Intracranial Pressure Recordings Research Articles

P049 RENOVASCULAR HYPERTENSIVE RATS (2K1C) HAVE REDUCED INTRACRANIAL COMPLIANCE INDUCED BY RAISED VENTRICULAR VOLUME COMPARED TO NORMOTENSIVE RATS

Background and Objective: Intracerebroventricular (ICV) infusions of increased volumes of saline can be used to study intracranial compliance (ICC). Since the two-kidneys,1-clip (2K1C) rat model of renovascular hypertension has an enhanced baseline level of intracranial pressure (ICP), the present study aimed to verify the effect of ICV infusions of 0.15 M NaCl on ICP and ICC in 2K1C rats. Methods: Male Holtzman rats (180-210 g) were randomly separated to be normotensive (NT; sham surgery, n = 5) or with 2K1C (n = 5), done by a partial left renal artery occlusion. Six weeks after, rats were anaesthetized with urethane (1.2 g/kg body weight, i.v.), tracheostomized, placed under artificial ventilation, and had an ICP sensor and a needle inserted into the lateral ventricle for, respectively, ICP recording and ICV 0.15 M infusions (30, 60 and 90 μL, at 100 μL/min). There was a 20-minute interval between each infusion. ICC was calculated by the ratio of volume change to ICP change [ICC = ΔV (μL)/Δ ICP (mmHg)]. Results: Baseline MAP, ICP, and P2/P1 ratio of 2K1C rats (166 ± 6 mmHg; 15.7 ± 1.7 mmHg; 1.6 ± 0.1, respectively) were higher than the ones in NT rats (94 ± 5 mmHg; 10.1 ±1.4 mmHg; 0.7 ± 0.1 respectively; p<0.05 vs 2K-1C). ICV infusions induced increased ICP in 2K1C rats (19 ±0.5; 42 ±1.2 and 55 ±5.5 mmHg, vs NT: 8 ±0.6; 25 ±3.2 and 36 ± 4.9 mmHg, respectively at 30, 60 and 90 μL infusion; p<0.05). In addition, 2K1C rats presented a reduced ICC only at 30 μl infusion (5.6 ±1.4, vs NT: 11.4 ±0.9; p<0.05). Conclusions: These findings suggest that renovascular hypertension impairs ICC to the well-documented increase in ICP. Support: FAPESP, CNPq.

Hyperosmolar therapy response in traumatic brain injury: Explainable artificial intelligence based long-term time series forecasting approach

In the neurological intensive care setting implementing tier-based therapy, osmotic therapy serves as an intermediate approach for reducing intracranial pressure (ICP). However, discussions regarding quantitative and specific criteria for the maintenance and transition of treatment remain limited. This study proposes an explainable neural network forecasting of physiological responses after osmotic therapy administration for the purpose of treatment guidance. Recordings of arterial blood pressure and intracranial pressure were obtained from 107 patients with traumatic brain injury. To maintain adequate intracranial pressure, arterial blood pressure, and cerebral perfusion pressure, 20 % mannitol (100 ml; no. infusion, 3,571) and 11.3 % hypertonic saline (40 ml; no. infusion, 574) were administered. The LTSF-NLinear model was used to predict the target signal response for the subsequent 1 h. Six prediction models were derived by combining two agents (mannitol or hypertonic saline) and three target signals (mean arterial blood pressure, mean intracranial pressure and cerebral perfusion pressure). To validate the model’s robustness while considering patient heterogeneity, group (5)-fold cross-validation was implemented. To assess the predictive ability of the proposed model for adverse clinical events, binary classification of hypotension, intracranial hypertension, and cerebral hypoperfusion was performed. The overall function of the model was elucidated using linear weight visualization. Additionally, the DeepSHAP application allows for a detailed investigation of the prediction process for a single case. The relationship between response to osmotic therapy and patient outcomes was statistically significant. The proposed models achieved reasonable performance, with R2 score > 0.8 for physiological signal predictions and accuracy > 0.9 for event predictions. Through global explanation, the recent values of mean arterial blood pressure, mean intracranial pressure, and cerebral perfusion pressure of input signals significantly influenced physiological responses after osmotic treatment. In the context of local explanation (a single case), it was possible to determine how physiological state influenced the response. The proposed model is expected to provide objective and quantitative information on osmotherapy in neurological intensive care environments, enabling guidance for alternative and aggressive treatments. Thus, it can potentially aid in enhancing the prognosis of patients with traumatic brain injury and improving the clinical workflow. Moreover, the global and local explanations of the proposed model can provide valuable insights for future researchers.

