Cryptococcal meningoencephalitis (CME) is a major cause of death and disability, and intracranial hypertension is a leading, treatable contributor to mortality and neurologic sequelae. Across CME cohorts, markedly elevated cerebrospinal fluid (CSF) opening pressure is common and often occurs despite minimal ventriculomegaly or diffuse edema on neuroimaging. This review synthesizes clinical, microbiological, imaging, pathological, and experimental evidence to define priorities for mechanistic research. Intracranial pressure (ICP) physiology predicts that once intracranial compliance is exhausted, small volume changes can produce rapid pressure increases, making CSF dynamics central to many intracranial hypertension syndromes. In CME, the frequent, rapid improvement after therapeutic CSF drainage, followed by pressure re-accumulation, supports a CSF outflow-limited mechanism for ICP. Convergent observations, including correlations between opening pressure and fungal/capsular polysaccharide burden and postmortem localization of organisms and polysaccharide at candidate CSF efflux sites, support a model of increased CSF outflow resistance. Potential modifiers include cryptococcal phenotypes (e.g., capsule size/architecture, aggregation), host immune and osmotic states, and disruption of perivascular ("glymphatic") transport that may alter clearance and compliance. Alternative dominant mechanisms (e.g., mass effect, obstructive hydrocephalus, venous sinus thrombosis, or inflammatory edema in immune reconstitution inflammatory syndrome/post-infectious inflammatory response syndrome) likely account for a minority of cases but remain clinically important. Current ICP control relies on invasive CSF drainage, and empiric pharmacologic approaches have not translated well, meaning progress will depend on both clinical and basic science research that link fungal and host factors to ICP trajectories, quantify efflux-site burden, directly measure outflow resistance, and explore adjunctive therapeutics that address CSF efflux and fungal clearance.

After acute brain injuries, optimizing cerebral perfusion pressure (CPP) is critical for preventing secondary brain insults, yet current fixed CPP targets may not be ideal for all patients due to individual variability in cerebrovascular autoregulation (CA). The concept of"optimal CPP" (CPPopt) or "optimal mean arterial pressure" (MAPopt) identifies the specific pressure range where CA is most effective. The Pressure-Reactivity Index (PRx), derived from invasive intracranial pressure (ICP) and arterial blood pressure (ABP) monitoring, is a well-established means for assessing CA and MAPopt. This study aimed to investigate the ability of noninvasive surrogate ICP waveforms, specifically the P2/P1 ratio acquired using a cranial deformation sensor (B4C), to determine MAPopt in patients with acute brain injury, and to compare its efficacy with the established invasive PRx method. This paper provides a retrospective analysis of data from a multicenter prospective observational study of intensive care patients with severe brain injuries requiring invasive ICP monitoring. Continuous invasive ABP and ICP data were collected alongside noninvasive ICP waveforms using the B4C sensor. MAPopt was determined for each monitoring session using two methods: (1) the nadir of a polynomial regression curve fitted to PRx values (correlation between ICP and ABP) stratified by 1 mmHg MAP intervals, and (2) the nadir of a polynomial regression curve fitted to the noninvasive P2/P1 ratio, also stratified by MAP intervals. Repeated measures correlation was used to analyze their correspondence and P2/P1 ratio ranges within MAPopt limits, whereas Bland-Altman analysis for the methods agreement. A total of 114 patients were included in the study, 68% severe traumatic brain injury and 15% spontaneous subarachnoid hemorrhage. Analysis of optimal MAP for each session revealed a strong linear relationship between the MAPopt derived from the invasive PRx and the noninvasive P2/P1 ratio (r = 0.905, p<0.0001). Bland-Altman analysis demonstrated good agreement between the two methods, with a mean difference of+2.00 mmHg and 95% limits of agreement ranging from −9.87 mmHg to +13.86 mmHg. The noninvasive P2/P1 ratio, serving as a marker of intracranial compliance, may effectively and accurately infer the optimal systemic mean arterial pressure. A noninvasive neuromonitoring tool may enable personalized, bedside-guided therapeutic management, significantly widening the assessment of cerebrovascular autoregulation in critical care settings.

Intracranial compliance is influenced by sex in older adults.

