Surgery in octogenarians with intracranial meningiomas improves functional outcome at 1 year.

PURPOSE: The population is aging, and age remains an important factor in deciding surgical candidacy for intracranial tumors. The natural history and surgical behavior of meningiomas in octogenarians are not well understood. We evaluated the surgical and functional outcomes, including survival, among octogenarians with intracranial meningiomas in a single institution. METHODS: The Tumor Registry (2004-2021) was used to identify octogenarian patients (ages 80-89) diagnosed with intracranial meningioma. Primary endpoints were 1-year survival and functional outcome measured with mRS postsurgery. Kaplan-Meier, univariable Log-rank tests, and multivariable Cox hazards proportional regression models were used for assessing factors associated with overall survival (OS) in octogenarians with meningiomas who underwent surgery; logistic regression and McNemar's were used to further characterize risk factors affecting functional surgical outcome at 1 year. RESULTS: Thirty octogenarians with intracranial meningioma who underwent surgery were identified. Median age was 82.5 years and 66.6% were female patients. The 1-year median postsurgical survival probability for all octogenarians with meningioma was 86.3% and no intraoperative mortality was observed. Frailty (mFI-5, p = 0.84), tumor grade (p = 0.11), tumor size (p = 0.22), extent of resection (p = 0.35), and Karnofsky scale on admission (p = 0.93) did not significantly affect the survival in octogenarians with meningiomas which were treated surgically. The 1-year postoperative functional status of octogenarian meningioma patients who underwent surgery was significantly improved compared to pre-op mRS (McNemar's chi-squared = 9.6, df = 1, p-value = 0.001946). CONCLUSION: In octogenarians with meningiomas, surgical intervention significantly improves the pre-operative modified Rankin Scale at 1 year postsurgery in this cohort.

Aquaporins in Brain Edema and Neuropathological Conditions.

The aquaporin (AQP) family of water channels are a group of small, membrane-spanning proteins that are vital for the rapid transport of water across the plasma membrane. These proteins are widely expressed, from tissues such as the renal epithelium and erythrocytes to the various cells of the central nervous system. This review will elucidate the basic structure and distribution of aquaporins and discuss the role of aquaporins in various neuropathologies. AQP1 and AQP4, the two primary aquaporin molecules of the central nervous system, regulate brain water and CSF movement and contribute to cytotoxic and vasogenic edema, where they control the size of the intracellular and extracellular fluid volumes, respectively. AQP4 expression is vital to the cellular migration and angiogenesis at the heart of tumor growth; AQP4 is central to dysfunctions in glutamate metabolism, synaptogenesis, and memory consolidation; and AQP1 and AQP4 adaptations have been seen in obstructive and non-obstructive hydrocephalus and may be therapeutic targets.

Permeability of the arachnoid and pia mater. The role of ion channels in the leptomeningeal physiology.

PURPOSE: The purpose of this paper is to study the ionic permeability of the leptomeninges related to the effect of ouabain (sodium-potassium-ATPase inhibitor) and amiloride (epithelial sodium channel (ENaC) inhibitor) on the tissue, as well as identify the presence of ion channels. METHODS: Cranial leptomeningeal samples from 26 adult sheep were isolated. Electrophysiological measurements were performed with Ussing system and transmembrane resistance values (R(TM) in Ω*cm(2)) obtained over time. Experiments were conducted with the application of ouabain 10(-3) M or amiloride 10(-5) M at the arachnoidal and pial sides. Immunohistochemical studies of leptomeningeal tissue were prepared with alpha-1 sodium-potassium-ATPase (ATP1A1), beta-ENaC, and delta-ENaC subunit antibodies. RESULTS: The application of ouabain at the arachnoidal side raised the transmembrane resistance statistically significantly and thus decreased its ionic permeability. The addition of ouabain at the pial side led also to a significant but less profound increment in transmembrane resistance. The addition of amiloride at the arachnoidal or pial side did not produce any statistical significant change in the R(TM) from controls (p > 0.05). Immunohistochemistry confirmed the presence of the ATP1A1 and beta- and delta-ENaC subunits at the leptomeninges. CONCLUSIONS: In summary, leptomeningeal tissue possesses sodium-potassium-ATPase and ENaC ion channels. The application of ouabain alters the ionic permeability of the leptomeninges thus reflecting the role of sodium-potassium-ATPase. Amiloride application did not alter the ionic permeability of leptomeninges possibly due to localization of ENaC channels towards the subarachnoid space, away from the experimental application sites. The above properties of the tissue could potentially be related to cerebrospinal fluid turnover at this interface.