Intracranial pulse pressure amplitude as an indicator of intracranial compliance: observations in symptomatic children with Chiari malformation type I.

Reduced intracranial compliance (ICC) may be an important factor in the pathophysiology of Chiari malformation type I (CM-I). However, direct measurement of ICC is controversial because of its invasiveness, particularly in children. Instead, ICC may be estimated from continuous measurements of intracranial pressure (ICP), where the metric mean wave amplitude (MWA) has been found to be more useful as a surrogate marker of ICC than mean ICP. This observational study investigated the distribution of MWA and mean ICP in symptomatic children with CM-I, as well as their association with clinical and radiological findings. From a consecutive series of children treated for CM-I at a single institution between 2006 and 2023, the authors analyzed ICP scores in those who underwent an overnight preoperative ICP recording in which MWA was calculated. Clinical and radiological data were retrieved from the patient records. Thirty-seven children (mean age 12.4 ± 3.6 years) with symptomatic CM-I were identified. From the overnight ICP measurements, the average MWA was 5.2 ± 1.3 mm Hg: 56% of children had an abnormal MWA (> 5 mm Hg) and 33% had a borderline MWA (4-5 mm Hg). In contrast, the average mean ICP was 9.7 ± 4.1 mm Hg: 8% of children had an abnormal mean ICP (> 15 mm Hg) and 41% had a borderline mean ICP (10-15 mm Hg). Thus, more children were found to have an abnormal MWA than an abnormal mean ICP (p < 0.001). MWA was significantly higher in the subgroup of children with medullary compression in the foramen magnum, as seen on MRI, than in those without (5.6 ± 1.0 mm Hg vs 4.7 ± 1.4 mm Hg, p = 0.03), whereas a similar difference was not observed for mean ICP (9.9 ± 4.6 mm Hg vs 9.7 ± 3.7 mm Hg, p = 0.889). In this cohort of symptomatic children with CM-I, MWA was more frequently abnormal than mean ICP, with a clinically significant discrepancy in half of the patients. Moreover, MWA was significantly higher in patients with medullary compression. Based on these findings, the authors' interpretation is that in children with CM-I, the ICC may be reduced, as indicated by increased MWA, even though the mean ICP is within normal thresholds.

Effect of Decompressive Craniectomy on Intracranial Pressure Waveforms and Vascular Reactivity: A Systematic Scoping Review.

Decompressive craniectomy (DC) primarily aims at decreasing intracranial pressure (ICP) by allowing for the brain tissue to expand. However, it is uncertain to what extent DC impacts the transmission of vasogenic slow waves and thus the validity and utility of the pressure reactivity index (PRx). The purpose of this systematically performed scoping review is to assess the current knowledge of the impact of DC on ICP waveforms and measures of vascular reactivity. This scoping review considered studies including patients over 18 years old suffering from acute brain injuries (ABIs), who underwent secondary DC and had a perioperative (pre/post-DC) recording of ICP or waveform analysis. A search was conducted in EMBASE, PubMed, Web of Science, Scopus, and Medline from November 2023 till January 2024, yielding 787 studies. Duplicated studies were automatically removed, and two researchers independently screened the remaining studies. After examining 586 titles and abstracts, 38 full-text studies were assessed for eligibility, and 4 studies were included in the final review. The review suggests that cerebrovascular reactivity and slow waves are altered after DC, with positive PRx values and reduced slow power. One study suggested that the nature of slow waves and interactions is on the whole largely preserved. However, the findings should be interpreted with caution due to methodological limitations and the low number of studies.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. Individualized limits of autoregulation were computed in 55 patients (mean age 38years, mean monitoring time 92h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14mm Hg to 79 ± 17mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6mm Hg to 21.9 ± 5.6mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60min after compared with before an intervention (11% vs. 23%, p = 0.05). Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

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.

