Search Results (100)

Background and Objectives: Severe complications associated with cervical hyperextension during general anesthesia have been reported. The question is whether some of the cerebral/spinal ischemic complications could be partially related to the position itself. Cerebral oximetric monitoring, combined with optic nerve sheath diameter and cognitive function in non-anesthetized healthy volunteers, should provide more extensive information about the effects of cervical hyperextension, independent of anesthesia. Materials and Methods: 51 healthy volunteers with no vertebrobasilar abnormalities completed the study and were included in statistical analysis. Primary outcomes were cervical blood flow and cerebral relative hemoglobin change. The secondary outcomes were optic nerve sheath diameter and cognitive function assessment. After baseline Doppler ultrasonography of the cervical vessels, Mini-Mental State Examination, Montreal Cognitive Assessment, and optic nerve sheath diameter measurements at T0, volunteers underwent cervical hyperextension > 30°, with assessments repeated at the first and 30th minutes (T1, T30). Relative total, oxi-, and deoxyhemoglobin changes were assessed every 5 min. Results: Peak systolic velocities in the jugular veins at T1 and T30 were significantly lower than those at baseline (p1 and p2 < 0.001). After hyperextension, deoxyhemoglobin changes significantly increased at T1 and T30 (p1 < 0.001). The optic nerve sheath diameter increased at T30 compared to the baseline (p < 0.001). Cognitive scores improved at T30 (p = 0.044 and p < 0.001, respectively). Conclusions: Cervical hyperextension causes a significant increase in relative total and deoxyhemoglobin changes, which are related to acute cerebral congestion by severely impairing cerebral venous flow. A significant change in optic nerve sheath diameter indirectly indicates increased intracranial pressure. Full article

Background: Mechanical ventilation compromises airway clearance, with expiratory flow bias (EFB) being a critical determinant of mucus transport. The rapid chest compression technique (RCCT) generates high EFB, yet evidence in neurocritical patients is limited due to concerns regarding intracranial pressure (ICP). This secondary analysis of a randomized controlled trial examined the effects of RCCT on ventilatory mechanics and physiology in acute brain-injured patients under invasive ventilation. Methods: Fifty neurocritical patients were randomized to RCCT (Intervention) or passive leg mobilization (Control). RCCT was applied bilaterally during expiration once every three respiratory cycles for 5 min; controls underwent 5 min of passive cycling. EFB, derived from inspiratory and expiratory peak flows, was assessed at baseline (T–5), during intervention (T0–T5), and post-intervention (T+5, T+30). Arterial blood gases, mean arterial pressure (MAP), heart rate (HR), and ICP were also analyzed. Group comparisons used parametric/non-parametric tests; associations were explored via Spearman’s rho. Results: Baseline EFB did not differ between groups. From T0 to T5, Intervention patients showed significantly higher EFB (all p < 0.001). PaCO₂ decreased within the Intervention group (p = 0.015) but not in controls (p = 0.601). No between-group ΔPaCO₂ differences emerged. At T5, HR correlated negatively with EFB (ρ = −0.49, p = 0.013). No associations were found with age, sex, lesion type, MAP, or ICP. Conclusions: RCCT effectively increased EFB in ventilated neurocritical patients without affecting ICP, supporting its safety and potential role in airway clearance. Full article

