Cerebrospinal Fluid Circulation Research Articles

Navigated Endoport in the Purely Endoscopic Microsurgery of Intraventricular and Other Deep-Seated Brain Lesions: A Case Report

<p><strong>Objective. </strong>Brain parenchyma retraction is often necessary to reach various deep brain lesions during surgery. In order to minimise the incidence of the brain retraction injury, an endoport system may be employed. We present a report of a navigated endoport system in conjunction with an purely endoscopic microsurgery that was used in a patient with a deep-seated subependymoma.</p><p><strong>Case Report. </strong>A navigated endoport with purely endoscopic microsurgery were used in a patient with a tumour</p><p>located in the frontal horn of the left lateral ventricle. The endoport channel was made of a polyvinyl sheet that was cut into a 7 cm square, rolled into a tubular structure that was wrapped around the neuronavigational probe, and inserted in the access trajectory to the tumour. The endoport tube was then expanded with a balloon to a diameter of 7 mm and a surgical corridor was thus formed. During the purely endoscopic microsurgical lesionectomy, the tumour was completely removed from the frontal horn. The foramen of Monro was released and the septum pellucidum was perforated for better cerebrospinal fluid circulation. Histopathological examination confirmed the tumour as subependymoma. The recovery of the patient was unremarkable.</p><p><strong>Conclusion. </strong>The expandable endoport system supplemented with neuronavigation is a safe and efficient option for deep-seated tumour removal. The tubular shape of the retractor enables standard microsurgical techniques through minimally invasive approaches and offers an excellent visualization of the underlying lesion.</p>

External Ventricular Drainage in Patients With Acute Aneurysmal Subarachnoid Hemorrhage After Microsurgical Clipping: Our 2006-2018 Experience and a Literature Review.

IntroductionThe placement of an external ventricular drain (EVD) is widely practiced in neurosurgery for various diseases and conditions accompanied by impaired cerebrospinal fluid (CSF) circulation, intracranial hypertension (ICHyp), intraventricular hemorrhage (IVH), and hydrocephalus. Specialists have been using this method in patients with acute aneurysmal subarachnoid hemorrhage (aSAH) for more than 50 years. Extensive experience gained at the Burdenko Neurosurgical Center (BNC) in Moscow, the Russian Federation, in the surgical treatment of patients with acute aSAH enabled us to describe the results of using an EVD in patients after microsurgery. The objective of the research was to assess the effectiveness and safety of the EVD and clarify the indications for the microsurgical treatment of aneurysms in patients with acute SAH.Materials and methodsFrom 2006 until the end of 2018, 645 patients registered in the BNC database underwent microsurgery for acute (0-21 days) aSAH. During the case study, we assessed the severity of hemorrhage according to the Fisher scale, the condition of patients on the Hunt-Hess (H-H) scale during surgery, the time of placement of EVD (before, during, and after surgery), and the duration of EVD. The number of patients with parenchymal intracranial pressure (ICP) transducers was assessed by the degree of correlation of ICP data through the EVD and parenchymal ICP transducer. One of the aims of the research was to compare the frequency of using EVD and decompressive craniectomy (DCH). The incidence of EVD-associated meningitis was analyzed. The need for a ventriculoperitoneal shunt (VPS) in patients after using EVD was also assessed. Overall outcomes were assessed using a modified Rankin scale (mRS) at the time of patient discharge. Exclusion criteria were as follows: patients aged less than 18 years and the lack of assessed data. Patients undergoing endovascular and conservative treatments also were excluded.ResultsAmong the patients enrolled in the study, 22% (n=142) had EVD. Among these, 99 cases (69.7%) had EVD installed in the operating room just before the start of the surgical intervention. In some cases, ventriculostomy was performed on a delayed basis (16.3%). A satisfactory outcome (mRS scores of 1 and 2) was observed in 24.7% (n=35). Moderate and profound disability at the time of discharge was noted in 55.7% (n=79). Vegetative outcome at discharge was noted in 8.4% (n=12), and mortality occurred in 12.3% (n=15).ConclusionEVD ensures effective monitoring and reduction of ICP. EVD is associated with a relatively low risk of infectious, liquorodynamic, and hemorrhagic complications and does not worsen outcomes when used in patients with aSAH. We propose that all patients in the acute stage of SAH with H-H severity of III-V should receive EVD immediately before surgery.