Effects of caffeine on intracranial pressure and pain perception in freely moving rats.

Caffeine, a non-selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses. Female Sprague-Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120 mg/kg intraperitoneally) was given. In a second group (non-implanted), the acute effects of 30 mg/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross-over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus. A single dose of 30 mg/kg caffeine lowered the ICP by 35% at 165 min after administration (saline: 0.16 ± 0.9 vs caffeine: -1.18 ± 0.9 ΔmmHg, p = 0.0098) and lasted up to 12 h. Administration of 120 mg/kg caffeine showed a faster onset of decrease in ICP within 15 min by 50% (p = 0.0018) and lasted up to 12 h. The periorbital pain thresholds were higher after 1 h (saline: 224.6 ± 15.1 vs caffeine: 289.5 ± 8.7 g, p = 0.005) and lasted up to 5 h. Caffeine-treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR1 was found in the choroid plexus. This study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.

Pressure Time Dose as a Representation of Intracranial Pressure Burden and Its Dependency on Intracranial Pressure Waveform Morphology at Different Time Intervals.

Intracranial pressure (ICP) burden or pressure time dose (PTD) is a valuable clinical indicator for pending intracranial hypertension, mostly based on threshold exceedance. Pulse frequency and waveform morphology (WFM) of the ICP signal contribute to PTD. The temporal resolution of the ICP signal has a great influence on PTD calculation but has not been systematically studied yet. Hence, the temporal resolution of the ICP signal on PTD calculation is investigated. We retrospectively analysed continuous 48 h ICP recordings with high temporal resolution obtained from 94 patients at the intensive care unit who underwent neurosurgery due to an intracranial haemorrhage and received an intracranial pressure probe (43 females, median age: 72 years, range: 23 to 88 years). The cumulative area under the curve above the threshold of 20 mmHg was compared for different temporal resolutions of the ICP signal (beat-to-beat, 1 s, 300 s, 1800 s, 3600 s). Events with prolonged ICP elevation were compared to those with few isolated threshold exceedances. PTD increased for lower temporal resolutions independent of WFM and frequency of threshold exceedance. PTDbeat-to-beat best reflected the impact of frequency of threshold exceedance and WFM. Events that could be distinguished in PTDbeat-to-beat became magnified more than 7-fold in PTD1s and more than 104 times in PTD1h, indicating an overestimation of PTD. PTD calculation should be standardised, and beat-by-beat PTD could serve as an easy-to-grasp indicator for the impact of frequency and WFM of ICP elevations on ICP burden.

Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration.

Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

Glucocorticoids modify intracranial pressure in freely moving rats

BackgroundGlucocorticoids (GCs) are widely prescribed for a variety of inflammatory diseases, but they are also used to treat raised intracranial pressure (ICP) caused by trauma or oedema. However, it is unclear if GCs independently modulate ICP and if GCs are involved in normal ICP regulation. In this study, we aimed to assess the ICP modulatory effects of GCs and their molecular consequences on choroid plexus (CP).MethodsAdult female rats were implanted with telemetric ICP probes for physiological, continuous ICP recordings in a freely moving setup. Rats received prednisolone or vehicle via oral gavage in a randomized acute (24 h) ICP study. In a subsequent study rats received corticosterone or vehicle in drinking water for a 4-week chronic ICP study. CP were removed, and the expression of genes associated with cerebrospinal fluid secretion were assessed.ResultsA single prednisolone dose reduced ICP by up to 48% (P < 0.0001), where ICP was reduced within 7 h and was maintained for at least 14 h. Prednisolone increases ICP spiking (P = 0.0075) while not altering ICP waveforms. Chronic corticosterone reduces ICP by up to 44%, where ICP was lower for the entirety of the 4-week ICP recording period (P = 0.0064). ICP daily periodicity was not altered by corticosterone. Corticosterone ICP reduction was not accompanied by ICP spike differences or alteration in ICP spike periodicity. Chronic corticosterone treatment had modest effects on CP gene expression, lowering the expression of Car2 at CP (P = 0.047).ConclusionsGCs reduce ICP in both the acute and chronic setting to a similar degree. Moreover, GCs did not modify the diurnal rhythm of ICP, suggesting the diurnal variation of ICP periodicity is not under explicit control of GCs. ICP disturbances should be considered a consequence of GC therapy. Based on these experiments, GCs may have broader ICP therapeutic uses, but side effects must be taken into consideration.

