BACKGROUND: Pediatric idiopathic intracranial hypertension (IIH) is a rare and challenging condition. As implied by the nomenclature, the etiologies remain unknown, and multiple etiologies are being investigated. In this study, we explored the potential role of increased systemic or cerebral venous pressure in the pathogenesis.
METHODS: An observational cohort study following the STROBE guidelines, including prepubertal children with clinical symptoms and imaging findings consistent with IIH referred to the neurosurgical department, was conducted. The patients underwent a comprehensive diagnostic protocol, including MRI, continuous intracranial pressure (ICP) monitoring, and endovascular venography with venous pressure measurements.
RESULTS: The study included 11 consecutive patients (six boys and five girls) with an average age of 2.3 years, and an average BMI of 18.4. Among these, one patient was found to have venous stenosis with a gradient; the other 10 patients presented with normal intracranial anatomy. All patients exhibited elevated venous pressures, with an average superior sagittal sinus pressure of 18.9 mmHg, average internal jugular vein pressure of 17.0 mmHg, and average central venous pressure of 15.9 mmHg. Daytime ICP averaged 12.9 mmHg, whereas nighttime ICP averaged 17.2 mmHg with either A- or B-waves in 10 of the 11 patients. Despite pathological ICP, only three patients had papilledema.
CONCLUSIONS: All patients had an increased systemic venous pressure, indicating a possible pathological factor for prepubertal IIH. Additionally, our findings show that young children often only partly meet the Friedman criteria due to a lack of papilledema, emphasizing the need for pediatric-specific diagnostic criteria. Further large-scale studies are needed to confirm these findings and to explore the underlying reasons for this increase in venous pressure and potential new treatment avenues.

OBJECTIVE: Detecting increased intracranial pressure early in pediatric patients is essential, as early initiation of therapy prevents morbidity and mortality. The objective of this study was to determine the diagnostic accuracy of the optic nerve sheath diameter (ONSD) measured via ultrasound for the prediction of increased intracranial pressure.
METHODS: Four databases, namely, PubMed, EMBASE, Scopus, and CINAHL, were searched for this systematic review and meta-analysis. The study\'s predefined inclusion criteria considered diagnostic accuracy, cross-sectional, prospective observational, and retrospective studies with a focus on children with elevated intracranial pressure from causes such as traumatic brain injury and cerebral edema, the diagnostic accuracy of the optic nerve sheath diameter measured using ultrasound was assessed. The primary outcome measures included sensitivity and specificity. The study included invasive monitoring (external ventricular drain) and noninvasive measures as the gold standards for increased intracranial pressure. Two authors extracted and reviewed the data. Baseline data, outcome measures, and diagnostic accuracy data were extracted.
RESULTS: Twenty-five studies with 1591 patients and 3143 ONSD measurements via ultrasound were analyzed. The pooled sensitivity and specificity of the ONSD measured via ultrasound for the prediction of increased intracranial pressure were 92% (86%-96%) and 89% (77%-96%), respectively. The pooled positive and negative likelihood ratios were 8.6 and 0.08, respectively.
CONCLUSIONS: Optic nerve ultrasonography stands out as a precise and valuable diagnostic tool applicable across diverse patient populations and clinical scenarios. We recommend routine ocular ultrasound for optic nerve sheath diameter measurement in pediatric patients to increase the accuracy of diagnosing increased intracranial pressure.

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ≥10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds.

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage, and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and nonnervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising noninvasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP.

UNASSIGNED: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse perinatal outcomes. Previous studies have demonstrated that the placenta of an ICP pregnancy differs in morphology and gene expression from the placenta of a normal pregnancy. To date, however, the genetic mechanism by which ICP affects the placenta is poorly understood. Therefore, the aim of this study was to investigate the differences in main cell types, gene signatures, cell ratio, and functional changes in the placenta between ICP and normal pregnancy.
UNASSIGNED: Single-cell RNA sequencing (scRNA-seq) technology was used to detect the gene expression of all cells at the placental maternal-fetal interface. Two individuals were analyzed - one with ICP and one without ICP. The classification of cell types was determined by a graph-based clustering algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R software phyper () function and DAVID website. The differentially expressed genes (DEGs) encoding transcription factors (TFs) were identified using getorf and DIAMOND software.
UNASSIGNED: We identified 14 cell types and 22 distinct cell subtypes that showed unique functional properties. Additionally, we found differences in the proportions of fibroblasts 1, helper T (Th) cells, extravillous trophoblasts, and villous cytotrophoblasts, and we observed heterogeneity of gene expression between ICP and control placentas. Furthermore, we identified 263 DEGs that belonged to TF families, including zf-C2H2, HMGI/HMGY, and Homeobox. In addition, 28 imprinted genes were preferentially expressed in specific cell types, such as PEG3 and PEG10 in trophoblasts as well as DLK1 and DIO3 in fibroblasts.
UNASSIGNED: Our results revealed the differences in cell-type ratios, gene expression, and functional changes between ICP and normal placentas, and heterogeneity was found among cell subgroups. Hence, the imbalance of various cell types affects placental activity to varying degrees, indicating the complexity of the cell networks that form the placental tissue system, and this alteration of placental function is associated with adverse events in the perinatal period.