Automated Analysis of Cerebrospinal Fluid Flow and Motile Cilia Properties in The Central Canal of Zebrafish Embryos.

Circulation of cerebrospinal fluid (CSF) plays an important role during development. In zebrafish embryo, the flow of CSF has been found to be bidirectional in the central canal of the spinal cord. In order to compare conditions and genetic mutants across each other, we recently automated the quantification of the velocity profile of exogenous fluorescent particles in the CSF. We demonstrated that the beating of motile and tilted cilia localized on the ventral side of the central canal was sufficient to generate locally such bidirectionality. Our approach can easily be extended to characterize CSF flow in various genetic mutants. We provide here a detailed protocol and a user interface program to quantify CSF dynamics. In order to interpret potential changes in CSF flow profiles, we provide additional tools to measure the central canal diameter, characterize cilia dynamics and compare experimental data with our theoretical model in order to estimate the impact of cilia in generating a volume force in the central canal. Our approach can also be of use for measuring particle velocity in vivo and modeling flow in diverse biological solutions.

Effects of Cranioplasty After Decompressive Craniectomy on Neurological Function and Cerebral Hemodynamics in Traumatic Versus Nontraumatic Brain Injury.

After decompressive craniectomy (DC), cranioplasty (CP) can help to normalize vascular and cerebrospinal fluid circulation besides improving the patient's neurological status. The aim of this study was to investigate the effects of CP on cerebral hemodynamics and on cognitive and functional outcomes in patients with and without a traumatic brain injury (TBI). Over a period of 3years, 51 patients were included in the study: 37 TBI patients and 14 non-TBI patients. The TBI group was younger (28.86±9.71 versus 45.64±9.55years, P=0.0001), with a greater proportion of men than the non-TBI group (31 versus 6, P=0.011). Both groups had improved cognitive outcomes (as assessed by the Mini-Mental State Examination) and functional outcomes (as assessed by the Barthel Index and Modified Rankin Scale) 90days after CP. In the TBI group, the mean velocity of blood flow in the middle cerebral artery ipsilateral to the cranial defect increased between the time point before CP and 90days after CP (34.24±11.02 versus 42.14±10.19cm/s, P=0.0001). In conclusion, CP improved the neurological status in TBI and non-TBI patients, but an increment in cerebral blood flow velocity after CP occurred only in TBI patients.

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p<0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p<0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.

Chapter 14 - Lamina terminalis fenestration: An important neurosurgical corridor

Cerebrospinal fluid (CSF) disorders are challenging conditions in neurosurgical practice. The majority of CSF is contained in the basal cisterns of the brain, which are subarachnoid compartments that communicate with each other, and contribute to the circulation of CSF. Yaşargil et al. (1976) was the first to provide the systematic classification and naming of the basal cisterns. The lamina terminalis (LT) starts from the gyrus rectus and descends to the lateral aspect of the optic chiasm. It is a thick arachnoidal membrane delineating the anterior wall of the third ventricle that borders the LT cistern. With the introduction of the operating microscope and the progressive development of modern neurosurgery, the arachnoid and basal cisterns have been used as surgical corridors in order to reach deep areas of the brain and to release CSF for brain relaxation. In this way, the LT is used as a surgical corridor for the treatment of several conditions such as obstructive hydrocephalus and diencephalic tumors. In this chapter, we will describe the anatomy of the LT, possible conditions treated by opening the LT, the different surgical approaches to opening the LT, along with their advantages and disadvantages.

Mathematical Modelling in Hydrocephalus.

Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions. This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus. Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.

The Role of Cerebrospinal Fluid Dynamics in Normal Pressure Hydrocephalus Diagnosis and Shunt Prognostication.