Arterial and Intracranial Hypotension During and Following Exercise

Exercise induced arterial hypertension and post-exercise arterial hypotension (PEH) are well-described phenomena with direct impact on cerebral blood flow. Cerebral perfusion pressure is given by the difference between mean arterial pressure at brain-level (MAPbrain) and intracranial pressure (ICP), however, little is known about effects of moderate aerobic exercise on ICP. We hypothesize that moderate exercise does not increase ICP thereby facilitating the augmented cerebral blood flow and that a post-exercise decrease in ICP is a contributing mechanism to maintained cerebral blood flow during PEH.Non-invasive (N=14) and invasive (N=3) ICP recordings and cardiovascular parameters were measured upright and supine before, during, and after 30 minutes of seated moderate aerobic bicycle exercise. Exercise elevated MAPbrain from 68±4 to 82±7 mmHg (mean±SEM, P&lt;0.05) without elevating ICP, thus increasing CPP (72±3 to 87±6 mmHg, P&lt;0.05). Compared to before exercise, we found significant PEH with a decrease in MAPbrain of 5±3% (5 mmHg; P&lt;0.05), predominantly driven by a 26±5% (P&lt;0.0001) decrease in total peripheral resistance (TPR). Because post-exercise ICP decreased concomitantly by 58±20% (P&lt;0.0001) CPP remained unchanged. Recovery of ICP towards baseline was similarly correlated to TPR-recovery (R2=0.92, P&lt;0.001), all variables returned to baseline within one hour.Here, we show for the first time ICP during and following aerobic exercise and consequences for cerebral perfusion. Periodic PEH is cardio-vascular protective and has long-term benefits for hypertensive patients, here we suggest that post-exercise decreases in ICP could similarly be cerebo-protective and in part explain the long-term beneficial effects of exercise for cerebral health and cognition. This work was supported by NASA grant no 80NSSC19K0020 and the Novo Nordic Foundation grant no NNF15OC0019196 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Accuracy of Manual Intracranial Pressure Recording Compared to a Computerized High-Resolution System: A CENTER-TBI Analysis

BackgroundMonitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually on bedside charts; these data have been used in large observational and interventional trials. However, ICP and CPP may change rapidly and frequently, so data recorded in medical charts might underestimate actual ICP and CPP shifts. The aim of this study was to evaluate the accuracy of manual data annotation for proper capturing of ICP and CPP. For this aim, we (1) compared end-hour ICP and CPP values manually recorded (MR) with values recorded continuously by computerized high-resolution (HR) systems and (2) analyzed whether MR ICP and MR CPP are reliable indicators of the burden of intracranial hypertension and low CPP.MethodsOne hundred patients were included. First, we compared the MR data with the values stored in the computerized system during the first 7 days after admission. For this point-to-point analysis, we calculated the difference between end-hour MR and HR ICP and CPP. Then we analyzed the burden of high ICP (> 20 mm Hg) and low CPP (< 60 mm Hg) measured by the computerized system, in which continuous data were stored, compared with the pressure–time dose based on end-hour measurements.ResultsThe mean difference between MR and HR end-hour values was 0.02 mm Hg for ICP (SD 3.86 mm Hg) and 1.54 mm Hg for CPP (SD 8.81 mm Hg). ICP > 20 mm Hg and CPP < 60 mm Hg were not detected by MR in 1.6% and 5.8% of synchronized measurements, respectively. Analysis of the pathological ICP and CPP throughout the recording, however, indicated that calculations based on manual recording seriously underestimated the ICP and CPP burden (in 42% and 28% of patients, respectively).ConclusionsManual entries fairly represent end-hour HR ICP and CPP. However, compared with a computerized system, they may prove inadequate, with a serious risk of underestimation of the ICP and CPP burden.

