Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP >20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values.

It was recently found in traumatic brain injury (TBI) that ICP variability (ICPV) predicted favorable outcome. We hypothesized that ICPV may depend on intracranial compliance, unstable blood pressure and cerebral vasomotion. In this study, we aimed to further investigate the explanatory variables for ICPV and its relation to outcome. Data from 362 TBI patients were retrospectively analyzed day 2 to 5 post-injury. ICPV was evaluated in three ways. First, variability in the sub-minute time interval (similar to B waves) was calculated as the amplitude of the ICP slow waves using a bandpass filter, limiting the analysis to oscillations of 55 to 15 s (ICP AMP 55-15). The second and third ICPV measures were calculated as the deviation from the mean ICP averaged over 30 min (ICPV-30m) and 4 h (ICPV-4h), respectively. All ICPV measures were associated with a reduced intracranial pressure/volume state (high ICP and RAP) and high blood pressure variability in multiple linear regression analyses. Higher ICPV was associated with better pressure reactivity in the univariate, but not the multiple analyses. All ICPV measures were associated with favorable outcome in univariate analysis, but only ICP AMP 55-15 and ICPV-30m did so in the multiple logistic regression analysis. Higher ICPV can be explained by a reduced intracranial compliance and variations in cerebral blood volume due to the vessel response to unstable blood pressure. As ICP AMP 55-15 and ICPV-30m independently predicted favorable outcome, it may represent general cerebral vessel activity, associated with better cerebral blood flow regulation and less secondary insults.

(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for "non-invasive AND ICP AND (measurement OR monitoring)" and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.

Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.

Cognitive impairments have been reported in idiopathic intracranial hypertension; however, evidence supporting these deficits is scarce and contributing factors have not been defined. Using a case-control prospective study, we identified multiple domains of deficiency in a cohort of 66 female adult idiopathic intracranial hypertension patients. We identified significantly impaired attention networks (executive function) and sustained attention compared to a body mass index and age matched control group of 25 healthy female participants. We aimed to investigate how cognitive function changed over time and demonstrated that deficits were not permanent. Participants exhibited improvement in several domains including executive function, sustained attention and verbal short-term memory over 12-month follow-up. Improved cognition over time was associated with reduction in intracranial pressure but not body weight. We then evaluated cognition before and after a lumbar puncture with acute reduction in intracranial pressure and noted significant improvement in sustained attention to response task performance. The impact of comorbidities (headache, depression, adiposity and obstructive sleep apnoea) was also explored. We observed that body mass index and the obesity associated cytokine interleukin-6 (serum and cerebrospinal fluid) were not associated with cognitive performance. Headache severity during cognitive testing, co-morbid depression and markers of obstructive sleep apnoea were adversely associated with cognitive performance. Dysregulation of the cortisol generating enzyme 11β hydroxysteroid dehydrogenase type 1 has been observed in idiopathic intracranial hypertension. Elevated cortisol has been associated with impaired cognition. Here, we utilized liquid chromatography-tandem mass spectrometry for multi-steroid profiling in serum and cerebrospinal fluid in idiopathic intracranial hypertension patients. We noted that reduction in the serum cortisol:cortisone ratio in those undergoing bariatric surgery at 12 months was associated with improving verbal working memory. The clinical relevance of cognitive deficits was noted in their significant association with impaired reliability to perform visual field tests, the cornerstone of monitoring vision in idiopathic intracranial hypertension. Our findings propose that cognitive impairment should be accepted as a clinical manifestation of idiopathic intracranial hypertension and impairs the ability to perform visual field testing reliably. Importantly, cognitive deficits can improve over time and with reduction of intracranial pressure. Treating comorbid depression, obstructive sleep apnoea and headache could improve cognitive performance in idiopathic intracranial hypertension.

Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH). Methods: Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression. Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11-0.63 (p = 0.002); OR = 0.18, 0.04-0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15-0.63 (p = 0.001); OR 0.30, 95% CI 0.11-0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01). Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.

Compensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6 months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort.