Over the years, there have been several reports and trials of the resistance to cerebrospinal fluid (CSF) outflow (Rout) in normal pressure hydrocephalus (NPH). This work aimed to revisit the utility of testing CSF circulation in a large population of patients clinically presenting with NPH. We retrospectively analyzed the data of 369 NPH patients-either shunted or with endoscopic third ventriculostomy (ETV)-in Cambridge between 1992 and 2018. We determined the patients' outcomes (improvement versus no improvement at 6months) by applying a threshold on R out values and compared our results with those of existing literature. We also conducted a correlation analysis between all variables and calculated Chi-Statistics (as a measure of separability between improvement and no improvement outcomes) to determine a subset of variables which achieved the highest accuracy in prediction of outcome. In our dataset, R out of 18mmHg*min/mL achieved the highest Chi-statistics of 9.7 with p-value <0.01 when adjusted for age. In addition to R out, intracranial pressure (ICP) values at the baseline and plateau, CSF production rate and ICP amplitude to slope ratio showed significant Chi-Statistics values (more than 5). Using these variables, an overall accuracy of 0.70±0.09 was achieved for prediction of the shunt outcome. Rout can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Critical, multivariable approaches are required to comprehend CSF dynamics and pressure-volume compensation in NPH. Outcome definition and assessment could also be brought to question.

Dynamic disequilibrium of macromolecular transport as possible mechanism for hydrocephalus associated with long-term spaceflight

Hydrocephalus associated with long term spaceflight (HALS) for missions lasting over five months is well described but poorly understood. While structural changes of the brain due to microgravitational forces affecting the circulation of cerebrospinal fluid (CSF) have been described as one potential cause, we propose an alternative hypothesis based on dynamic disequilibrium of macromolecular transport across the blood brain barrier. We propose that factors altering physiology under conditions of spaceflight such as microgravity, hypercapnia, venous hypertension, medications, and dietary substances contribute to increased protein load in the ventricles and/or contribute to impairment of transport out of the ventricles that results in HALS. Individual variation in the genetic expression of efflux transporters (p-glycoprotein) has been shown to correlate with the presence and degree of hydrocephalus in animal studies. We describe the evidence behind this concept and propose how these factors can be studied in order to determine the underlying pathogenesis which is imperative in order to cure or prevent HALS.

Posthemorrhagic Hydrocephalus With Decompensation Of Cerebrospinal Fluid Dynamics In Newborns: New In Treatment Tactics

Background ― Posthemorrhagic hydrocephalus in newborns with occlusion of cerebrospinal fluid leads to decompensation of cerebrospinal fluid dynamics. There is no single method that meets all the criteria for the effectiveness and safety of treatment. The study goal was to investigate the use of coronary translambdoid subarachnoid ventriculostomy (CTSV) and ventricular subarachnoid stenting (VSS) in the treatment of neonatal hydrocephalus. Material and Methods ― The analysis of the posthemorrhagic hydrocephalus treatment in 327 newborns for the period of 2000-2018 in Crimea. Two groups have been identified. In the Group 1, 184 children underwent standard treatment according to the ‘LVV protocol’ with lumbar and ventricular punctures with 20-22G needles, while with progression of hydrocephalus, with ventriculosubgaleal drainage and ventriculoperitoneal shunt. In 143 children with occlusion and ventricular block, the treatment complex included CTSV – RF Patent No. 2715535, and ventricular drainage by the ventricular subarachnoid stenting (VSS) – RF Patent No. 2721455. Results ― An increase in the treatment radicality under CTSV is achieved through the use of the cerebral needles of a larger diameter (14G) and puncture access zones, elimination of occlusion, while under VSS, restoration of intracranial circulation and absorption of cerebrospinal fluid is ensured by prolonged sanitation with a saline solution of cerebrospinal fluid spaces. A positive outcome with compensation for hydrocephalus was achieved in 75.4% of cases versus 28.2% under the conventional protocol (p&lt;0.001). In other cases, the imbalance of production and absorption of cerebrospinal fluid remained, which required the integration of the VSS with the peritoneal segment of the shunt, without further replacement and reinstallation of the system. Conclusion ― Our results allow us to consider the effectiveness of CTSV and VSS inclusion in the contemporary algorithm for the treatment of decompensated posthemorrhagic hydrocephalus in newborns.

