Intraventricular Cerebrospinal Fluid Research Articles

Predicting the need for cerebrospinal fluid shunt implantation after spontaneous intracerebral hemorrhage: a challenging task.

The development of persistent hydrocephalus in patients after spontaneous intracerebral hemorrhage (ICH) is still poorly understood, and many variables predicting the need for a cerebrospinal fluid (CSF)-shunt have been described in the literature with varying results. The aim of this study is to find predictive factors for shunt dependency. We performed a retrospective, single-center study of 99 neurosurgically treated patients with spontaneous ICH. Variables, including age, Glasgow Coma Scale (GCS), intraventricular hemorrhage (IVH), location of hemorrhage, acute hydrocephalus, and volumetric analysis of IVH, ICH, and intraventricular CSF were compared between patients with and without CSF-shunt implantation. Furthermore, receiver operating characteristics (ROC) for ICH, IVH, and intraventricular CSF volume parameters were calculated. CSF-shunt implantation was performed significantly more often in patients after thalamic (p = 0.03) and cerebellar ICH (p = 0.04). Moreover, a lower ratio between the total hemorrhage volume and intraventricular CSF volume (p = 0.007), a higher IVH distribution in the third ventricle, and an acute hydrocephalus (p < 0.001) with an increased intraventricular CSF volume (p < 0.001) were associated with shunt dependency. Our ROC model demonstrated a sensitivity of 82% and a specificity of 65% to predict the necessity for a shunt at a cutoff value of 1.9 with an AUC of 0.835. Volumetric analysis of ICH, IVH, and intraventricular CSF may improve the prediction of CSF shunt implantation in patients with spontaneous ICH.

BIOM-27. CELL-FREE DNA-BASED LIQUID BIOPSIES FOR THE REAL-TIME TRACKING OF TUMOR BURDEN AND TREATMENT RESPONSE IN GLIOBLASTOMA

Abstract Cell-free DNA (cfDNA) are short fragments of DNA that are released by apoptotic or necrotic cells into bodily fluids. It has emerged as a potential diagnostic tool allowing for the detection and analysis of tumor-derived biomarkers in cancer. Despite the detailed view provided by clinical imaging, its inability to quantify tumor burden and distinguish between pseudo-progression and pseudo-response poses a challenge for patients. In this study, we sought to investigate the effectiveness of cfDNA as a liquid biopsy tool to track tumor burden and disease progression in real time in different glioblastoma models and through different types of biofluids. To examine the feasibility of cfDNA-based tumor tracking we cultivated several patient-derived glioblastoma lines, purified cfDNA and performed sequencing. Further analysis revealed that dead cells were associated with an elevated cfDNA yield and altered fragment size profiles. Genomic sequencing revealed consistent variants shared across serial cfDNA timepoints, strengthening the suggestion that cfDNA can be used as a non-invasive biomarker. In order to demonstrate the clinical implications of our methodology, we collected a preliminary batch of n = 43 longitudinal intraventricular cerebrospinal fluid (CSF) samples from a patient that underwent CAR-T treatment over the span of two years. We observed a marked increase in cfDNA yield post-treatment compared to samples taken prior to treatment administration. Furthermore, cfDNA-based estimates of tumor burden measured as allele fraction specific to the tumor, tracked with clinical imaging-based tumor size estimates. These preliminary findings provide compelling evidence supporting the clinical utility of cfDNA analysis in monitoring the effectiveness and dynamics of CAR-T treatment. By tracking cfDNA levels in CSF, we can identify patterns reflecting treatment response and aid in assessing the therapeutic efficiency of CAR-T treatment in glioma patients. Further investigations with larger patient cohorts and more comprehensive data analysis to validate these findings are actively underway.

A Minimal PBPK Model for Plasma and Cerebrospinal Fluid Pharmacokinetics of Trastuzumab after Intracerebroventricular Administration in Patients with HER2-Positive Brain Metastatic Localizations.

Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in human plasma and cerebrospinal fluid (CSF) after simultaneous icv and intravenous (iv) administration using a minimal physiologically-based pharmacokinetic model (mPBPK) and to perform simulations of alternative dosing regimens to achieve therapeutic concentrations in CSF. Plasma and CSF PK data were collected in two patients with HER2-positive brain localizations. A mPBPK model for mAbs consisting of four compartments (tight and leaky tissues, plasma and lymph) was enriched by an additional compartment for ventricular CSF. The comparison between observed and model-predicted concentrations was evaluated using prediction error (PE). The developed mPBPK model described plasma and CSF trastuzumab concentrations reasonably well with mean PE for plasma and CSF data of 41.8% [interquartile range, IQR = -9.48; 40.6] and 18.3% [-36.7; 60.6], respectively, for patient 1 and 11.4% [-10.8; 28.7] and 22.5% [-27.7; 77.9], respectively, for patient 2. Trastuzumab showed fast clearance from CSF to plasma with Cmin,ssof 0.56 and 0.85mg/L for 100 and 150mg q1wk, respectively. Repeated dosing of 100 and 150mg q3day resulted in Cmin,ssof 10.3 and 15.4mg/L, respectively. Trastuzumab CSF target concentrations are achieved rapidly and maintained above 60mg/L from 7days after a continuous perfusion at 1.0mg/h. Continuous icv infusion of trastuzumab at 1.0mg/h could be an alternative dosing regimen to rapidly achieve intraventricular CSF therapeutic concentrations.

Correspondence between development of cytotoxic edema and cerebrospinal fluid volume and flow in the third ventricle after ischemic stroke

ObjectivesThe importance of monitoring cerebrospinal fluid for the development of edema in ischemic stroke has been emphasized; however, studies on the relationship between intraventricular cerebrospinal fluid behavior and edema through longitudinal observations and analysis are rare. This study aimed to investigate the correlation between the development of cytotoxic edema and cerebrospinal fluid volume and flow in the third ventricle after ischemic stroke. Materials and methodsThe ventricle and edema regions were obtained using apparent diffusion coefficients and T2 and subdivided into lateral/ventral 3rd ventricles and cytotoxic/vasogenic (or cyst) edema, respectively. In rat models of ischemic stroke, the volume and flow (via the pseudo-diffusion coefficient [D*]) of the ventricles and edema volumes were longitudinally monitored for up to 45 days after surgery. ResultsThe volume of cytotoxic edema increased in the hyperacute and acute phases, whereas the volume (r = -0.49) and median D* values (r = -0.48 in the anterior-posterior direction) of the ventral 3rd ventricle both decreased, showing negative correlations with the volume of cytotoxic edema. In contrast, the volume of vasogenic edema/cyst was positively correlated with the volume (r = 0.73) and median D* values (r = 0.78 in the anterior-posterior direction) of the lateral ventricle in the subacute and chronic phases. ConclusionsThis study showed that the evolution of cerebrospinal fluid volume and flow in the ventricles was associated with edema progression at different time points in the ischemic stroke brain. This provides an efficient framework for monitoring and quantifying the interplay between cerebrospinal fluid and edema.

Evaluation of the Cerebrospinal Fluid Flow Dynamics with Microvascular Imaging Ultrasound in Infants.