The optimization of cerebral perfusion through individualized hemodynamic strategies has emerged as a relevant strategy in critical care. The brain4care (B4C) System offers a non-invasive method to monitor intracranial compliance (ICC) via the P2/P1 ratio, a marker of intracranial dynamics. This study evaluated the impact of ICC-guided management on clinical and economic outcomes. This retrospective observational study included 102 critically ill patients at the Intensive Care Unit (ICU) of Nove de Julho Hospital, São Paulo, Brazil. Fifty-one patients underwent ICC-guided mean arterial pressure (MAP) management using the B4C System; 51 received standard care. The primary outcome was ICU mortality. Secondary outcomes included 30-day readmission, ICU and total hospital length of stay (LOS), discharge disposition, and Glasgow Coma Scale at discharge. Exploratory outcomes included hospital-perspective cost consequences based on LOS and readmissions. ICC-guided management was associated with lower ICU mortality (5.88% vs. 37.25%, p = 0.0003) and fewer 30-day readmissions (12.50% vs. 38.70%, p = 0.014). ICU and total hospital LOS did not differ significantly between groups. Discharge home was more frequent in the ICC-guided group (58.8% vs. 27.5%). In an exploratory hospital-perspective cost-consequence analysis, readmission-related savings were estimated at USD $3,878 per patient, and LOS-related cost differences were reported as unit-cost impacts and interpreted cautiously given non-significant LOS differences. ICC-guided MAP management supported by the B4C System was associated with lower ICU mortality, fewer readmissions, and lower estimated costs. Prospective multicenter studies are needed to confirm these findings.

Traumatic brain injury (TBI) is a major cause of death and disability, but invasive intracranial pressure (ICP) monitoring is risky, and current non-invasive methods lack the resolution and reliability needed for continuous clinical use. We present a multidimensional, non-invasive single-electrode capacitance (SEC) sensing system for continuous TBI monitoring. Carbon-nanotube paper composite (CPC) electrodes detect regional ICP changes through permittivity variations driven by cerebrovascular pulsations, cerebrospinal fluid (CSF) thickness changes, and brain tissue microvibrations. Surrogate tissue model testing confirms sensitivity to CSF layer thickness, water layer height, vessel wall thickness, and vessel diameter. In vivo pig testing, we analyze the correlation between multisite SEC signals and ICP to identify potential novel sensing metrics. In TBI experiments, these metrics are further evaluated by examining dynamic, cross-hemispheric relationships using four SEC sensors to capture spatially resolved pathophysiology before and after injury. Statistical and machine-learning (ML) approaches are applied to derive novel digital markers and to estimate conventional indices of cerebral autoregulation and intracranial compliance from non-invasive features. Together, this wearable system enables portable, spatially resolved neurocritical monitoring across diverse clinical environments.

Understanding whether acupuncture can influence intracranial pressure (ICP) and cerebral hemodynamics remains a relevant and insufficiently explored question in contemporary neurovascular research. This editorial synthesizes early experimental observations with recent clinical and technological advances to reassess the cerebral effects of acupuncture from a modern perspective. Evidence from clinical studies indicates that acupuncture can alter cerebral blood flow velocity and regional perfusion, suggesting an interaction with cerebrovascular regulation beyond placebo-related mechanisms. Experimental models further support these findings by demonstrating improved cerebral perfusion, neuroprotection, and preservation of blood–brain barrier integrity following manual needle acupuncture or electroacupuncture stimulation. Recent advancements in non-invasive ICP monitoring, multimodal neurovascular assessment, and computational modelling enable a more precise evaluation of subtle changes in pressure and flow than was previously possible. Although definitive clinical data on sustained or therapeutic ICP modulation remain limited, the reproducibility of cerebral physiological responses highlights the importance of careful monitoring, particularly in patients with altered autoregulation or reduced intracranial compliance. Revisiting early acupuncture research with contemporary methodologies may enhance safety assessments and help define the role of acupuncture as a neuromodulatory intervention with effects on cerebral physiology.

Transcranial Photobiomodulation Ameliorates Cerebrovascular and Meningeal Lymphatic Dysfunction after Repetitive Concussion: A Multimodal Optical Study in Mice.