For many years, noninvasive methods to measure intracranial pressure (ICP) have been unsuccessful. However, such methods are crucial for the assessment of patients with nonpenetrating traumatic brain injuries (TBIs) who are unconscious. In this study, we explored the use of transcranial transmission ultrasound (TTUS) to gather experimental data through brain pulsatility, assessing its effectiveness in detecting high ICP using machine learning analysis. We included patients with severe TBI under invasive ICP monitoring in our intensive care unit. During periods of both normal and elevated ICP, we simultaneously recorded ICP, arterial blood pressure, heart rate, and TTUS measurements. Our classification model was based on data from 9 patients, encompassing 387 instances of elevated ICP (>15 mmHg) and 345 instances of normal ICP (<10 mmHg), and validated through a leave-one-subject-out method. The study, conducted from October 2021 to October 2022, involved 25 patients with an average age of 61.6 ± 17.6 years, producing 279 datasets with an average ICP of 11.3 mmHg (1st quartile 6.1 mmHg; 3rd quartile 14.8 mmHg). The automated TTUS analysis effectively identified ICP values over 15 mmHg with 100% sensitivity and 47% specificity. It achieved a 100% negative predictive value and a 14% positive predictive value. This suggests that TTUS can accurately rule out high ICP above 15 mmHg in TBI patients, indicating patients who may need immediate imaging or intervention. These promising results, if confirmed and expanded in larger studies, could lead to the first reliable, noninvasive screening tool for detecting elevated ICP.

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders.

OBJECTIVE: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup.
METHODS: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated.
RESULTS: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042).
CONCLUSIONS: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

UNASSIGNED: Aneurysmal subarachnoid hemorrhage (aSAH) often necessitates prolonged sedation to manage elevated intracranial pressure (ICP) and to prevent secondary brain injury. Optimal timing and biomarkers for predicting adverse events (AEs) during interruption of sedation (IS) after prolonged sedation are not well established. To guide sedation management in aSAH, we aimed to explore the frequency, risk factors, and outcomes of IS in aSAH.
UNASSIGNED: In a retrospective cohort study, a total of 148 patients with aSAH from January 2015 to April 2020 were screened. In total, 30 patients accounting for 42 IS were included in the analysis. Adverse events (AEs) during IS were used as core outcome measures and were categorized into neurological and non-neurological AEs. Baseline characteristics, clinical parameters before IS, AEs, and functional outcomes were collected using health records. Statistical analysis used generalized linear mixed-effects models with regularization to identify candidate predictors with subsequent bootstrapping to test model stability. As an exploratory analysis, multivariate linear and logistic regression was used to analyze the association between IS and intensive care unit length of stay, duration of mechanical ventilation, and functional outcomes.
UNASSIGNED: The mean age was 56.9 (SD 14.8) years, and a majority of the patients presented with poor-grade SAH (16/30, 53.3%). Neurological and non-neurological AEs occurred in 60.0% (18/30) of the patients. Timing, number of IS attempts, ICP burden, craniectomy status, level of consciousness, heart rate, cerebral perfusion pressure, oxygen saturation, fraction of inspired oxygen, and temperature were selected as candidate predictors. Through bootstrapping, elapsed time since disease onset (OR 0.85, 95% confidence interval (95% CI) 0.75-0.97), ICP burden (OR 1.24, 95% CI 1.02-1.52), craniectomy (OR 0.68, 95% CI 0.48-0.69), and oxygen saturation (OR, 0.80 0.72-0.89) were revealed as relevant biomarkers for neurological AEs, while none of the pre-selected predictors was robustly associated with non-neurological AEs.
UNASSIGNED: In aSAH, complications during the definite withdrawal of sedation are frequent but can potentially be predicted using clinical parameters available at the bedside. Prospective multicenter studies are essential to validate these results and further investigate the impact of IS complications.

UNASSIGNED: Dilatation of the optic nerve sheath diameter and swelling of the optic disc are known phenomena associated with intracranial pressure elevation.
UNASSIGNED: Do sex and disease etiology have an impact on the development of optic disc elevation and optic nerve sheath extension in children in the setting of ICP elevation? Fundoscopic papilledema and point-of-care-ultrasound techniques-optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE) - were compared in this regard.
UNASSIGNED: 72 children were included in this prospective study; 50 with proven pathology (e.g. pseudotumor cerebri, tumor), 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array-transducer. This was compared with fundoscopic optic disc findings and in 28 patients with invasive ICP values, stratified for sex and etiology.
UNASSIGNED: In patients with proven disease, significant more girls (69%) had fundoscopic papilledema compared with boys (37%, p < 0.05). Girls had also larger US-ODE values (0.86 ± 0.36 mm vs. 0.65 ± 0.40 mm in boys). 80% of tumor patients had initial papilledema (100% girls, 79% boys), compared with 50% in pseudotumor cerebri (PTC) (83% girls, 30% boys). US-ONSD had no sex- and no etiology-specificity.
UNASSIGNED: Presence of papilledema appears to be influenced by sex and etiology, whereas US-ONSD is not. Girls seem more likely to develop papilledema under similar conditions. Male sex and PTC appear as risk factors for being undetected by fundoscopic findings. US-ONSD and US-ODE seem useful tools to identify pathologies with potentially increased ICP requiring treatment in children regardless of sex and etiology.