Effect of Surgical Arachnoid Plasty on Functional Outcome in Aneurysmal Subarachnoid Hemorrhage

Various techniques have been performed to reduce subarachnoid clotting during aneurysmal neck clipping surgery. We considered that maintaining the physiologic cerebrospinal fluid circulation by performing arachnoid plasty after clipping during surgery would lead to the accelerated clearance of the subarachnoid clot. Patients in a prospectively maintained aneurysmal subarachnoid hemorrhage (aSAH) database at our institution and with aSAH that fulfilled the criteria were selected for this study. The incidence of delayed cerebral ischemia, angiographic vasospasm, 3-month functional outcome, and the amount of subarachnoid clot on computed tomography were compared between the 2 groups after matching. From 2006 through 2016, 228 clipping cases met the inclusion criteria. Using propensity score matching, 89 cases of clipping without arachnoid plasty were matched to 89 cases of clipping with arachnoid plasty. Univariate analyses showed that arachnoid plasty significantly reduced the occurrence of hydrocephalus and incidence of poor outcome. Arachnoid plasty statistically significantly reduces the occurrence of hydrocephalus (odds ratio 0.267, 95% confidence interval 0.074-0.963, P < 0.05). Multivariate analysis also showed that arachnoid plasty was the factor reducing poor outcome at 3 months after aSAH (odds ratio 0.222, 95% confidence interval 0.075-0.661, P < 0.01). The present study suggests that good hematoma clearance due to arachnoid formation reduced brain damage, cerebral vasospasm, and hydrocephalus, resulting in significantly fewer cases with poor functional prognosis. It therefore follows that procedures such as arachnoid plasty should be taken into consideration in order to improve outcome in surgical clipping.

In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces

BackgroundHydrocephalus, the pathological expansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles, is a common, deadly disease. In the adult, cardiac and respiratory forces are the main drivers of CSF flow within the brain ventricular system to remove waste and deliver nutrients. In contrast, the mechanics and functions of CSF circulation in the embryonic brain are poorly understood. This is primarily due to the lack of model systems and imaging technology to study these early time points. Here, we studied embryos of the vertebrate Xenopus with optical coherence tomography (OCT) imaging to investigate in vivo ventricular and neural development during the onset of CSF circulation.MethodsOptical coherence tomography (OCT), a cross-sectional imaging modality, was used to study developing Xenopus tadpole brains and to dynamically detect in vivo ventricular morphology and CSF circulation in real-time, at micrometer resolution. The effects of immobilizing cilia and cardiac ablation were investigated.ResultsIn Xenopus, using OCT imaging, we demonstrated that ventriculogenesis can be tracked throughout development until the beginning of metamorphosis. We found that during Xenopus embryogenesis, initially, CSF fills the primitive ventricular space and remains static, followed by the initiation of the cilia driven CSF circulation where ependymal cilia create a polarized CSF flow. No pulsatile flow was detected throughout these tailbud and early tadpole stages. As development progressed, despite the emergence of the choroid plexus in Xenopus, cardiac forces did not contribute to the CSF circulation, and ciliary flow remained the driver of the intercompartmental bidirectional flow as well as the near-wall flow. We finally showed that cilia driven flow is crucial for proper rostral development and regulated the spatial neural cell organization.ConclusionsOur data support a paradigm in which Xenopus embryonic ventriculogenesis and rostral brain development are critically dependent on ependymal cilia-driven CSF flow currents that are generated independently of cardiac pulsatile forces. Our work suggests that the Xenopus ventricular system forms a complex cilia-driven CSF flow network which regulates neural cell organization. This work will redirect efforts to understand the molecular regulators of embryonic CSF flow by focusing attention on motile cilia rather than other forces relevant only to the adult.