Hydrocephalus and aquaporins: lessons learned from the bench.

PURPOSE: Hydrocephalus is a common disorder of defective cerebrospinal fluid (CSF) turnover. The identification of the aquaporin water channels (AQPs) led to the study of their role in the composition of biological fluids including CSF. The purpose of this study is to review the potential role of aquaporins in the pathogenesis, compensation, and possibly treatment of hydrocephalus. METHODS: We performed a MEDLINE search using the terms "aquaporin AND hydrocephalus." The search returned a total of 20 titles. Eleven studies fulfilled the criteria for this review. RESULTS: Most studies were performed in animal models. The expression of AQPs in hydrocephalus is significantly altered. Aquaporin-1 levels at the choroid plexus are decreased in most models of hydrocephalus while CSF production and intracranial pressure are reduced in AQP1 knockout mice. In contrast, the expression of AQP4 in hydrocephalus is increased at its sites of expression. Aquaporin-4 knockout mice show a decreased clearance of brain edema via blood-CSF and blood-brain barrier (BBB) pathways and decreased survival in hydrocephalus models. CONCLUSIONS: Aquaporin-1 is highly expressed at the choroid plexus and is related to CSF production. Aquaporin-4 is expressed at the ependyma, glia limitans, and at the perivascular end feet processes of astrocytes of the BBB, facilitating the water movement across these tissue interfaces. The observations obtained from animal studies and few cases in humans indicate an adaptive and protective role of AQPs in hydrocephalus by decreasing CSF production and increasing edema clearance. Aquaporins are attractive targets for the pharmaceutical treatment of hydrocephalus.

Automated Lateral Ventricular and Cranial Vault Volume Measurements in 13,851 Patients Using Deep Learning Algorithms.

BACKGROUND: No large dataset-derived standard has been established for normal or pathologic human cerebral ventricular and cranial vault volumes. Automated volumetric measurements could be used to assist in diagnosis and follow-up of hydrocephalus or craniofacial syndromes. In this work, we use deep learning algorithms to measure ventricular and cranial vault volumes in a large dataset of head computed tomography (CT) scans. METHODS: A cross-sectional dataset comprising 13,851 CT scans was used to deploy U-Net deep learning networks to segment and quantify lateral cerebral ventricular and cranial vault volumes in relation to age and sex. The models were validated against manual segmentations. Corresponding radiologic reports were annotated using a rule-based natural language processing framework to identify normal scans, cerebral atrophy, or hydrocephalus. RESULTS: U-Net models had high fidelity to manual segmentations for lateral ventricular and cranial vault volume measurements (Dice index, 0.878 and 0.983, respectively). The natural language processing identified 6239 (44.7%) normal radiologic reports, 1827 (13.1%) with cerebral atrophy, and 1185 (8.5%) with hydrocephalus. Age-based and sex-based reference tables with medians, 25th and 75th percentiles for scans classified as normal, atrophy, and hydrocephalus were constructed. The median lateral ventricular volume in normal scans was significantly smaller compared with hydrocephalus (15.7 vs. 82.0 mL; P < 0.001). CONCLUSIONS: This is the first study to measure lateral ventricular and cranial vault volumes in a large dataset, made possible with artificial intelligence. We provide a robust method to establish normal values for these volumes and a tool to report these on CT scans when evaluating for hydrocephalus.

