefficient. We also compared infusion-tested TBI patients selected for shunting versus those not selected for shunting (consultant decision based on clinical and radiological assessment and the infusion results). Finally, we used data from a group of shunted idiopathic Normal Pressure Hydrocephalus (iNPH) patients for comparison.ResultsGroup A consisted of 36 patients with post-traumatic ventriculomegaly and Group B of 45 iNPH shunt responders. AMP and dAMP were significantly lower in Group A than B (0.55 ± 0.39 vs 1.02 ± 0.72; p < 0.01 and 1.58 ± 1.21 vs 2.76 ± 1.5; p < 0.01. RAP baseline was not significantly different between the two. Elasticity was higher than the normal limit in all groups (average 0.18 1/ml). Significantly higher Rout was present in those with probable PTH selected for shunting compared with unshunted. Mild/moderate hydrocephalus, ex-vacuo ventriculomegaly/encephalomalacia were inconsistently reported in PTH patients.ConclusionsRout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus or atrophy reported on CT/MRI. Compliance appears reduced in PTH.

The Impact of Vasopressor and Sedative Agents on Cerebrovascular Reactivity and Compensatory Reserve in Traumatic Brain Injury: An Exploratory Analysis.

The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500 h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx <0 prior), a statistically significant increase in PRx was seen. However, this may not indicate deteriorating cerebrovascular reactivity as the final PRx (∼0.05) may still be considered to be intact cerebrovascular reactivity. As such, this finding with regards to propofol remains “weak.” This study indicates that commonly administered sedative and vasopressor agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity or compensatory reserve in TBI. These results should be considered preliminary, requiring further investigation.

Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients: an Exploratory Analysis

BackgroundFailure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.MethodsWe conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.ResultsWe observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.ConclusionsOur preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

Observations on the Cerebral Effects of Refractory Intracranial Hypertension After Severe Traumatic Brain Injury

BackgroundRaised intracranial pressure (ICP) is a prominent cause of morbidity and mortality after severe traumatic brain injury (TBI). However, in the clinical setting, little is known about the cerebral physiological response to severe and prolonged increases in ICP.MethodsThirty-three severe TBI patients from a single center who developed severe refractory intracranial hypertension (ICP > 40 mm Hg for longer than 1 h) with ICP, arterial blood pressure, and brain tissue oxygenation (PBTO2) monitoring (subcohort, n = 9) were selected for retrospective review. Secondary parameters reflecting autoregulation (including pressure reactivity index—PRx, which was available in 24 cases), cerebrospinal compensatory reserve (RAP), and ICP pulse amplitude were calculated.ResultsPRx deteriorated from 0.06 ± 0.26 a.u. at baseline levels of ICP to 0.57 ± 0.24 a.u. (p < 0.0001) at high levels of ICP (> 50 mm Hg). In 4 cases, PRx was impaired (> 0.25 a.u.) before ICP was raised above 25 mm Hg. Concurrently, PBTO2 decreased from 27.3 ± 7.32 mm Hg at baseline ICP to 12.68 ± 7.09 mm Hg at high levels of ICP (p < 0.001). The pulse amplitude of the ICP waveform increased with increasing ICP but showed an ‘upper breakpoint’—whereby further increases in ICP lead to decreases in pulse amplitude—in 6 out of the 33 patients.DiscussionSevere intracranial hypertension after TBI leads to decreased brain oxygenation, impaired pressure reactivity, and changes in the pulse amplitude of ICP. Impaired pressure reactivity may denote increased risk of developing refractory intracranial hypertension in some patients.