BACKGROUND: Mannitol is widely used in neurosurgical units to mitigate raised intracranial pressure and cerebral edema, crucial in postoperative management. Its hyperosmolar properties reduce brain extracellular fluid, thereby altering cerebral perfusion and cardiac dynamics. However, the temporal and combined effects of mannitol on cardiovascular and cerebrovascular parameters remain inadequately explored in postoperative settings.
METHODS: This prospective observational study enrolled 20 adult patients who underwent elective craniotomies for tumor excision. Mannitol was administered to the patients at a dose of 0.5 mg/kg/dose as a bolus dose over 20 to 30 minutes. The time interval was eight hours between the doses (scheduled dosing). Patients received their first dose of mannitol in the ICU after eight hours of intraoperative dose. The patients were given mannitol for two postoperative days and followed up for two days in the postoperative period. Transthoracic echocardiography and transcranial color Doppler were used to assess cardiovascular and cerebrovascular parameters at multiple intervals post-mannitol administration.
RESULTS: Significant increases in mean flow velocities were observed bilaterally immediately post-mannitol administration on the first postoperative day, indicative of improved cerebral blood flow. However, these changes were transient, with no significant variations noted on the second postoperative day. Cerebrovascular resistance, as measured by the pulsatility index, showed non-significant changes bilaterally across both days. Cardiovascular parameters, including stroke volume and cardiac output, remained stable throughout the study period.
CONCLUSIONS: Mannitol administration at 0.5 g/kg in postoperative neurosurgical patients transiently improves cerebral perfusion without causing significant hemodynamic instability. This study underscores the importance of monitoring both cerebrovascular and cardiovascular parameters post-mannitol administration to optimize patient management and outcomes.

UNASSIGNED: This study aimed to assess the impact of multimodal monitoring on predicting the prognosis of patients with spontaneous intracerebral hemorrhage (SICH) and to examine the feasibility of using noninvasive near-infrared spectroscopy (NIRS) for monitoring clinical prognosis.
UNASSIGNED: Clinical data of 38 patients with SICH who underwent surgery in the Department of Neurosurgery of Shaanxi Provincial People\'s Hospital from May 2022 to December 2022 were retrospectively analyzed. The patients were categorized into two groups based on the Glasgow Outcome Scale (GOS) 3 months after operation: poor outcome group (GOSI-III) and good outcome group (GOSIV and V). Multimodal monitoring included invasive intracranial pressure (ICP), brain temperature (BT), internal jugular venous oxygen saturation (SjvO2), and noninvasive NIRS. NIRS monitoring comprised the assessment of brain tissue oxygen saturation (StO2), blood volume index (BVI), and tissue hemoglobin index (THI). The prognostic differences between the two groups were compared. The predictive values were evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC).
UNASSIGNED: ICP, BT, BVI, and THI in the good prognosis group were lower than those in the poor prognosis group. The SjvO2 and StO2 in the group with a good prognosis were higher than those in the group with a poor prognosis.
UNASSIGNED: The levels of ICP, BT, SjvO2, StO2, BVI, and THI reflect the changes in brain function and cerebral blood flow and significantly correlate with the prognosis of patients with SICH. NIRS monitoring has a high clinical utility in assessing the prognosis.

UNASSIGNED: Numerous complex physiological models derived from intracranial pressure (ICP) monitoring data have been developed. More recently, techniques such as machine learning are being used to develop increasingly sophisticated models to aid in clinical decision-making tasks such as diagnosis and prediction. Whilst their potential clinical impact may be significant, few models based on ICP data are routinely available at a patient\'s bedside. Further, the ability to refine models using ongoing patient data collection is rare. In this paper we identify and discuss the challenges faced when converting insight from ICP data analysis into deployable tools at the patient bedside.
UNASSIGNED: To provide an overview of challenges facing implementation of sophisticated ICP models and analyses at the patient bedside.
UNASSIGNED: A narrative review of the barriers facing implementation of sophisticated ICP models and analyses at the patient bedside in a neurocritical care unit combined with a descriptive case study (the CHART-ADAPT project) on the topic.
UNASSIGNED: Key barriers found were technical, analytical, and integrity related. Examples included: lack of interoperability of medical devices for data collection and/or model deployment; inadequate infrastructure, hindering analysis of large volumes of high frequency patient data; a lack of clinical confidence in a model; and ethical, trust, security and patient confidentiality considerations governing the secondary use of patient data.
UNASSIGNED: To realise the benefits of ICP data analysis, the results need to be promptly delivered and meaningfully communicated. Multiple barriers to implementation remain and solutions which address real-world challenges are required.