Microvascular imaging ultrasound (MVI) can detect slow blood flow in small-caliber cerebral vessels. This technology may help assess flow in other intracranial structures, such as the ventricular system. In this study, we describe the use of MVI for characterizing intraventricular cerebrospinal fluid (CSF) flow dynamics in infants. We included infants with brain ultrasound that had MVI B-Flow cine clips in the sagittal plane. Two blinded reviewers examined the images, dictated a diagnostic impression, and identified the third ventricle, cerebral aqueduct, fourth ventricle, and CSF flow direction. A third reviewer evaluated the discrepancies. We evaluated the association of visualization of CSF flow as detectable with MVI, with the diagnostic impressions. We also assessed the inter-rater reliability (IRR) for detecting CSF flow. We evaluated 101 infants, mean age 40 ± 53 days. Based on brain MVI B-Flow, a total of 49 patients had normal brain US scans, 40 had hydrocephalus, 26 had intraventricular hemorrhage (IVH), and 14 had hydrocephalus+IVH. Using spatially moving MVI signal in the third ventricle, cerebral aqueduct, and fourth ventricle as the criteria for CSF flow, CSF flow was identified in 10.9% (n = 11), 15.8% (n = 16), and 16.8% (n = 17) of cases, respectively. Flow direction was detected in 19.8% (n = 20) of cases; 70% (n = 14) was caudocranial, 15% (n = 3) was craniocaudal, and 15% (n = 3) bidirectional, with IRR = 0.662, p < 0.001. Visualization of CSF flow was significantly associated with the presence of IVH alone (OR 9.7 [3.3-29.0], p < 0.001) and IVH+hydrocephalus (OR 12.4 [3.5-440], p < 0.001), but not with hydrocephalus alone (p = 0.116). This study demonstrates that MVI can detect CSF flow dynamics in infants with a history of post-hemorrhagic hydrocephalus with a high IRR.

Concordance of Alzheimer's Disease-Related Biomarkers Between Intraventricular and Lumbar Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus.

Alzheimer's disease cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau 181 (P-tau181) are widely used. However, concentration gradient of these biomarkers between intraventricular (V-CSF) and lumbar CSF (L-CSF) has been demonstrated in idiopathic normal pressure hydrocephalus (iNPH), potentially affecting clinical utility. Here we aim to provide conversion factors for clinical and research use between V-CSF and L-CSF. Altogether 138 iNPH patients participated. L-CSF samples were obtained prior to shunt surgery. Intraoperative V-CSF samples were obtained from 97 patients. Post-operative follow-up L- and V-CSF (shunt reservoir) samples of 41 patients were obtained 1-73 months after surgery and then after 3, 6, and 18 months. CSF concentrations of Aβ42, T-tau, and P-tau181 were analyzed using commercial ELISA assays. Preoperative L-CSF Aβ42, T-tau, and P-tau181 correlated to intraoperative V-CSF (ρ= 0.34-0.55, p < 0.001). Strong correlations were seen between postoperative L- and V-CSF for all biomarkers in every follow-up sampling point (ρs Aβ42: 0.77-0.88, T-tau: 0.91-0.94, P-tau181: 0.94-0.96, p < 0.0001). Regression equations were determined for intraoperative V- and preoperative L-CSF (Aβ42: V-CSF = 185+0.34*L-CSF, T-tau: Ln(V-CSF) = 3.11+0.49*Ln(L-CSF), P-tau181: V-CSF = 8.2+0.51*L-CSF), and for postoperative V- and L-CSF (Aβ42: V-CSF = 86.7+0.75*L-CSF, T-tau: V-CSF = 86.9+0.62*L-CSF, P-tau181: V-CSF = 2.6+0.74*L-CSF). Aβ42, T-tau, and P-tau181 correlate linearly in-between V- and L-CSF, even stronger after CSF shunt surgery. Equations presented here, provide a novel tool to use V-CSF for diagnostic and prognostic entities relying on the L-CSF concentrations and can be applicable to clinical use when L-CSF samples are not available or less invasively obtained shunt reservoir samples should be interpreted.