Targeted temperature management and PbtO2 in traumatic brain injury

IntroductionTargeted Temperature Management (TTM) to normothermia is widely used in traumatic brain injury (TBI). We investigated the effects to of TTM to normothermia patients with TBI (GCS≤12) monitored with multimodality monitoring, to better understand the physiological consequences of this intervention. Research questionIn TBI patients cooled to normothermia and in which brain oxygenation deteriorates, are there changes in physiological parameters which are pertinent to brain oxygenation? Material and method102 TBI patients with continuous recordings of intracranial pressure (ICP) and brain oxygen tension (PbtO2) were studied retrospectively. Non-continuous arterial carbon dioxide (PaCO2) and oxygen (PaO2) tensions, and core body temperature (Tc) were added. PaO2 and PaCO2 were also corrected for Tc. Transitions from elevated Tc to normothermia were identified in 39 patients. The 8 h pre and post the transition to normothermia were compared. Data is given as median [IQR] or mean (SD). ResultsOverall, normothermia reduced ICP (12 [9–18] −11 [8–17] mmHg, p < 0.009) and Tcore (38.3 [0.3]-36.9 [0.4] oC, p < 0.001), but not PbtO2 (23.3 [16.6]-24.4 [17.2–28.7] mmHg, NS). Normothermia was associated with a fall in PbtO2 in 18 patients (24.5 [9.3] −20.8 [7.6] mmHg). Only in those with a fall in PbtO2 with cooling did ICP (15 [10.8–18.5] −12 [7.8–17.3] mmHg, p = 0.002), and temperature corrected PaCO2 (5.3 [0.5]- 4.9 [0.8] kPa, p = 0.001) decrease. Discussion and conclusionA reduction in PbtO2 was only present in the subgroup of patients with a fall in temperature corrected PaCO2 with cooling. This suggests that even modest temperature changes could result in occult hyperventilation in some patients. pH stat correction of ventilation may be an important factor to consider in future TTM protocols.

Treadmill locomotion in the American alligator (Alligator mississippiensis) produces dynamic changes in intracranial cerebrospinal fluid pressure

To examine the influence of movement on cerebrospinal fluid (CSF) dynamics, intracranial subdural pressure recordings were taken from sub-adult alligators (Alligator mississippiensis) locomoting on a treadmill. Pressure recordings documenting the cardiac, ventilatory, and barostatic influences on the CSF were in good agreement with previous studies. During locomotion the CSF exhibits sinusoidal patterns of pressure change that spanned a mean amplitude of 56 mm Hg, some 16 × the amplitude of the cardiac-linked pulsations. These sinusoidal CSF pulsations were closely linked to the locomotor kinematics, particularly the lateral oscillations of the alligator’s head. Data recorded from the freely moving alligators suggest that fluid inertia, body cavity pressures, and likely other factors all influence the CSF pressure. The clear relationship between movement and CSF pressure described in this study suggests that the paucity of studies examining human CSF dynamics during movement should be addressed.

Physiological Mechanisms and Significance of Intracranial B Waves.

