Exposure to topiramate and acetazolamide causes endocrine disrupting effects in female rats during estrus.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues. METHODS: Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA. RESULTS: Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands. CONCLUSION: These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.

Are the ICHD-3 criteria for headache attributed to idiopathic intracranial hypertension valid? Headache phenotyping and field-testing in newly diagnosed idiopathic intracranial hypertension.

BACKGROUND: Headache burden is substantial in idiopathic intracranial hypertension. The classification of idiopathic intracranial hypertension headache by the International Classification of Headache Disorders (ICHD) is an important tool for research and clinical purposes. METHODS: We phenotyped headaches and tested sensitivity and specificity of the ICHD-3 criteria for idiopathic intracranial hypertension headache in a prospective cohort of patients suspected of idiopathic intracranial hypertension at two tertiary headache centers. RESULTS: Sensitivity was 93% and specificity was 100% of ICHD-3 criteria for idiopathic intracranial hypertension-related headache validated in idiopathic intracranial hypertension (n = 140) and patients in whom idiopathic intracranial hypertension was suspected but disproven (n = 103). The phenotype of new/worsened headaches related to idiopathic intracranial hypertension suspicion was equally migraine-like (p = 0.76) and tension-type-like (p = 0.08). Lumbar puncture opening pressure was higher (p < 0.0001) and pulsatile tinnitus more frequent (p < 0.0001) in idiopathic intracranial hypertension patients, but neither improved the applicability of the headache criteria, nor did papilledema. CONCLUSION: Headache phenotype is not distinct in idiopathic intracranial hypertension. ICHD-3 criteria for idiopathic intracranial hypertension headache are sensitive and specific, but simplicity can be improved without compromising accuracy. We propose that a new or worsened headache temporally related to active idiopathic intracranial hypertension is a sufficient criterion for idiopathic intracranial hypertension headache regardless of headache phenotype or accompanying symptoms, and that elements of idiopathic intracranial hypertension diagnostics (papilledema and opening pressure) be segregated from headache criteria.Trial Registration: ClinicalTrials.gov Identifier: NCT04032379.

Investigating the effects of tilting the postural drainage lithotripsy system on cerebral blood flow, intracranial pressure, heart rate, and blood pressure.

PURPOSE: To investigate the effect of the postural drainage lithotripsy system developed by our experimental team on the vital signs of patient with urinary stones during the stone removal process. METHODS: Four groups of 15 subjects (0°, 10°, 40°, and 70°) were subjected to different angles of head-down tilt to measure middle cerebral artery blood flow velocity (MCAv), cerebrovascular conductance coefficient (CVCi), intracranial pressure (nICP), heart rate (HR), and mean arterial blood pressure (MAP). RESULTS: As the angle of HDT changed, MCAv values, nICP values, CVCi values, HR values, and MAP values changed significantly (all P ≤ 0.001), and the difference was statistically significant. During 10°HDT, despite a slight increase in nICP, the other measurements remained stable. During 40°HDT, only the MCAv values did not change significantly, whereas the rest of the measures were significantly altered. During 70°HDT, all indicators changed significantly. CONCLUSIONS: The significant alterations in cerebral blood flow, intracranial pressure, and hemodynamics induced during the treatment of renal residual fragments with postural drainage should be used with caution in individuals with cerebrovascular accidents. CHINA CLINICAL TRIALS REGISTRY: ChiCTR2300070671; Registration date: 2023-04-18.

NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis: case report and review of literature.

BACKGROUND: We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic. CASE: The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity. LITERATURE REVIEW: We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later. CONCLUSION: As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.