Spinal cord traction, vascular compromise, hypoxia, and metabolic derangements in the pathophysiology of tethered cord syndrome.

OBJECT: The definition of tethered cord syndrome (TCS) relies mainly on radiological criteria and clinical picture. The presence of a thickened filum terminale and a low-lying conus medullaris in symptomatic patients is indicative of TCS. The radiological definition of TCS does not take into account cases that involve a normal-lying conus medullaris exhibiting symptoms of the disease. METHODS: The authors performed a MEDLINE search using the terms "tethered cord" and "pathophysiology." The search returned a total of 134 studies. The studies were further filtered to identify mostly basic research studies in animal models or studies related to the biomechanics of the filum terminale and spinal cord. RESULTS: Spinal cord traction and the loss of filum terminale elasticity are the triggers that start a cascade of events occurring at the metabolic and vascular levels leading to symptoms of the disease. Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases. CONCLUSIONS: Although classically defined as a disease of a low-lying conus medullaris, the pathophysiology of TCS is much more complex and is dependent on a structural abnormality, with concomitant altered metabolic and vascular sequelae. Given the complex mechanisms underlying TCS, it is not surprising that the radiological criteria do not adequately address all presentations of the disease.

Role of the S100B serum biomarker in the treatment of children suffering from mild traumatic brain injury.

OBJECT: The aim of this study was to provide a systematic update of the current literature regarding the clinical role of the S100B serum biomarker in the initial evaluation of children who have sustained a mild traumatic brain injury (TBI). METHODS: Searches in MEDLINE were defined with the keywords "mild TBI children S100," "mild TBI pediatric S100," and "children S100 brain injury." From the pool of obtained studies, those that had the inclusion criteria of mild TBI only or mixed types of TBI but including detailed information about groups of children with mild TBI were used. RESULTS: Few studies were identified and fewer included more than 100 cases. The prospective studies showed that the S100B biomarker levels could be influenced by patient age and the time frame between head injury and blood sampling. Moreover, extracranial sources of S100B or additional injuries could influence the measured levels of this biomarker. A normal value of S100B in children with mild TBI could rule out injury-associated abnormalities on CT scans in the majority of reported cases. CONCLUSIONS: The vulnerability of S100B serum levels to the influences of patient age, blood sampling time, and extracranial S100B release limits the biomarker's role in the initial evaluation of children with mild TBI. The application of S100B in pediatric mild TBI cases has an elusive role, although it could help in selected cases to avoid unnecessary head CT scans.

Factors Predictive of Adjacent Segment Disease After Lumbar Spinal Fusion.

OBJECTIVE: Adjacent segment disease (ASD) is a long-term complication of lumbar spinal fusion. This study aims to evaluate demographic and operative factors that influence development of ASD after fusion for lumbar degenerative pathologies. METHODS: A retrospective cohort study was performed on patients undergoing instrumented lumbar fusion for degenerative disorders (spondylolisthesis, stenosis, or intervertebral disk degeneration) with a minimum follow-up of 6 months. RESULTS: Our inclusion criteria were met by 568 patients; 29.4% of patients had developed surgical ASD. Median follow-up was 2.8 years. Multivariate logistic regression analysis showed that decompression of segments outside the fusion construct had higher ASD (odds ratio = 2.6; P < 0.001), and those undergoing fusion for spondylolisthesis had lower ASD (odds ratio = 0.47; P = 0.003). CONCLUSIONS: Results of our study show that the most important surgical factor contributing to ASD is decompression beyond fused levels. Hence caution should be exercised when decompressing spinal segments outside the fusion construct. Conversely, spondylolisthesis patients had the lowest ASD rates in our cohort.

Intracranial hypertension after Chiari decompression resolving after removal of a levonorgestrel-releasing intrauterine device: case report.