Concordance of CSF AD biomarkers between intraventricular and lumbar CSF in iNPH

AbstractBackgroundThe core Alzheimer’s Disease cerebrospinal fluid (CSF) biomarkers, amyloid β 1‐42 (Aβ42), total tau (T‐tau) and phosphorylated tau 181 (P‐tau181), have presented added value for differential diagnostics in the field of neurodegenerative diseases. Moreover, the concentration gradient of these biomarkers between intraventricular (V‐CSF) and lumbar region CSF (L‐CSF) has been partly established for idiopathic normal pressure hydrocephalus (iNPH) patients. In this study, we aim to provide conversion factors between V‐CSF and L‐CSF.MethodAltogether 138 patients were diagnosed for possible iNPH and received ventriculoperitoneal shunt. Lumbar CSF samples were obtained 3‐months prior shunt surgery. Additional intraoperative interventricular CSF samples were obtained from 97 patients. Furthermore, follow‐up samples of 41 patients were obtained 0‐, 3‐, 6‐ and 18‐months (0M, 3M, 6M, 18M) postoperatively by shunt valve and lumbar punctures. Aβ42, T‐tau and P‐tau181 CSF concentrations of samples collected were analyzed using Elecsys (Cohort of 97 patients) and Innotest (Cohort of 41 patients) assays.ResultPreoperative L‐CSF Aβ42, T‐tau and P‐tau181 associated to intraoperative V‐CSF (Sprearman ρ=0.54 Aβ42, r=0.34 T‐tau, r=0.55 P‐tau, all p&lt;0.001). Strong associations were seen between postoperative L‐ and V‐CSF for all biomarkers in the every follow‐up sampling point (Spearman ρ Aβ42: 0M=.77, 3M=.88, 6M=.83, 18M=.84) (T‐tau: 0M=.92, 3M=.91, 6M=.92, 18M=.94) (P‐tau181: 0M=.96, 3M=.95, 6M=.94, 18M=.94) (all p&lt;0.0001). Regression equations were determined for intraoperative V‐CSF and preoperative L‐CSF (Aβ42: V‐CSF=185+0.34*L‐CSF, T‐tau: Ln(V‐CSF)=3.11+0.49*Ln(L‐CSF) and P‐tau181: V‐CSF=8.2+0.51*L‐CSF, all p&lt;0.01), and for postoperative V‐CSF and L‐CSF (Aβ42: V‐CSF=86.7+0.75*L‐CSF, T‐tau: V‐CSF=86.9+0.62*L‐CSF and P‐tau181: V‐CSF=1.9+0.75*L‐CSF all p&lt;0.0001).ConclusionThe Aβ42, T‐tau and P‐tau181 showed linear dependency between ventricular and lumbar CSF for preoperative L‐CSF and intraoperative V‐CSF as well as for postoperatively collected L‐CSF and V‐CSF. The regression equations based on these findings provide a novel tool to use V‐CSF for diagnostics and prognostics entities that rely on the lumbar CSF concentrations.

Insights on the Hydrodynamics of Chiari Malformation.

Background: We propose that the appearance of a ptosis of the cerebellar tonsils and syringomyelia is linked to its own hemohydrodynamic mechanisms. We aimed to quantify cerebrospinal fluid (CSF) and cerebral blood flow to highlight how neurofluid is affected by Chiari malformations type 1(CMI) and its surgery. Methods: We retrospectively included 21 adult patients with CMI who underwent pre- and postoperative phase contrast MRI (PCMRI) during the period from 2001 to 2017. We analyzed intraventricular CSF, subarachnoid spaces CSF, blood, and tonsils pulsatilities. Results: In preoperative period, jugular venous drainage seems to be less preponderant in patients with syringomyelia than other patients (venous correction factor: 1.49 ± 0.4 vs. 1.19 ± 0.1, p = 0.05). After surgery, tonsils pulsatility decreased significantly (323 ± 175 μL/cardiac cycle (CC) vs. 194 ± 130 μL/CC, p = 0.008) and subarachnoid CSF pulsatility at the foramen magnum increased significantly (201 ± 124 μL/CC vs. 363 ± 231 μL/CC, p = 0.02). After surgery, we found a decrease in venous flow amplitude (5578 ± 2469 mm3/s vs. 4576 ± 2084 mm3/s, p = 0.008) and venous correction factor (1.98 ± 0.3 vs. 1.20 ± 0.3 mm3/s, p = 0.004). Conclusions: Phase-contrast MRI could be a useful additional tool for postoperative evaluation and follow-up, and is complementary to morphological imaging.

The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts.

Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.

Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes.

BackgroundThe human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one.ObjectiveTo work out a descriptive model of brain structural and functional changes in normal aging.Materials and MethodsBy using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U-test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T-test.ResultsWhite matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age.ConclusionThe article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results.