UNASSIGNED: Intracranial pressure (ICP) monitoring is commonly used in investigating the aetiology of chronic paediatric neurological conditions. A series of high-amplitude spikes has been observed in overnight ICP recordings of some children, many of whom have hydrocephalus or craniosynostosis.
UNASSIGNED: This clinical evaluation aimed to define the spike pattern, describe the patient group in which it is most likely to occur, and conduct high-resolution waveform analysis.
UNASSIGNED: ICP waveforms from 40 patients aged 0-5 years (inclusive), recorded between 2017 and 2021 at the Royal Hospital for Children Glasgow, were retrospectively analysed. The pattern was defined through visual inspection of regions of interest by two reviewers. Patients were stratified using demographic and clinical data. R software was used to perform regression and high-resolution waveform analyses.
UNASSIGNED: The spike pattern was defined as the presence of 2 consecutive spikes with an amplitude of at least 8 mmHg, with a gap of at least 30 min between spikes. In the adjusted Poisson regression, age was significantly associated with the number of spikes (IRR 0.8, 95% CI 0.70 to 0.92, p-value 0.001).
UNASSIGNED: Younger age was significantly associated with an increased number of spikes in this cohort. Investigation of clinical consequences of the spikes is warranted.

Meningitis is a significant health concern globally, with enterovirus (EV) being the most common cause of viral meningitis in adults. We discuss the case of a 57-year-old female patient with enteroviral meningitis manifesting as pseudotumor cerebri, posing significant clinical challenges. She presented with symptoms, signs, and radiological evidence suggesting idiopathic intracranial hypertension. The CSF analysis showed pleocytosis, which led to further investigations that unveiled a positive case of EV by real-time reverse transcription polymerase chain reaction analysis. This case highlights the fact that not all cases of raised intracranial pressure are detrimental or recalcitrant. It accentuates the need for thorough diagnostic evaluation and emphasizes the potential for favorable outcomes with conservative management.

OBJECTIVE: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time.
METHODS: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms.
RESULTS: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03).
CONCLUSIONS: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

BACKGROUND: Moderate-to-severe traumatic brain injury (TBI) has a global mortality rate of about 30%, resulting in acquired life-long disabilities in many survivors. To potentially improve outcomes in this TBI population, the management of secondary injuries, particularly the failure of cerebrovascular reactivity (assessed via the pressure reactivity index; PRx, a correlation between intracranial pressure (ICP) and mean arterial blood pressure (MAP)), has gained interest in the field. However, derivation of PRx requires high-resolution data and expensive technological solutions, as calculations use a short time-window, which has resulted in it being used in only a handful of centers worldwide. As a solution to this, low resolution (longer time-windows) PRx has been suggested, known as Long-PRx or LPRx. Though LPRx has been proposed little is known about the best methodology to derive this measure, with different thresholds and time-windows proposed. Furthermore, the impact of ICP monitoring on cerebrovascular reactivity measures is poorly understood. Hence, this observational study establishes critical thresholds of LPRx associated with long-term functional outcome, comparing different time-windows for calculating LPRx as well as evaluating LPRx determined through external ventricular drains (EVD) vs intraparenchymal pressure device (IPD) ICP monitoring.
METHODS: The study included a total of n = 435 TBI patients from the Karolinska University Hospital. Patients were dichotomized into alive vs. dead and favorable vs. unfavorable outcomes based on 1-year Glasgow Outcome Scale (GOS). Pearson\'s chi-square values were computed for incrementally increasing LPRx or ICP thresholds against outcome. The thresholds that generated the greatest chi-squared value for each LPRx or ICP parameter had the highest outcome discriminatory capacity. This methodology was also completed for the segmentation of the population based on EVD, IPD, and time of data recorded in hospital stay.
RESULTS: LPRx calculated with 10-120-min windows behaved similarly, with maximal chi-square values ranging at around a LPRx of 0.25-0.35, for both survival and favorable outcome. When investigating the temporal relations of LPRx derived thresholds, the first 4 days appeared to be the most associated with outcomes. The segmentation of the data based on intracranial monitoring found limited differences between EVD and IPD, with similar LPRx values around 0.3.
CONCLUSIONS: Our work suggests that the underlying prognostic factors causing impairment in cerebrovascular reactivity can, to some degree, be detected using lower resolution PRx metrics (similar found thresholding values) with LPRx found clinically using as low as 10 min-by-minute samples of MAP and ICP. Furthermore, EVD derived LPRx with intermittent cerebrospinal fluid draining, seems to present similar outcome capacity as IPD. This low-resolution low sample LPRx method appears to be an adequate substitute for the clinical prognostic value of PRx and may be implemented independent of ICP monitoring method when PRx is not feasible, though further research is warranted.