Background/Objectives: Spontaneous intracranial hypotension (SIH), caused by spinal cerebrospinal fluid (CSF) leakage, commonly presents with orthostatic headache and CSF hypovolemia. While CSF dynamics in the cerebral aqueduct are well studied, alterations in spinal CSF flow remain less defined. We aimed to quantitatively assess spinal CSF flow at C2 using phase-contrast (PC) MRI enhanced by artificial intelligence (AI) and to evaluate its utility for diagnosing SIH and predicting responses to epidural blood patch (EBP). Methods: We enrolled 31 patients with MRI-confirmed SIH and 26 age- and sex-matched healthy volunteers (HVs). All participants underwent ECG-gated cine PC-MRI at the C2 level and whole-spine MR myelography. AI-based segmentation using YOLOv4 and a pulsatility-based algorithm was used to extract quantitative CSF flow metrics. Between-group comparisons were analyzed using Mann–Whitney U tests, and receiver operating characteristic (ROC) analysis was used to evaluate diagnostic and predictive performance. Results: Compared to HVs, SIH patients showed significantly reduced CSF flow parameters across all metrics, including upward/downward mean flow, peak flow, total flow per cycle, and absolute stroke volume (all p < 0.001). ROC analysis revealed excellent diagnostic accuracy for multiple parameters, particularly downward peak flow (AUC = 0.844) and summation of peak flow (AUC = 0.841). Importantly, baseline CSF flow metrics significantly distinguished patients who required one versus multiple epidural blood patches (EBPs) (all p < 0.001). ROC analysis demonstrated that several parameters achieved near-perfect to perfect accuracy in predicting EBP success, with AUCs up to 1.0 and 100% sensitivity/specificity. Conclusions: AI-enhanced PC-MRI enables the robust, quantitative evaluation of spinal CSF dynamics in SIH. These flow metrics not only differentiate SIH patients from healthy individuals but also predict response to EBP treatment with high accuracy. Quantitative CSF flow analysis may support both diagnosis and personalized treatment planning in SIH. Full article

Flow-diverting stents (FDS) are sophisticated endovascular devices that aim to modulate blood flow and promote aneurysm thrombosis while maintaining branch vessel patency. Initially designed and developed for the treatment of intracranial aneurysms, these devices have since been applied to the peripheral circulation. However, they are still used sporadically, largely due to a lack of the scientific evidence supporting its use in visceral aneurysms. This review article aims to provide an overview of the current data on the clinical outcomes from the use of FDS in the treatment of complex visceral and renal aneurysms or pseudoaneurysms and to assess the added value of these devices. Full article

Optical brain monitoring techniques, including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), and photoplethysmography (PPG) have gained attention for their non-invasive, affordable, and portable nature. These methods offer real-time insights into cerebral parameters like cerebral blood flow (CBF), intracranial pressure (ICP), and oxygenation. However, confounding factors like extracerebral layers, skin pigmentation, skull thickness, and brain-related pathologies may affect measurement accuracy. This review examines the potential impact of confounders, focusing on in vitro studies that use phantoms to simulate human head properties under controlled conditions. A systematic search identified six studies on extracerebral layers, two on skin pigmentation, two on skull thickness, and four on brain pathologies. While variation in phantom designs and optical devices limits comparability, findings suggest that the extracerebral layer and skull thickness influence measurement accuracy, and skin pigmentation introduces bias. Pathologies like oedema and haematomas affect the optical signal, though their influence on parameter estimation remains inconclusive. This review highlights limitations in current research and identifies areas for future investigation, including the need for improved brain phantoms capable of simulating pulsatile signals to assess the impact of confounders on PPG systems, given the growing interest in PPG-based cerebral monitoring. Addressing these challenges will improve the reliability of optical monitoring technologies. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

During aging, the brain vasculature undergoes significant deterioration characterized by increased arterial tortuosity, compromised blood–brain barrier integrity, and reduced cerebral blood flow, all of which contribute to various neurological disorders. Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies to alleviate aging-associated neurological diseases. In this study, we investigated the role of aging-related genes in brain vascular development using zebrafish as an in vivo model. By thoroughly analyzing scRNA-seq datasets of mid- and old-aged brain vascular endothelial cells (human/mouse), we found ribosomal protein S20 (rps20) significantly down-regulated during aging. qPCR analysis and whole-mount in situ hybridization validated a high expression of rps20 during early zebrafish development, which progressively decreased in adult and aged zebrafish brains. Functional studies using the CRISPR/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos. In conclusion, our findings demonstrate that rps20 is essential for proper brain vascular development and the maintenance of vascular homeostasis in zebrafish, revealing a novel mechanism by which aging-related genes regulate brain vascular development. This study provides new insights that may aid in understanding and treating aging-associated vascular malformations and neurological pathologies. Full article