Novel Approaches to the Treatment of Idiopathic Intracranial Hypertension.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) typically affects women of childbearing age, is associated with recent weight gain, and can result in debilitating headache as well as papilledema that can cause vision loss. There have been advances in the medical and surgical treatment of affected patients with IIH that can improve outcomes and tolerability of therapy. RECENT FINDINGS: Medical treatment with agents that lower intracranial pressure through pathways other than carbonic anhydrase inhibition are being developed, and medically-directed weight loss as well as bariatric surgery now may be considered as primary therapy. New surgical options including venous sinus stenting have shown efficacy even with cases of severe vision loss. Our treatment options for IIH patients are becoming more diverse, and individualized treatment decisions are now possible to address specific components of the patient's disease manifestations and to lead to IIH remission.

The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study.

BACKGROUND: The use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI. MATERIALS AND METHODS: This is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman's rank test. RESULTS: We studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3-16.4) to 15.4 (12.0-19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4-55.6) to 56.4 (49.6-61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01-0.24) to 0.43 (0.34-0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8-3.7) to 4.3 (2.5-5.6) µM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2-2.9) to 2.7 (1.4-4.0) µM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9-5.3) to 7.8 (5.2-10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx. CONCLUSIONS: In ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

Critical thresholds of long-pressure reactivity index and impact of intracranial pressure monitoring methods in traumatic brain injury.

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. CONCLUSION: 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.

Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

BACKGROUND: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed. OBJECTIVE: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt). METHODS: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold. RESULTS: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt. CONCLUSIONS: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.

Endovascular stenting for cerebral venous sinus stenosis secondary to meningioma invasion.

INTRODUCTION: Symptomatic intracranial hypertension (IH) due to venous outflow obstruction secondary to dural venous sinus (DVS) tumoral invasion affects up to 3% of intracranial meningioma patients. The literature regarding endovascular therapies of such patients is limited to a few case reports and a recent single-centre case series. PURPOSE: We describe our single-centre experience of endovascular therapy in patients with clinically symptomatic IH secondary to DVS meningioma invasion. METHODS: We performed a retrospective review of clinical and radiological data of all patients with refractory IH and meningiomas invading the DVS who were referred for possible DVS venoplasty and stenting. Seven endovascular procedures in six female patients were done. Presumed secondarily induced lateral transverse sinus stenosis was also stented in four patients as part of the primary intervention. RESULTS: All patients experienced complete symptomatic resolution at 6-month follow-up. Five patients had no symptom recurrence over a mean follow-up period of 3.5 years. One patient with multiple meningiomas developed recurrent IH 2 years following stenting secondary to in-stent tumour re-invasion. This was re-stented with consequent 6 months post-retreatment symptomatic relief at the time of writing. No procedure-related complications occurred. CONCLUSION: In the setting of DVS stenosis secondary to meningioma invasion, endovascular therapy is a safe and successful therapeutic option with promising mid-term results. The procedure should be considered in cases where complete surgical tumour resection is unlikely or carries a significant risk. If present, secondarily induced stenoses at the lateral ends of the transverse sinuses should also be considered for treatment.

Cranial bone thickness and density anomalies quantified from CT images can identify chronic increased intracranial pressure.

PURPOSE: The diagnosis of chronic increased intracranial pressure (IIP)is often based on subjective evaluation or clinical metrics with low predictive value. We aimed to quantify cranial bone changes associated with pediatric IIP using CT images and to identify patients at risk. METHODS: We retrospectively quantified local cranial bone thickness and mineral density from the CT images of children with chronic IIP and compared their statistical differences to normative children without IIP adjusting for age, sex and image resolution. Subsequently, we developed a classifier to identify IIP based on these measurements. Finally, we demonstrated our methods to explore signs of IIP in patients with non-syndromic sagittal craniosynostosis (NSSC). RESULTS: We quantified a significant decrease of bone density in 48 patients with IIP compared to 1,018 normative subjects (P < .001), but no differences in bone thickness (P = .56 and P = .89 for age groups 0-2 and 2-10 years, respectively). Our classifier demonstrated 83.33% (95% CI: 69.24%, 92.03%) sensitivity and 87.13% (95% CI: 84.88%, 89.10%) specificity in identifying patients with IIP. Compared to normative subjects, 242 patients with NSSC presented significantly lower cranial bone density (P < .001), but no differences were found compared to patients with IIP (P = .57). Of patients with NSSC, 36.78% (95% CI: 30.76%, 43.22%) presented signs of IIP. CONCLUSION: Cranial bone changes associated with pediatric IIP can be quantified from CT images to support earlier diagnoses of IIP, and to study the presence of IIP secondary to cranial pathology such as non-syndromic sagittal craniosynostosis.