Levonorgestrel-releasing intrauterine devices (LIUDs) are thought to release this progestin locally in the uterus to limit side effects. Authors here present a case of treatment-refractory hydrocephalus and pseudomeningocele (PMC), both of which fully resolved after LIUD removal.A 35-year-old woman with an implanted LIUD developed symptomatic PMC and hydrocephalus after suboccipital craniectomy for Chiari malformation type I. Over the next 8 months, she underwent ventriculoperitoneal shunt placement and two attempts at needle decompression of the fluid collection, which did not relieve her symptoms or the PMC, except for a few days at a time. Subsequently, she had her LIUD removed. Three weeks after removal of the LIUD, her symptoms as well as the fluid collection resolved completely without any further intervention. Thus, the increased intracranial pressure and associated persistence of the PMC may be partially attributed to the LIUD.This case indicates that a persistent problem (PMC and intracranial hypertension) that may be associated with the LIUD rapidly resolves after its removal. Implication of LIUDs as the cause of intracranial hypertension is still a matter of controversy. Further studies are needed to evaluate any potential causal relationship between LIUDs and intracranial hypertension, and physicians are advised to consider this scenario in their differential diagnosis.

Civilian Gunshot Wounds to the Head: Prognostic Factors Affecting Mortality: Meta-Analysis of 1774 Patients.

Civilian gunshot wounds to the head (cGSWH) are devastating, but there is no consensus regarding prognosis and management. Therefore, we conducted a meta-analysis to identify prognostic factors associated with mortality. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were queried for retrospective cohort studies of isolated cGSWH reporting mortality prognostic factors. Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Study quality was assessed using the Newcastle-Ottawa scale. Primary outcome was mortality. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived using random-effects models. Seventeen (17) observational studies (1774 patients) were identified and included. Factors associated with mortality were: age >40 years (OR, 3.44; 95% CI [1.71-6.91]), suicide attempt (5.78; [3.07-10.87]), Glasgow Coma Scale (GCS) 3-8 compared with 9-15 (38.02; [21.98-65.77]), GCS 3-5 versus 6-8 (15.38; [6.72-35.23], bilateral fixed and dilated pupils versus normal (67.12; [16.67-270.22]), and versus unilateral fixed and dilated pupil (25.35; [5.82-110.41]), dural penetration (29.07; [4.30-196.53]) and bihemispheric (4.23; [2.32-7.68]), and multi-lobar injuries (6.53; [1.99-21.42]). Selection for operative management, according to expert neurosurgical opinion, was protective (0.06; [0.01-0.22]). This is the first meta-analysis on cGSWH mortality prognostic factors. Increasing age, suicide attempt, lower GCS, bilateral mydriasis, dural penetration, and bihemispheric and multi-lobar injury are associated with increased mortality. This study can serve as a guide to clinicians and will provide directions for future research to develop evidence-based management algorithms.

Intraocular Silicone Oil Migration into the Ventricles Resembling Intraventricular Hemorrhage: Case Report and Review of the Literature.

BACKGROUND: Intracranial silicone migration is a rare complication of ocular silicone oil endotamponade and may resemble intraventricular hemorrhage. The etiology of the phenomenon is challenging to understand. CASE DESCRIPTION: In an effort to shed light on this phenomenon, we report a case of a 67-year-old woman with ocular silicone oil endotamponade on the left eye due to retinal detachment who presented with headache to the emergency department. The imaging work-up revealed intraventricular silicone oil migration. CONCLUSIONS: The literature is reviewed through the perspective of pathophysiology. The migration of intraocular silicone oil into the ventricular system provides both an important complication for clinicians to be aware of, as well as a paradigm reminding us that cerebrospinal fluid spaces may have more extensive communications with other body compartments than previously thought.

Propranolol Treatment of Cavernous Malformations with Symptomatic Hemorrhage.