Two‐point dynamic observation of Alzheimer’s disease cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

AbstractBackgroundExtensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one‐point observation.ObjectiveTo investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients.MethodsWe analyzed CSF concentrations of tau, amyloid‐β (Aβ) 42 and 40, and leucine rich α‐2‐glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two‐point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo‐peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF).ResultsTau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aβ42 (LD/FD = 0.80, p &lt; 0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p &lt; 0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with LD concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively.ConclusionsDynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH. CSF circulation is disturbed in iNPH and old style one‐point CSF biomarker observation can be misestimated. This study detected dynamic changes of CSF biomarkers in iNPH during routine tap test and revealed the linkage between 1ml Last Drip of lumbar CSF and ventricular CSF.

Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging

BackgroundContinuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear.MethodsDynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes.ResultsBased on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces.ConclusionsCollectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

Risk factors for hydrocephalus following fourth ventricle tumor surgery: A retrospective analysis of 121 patients

Most patients who present with a fourth ventricle tumor have concurrent hydrocephalus, and some demonstrate persistent hydrocephalus after tumor resection. There is still no consensus on the management of hydrocephalus in patients with fourth ventricle tumor after surgery. The purpose of this study was to identify the factors that predispose to postoperative hydrocephalus and the need for a postoperative cerebrospinal fluid (CSF) diversion procedure. We performed a retrospective analysis of patients who underwent surgery of the fourth ventricle tumor between January 2013 and December 2018 at the Department of Neurosurgery in West China Hospital of Sichuan University. The characteristics of patients and the tumor location, tumor size, tumor histology, and preventive external ventricular drainage (EVD) that were potentially correlated with CSF circulation were evaluated in univariate and multivariate analysis. A total of 121 patients were enrolled in our study; 16 (12.9%) patients underwent postoperative CSF drainage. Univariate analysis revealed that superior extension (p = 0.004), preoperative hydrocephalus (p<0.001), and subtotal resection (p<0.001) were significantly associated with postoperative hydrocephalus. Multivariate analysis revealed that superior extension (p = 0.013; OR = 44.761; 95% CI 2.235-896.310) and subtotal resection (p = 0.005; OR = 0.087; 95% CI 0.016-0.473) were independent risk factors for postoperative hydrocephalus after resection of fourth ventricle tumor. Superior tumor extension (into the aqueduct) and failed total resection of tumor were identified as independent risk factors for postoperative hydrocephalus in patients with fourth ventricle tumor.

Acute Presentation of Normal Pressure Hydrocephalus After Transcatheter Aortic Valve Implantation: A Novel Interaction Between the First and Third Circulations

Idiopathic normal pressure hydrocephalus (iNPH) negatively affects gait and cognition abilities and urine continence in the elderly. It is associated with systemic hypertension, although the exact pathophysiology is still unknown. A correlation to increased intracranial pulsatility and decreased compliance was suggested. Transcatheter aortic valve implantation (TAVI) is increasingly used in the treatment of severe AS. New-onset systemic hypertension affects some patients after TAVI. To identify any association between aortic valve replacement and the development of NPH. A cohort was created retrospectively of all patients who were evaluated for NPH with cerebrospinal fluid (CSF) tap test at a single institute during 2014-2019. Patients were reviewed for a past medical history of aortic valvular disease or aortic valve replacement. A total of 242 patients underwent evaluations for NPH. Of these patients, 133 were considered to have iNPH. Six patients underwent aortic valve replacement before the initial symptoms of NPH: 1 surgical and 5 TAVI. The time from aortic valve replacement to the initial NPH symptoms was <6 months in 3 patients (as low as 1 month in 2 of them). Two patients had functional improvement after CSF tap test and proceeded to receive a shunt, 4 and 6 months after TAVI, respectively. Two patients developed hypertension after TAVI. Pulse pressure increased by >10 mm Hg in 3 patients after TAVI. This is the first case series of symptomatic NPH after TAVI. In this unique subgroup, NPH symptoms can develop rapidly. Post-TAVI iNPH represents a novel interaction between the blood and CSF circulations.