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings

BackgroundIdiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort.MethodA literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls.ResultsThe literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05).ConclusionsOur literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

Human brain FE modeling including incompressible fluid dynamics of intraventricular cerebrospinal fluid

Elucidating the mechanisms of mild traumatic brain injuries (mild TBIs), including concussions, is important for developing brain injury criteria and designing head protection devices. Using a finite element (FE) model of the human brain to predict the deformation of the brain parenchyma during a head impact could provide mechanical insights on mild TBIs. However, most conventional brain FE models do not consider how fluid behavior and the perfusion pressure of the cerebrospinal fluid (CSF) will affect brain deformation. This study proposes a novel brain FE model that uses incompressible fluid dynamics (ICFD) to represent the fluid behavior of CSF in the ventricle. In the model with ICFD, the validation accuracy scores on the brain strain during a head impact with a rotational acceleration were significantly higher than those in the model without ICFD. Reconstruction simulations based on two reported mild TBI cases from a rear-end collision and an American football game were conducted using the model with and without ICFD. We found that the maximum principal strain values in the subcortical region and corpus callosum of the model with ICFD were higher and lasted longer than those of the model without ICFD, and this tendency was further enhanced when perfusion pressure was applied. These findings suggested that the fluid behavior and perfusion pressure of the intraventricular CSF could significantly affect the deformation of the brain parenchyma during head impacts. The proposed brain multiphysical FE model could enhance the understanding of mild TBI mechanisms. Statement of SignificanceMild TBIs or concussions can result from brain deformations caused by the rapid acceleration of the head in the situations such as falls, vehicular accidents, and collisions in sports-related activities. A FE analysis is an effective tool for simulating head impact scenarios associated with mild TBIs and estimating the brain strain. Accurate prediction of mild TBIs requires a brain FE model with high biofidelity. Here, we firstly revealed that the validation accuracy of the model on the brain strain can be improved by considering the fluid behavior of intraventricular CSF. By analyzing existing mild TBI cases using the proposed model, the fluid behavior and perfusion pressure of the CSF were found to significantly affect the brain strain history, resulting in an outcome similar to the clinical symptom. The proposed multiphysical brain model could potentially provide new mechanical insights and further understanding of mild TBIs. Additionally, these findings in this study could be useful in developing brain injury criteria and designing protective equipment.