Beyond pressure: intracranial compliance and retinal biomarkers in idiopathic normal pressure hydrocephalus

Spaceflight and ground-based models cause fluidshift to the upper part of the body, especially the head. Intracranial compliance (ICC) and cardiovascular autonomic modulation (CAM) can be impacted, impairing cerebral blood flow. ICC is poorly explored but important for astronauts’ health. Also, microgravity can reduce brain activity and affect cerebral functions. Fluidshift models are relevant for understanding its effects and the most used one is head-down tilt (HDT). Thus, this study aimed to investigate the immediate effects of HDT at -6º and − 15º on ICC, CAM and brain oscillations in healthy individuals. Sixty-one subjects (22 females) participated in the study (age 32.7 ± 6.2 years). The 30-minute HDT protocol was performed at -6º and − 15º. ICC was assessed non-invasively through the strain gauge sensor, from brain4care system, along with CAM and cortical activity during cognitive and motor tests. Participants had an increase in the ICP P2/P1 ratio when comparing pre and HDT at -6º (p = 0.004) and a trend toward elevation at -15º (p = 0.058). The sympathetic component of CAM was predominant in both HDT, and brain oscillations were reduced in most tests. The study suggests that acute HDT can reduce ICC, altering sympathovagal balance and causing cortical inhibition.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26319-z.

This review synthesizes recent advancements in understanding intracranial compliance (ICC) pathophysiology, explores novel monitoring techniques, and discusses their evolving clinical implications. We highlight how a shift from static intracranial pressure (ICP) thresholds to dynamic ICC assessment is transforming the management of acute brain injury. ICC is the brain's ability to accommodate volume changes without significant ICP elevation, is a critical determinant of outcome in neurocritical care. The paradigm in ICC is evolving from a focus on absolute ICP values to a dynamic, continuous assessment of the brain's compensatory capacity. Emerging concepts extend the classical Monro-Kellie doctrine, incorporating the dynamic roles of cerebrospinal fluid circulation, including the glymphatic system, in maintaining intracranial homeostasis. Integrating new pathophysiological insights with advanced monitoring tools holds immense potential to refine clinical decision-making, enabling more proactive and personalized interventions, ultimately improving outcomes for patients with acute brain injury. To achieve such goal, both invasive and noninvasive advanced monitoring techniques now provide real-time insights into ICC status. ICP waveform analysis offers granular information on compensatory reserve and cerebral autoregulation. Noninvasive methods, such as cranial micro-deformation sensors and transcranial Doppler-derived parameters offer accessible bedside assessment. These tools, alongside others such as optic nerve sheath ultrasound and pupillometry, facilitate earlier detection of decompensation, guide individualized therapy and improve prognostication.