Background: Intracranial pressure (ICP) monitoring is crucial in managing acute brain injury (ABI) to prevent secondary brain injury. While invasive techniques remain the gold standard, they can carry notable risks, such as infection and hemorrhage. Non-invasive techniques are increasingly used, but their inter-modality correlation and concordance have not been systematically evaluated. This study aimed to assess the correlation and concordance among four commonly used non-invasive neuromonitoring tools in patients with ABI undergoing invasive ICP monitoring. Methods: This was a secondary analysis of prospectively collected data from 100 adult patients admitted to the intensive care unit with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) who underwent invasive ICP monitoring. Simultaneous assessments using optic nerve sheath diameter (ONSD), transcranial Doppler-derived pulsatility index (PI), estimated ICP (eICP), and the neurological pupil index (NPi) were performed. Correlation between modalities was assessed using Spearman’s correlation coefficient (ρ), and concordance was evaluated with Cohen’s kappa coefficient (k). Results: We found weak correlations between ONSD and PI (ρ = 0.29), ONSD and NPi (ρ = −0.33), and PI and NPi (ρ = −0.33); moderate correlations between ONSD and eICP (ρ = 0.54) and PI and eICP (ρ = 0.48); and a strong inverse correlation between eICP and NPi (ρ = −0.71; all p < 0.05). Concordance was generally low, with the highest agreement between PI and eICP (k = 0.69). Most other tool pairings showed poor-to-fair concordance (k ≤ 0.30). Conclusions: Non-invasive neuromonitoring tools show variable correlation and limited agreement, suggesting they are not interchangeable. Each modality captures different aspects of cerebral physiology, supporting the use of a multimodal approach to improve accuracy in ICP estimation. Full article

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. Full article

In this study, pharmacotherapies of abdominal compartment syndrome (ACS) and intra-abdominal hypertension (IAH) in animal studies were reviewed from the perspective of ACS/IAH as failed cytoprotection issues, as non-specific injuries, and from the point of view of the cytoprotection concept as resolution. Therefore, this review challenges the unresolved theoretical and practical issues of severe multiorgan failure, acknowledged significance in clinics, and resolving outcomes (i.e., open abdomen). Generally, the reported agents not aligned with cytoprotection align with current pharmacotherapy limitations and have (non-)confirmed effectiveness, mostly in only one organ, mild/moderate IAH, prophylactic application, and provide only a tentative resolution. Contrarily, stable gastric pentadecapeptide BPC 157 therapy, as a novel and relevant cytoprotective mediator having pleiotropic beneficial effects, simultaneously resolves many targets, resolving established disturbances, specifically compression/ischemia (grade III and grade IV), and decompression/advanced reperfusion. BPC 157 therapy rapidly activates collateral bypassing pathways, and, in ACS and IAH, and later, in reperfusion, there is a “bypassing key” (i.e., azygos vein direct blood flow delivery). This serves to counteract multiorgan and vessel failure, including lesions and hemorrhages in the brain, heart, lung, liver, kidney and gastrointestinal tract, thrombosis, peripherally and centrally, intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, occlusion/occlusion-like syndrome, advanced Virchow triad circumstances, and free radical formation acting as a membrane stabilizer and free radical scavenger. Likewise, not only in ACS/IAH resolving, but also in other occlusion/occlusion-like syndromes, this “bypassing key” could be an effect of the essential endothelial cytoprotective capacity of BPC 157 and a particular modulatory effect on the NO-system, and a rescuing impact on vasomotor tone. Full article

Background: Chronic ischemic stroke presents a significant challenge in neurology, with limited therapeutic options available for long-term recovery. During cerebral infarction, anti-inflammatory phenotype microglia/macrophages produce anti-inflammatory cytokines and neurotrophic factors that facilitate the process of brain repair. However, obtaining sufficient anti-inflammatory microglia/macrophages from the human central nervous system is challenging. Bone marrow-derived inducible microglia-like cells (BM-iMGs) with an anti-inflammatory microglial phenotype were explored to induce neuroprotective properties. Here, we transplanted BM-iMGs into the brain of middle cerebral artery occlusion (MCAO) model male mice to explore their potential for treating chronic ischemic stroke. Methods: Bone marrow-derived mononuclear cells (BM-MNCs) were isolated from green fluorescent protein mice and incubated with granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4 to induce BM-iMGs with an anti-inflammatory phenotype. BM-iMGs were transplanted into the brains of mice on day 14 after MCAO, and behavioral tests, histology, cerebral blood flow, and gene expression were evaluated. Results: An intracranial injection of BM-iMGs promoted neurobehavioral recovery, reduced neuronal cell loss, suppressed neuroinflammatory astrocytic and microglial responses in the brain, and increased cortical surface cerebral blood flow in MCAO mice. Furthermore, neuroprotective genes were upregulated, whereas proinflammatory genes were downregulated. Conclusions: The intracranial injection of BM-iMG cells shows significant potential as a novel therapy for chronic ischemic stroke. Full article