BACKGROUND: Cerebral cavernous malformations are more common than generally thought, affecting approximately 1 in every 250 adults. Most of these lesions are asymptomatic or have a relatively benign course, but a small minority behave aggressively and present with recurrent episodes of symptomatic hemorrhage. A safe and effective medical treatment option for the management of this latter group would be useful. Propranolol has recently been shown to be effective in the treatment of infantile hemangioma, a close pathologic counterpart of cavernous malformations. These results suggest a potential role for propranolol treatment in the management of patients with symptomatic cavernous malformations. METHODS: Low-dose propranolol (20 mg, three times daily) was used to treat 2 adult female patients in their mid- to late fifties, both of whom had symptomatic cavernous malformations and a history of repeated hemorrhage. Serial magnetic resonance imaging studies after the initiation of propranolol demonstrated regression of the lesions and no evidence of recurrent hemorrhage. CONCLUSIONS: Propranolol may offer a safe and effective treatment for patients who have cavernous malformations with symptomatic hemorrhage. Additional studies are needed to confirm these findings.

Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.

OBJECTIVES: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. DESIGN AND METHODS: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. RESULTS: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean±SEM) of Sesn2 in patients with MPEs was 0.54±0.22ng/mL while in BPEs it was 0.12±0.04ng/mL (p=0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p=0.89 and p=0.64 respectively). CONCLUSIONS: Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells.

Real-time monitoring of changes in brain extracellular sodium and potassium concentrations and intracranial pressure after selective vasopressin-1a receptor inhibition following focal traumatic brain injury in rats.

Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na(+) and K(+) concentrations ([Na(+)]e; [K(+)]e). Ion-selective Na(+) and K(+) electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na(+)]e, [K(+)]e, and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na(+)]e to 80.1 ± 15 and 87.9 ± 7.9 mM and increase in [K(+)]e to 20.9 ± 3.8 and 13.4 ± 3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p<0.001 vs. baseline; ns between groups). Importantly, [Na(+)]e in CCI-SR49059-ISE was reduced 5-20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na(+)]e recovery. In contrast, [K(+)]e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na(+)]e recovery and reduced ICP. By augmenting the [Na(+)]e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI.

Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury.

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm(2)) versus sham groups (78.3±0.1%; 9.5±0.9 µm(2)), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8µm(2)). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03±0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema.

Nano-TiO2 particles impair adhesion of airway epithelial cells to fibronectin.

Titanium dioxide engineered nanoparticles (nano-TiO(2)) are widely used in the manufacturing of a number of products. Due to their size (<100 nm), when inhaled they may be deposited in the distal lung regions and damage Clara cells. We investigated the mechanisms by which short-term (1-h) incubation of human airway Clara-like (H441) cells to nano-TiO(2) (6 nm in diameter) alters the ability of H441 cells to adhere to extracellular matrix. Our results show that 1h post-incubation, there was a 3-fold increase of extracellular H(2)O(2), increased intracellular oxidative stress as demonstrated by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation, and a 5-fold increase of phosphor-ERK1/2 as measured by Western blotting. These changes were accompanied by a 25% decrease of H441 adherence to fibronectin (p<0.05 compared to vehicle incubated H441 cells). Pretreatment with the ERK1/2 inhibitor U0126 for 3h, partially prevented this effect. In conclusion, short-term exposure of H441 cells to nano-TiO(2) appears to reduce adherence to fibronectin due to oxidative stress and activation of ERK1/2.

Assessment of locomotion in chlorine exposed mice by computer vision and neural networks.

Assessment of locomotion following exposure of animals to noxious or painful stimuli can offer significant insights into underlying mechanisms of injury and the effectiveness of various treatments. We developed a novel method to track the movement of mice in two dimensions using computer vision and neural network algorithms. By using this system we demonstrated that mice exposed to chlorine (Cl(2)) gas developed impaired locomotion and increased immobility for up to 9 h postexposure. Postexposure administration of buprenorphine, a common analgesic agent, increased locomotion and decreased immobility times in Cl(2)- but not air-exposed mice, most likely by decreasing Cl(2)-induced pain. This method can be adapted to assess the effectiveness of various therapies following exposure to a variety of chemical and behavioral noxious stimuli.