Venous sinus stenting (VSS) has emerged as an effective treatment for selected patients with idiopathic intracranial hypertension (IIH) who fail maximal medical therapy. With its expanding adoption, recognition of rare but catastrophic complications is essential. We present the case of a 21‐year‐old female with IIH who failed medical treatment and was found to have bilateral stenosis at transverse‐sigmoid sinus junction with manometry showing 12 mmHg and 13 mmHg pressure gradients on the left and right side respectively. A stent was deployed in the right transverse‐sigmoid sinus with successful reduction of pressure gradient to 4 mmHg. Intraoperative EEG and somatosensory evoked potentials (SSEPs) remained normal throughout the procedure. Following a technically successful procedure, upon awakening from general anesthesia, the patient was unresponsive, with non reactive pinpoint pupils, absent vestibulo‐ocular reflexes, and extensor posturing in all four extremities. Emergent flat panel CT didn’t reveal acute intracranial hemorrhage, and neither did a helical head CT, but acute cerebellar tonsillar herniation and basal cistern effacement with mild supratentorial hydrocephalus was noted. CTA confirmed stent patency, but showed hypoenhancement of vertebrobasilar system relative to anterior circulation, suggesting regional impairment in cerebral perfusion pressure (CPP). Repeat neurophysiological monitoring following minimal brain activity on clinical exam, 15‐30 min after the previous recording, revealed profoundly suppressed EEG and SSEP's. IV Mannitol was administered and repeat digital subtraction angiography (DSA) confirmed stent patency without in‐stent stenosis and no increased ICP or pressure gradient across the stent. After the second DSA, the patient started following simple commands, and was extubated. Her exam was remarkable for bilateral CN VI palsy with direction beating horizontal and vertical nystagmus, subtle right facial droop, as well as right sided drift, bilateral Hoffman's and sustained ankle clonus. Subsequent CT revealed improved patency of basal cisterns and re‐expansion of temporal horns, but showed new hyperattenuations in the interpeduncular cistern, tentorial leaflets, and falx concerning for subdural hemorrhage (SDH), as well as sulcal hyperdensities concerning for subarachnoid hemorrhage (SAH). MRI showed no acute ischemia. Within the next day, despite the new hemorrhagic findings, symptoms had largely resolved, except for persistent midline ataxia. This case highlights a rare but serious constellation of complications following VSS for IIH, including acute spontaneous cerebellar tonsillar herniation, transient brainstem dysfunction, and subsequent SDH and SAH. Rapid hemodynamic shifts and altered intracranial venous compliance in patients with longstanding venous hypertension may precipitate hydrocephalus and tonsillar herniation. Elevated posterior fossa pressure can in turn compromise vertebrobasilar CPP, providing a plausible explanation for the transient neurological decline. Potential mechanisms include acute intracranial hypotension, or transient venous outflow obstruction of the vein of Labbé at the stented site, either from the stent construct itself or acute thrombosis. Intracranial hypotension after pressure reduction might ultimately have caused tonsillar herniation with consequent tearing of fragile bridging veins resulting in SAH and SDH that appeared on subsequent imaging. This case underscores the importance of vigilant multidisciplinary post‐stenting monitoring. Timely identification and intervention is the difference between irreversible brain injury and full recovery as in this case.

The diagnosis of normal-pressure hydrocephalus (NPH) can be challenging, particularly distinguishing between shunt-responsive and non-responsive patients. Overlapping clinical symptoms with aging and neurodegenerative diseases such as Alzheimer's and Parkinson's may hinder its diagnosis. Thus, more effective diagnostic tools are necessary To compare non-invasive techniques, such as electroencephalography (EEG), transcranial Doppler (TCD), intracranial compliance (ICC) measurement, and optical coherence tomography (OCT), with invasive procedures, such as lumbar puncture (LP) and infusion tests (IT), in the prediction of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus (iNPH). A systematic search of PubMed, Embase, and the Cochrane Library from 2013 to March 2023 identified studies that evaluated both invasive procedures (e.g., LP, IT) and non-invasive methods (e.g., EEG, TCD, ICC, OCT). Ten studies including 401 elderly patients with iNPH were analyzed. EEG biomarkers consistently differentiated responders, with three reproducible patterns: decreased frontal theta/delta power, increased temporal gamma power (sensitivity 83%, specificity 88%), and alpha rhythm normalization. Non-responders showed persistent slow delta waves in the frontal region and beta asymmetry. TCD revealed a 20% increase in the middle cerebral artery flow velocity after cerebrospinal fluid withdrawal in responders, correlating with motor improvement. OCT showed thinner ganglion cell layers in responders, while ICC suggested changes in brain compliance. Combined, these biomarkers may contribute to a more comprehensive predictive framework. While promising, non-invasive iNPH biomarkers remain insufficiently validated. No non-invasive test currently matches the reliability of invasive methods, which continue to represent the gold standard. Long-term data are lacking, and these tools should be considered as complementary rather than replacements for standard diagnostics.