ObjectiveRecently published studies have described slow spontaneous cerebral blood flow (CBF) and cerebrospinal fluid (CSF) oscillations measured by magnetic resonance imaging (MRI) as potential drivers of brain glymphatic flow, with a similar frequency as intracranial B-waves. Aiming to establish the relationship between these waveforms, we performed additional analysis of frequency and waveform parameters, of our previously published transcranial Doppler (TCD) and intracranial pressure (ICP) recordings of intracranial B waves, to compare to published MRI frequency measurements of CBF and CSF slow oscillations.Patients and MethodsWe analyzed digital recordings of B waves in 29 patients with head injury, including middle cerebral artery (MCA) flow velocity (FV), ICP, end tidal CO2, and arterial blood pressure (ABP). A subset of these recordings demonstrated high B wave activity and was further analyzed for parameters including frequency, interaction, and waveform distribution curve features. These measures were compared to published similar measurements of spontaneous CBF and CSF fluctuations evaluated using MRI.ResultsIn patients with at least 10% amplitude B wave activity, the MCA blood flow velocity oscillations comprising the B waves, had a maximum amplitude at 0.0245 Hz, and time derivative a maximum amplitude at 0.035 Hz. The frequency range of the B waves was between 0.6–2.3 cycles per min (0.011-0.038 Hz), which is in the same range as MRI measured CBF slow oscillations, reported in human volunteers. Waveform asymmetry in MCA velocity and ICP cycles during B waves, was also similar to published MRI measured CBF slow oscillations. Cross-correlation analysis showed equivalent time derivatives of FV vs. ICP in B waves, compared to MRI measured CBF slow oscillations vs. CSF flow fluctuations.ConclusionsThe TCD and ICP recordings of intracranial B waves show a similar frequency range as CBF and CSF flow oscillations measured using MRI, and share other unique morphological wave features. These findings strongly suggest a common physiological mechanism underlying the two classes of phenomena. The slow blood flow and volume oscillations causing intracranial B waves appear to be part of a cascade that may provide a significant driving force for compartmentalized CSF movement and facilitate glymphatic flow.

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

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

Intraoperative Measurement of Intracranial Pressure During Cranial Vault Remodeling in Children with Craniosynostosis.

Purpose In this study, we analyzed the utility of intracranial pressure (ICP) monitoring intraoperatively for deciding height reduction and need for cerebrospinal fluid (CSF) diversion during cranial vault remodeling in children with multisutural craniosynostosis (CS). Methods This is a retrospective observational study of children who underwent surgery for CS and ICP monitoring during surgery. The ICP was monitored using an external ventricular drainage catheter. The ICP monitoring was continued during the entire procedure. Results A total of 28 (19 boys) children with the involvement of two or more sutures underwent ICP monitoring during surgery. The commonest pattern of suture involvement was bicoronal seen in 16 (57.1%) children followed by pancraniosynostoses in eight (28.6%) cases. The mean opening ICP was 23 mm Hg, which dropped to 10.9 mm Hg after craniotomy. The ICP increased transiently to 19.5 mm Hg after height reduction, and the mean ICP at closure was 16.2 mm Hg. The ICP recordings helped in undoing the height reduction in two children and ventriculoperitoneal shunt after surgery in two children. Conclusions Intraoperative monitoring of ICP helps in deciding the type of cranial vault remodeling and the need for CSF diversion after surgery.

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

PurposeSlow vasogenic waves in arterial blood pressure (ABP), intracranial pressure (ICP) and cerebral blood flow velocity (FV) carry information on multiple brain homeostatic control mechanisms. This work presents an approach to evaluate causal relation between oscillatory modes of these signals as an alternative to time or frequency domain Granger analysis. MethodsForty-five patients with simultaneous recordings of ICP, ABP and FV during CSF infusion studies were examined retrospectively. Each time series was decomposed into ten intrinsic mode functions (IMFs) via Ensemble Empirical Mode Decomposition (EEMD) and, afterwards, Granger causality (GC) was computed. ResultsSlow waves of ICP, ABP and FV were reconstructed from mode functions IMF6-9 of each time series, covering a frequency range between 0.013 and 0.155 Hz. Most significant connections were from FV to ICP, being stronger during elevation of mean ICP during infusion study. No G-causality was found between any of the IMFs during the baseline phase. ConclusionNonlinearity and nonstationarity of the cerebral and systemic signals can be addressed using EEMD decomposition There is a causal influence of slow waves of FV on slow waves on ICP during the plateau phase of the infusion study for a frequency band between 0.095 and 0.155 Hz. This relationship is magnified during mild intracranial hypertension.

Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

BackgroundAfter traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.MethodsCollaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).ResultsTwenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.ConclusionsPatients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.