Multiloculated Hydrocephalus: Surgical Techniques

Objective: Hydrocephalus shunt remains as the most common treatment choice for nonobstructive hydrocephalus, but in some cases multiloculated hydrocephalus (MH) remains a difficult neurosurgical disease despite of the different therapeutic options available. In children with MH multiple shunt procedures combined with neuroendoscopy may be required.(1) The rationale for neuroendoscopy in such complex cysts and multiloculated hydrocephalus is also to open several compartments to the normal fluid-filled spaces, minimize the number of isolated/loculated CSF spaces, and decrease shunt dependency and the number of proximal shunt catheters.(2) In such cases our major objective is keep the children with one or no one shunt and with one normal intracranial pressure (ICP).&#x0D; Most patients with multiloculated hydrocephalus are infants with a severe disability who present with high intracranial pressure. Multiple shunting was a routine practice so far to normalize the intracranial pressure, but in these cases shunt complications could be quite common including shunt infection, malposition and malfunction which needed more shunt revision surgeries.(1, 3)&#x0D; Neuroendoscopy has changed the treatment options for complex multiloculated hydrocephalus. The possibility to do several fenestrations and change multiples cysts in one simple cyst or ventricle was one important improvement in MH treatment.(4-6)&#x0D; In this review we will discuss aspects related to etiology, surgical techniques, and results in multiloculated hydrocephalus.&#x0D; &#x0D; Methods: The authors carried out a literature review on multiloculated hydrocephalus and evaluated a series of personal cases operated in the recent years.&#x0D; The keywords loculated hydrocephalus and surgical technique were used in Pubmed database website. Fifty-two articles were obtained and reviewed. From these publications we select the most relevant ones for the presentation. The articles were divided according to the main subject, with articles on etiology, surgical techniques and outcomes were selected.&#x0D; We also reviewed some difficult cases with MH from personal experience. In all of those cases endoscopy procedures were performed associated to shunt procedures in all cases. The authors described some different techniques of cyst fenestration and the association to shunt or not.&#x0D; Results/Discussion: Neuroendoscopy has changed the treatment in MH. This is a very difficult and interesting disease. Common risk factors for the development of MH include intraventricular hemorrhage, bacterial meningitis, shunt infection, and cerebrospinal fluid (CSF) overdrainage from shunt placement (rare). The magnetic resonance imaging (MRI) or computerized tomography (CT) scan with evidence of septations causing marked nonuniform compartmentalization and enlargement within the ventricular system are the most important ways to do the diagnosis of MH. Predisposing factors include low birth weight, prematurity, perinatal complications, and congenital malformation.&#x0D; Although the full pathogenesis of MLH remains unclear, it is known that inflammation leads to subependymal gliosis, which produces glial tufts and septations that occlude the normal ventricle system. Septations also develop via organization of intraventricular exudate and debris from ventriculitis.&#x0D; Despite os clinical history of poor outcome, head circuference increase and prior infection or brain bleeding, we need image to perform the diagnosis. Types of loculated hydrocephalus could be divided in: multiloculated and uniloculated. The most important classification was done by Spennato.(5) He divided in five types:&#x0D; 1) hydrocephalus with multiple intraventricular septations;&#x0D; 2) isolated lateral ventricle/unilateral hydrocephalus;&#x0D; 3) entrapped temporal horn;&#x0D; 4) isolated fourth ventricle;&#x0D; 5) expanding cavum septi pellucidi/cavum vergae&#x0D; Using the endoscope to treat MH has some advantages.(7, 8) This is a less invasiveness and this is very important in kids.(6) Avoidance of brain retraction, less blood loss, faster operation time, and shorter hospital stay. But endoscopy has some risk and possible complications. It also has several disadvantages. A subdural hematoma and/or hygroma may form, but the incidence of this is lower than with open craniotomy. The risk of ventriculitis, CSF leakage (subcutaneous CSF collection), and hemorrhage are reported to be like that with open craniotomy. Intraoperative bleeding can usually be easily managed by irrigation or coagulation. However, handling of significant intraoperative bleeding is not as easy in endoscopy as in open craniotomy.(9)&#x0D; Some new technologies could improve the outcome and avoid risk and complications.(10, 11) Navigation could be used in two forms:&#x0D; &#x0D; Navigation system is used to planning the entry point and the endoscopy trajectory&#x0D; Endoscopy guided and navigation during all surgical time.&#x0D; &#x0D; The evaluation of results is presented in different ways in the literature. The main outcomes observde for measuring results were: hydrocephalus control or not, number of surgery performed and number of catheters used.(4) Shunt Independence is rare.&#x0D; Conclusion: Multiloculated hydrocephalus is one difficult disease to treat.(4) Neuroendoscopy cyst fenestration was one great improvement in treatment of MH, but after this new procedure the clinical outcome still no so good. Endoscopy is important to decrease the number of shunts and surgeries.&#x0D;

The role of diffusion tensor imaging in idiopathic normal pressure hydrocephalus: A literature review.

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome that comprises a triad of gait disturbance, dementia and urinary incontinence, associated with ventriculomegaly in the absence of elevated intraventricular cerebrospinal fluid (CSF) pressure. It is important to identify patients with iNPH because some of its clinical features may be reversed by the insertion of a CSF shunt. The diagnosis is based on clinical history, physical examination and brain imaging, especially magnetic resonance imaging (MRI). Recently, some papers have investigated the role of diffusion tensor imaging (DTI) in evaluating white matter alterations in patients with iNPH. DTI analysis in specific anatomical regions seems to be a promising MR biomarker of iNPH and could also be used in the differential diagnosis from other dementias. However, there is a substantial lack of structured reviews on this topic. Thus, we performed a literature search and analyzed the most recent and pivotal articles that investigated the role of DTI in iNPH in order to provide an up-to-date overview of the application of DTI in this setting. We reviewed studies published between January 2000 and June 2020. Thirty-eight studies and four reviews were included. Despite heterogeneity in analysis approaches, the majority of studies reported significant correlations between DTI and clinical symptoms in iNPH patients, as well as different DTI patterns in patients with iNPH compared to those with Alzheimer or Parkinson diseases. It remains to be determined whether DTI could predict the success after CSF shunting.