Background: Cerebrospinal fluid (CSF) shunting remains a crucial intervention in the treatment of paediatric hydrocephalus. Overdrainage syndrome is a well-recognised but potentially severe complication, in which hyperostosis cranii ex vacuo—diffuse thickening of the cranial bones—emerges as an adaptive response to chronic intracranial hypotension. Currently, no established diagnostic criteria exist to reliably identify and classify this phenomenon, nor are there defined strategies to prevent associated complications of reduced intracranial compliance. Objective: This study aimed to characterise the morphoradiological and clinical phenotype of hyperostosis cranii ex vacuo in paediatric patients with long-term shunt dependency and to propose its classification as a fifth subtype of CSF overdrainage syndrome with direct implications for long-term neurosurgical care. Methods: A retrospective observational study was conducted on nine paediatric patients with radiologically confirmed diffuse calvarial thickening secondary to surgical treatment of hydrocephalus. Quantitative morphometric analysis of frontal, parietal, and occipital bones, sella turcica dimensions, and dural enhancement was performed using high-resolution neuroimaging. Clinical records were reviewed for hydrocephalus aetiology, shunt revision history, and neurological impairment. Results: All patients exhibited a mean two-fold increase in age-adjusted calvarial thickness. Premature craniosynostosis was identified in 33.3% of cases. Diffuse pachymeningeal enhancement was noted in all patients with contrast-enhanced imaging. Neurological comorbidities included epilepsy, spastic paraparesis, and features of Chiari type I malformation. Conclusions: Hyperostosis cranii ex vacuo represents a distinct and underrecognised consequence of chronic CSF overdrainage. We propose preliminary diagnostic criteria and a structured management pathway—from radiological recognition through ICP assessment to tiered surgical intervention. Formal recognition of this entity as a fifth subtype of CSF overdrainage syndrome may enhance early diagnosis, improve risk stratification, and guide long-term surveillance of shunted children.

Intracranial pressure (ICP) monitoring is widely used in the management of patients with traumatic brain injury (TBI). The morphology of the ICP waveform is considered to provide valuable insights into cerebrospinal compliance. This paper proposes a topological data analysis (TDA)-based methodology for ICP morphological analysis. About 1.2 million ICP waveforms from 60 TBI patients are utilized to construct a data map. This map is used for near real-time ICP morphology classification, subpeak identification, and big data visualization. The method allows ICP morphology class labels and subpeak labels annotated by SMEs on a subset of representative waveforms to quickly propagate to millions of unlabeled waveforms, which significantly reduces labelling effort. The proposed visualization allows the overlay of various ICP morphological features (e.g. P2/P1 ratio, ICP peak pressure) to provide insights into patients' physiological condition. The method is validated on 10,000 ICP waveforms from 10 patients, achieving an overall waveform classification accuracy of 96.1% and subpeak identification accuracy of 97.3%. The proposed method can track subtle changes in ICP waveform morphology, offering insight into evolving intracranial compliance beyond mean ICP values. By enabling real-time, interpretable monitoring, the method provides a tool to support individualized management and early intervention in TBI patient care.

Hypertension and intracranial hypertension are associated with distinct clinical contexts, encompassing both neurological and cardiovascular implications. Hypertension induces significant structural and functional alterations in cerebral arteries, such as vascular wall thickening, increased arterial stiffness, reduced vascular compliance, and endothelial dysfunction, all of which can contribute to elevated intracranial pressure. These vascular changes may impair the integrity of the blood-brain barrier and disrupt cerebral autoregulation, thereby diminishing the brain's ability to effectively regulate cerebral blood flow in response to physiological demands. The persistence of these dysfunctions over time may increase the risk of neurological outcomes, including stroke, cerebral edema, and cognitive impairment. Intracranial hypertension in turn may remain subclinical in patients with chronic hypertension, particularly when there is a gradual loss of intracranial compliance. This potential link highlights the need for further studies on the topic. Emerging evidence points to advances in noninvasive techniques for intracranial hypertension assessment, which may enable the early identification of altered intracranial dynamics and promote broader clinical application. Although the association between hypertension and intracranial hypertension has not yet been fully elucidated, the literature suggests overlapping mechanisms that may be clinically relevant. Combined assessment of blood pressure and intracranial parameters could represent a complementary strategy for better understanding cerebrovascular risk in selected populations. In this narrative review, we discuss the potential association between hypertension and intracranial hypertension, emphasizing their pathophysiological connections, contributing risk factors, and potential consequences for brain structure and function. Further research is needed to clarify these associations and their implications in clinical practice.