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, which were not seen following injury alone. Investigations also indicated that cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remained unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via the intracerebroventricular infusion of the Cath B inhibitor to the CA-074 methyl ester (CA-074Me) 2w following injury with or without secondary ICP elevation. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, CFPI only, or CFPI with subsequent ICP elevation to 20 mmHg. We assessed Cath B activity and evaluated the protein levels of Cath B and Cath B-binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of the total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption; however, the administration of CA-074Me alters Cath B localization and reduces hypersensitivity, emphasizing Cath B as an important component in late secondary pathologies.

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined.

OBJECTIVE: Treatment for intracranial pressure (ICP) has been increasingly informed by machine learning (ML)-derived ICP waveform characteristics. There are gaps, however, in understanding how ICP monitor type may bias waveform characteristics used for these predictive tools since differences between external ventricular drain (EVD) and intraparenchymal monitor (IPM)-derived waveforms have not been well accounted for.
OBJECTIVE: We sought to develop a proof-of-concept ML model differentiating ICP waveforms originating from an EVD or IPM.
METHODS: We examined raw ICP waveform data from the ICU physiology cohort within the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury multicenter study.
METHODS: Nested patient-wise five-fold cross-validation and group analysis with bagged decision trees (BDT) and linear discriminant analysis were used for feature selection and fair evaluation. Nine patients were kept as unseen hold-outs for further evaluation.
RESULTS: ICP waveform data totaling 14,110 hours were included from 82 patients (EVD, 47; IPM, 26; both, 9). Mean age, Glasgow Coma Scale (GCS) total, and GCS motor score upon admission, as well as the presence and amount of midline shift, were similar between groups. The model mean area under the receiver operating characteristic curve (AU-ROC) exceeded 0.874 across all folds. In additional rigorous cluster-based subgroup analysis, targeted at testing the resilience of models to cross-validation with smaller subsets constructed to develop models in one confounder set and test them in another subset, AU-ROC exceeded 0.811. In a similar analysis using propensity score-based rather than cluster-based subgroup analysis, the mean AU-ROC exceeded 0.827. Of 842 extracted ICP features, 62 were invariant within every analysis, representing the most accurate and robust differences between ICP monitor types. For the nine patient hold-outs, an AU-ROC of 0.826 was obtained using BDT.
CONCLUSIONS: The developed proof-of-concept ML model identified differences in EVD- and IPM-derived ICP signals, which can provide missing contextual data for large-scale retrospective datasets, prevent bias in computational models that ingest ICP data indiscriminately, and control for confounding using our model\'s output as a propensity score by to adjust for the monitoring method that was clinically indicated. Furthermore, the invariant features may be leveraged as ICP features for anomaly detection.