Intracranial Hemorrhage

Intracranial Hemorrhage

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus

Introduction: Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour. Objective: The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice. Methods: Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-μm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains. Results: Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10⁻⁶ μm² vs. 157.70 ± 21.88 × 10⁻⁶ μm²; 230.0 ± 44.1 × 10⁻⁶ μm² vs. 129.60 ± 3.72 × 10⁻⁶ μm², respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls. Conclusion: In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.

Safety Evaluation of Biportal Endoscopic Lumbar Discectomy: Assessment of Cervical Epidural Pressure During Surgery.

A prospective study. To evaluate the change in cervical epidural pressure (CEP) during biportal endoscopic lumbar discectomy (BELD). In percutaneous uniportal endoscopic lumbar discectomy, irrigation fluid (IF) introduced into the spinal canal during surgery can compress the thecal sac, and act as a potential risk for neurological complications by disturbing cerebrospinal fluid (CSF) circulation and increasing intracranial pressure. Thirty consecutive patients, who underwent BELD, which was performed under automated pump system, an infusion pressure of 30 mmHg were enrolled. The change in CEP on C7-T1 level was measured. CEP was measured in each of the five phases of the procedure (1st phase-making surgical portals; 2nd phase-creating a workspace; 3rd phase-performing neural decompression and discectomy; 4th phase-factitious increase of pressure by clogging the outflow; 5th phase-dismission from fluid irrigation system). Neurological complications and independent risk factors were evaluated. In the final 27 patients, changes in CEP during surgery were similar. The baseline CEP was 14.8 ± 2.8 mmHg, and the mean CEP in the 3rd phase 18.8 ± 5.1 mmHg was not significantly higher. In the 4th phase, however, the CEPs rose with linear correlation as the pressure increased. In the 5th phase, the elevated CEP returned to baseline in 2.5 ± 5.6 minutes. No patient had neurological complications. No statistically significant risk factors were observed. In BELD, which is performed to allow continuous lavage with infusion pressure set to 30 mmHg, CEP does not increase beyond the physiological range. Therefore, BELD may be considered as a potentially safe technique. 4.

Respiratory cerebrospinal fluid flow is driven by the thoracic and lumbar spinal pressures.

Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system. During inspiration increased venous return from the cranium is believed to draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration. We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures. These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory-related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections. It is accepted that during inspiration, cerebrospinal fluid (CSF) flows rostrally to compensate for decreased cranial blood volume, caused by venous drainage due to negative intrathoracic pressure. However, this mechanism does not explain observations of caudal CSF displacement during inspiration. Determining the drivers of respiratory CSF flow is crucial for understanding the pathophysiology of CSF flow disorders. To quantify the influence of respiration on CSF flow, real-time phase-contrast magnetic resonance imaging (MRI) was used to record CSF and blood flow, while healthy subjects (5:5 M:F, 25-50 years) performed either a brief expiratory or inspiratory effort between breaths. Transverse images were taken perpendicular to the spinal canal in the middle of the C3 and L2 vertebrae. The same manoeuvres were then performed after a nasogastric pressure catheter was used to measure the intrathoracic and abdominal pressures. During expiratory-type manoeuvres that elevated abdominal and intrathoracic pressures, epidural blood flow into the spinal canal increased and CSF was displaced rostrally. With inspiratory manoeuvres, the negative intrathoracic pressure drew venous blood from C3 and L2 towards the thoracic spinal canal, and cervical CSF was displaced both rostrally and caudally, despite the increased venous drainage. Regression analysis showed that rostral displacement of CSF at both C3 (adjusted R2 =0.53; P<0.001) and L2 (adjusted R2 =0.38; P<0.001) were associated with the abdominal pressure. However, with low abdominal pressure and comparably negative intrathoracic pressure, cervical CSF flowed caudally. These findings suggest that changes in both the cranial and spinal pressures need to be considered to understand respiratory CSF flow.