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.

Intracranial pressure (ICP) is the pressure within the cranium. ICP rise compresses brain vessels and reduces cerebral blood delivery. Massive ICP rise leads to cerebral ischemia, but it is also known to produce hypertension, bradycardia and respiratory irregularities due to a sympatho-adrenal mechanism termed Cushing response. One still unresolved question is whether the Cushing response is a non-synaptic acute brainstem ischemic mechanism or part of a larger physiological reflex for arterial blood pressure control and homeostasis regulation. We hypothesize that changes in ICP modulates sympathetic activity. Thus, modest ICP increase and decrease were achieved in mice and patients with respectively intra-ventricular and lumbar fluid infusion. Sympathetic activity was gauged directly by microneurography, recording renal sympathetic nerve activity in mice and muscle sympathetic nerve activity in patients, and gauged indirectly in both species by heart-rate variability analysis. In mice (n = 15), renal sympathetic activity increased from 29.9 ± 4.0 bursts.s-1 (baseline ICP 6.6 ± 0.7 mmHg) to 45.7 ± 6.4 bursts.s-1 (plateau ICP 38.6 ± 1.0 mmHg) and decreased to 34.8 ± 5.6 bursts.s-1 (post-infusion ICP 9.1 ± 0.8 mmHg). In patients (n = 10), muscle sympathetic activity increased from 51.2 ± 2.5 bursts.min-1 (baseline ICP 8.3 ± 1.0 mmHg) to 66.7 ± 2.9 bursts.min-1 (plateau ICP 25 ± 0.3 mmHg) and decreased to 58.8 ± 2.6 bursts.min-1 (post-infusion ICP 14.8 ± 0.9 mmHg). In patients 7 mmHg ICP rise significantly increases sympathetic activity by 17%. Heart-rate variability analysis demonstrated a significant vagal withdrawal during the ICP rise, in accordance with the microneurography findings. Mice and human results are alike. We demonstrate in animal and human that ICP is a reversible determinant of efferent sympathetic outflow, even at relatively low ICP levels. ICP is a biophysical stress related to the forces within the brain. But ICP has also to be considered as a physiological stressor, driving sympathetic activity. The results suggest a novel physiological ICP-mediated sympathetic modulation circuit and the existence of a possible intracranial (i.e., central) baroreflex. Modest ICP rise might participate to the pathophysiology of cardio-metabolic homeostasis imbalance with sympathetic over-activity, and to the pathogenesis of sympathetically-driven diseases.

Glucocorticoids (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).

Intracranial pressure (ICP) monitoring is important in many neurosurgical and neurological patients. The gold standard for monitoring ICP, however, is via an invasive procedure resulting in the placement of an intraventricular catheter, which is associated with many risks. Several noninvasive ICP monitoring techniques have been examined with the hope to replace the invasive techniques. The goal of this paper is to provide an overview of all modalities that have been used for noninvasive ICP monitoring to date.

Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI.