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article

Background/Objectives: The natural course of intracranial aneurysms (IAs) remains unclear. Many of them remain stable over time and few experience patterns of growth. The spontaneous regression of IAs without any microsurgical or endovascular treatment is a very rare phenomenon. This paper reports the case of a 56-year-old female who experienced spontaneous regression of her IA. Furthermore, it contains a systematic literature review to explore reported cases of spontaneous IA regression. Methods: The case of a 56-year old female patient who presented with an anterior communicating artery (ACom) IA that thrombosed spontaneously after 108 months follow-up is reported. Additionally, a systematic literature search was conducted using the Medline database to identify reported cases. Results: The IA showed spontaneous regression without any surgical or endovascular intervention. We identified 33 articles describing IAs with spontaneous regression. Reported reasons for spontaneous IA thrombosis included (1) anatomical factors like narrow aneurysmal necks; (2) coagulation pathway modifications, including antifibrinolytic activity that promotes thrombosis; and (3) hemodynamic changes such as altered blood flow dynamics and external vascular compression. These findings suggest that spontaneous regression, while rare and unpredictable, can be associated with distinct physiological and anatomical conditions. Conclusions: The spontaneous regression of IAs is an extremely rare phenomenon. It cannot reliably be predicted and may be associated with changes in the hemodynamic situation, specific anatomical constellations, or coagulation pathways. Full article

Objective: Cerebral vascularization is made of the symmetrical arterial system, with muscular walls, and the venous system, more variable and dominated by sinuses and jugular veins. Factors like age and posture influence this network, complicating its study. Phase-contrast MRI is the gold standard for quantifying cerebral circulation. This study aimed to quantify the dynamics of the cerebral blood system using PC-MRI. Materials and Methods: Thirty-six healthy adults participated. Imaging was performed on a 3T MRI (Philips Achieva) in a supine position. Two slices were acquired: intracranial and extracranial. In-house software analyzed flow curves over a cardiac cycle. Each vessel’s contribution was evaluated. Results: Extracranial venous drainage was categorized as jugular-dominant, equivalent, or peripheral-dominant. A similar classification applied intracranially. Intracranial flows showed low variability (5–9%), while extracranial venous flows, especially in the internal jugular veins, had higher variability (17–21%). Some extracranial veins were absent. Conclusions: There is significant venous heterogeneity in the extracranial region. PC-MRI enables the quantification of cerebral dynamics. Full article

Background and Objectives: Despite the growing amount of new research, the pathophysiology of glaucoma remains unclear. The aim of this study was to determine the relationship between intracranial pressure (ICP), ocular blood flow and structural optic nerve parameters. Materials and Methods: A prospective clinical study was conducted involving 24 patients with open-angle glaucoma and 25 healthy controls. Routine clinical examination was performed. Swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA) images were taken (DRI-OCT Triton, Topcon). The vessel density (VD) values of the ONH were calculated around the optic nerve head (ONH). An orbital Doppler device (Vittamed 205, Kaunas, Lithuania) was used for non-invasive ICP measurements. Color Doppler imaging (CDI) (Mindray M7, Shenzhen, China) was used for retrobulbar blood flow measurements in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs). Results: ICP was 8.35 ± 2.8 mmHg in the glaucoma group and 8.45 ± 3.19 mmHg in the control group (p = 0.907). In the glaucoma group, the VD of the superficial vascular plexus in the inferior-nasal (NI) sector of the ONH showed a correlation with ICP (r = 0.451, p = 0.05). In contrast, the control group exhibited weaker correlations. CRA peak systolic velocity (PSV) demonstrated significant moderate correlations with VD in multiple retinal layers, including the avascular retina layer in the temporal (T) sector (r = 0.637, p = 0.001). Conclusions: Lower ICP was significantly associated with the lower VD of the superficial plexus layer in the inferior-nasal sector in the glaucoma group, with the control group exhibiting weaker correlations in all sectors. Further longitudinal studies with larger sample sizes are needed to establish associations between intracranial pressure, ocular blood flow and ONH parameters. Full article