Implantable antennas for biomedical applications: a systematic review.

This review presents an in-depth examination of implantable antennas for various biomedical purposes. The development of implantable antennas, including their designs, materials, and operating principles, are introduced at the beginning of the discussion. An overview of the many kinds of implantable antennas utilized in implantable medical devices (IMDs) are presented in this study. The article then discusses the important factors to consider when developing implantable antennas for biomedical purposes, including implant placement, frequency range, and power needs. This investigation additionally examines the challenges and limitations encountered with implantable antennas, including the limited space available within the human body, the requirement for biocompatible materials, the impact of surrounding tissue on antenna performance, tissue attenuation, and signal interference. This review also emphasizes the most recent advances in implanted antenna technology, such as wireless power transmission, multiband operation, and miniaturization. Furthermore, it offers illustrations of several biomedical uses for implantable antennas, including pacemaker, capsule endoscopy, intracranial pressure monitoring, retinal prostheses, and bone implants. This paper concludes with a discussion of the future of implantable antennas and their possible use in bioelectronic medicine and novel medical implants. Overall, this survey offers a thorough analysis of implantable antennas in biomedical applications, emphasizing their importance in the development of implantable medical technology.

Clinical outcomes of bariatric surgery in patients with obesity and idiopathic intracranial hypertension.

INTRODUCTION: Obesity is a major risk factor for idiopathic intracranial hypertension (IIH). Effective therapeutics for preventing disease progression and alleviating symptoms are limited. This study aims to examine the effects of bariatric surgery on clinical outcomes of IIH. METHODS: We retrospectively collected data from the medical record of 97 patients with obesity and an existing diagnosis of IIH who underwent primary bariatric surgery at the Cleveland Clinic health system in the USA between 2005 and 2023. Pre- and postoperative data on presence of symptoms and clinical markers of IIH (headaches, visual field defects, papilledema, visual symptoms), intracranial pressure, and usage of IIH medications were compared. RESULTS: A total of 97 patients (98% female, median age 46.7 years, median BMI 48.3 kg/m2) with IIH who underwent bariatric surgery including Roux-en-Y gastric bypass (n = 66, 68%), sleeve gastrectomy (n = 27, 27.8%), and gastric banding (n = 4, 4.1%) were analyzed. In a median follow-up time of 3.0 years, the median total weight loss was 24% (interquartile range, 13-33%). There was a significant improvement in headache, papilledema, visual field deficits, and visual symptoms after bariatric surgery. The mean lumbar opening pressure before and after bariatric surgery was 34.8 ± 8.2 cm CSF and 24.2 ± 7.6 cm CSF, respectively, with a mean reduction of 10.7 cm CSF (95% confidence interval, 4.7 to 16.6), p = 0.003. The dosage of acetazolamide and topiramate, as well as the number of medications taken for IIH, decreased significantly after bariatric surgery (p < 0.001). CONCLUSION: For patients who have obesity, bariatric surgery is a viable treatment modality for alleviation or improvement of symptoms of IIH.

Understanding the development, pathogenesis, and injury response of meningeal lymphatic networks through the use of animal models.

Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune trafficking. Although these vessels were overlooked for centuries, they have now been characterized in humans, non-human primates, and rodents. Recent studies in mice have explored the stereotyped growth and expansion of MLVs in dura mater, the various transcriptional, signaling, and environmental factors regulating their development and long-term maintenance, and the pathological changes these vessels undergo in injury, disease, or with aging. Key insights gained from these studies have also been leveraged to develop therapeutic approaches that help augment or restore MLV functions to improve brain health and cognition. Here, we review fundamental processes that control the development of peripheral lymphatic networks and how these might apply to the growth and expansion of MLVs in their unique meningeal environment. We also emphasize key findings in injury and disease models that may reveal additional insights into the plasticity of these vessels throughout the lifespan. Finally, we highlight unanswered questions and future areas of study that can further reveal the exciting therapeutic potential of meningeal lymphatics.

Brain tissue oxygen combined with intracranial pressure monitoring versus isolated intracranial pressure monitoring in patients with traumatic brain injury: an updated systematic review and meta-analysis.

Monitoring intracranial pressure (ICP) is pivotal in the management of severe traumatic brain injury (TBI), but secondary brain injuries can arise despite normal ICP levels. Cerebral tissue oxygenation monitoring (PbtO2) may detect neuronal tissue infarction thresholds, enhancing neuroprotection. We performed a systematic review and meta-analysis to evaluate the effects of combined cerebral tissue oxygenation (PbtO2) and ICP compared to isolated ICP monitoring in patients with TBI. PubMed, Embase, Cochrane, and Web of Sciences databases were searched for trials published up to June 2023. A total of 16 studies comprising 37,820 patients were included. ICP monitoring was universal, with additional placement of PbtO2 in 2222 individuals (5.8%). The meta-analysis revealed a reduction in mortality (OR 0.57, 95% CI 0.37-0.89, p = 0.01), a greater likelihood of favorable outcomes (OR 2.28, 95% CI 1.66-3.14, p < 0.01), and a lower chance of poor outcomes (OR 0.51, 95% CI 0.34-0.79, p < 0.01) at 6 months for the PbtO2 plus ICP group. However, these patients experienced a longer length of hospital stay (MD 2.35, 95% CI 0.50-4.20, p = 0.01). No significant difference was found in hospital mortality rates (OR 0.81, 95% CI 0.61-1.08, p = 0.16) or intensive care unit length of stay (MD 2.46, 95% CI - 0.11-5.04, p = 0.06). The integration of PbtO2 to ICP monitoring improved mortality outcomes and functional recovery at 6 months in patients with TBI. PROSPERO (International Prospective Register of Systematic Reviews) CRD42022383937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=383937.

Simple detecting of elevated ICP through liquor flow after lumbar puncture.

Elevated intracranial pressure (ICP) is defined as a cerebrospinal fluid (CSF) opening pressure (OP) greater than 25 cmH2O. When a diagnostic lumbar puncture is performed it is useful to estimate also intracranial pressure. To do this it is required a presence of pressure gauges, which are currently the gold standard, not available in most resource-constrained contexts. We decided to evaluate whether it is possible to estimate it simply by counting the drops of cerebrospinal liquor, which are collected after lumbar puncture, according to Poiseuille's law. Was examined a sample of 52 patients, aged between 18 and 85 years, belonging to the emergency room of "Santa Maria delle Grazie" Hospital in Pozzuoli (Naples) who needed a diagnostic lumbar puncture (LP). The ICP was initially measured using a standard narrow-gauge manometer by attaching it to the spinal needle. After removing the pressure gauge, the number of drops of cerebrospinal fluid flowing from the spinal needle in 30  seconds was counted. A statistical analysis was made with linear regression and ROC analysis. OP as measured by standard manometry was raised on 17 occasions with CSF drop rate median of 47 drops/30 seconds and range 30-74 drops/30 seconds. OP was normal on 35 occasions with CSF drop rate median of 23 drops/30 seconds  with range of 14-34 drops/30 seconds. A linear regression analysis was performed which resulted in a Pearson correlation of 0.936 an adjusted R square of 0.874 (see Fig. 1). Analysis through ANOVA documented an F of 355.301 with p < 0.01 and Dubin Watson of 1.642. The analysis through ROC showed an AUC of 0.980, with a sensitivity of 100% and a specificity of 91% if chosen as a limit, 29 drops in 30 seconds  (Youden Index of 0.9140). Therefore, we have concluded, that although there are several precautions, like patient's position, it is technically feasible to indirectly estimate cerebrospinal fluid pressure with good accuracy by counting the drops of cerebrospinal fluid flowing from a 22 G spinal needle.

Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

Evaluation of the effect of fluid management on intracranial pressure in patients undergoing laparoscopic gynaecological surgery based on the ratio of the optic nerve sheath diameter to the eyeball transverse diameter as measured by ultrasound: a randomised controlled trial.

BACKGROUND: During gynecological laparoscopic surgery, pneumoperitoneum and the Trendelenburg position (TP) can lead to increased intracranial pressure (ICP). However, it remains unclear whether perioperative fluid therapy impacts ICP. The purpose of this research was to evaluate the impact of restrictive fluid (RF) therapy versus conventional fluid (CF) therapy on ICP in gynecological laparoscopic surgery patients by measuring the ratio of the optic nerve sheath diameter (ONSD) to the eyeball transverse diameter (ETD) using ultrasound. METHODS: Sixty-four patients who were scheduled for laparoscopic gynecological surgery were randomly assigned to the CF group or the RF group. The main outcomes were differences in the ONSD/ETD ratios between the groups at predetermined time points. The secondary outcomes were intraoperative circulatory parameters (including mean arterial pressure, heart rate, and urine volume changes) and postoperative recovery indicators (including extubation time, length of post-anaesthesia care unit stay, postoperative complications, and length of hospital stay). RESULTS: There were no statistically significant differences in the ONSD/ETD ratio and the ONSD over time between the two groups (all p > 0.05). From T2 to T4, the ONSD/ETD ratio and the ONSD in both groups were higher than T1 (all p < 0.001). From T1 to T2, the ONSD/ETD ratio in both groups increased by 14.3%. However, the extubation time in the RF group was shorter than in the CF group [median difference (95% CI) -11(-21 to -2) min, p = 0.027]. There were no differences in the other secondary outcomes. CONCLUSION: In patients undergoing laparoscopic gynecological surgery, RF did not significantly lower the ONSD/ETD ratio but did shorten the tracheal extubation time, when compared to CF. TRIAL REGISTRATION: ChiCTR2300079284. Registered on December 29, 2023.

Analysis of intracranial pressure waveform using a non-invasive method in individuals with craniosynostosis.

PURPOSE: Craniosynostosis can lead to symptoms resulting from cranial compliance (CC) changes and intracranial hypertension (ICH), which may cause cognitive and visual impairment. Non-invasive methods have emerged, including a new device that captures and processes the intracranial pressure waveform (ICPw) by the skull's oscillation. The present study evaluates ICPw obtained non-invasively (NIICPw) in patients with craniosynostosis. METHODS: This prospective, cross-sectional, and descriptive study was conducted at a single center. Patients diagnosed with craniosynostosis and who provided informed consent were included. A US Food and Drug Administration-approved mechanical extensometer device (Brain4Care Corp.) was used to obtain a NIICPw. An ophthalmologist did a point-of-care retinography to check the optic nerve papilla. The P2/P1 ratio and the morphology of the NIICPw were analyzed, as well as the retinography. RESULTS: Thirty-five patients were evaluated, and 42 registers were obtained because seven were assessed before and after the surgery. The two patients who presented papilledema had low CC (NIICPw shape Class 3 or 4). There was a significant association between NIICPw and papilledema. CONCLUSION: The ratio P2/P1 and the NIICPw morphology provided by a non-invasive monitor are related to CC changes before papilledema occurs. This is especially useful in patients with craniosynostosis because invasive ICP monitoring is not always feasible. Further studies are warranted to establish the clinical utility of NIICPw in patients with craniosynostosis.