Although the placement of an intraventricular catheter remains the gold standard method for the diagnosis of intracranial hypertension (ICH), the technique has several limitations including but not limited to its invasiveness. Current noninvasive methods, however, still lack robust evidence to support their clinical use. We aimed to estimate, as an exploratory hypothesis generating analysis, the discriminative power of four noninvasive methods to diagnose ICH. We prospectively collected data from adult intensive care unit (ICU) patients with subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage (IPH), and ischemic stroke (IS) in whom invasive intracranial pressure (ICP) monitoring had been placed. Measures were simultaneously collected from the following noninvasive methods: optic nerve sheath diameter (ONSD), pulsatility index (PI) using transcranial Doppler (TCD), a 5-point visual scale designed for brain Computed Tomography (CT), and two parameters (time-to-peak [TTP] and P2/P1 ratio) of a noninvasive ICP wave morphology monitor (Brain4Care[B4c]). ICH was defined as a sustained ICP > 20 mmHg for at least 5 min. We studied 18 patients (SAH = 14; ICH = 3; IS = 1) on 60 occasions with a mean age of 52 ± 14.3 years. All methods were recorded simultaneously, except for the CT, which was performed within 24 h of the other methods. The median ICP was 13 [9.8-16.2] mmHg, and intracranial hypertension was present on 18 occasions (30%). Median values from the noninvasive techniques were ONSD 4.9 [4.40-5.41] mm, PI 1.22 [1.04-1.43], CT scale 3 points [IQR: 3.0], P2/P1 ratio 1.16 [1.09-1.23], and TTP 0.215 [0.193-0.237]. There was a significant statistical correlation between all the noninvasive techniques and invasive ICP (ONSD, r = 0.29; PI, r = 0.62; CT, r = 0.21; P2/P1 ratio, r = 0.35; TTP, r = 0.35, p < 0.001 for all comparisons). The area under the curve (AUC) to estimate intracranial hypertension was 0.69 [CIs = 0.62-0.78] for the ONSD, 0.75 [95% CIs 0.69-0.83] for the PI, 0.64 [95%Cis 0.59-069] for CT, 0.79 [95% CIs 0.72-0.93] for P2/P1 ratio, and 0.69 [95% CIs 0.60-0.74] for TTP. When the various techniques were combined, an AUC of 0.86 [0.76-0.93]) was obtained. The best pair of methods was the TCD and B4cth an AUC of 0.80 (0.72-0.88). Noninvasive technique measurements correlate with ICP and have an acceptable discrimination ability in diagnosing ICH. The multimodal combination of PI (TCD) and wave morphology monitor may improve the ability of the noninvasive methods to diagnose ICH. The observed variability in non-invasive ICP estimations underscores the need for comprehensive investigations to elucidate the optimal method-application alignment across distinct clinical scenarios.

Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review.

Mechanical ventilation (MV) with positive end-expiratory pressure (PEEP) is commonly applied in patients with severe traumatic brain injury (sTBI). However, the individual responsiveness of intracranial pressure (ICP) to PEEP varies. Thus, identifying an indicator detecting ICP responsiveness to PEEP is of great significance. As central venous pressure (CVP) could act as an intermediary to transduce pressure from PEEP to ICP, we developed a new indicator, PICGap, representing the gap between baseline ICP and baseline CVP. The aim of the current study was to explore the relationship between PICGap and ICP responsiveness to PEEP.

The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats.

Idiopathic normal pressure hydrocephalus (iNPH) and late-onset idiopathic aqueductal stenosis (LIAS) are two forms of chronic adult hydrocephalus of different aetiology. We analysed overnight intracranial pressure (ICP) monitoring to elucidate ICP waveform changes characteristic for iNPH and LIAS to better understand pathophysiological processes of both diseases.

Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema/increased intracranial pressure modulated and single human pyramidal cell verified gene products identified here might be considered as novel pharmacological targets in cell type specific neuroprotection.

Elevated intracranial pressure (ICP) is observed in many brain disorders. Obesity has been linked to ICP pathogenesis in disorders such as idiopathic intracranial pressure (IIH). We investigated the effect of diet induced obesity (DIO) on ICP and clinically relevant sequelae. Rats were fed either a control or high fat diet. Following weight gain long term ICP, headache behavior, body composition and retinal outcome were examined. Post-hoc analysis of retinal histology and molecular analysis of choroid plexus and trigeminal ganglion (TG) were performed. DIO rats demonstrated raised ICP by 55% which correlated with the abdominal fat percentage and increased non-respiratory slow waves, suggestive of altered cerebral compliance. Concurrently, DIO rats demonstrated a specific cephalic cutaneous allodynia which negatively correlated with the abdominal fat percentage. This sensitivity was associated with increased expression of headache markers in TG. Additionally, DIO rats had increased retinal nerve fiber layer thickness in vivo associated with raised ICP with a subsequent post-hoc demonstration of neuroretinal degeneration. This study demonstrates for the first time that DIO leads to raised ICP and subsequent clinically relevant symptom development. This novel model of non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP such as IIH.