Each heartbeat generates a cardiac pressure wave that propagates through the brain and travels from large arteries through cerebrospinal fluid and brain tissue, compressing the venous sinuses and producing venous blood pulsatility. The delay between arterial and venous pulsation (A-V delay) is an insightful marker of intracranial compliance and the intracranial mechanical environment. We developed a novel approach to extract A-V delay from conventional resting-state functional MRI (fMRI) scans, leveraging fMRI’s sensitivity to vessel pulsations in large cerebral arteries and the superior sagittal sinus (SSS). This fully automated method was applied to the Human Connectome Project – Aging dataset to analyze 578 participants aged 35 to 90 years. The mean A-V delay was 78 ± 32 msec; it shortened by 4 msec for every decade of aging and was 12 msec faster in men than women, highlighting age-related and sex-specific differences. We also identified a within-SSS pattern of pulsations, characterized by an earlier posterior pulsation and a later anterior pulsation. This pattern opposes the direction of blood flow, supporting that the SSS is passively compressed and tied to a distinct intracranial pulse transmission. Overall, this work demonstrates the feasibility of extracting an fMRI-based A-V delay, uncovering a previously unexplored capability of fMRI. This approach broadens the potential applications of fMRI by adding a biomechanical dimension to fMRI’s established roles in evaluating neuronal and hemodynamic function. Given the widespread availability of fMRI, this approach can be applied in future studies to investigate biomechanical changes in various disease conditions.

Background: Cerebrospinal fluid (CSF) shunting remains a crucial intervention in the treatment of paediatric hydrocephalus. Overdrainage syndrome is a well-recognised but potentially severe complication, in which hyperostosis cranii ex vacuo-diffuse thickening of the cranial bones-emerges as an adaptive response to chronic intracranial hypotension. Currently, no established diagnostic criteria exist to reliably identify and classify this phenomenon, nor are there defined strategies to prevent associated complications of reduced intracranial compliance. Objective: This study aimed to characterise the morphoradiological and clinical phenotype of hyperostosis cranii ex vacuo in paediatric patients with long-term shunt dependency and to evaluate its classification as a distinct nosological entity within the spectrum of CSF overdrainage syndromes. Methods: A retrospective observational study was conducted on nine paediatric patients with radiologically confirmed diffuse calvarial thickening secondary to surgical treatment of hydrocephalus. Quantitative morphometric analysis of frontal, parietal, and occipital bones, sella turcica dimensions, and dural enhancement was performed using high-resolution neuroimaging. Clinical records were reviewed for hydrocephalus aetiology, shunt revision history, and neurological impairment. Results: All patients exhibited a mean two-fold increase in age-adjusted calvarial thickness. Premature craniosynostosis was identified in 33.3% of cases. Diffuse pachymeningeal enhancement was noted in all patients with contrast-enhanced imaging. Neurological comorbidities included epilepsy, spastic paraparesis, and features of Chiari type I malformation. Conclusion: Hyperostosis cranii ex vacuo represents a distinct and underrecognised consequence of chronic CSF overdrainage. Its formal classification as a fifth subtype of CSF overdrainage syndrome may improve diagnostic accuracy and inform long-term neurosurgical management in shunted paediatric populations.

Intracranial compliance (ICC) reflects the balance among intracranial volume components. Recent technological advances enable continuous, noninvasive assessment of ICC in neurocritical care settings. In this study, we aimed to correlate noninvasive ICC parameters derived from intracranial pressure (ICP) waveform morphology with the established amplitude-pressure index (RAP index), which is calculated using invasive ICP monitoring. Patients with traumatic brain injury underwent ventricular ICP monitoring. Simultaneously, ICP values and waveform characteristics were recorded using an external skull microdynamics sensor (brain4care) that provides surrogate waveform parameters, including the P2/P1 ratio and time-to-peak (TTP). The RAP index was calculated using dedicated software based on ICP values and pulse amplitude and was used to categorize patients into three groups: (1) adequate ICC, (2) compromised ICC, and (3) exhausted ICC. Noninvasive parameters (P2/P1 ratio and TTP) were then analyzed in relation to RAP index groupings. A total of 61 patients were included. Group 1 (adequate ICC) had a median ICP of 12.3 ± 5.4mm Hg, a P2/P1 ratio of 1.06 ± 0.3, and a TTP of 0.18 ± 0.09s. Group 2 (compromised ICC) had a median ICP of 13 ± 6.4mm Hg, a P2/P1 ratio of 1.15 ± 0.32, and a TTP of 0.23 ± 0.07s. Group 3 (exhausted ICC) had a median ICP of 19.45 ± 5.9mm Hg, a P2/P1 ratio of 1.31 ± 0.26, and a TTP of 0.25 ± 0.05s. Regression analysis revealed a statistically significant association between the noninvasive parameters and RAP index-based ICC classification (p < 0.0001). This study demonstrates a significant correlation between the RAP index and noninvasive ICP waveform-derived parameters, such as the P2/P1 ratio and TTP. These findings suggest that such noninvasive measures may serve as reliable indicators of ICC status. The critical ICP cut-off per RAP was 19.45 mmHg, below the current threshold for therapy escalation according to TBI guidelines. Although further prospective validation is required, this approach has the potential to facilitate earlier intervention before ICC deterioration and enable noninvasive monitoring, possibly improving outcomes in neurocritical care. NCT03144219. Registered 15 June 2017, http://www. gov/NCT03144219 . ClinicalTrials.gov identifier: NCT03144219.

Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive alternatives. This pilot study investigates a novel non-invasive method for monitoring ICP pulse waves through closed eyelids, using a specially designed, liquid-filled, fully passive sensor system named ‘Archimedes 02’. To our knowledge, this is the first technological approach that enables the non-invasive monitoring of ICP pulse waveforms via closed eyelids. This study involved 10 healthy volunteers, aged 26–39 years, who underwent resting-state non-invasive ICP pulse wave monitoring sessions using the ‘Archimedes 02’ device while in the supine position. The recorded signals were processed to extract pulse waves and evaluate their morphological characteristics. The results indicated successful detection of pressure pulse waves, showing the expected three peaks (P1, P2, and P3) in all subjects. The calculated P2/P1 ratios were 0.762 (SD = ±0.229) for the left eye and 0.808 (SD = ±0.310) for the right eye, suggesting normal intracranial compliance across the cohort, despite variations observed in some individuals. Physiological tests—the Valsalva maneuver and the Queckenstedt test, both performed in the supine position—induced statistically significant increases in the P2/P1 and P3/P1 ratios, supporting the notion that non-invasively recorded pressure pulse waves, measured through closed eyelids, reflect intracranial volume and pressure dynamics. Additionally, a transient hypoemic/hyperemic response test performed in the upright position induced signal changes in pressure recordings from the ‘Archimedes 02’ sensor that were consistent with intact cerebral blood flow autoregulation, aligning with established physiological principles. These findings indicate that ICP pulse waves and their dynamic changes can be monitored non-invasively through closed eyelids, offering a potential method for brain monitoring in patients for whom invasive procedures are not feasible.

ObjectiveEnlarged brain ventricles, compressed parasagittal cerebrospinal fluid spaces, steep callosal angle, dilated sylvian fissures and focal cortical sulcal dilatation are typical imaging features of idiopathic normal pressure hydrocephalus (iNPH). The pathophysiological mechanisms behind these morphological changes are poorly understood, but the hydrodynamic concepts of communicating hydrocephalus suggest that increased heartbeat related intracranial pulsations are involved in ventricular enlargement. In this cross-sectional study we analysed the association between the radiological findings of iNPH and the physiological intracranial pressure (ICP) waveform components.Methods117 patients with suspected iNPH underwent computerised overnight ICP monitoring with calculation of heartbeat related ICP pulse wave amplitude (calculated in the frequency domain, AMP, and time domain, MWA), amplitude of respiration induced ICP waves (RESP), power of slow vasogenic waves (SLOW), and index of cerebrospinal compensatory reserve (RAP). Radiological morphological data was recorded from computed tomography using Evans Index (EI), frontal occipital horn ratio (FOHR), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) score.ResultsThe strongest correlation was observed between SLOW and DESH (r = 0.44, p < 0.012). SLOW also correlated with ventricular size as measured with EI (r = 0.23, p = 0.045) and FOHR (r = 0.26, p = 0.037). ICP and RESP also correlated with DESH (r = 0.25, p = 0.037 and r = 0.25, p = 0.038, respectively). AMP and MWA were not correlated with the radiological data.ConclusionsMainly SLOW showed correlations with the morphological imaging features of iNPH. SLOW is influenced by vasomotion and intracranial compliance. This study suggests that the magnitude of ICP slow wave activity, but not ICP pulse component is related to the size of brain ventricles and DESH in iNPH.