Biomechanics of Periventricular Injury.

Periventricular injury is frequently noted as one aspect of severe traumatic brain injury (TBI) and the presence of the ventricles has been hypothesized to be a primary pathogenesis associated with the prevalence of periventricular injury in patients with TBI. Although substantial endeavors have been made to elucidate the potential mechanism, a thorough explanation for this hypothesis appears lacking. In this study, a three-dimensional (3D) finite element (FE) model of the human head with an accurate representation of the cerebral ventricles is developed accounting for the fluid properties of the intraventricular cerebrospinal fluid (CSF) as well as its interaction with the brain. An additional model is developed by replacing the intraventricular CSF with a substitute with brain material. Both models are subjected to rotational accelerations with magnitudes suspected to induce severe diffuse axonal injury. The results reveal that the presence of the ventricles leads to increased strain in the periventricular region, providing a plausible explanation for the vulnerability of the periventricular region. In addition, the strain-exacerbation effect associated with the presence of the ventricles is also noted in the paraventricular region, although less pronounced than that in the periventricular region. The current study advances the understanding of the periventricular injury mechanism as well as the detrimental effects that the ventricles exert on the periventricular and paraventricular brain tissue.

Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation - driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways - contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia-lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.

Neurofluids: A holistic approach to their physiology, interactive dynamics and clinical implications for neurological diseases

There is increasing interest in understanding the physiology of the extracellular fluid compartments in the central nervous system and their dynamic interaction. Such interest has been in part prompted by a vigorous resurgence of the role of the venous system, the recent discoveries of the meningeal lymphatics, the brain waste removal mechanisms and their potential link to neurological diseases, such as idiopathic intracranial hypertension, Ménière’s disease, migraine, small vessel disease, and most neurodegenerative diseases. The rigid cranial cavity houses several space-competing material compartments: the brain parenchyma (BP) and four extracellular fluids, namely arterial, venous, cerebrospinal fluid (CSF) and interstitial fluid (ISF). During cardiac pulsations, the harmonious, temporal and spatial dynamic interaction of all these fluid compartments and the BP assures a constant intracranial volume at all times, consistent with the Monro-Kellie hypothesis. The dynamic interaction involves high-pressure input of arterial blood during systole and efflux of CSF into the spinal subarachnoid space (SSAS) followed by venous blood exiting directly into the vertebral and internal jugular veins towards the heart and intraventricular CSF displacing caudally towards the SSAS. Arterial pulsatile energy is transmitted to the BP that contributes to the smooth movement of fluids in and out of the brain. Perturbing any of these fluid compartments will alter the entire brain dynamics, potentially increase intracranial pressure, affect perfusion and hamper clearance capacity of metabolic waste. This review of all major extracellular fluid compartments within the brain, advocates a holistic approach to our understanding of the fluid dynamics, rather than focusing on a single compartment when analyzing neurological diseases. This approach may contribute to advance our comprehension of some common neurological disorders, paving the way to newer treatment options.

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis.

Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, the specific contribution of each water channel to these functions remains unknown, being a subject of debate during the last years. Here, we analyzed in detail how AQP1 and AQP4 participate in different aspects of the CSF homeostasis such as the load and drainage of ventricles, and further explored if these proteins play a role in the ventricular compliance. To do that, we carried out records of intraventricular pressure and CSF outflow, and evaluated ventricular volume by magnetic resonance imaging in AQP1−/−, AQP4−/−, double AQP1−/−-AQP4−/− knock out and wild type mice controls. The analysis performed clearly showed that both AQPs have a significant participation in the CSF production, and additionally revealed that the double AQP1-AQP4 mutation alters the CSF drainage and the ventricular compliance. The data reported here indicate a significant extra-choroidal CSF formation mediated by AQP4, supporting the idea of an important and constant CSF production/absorption process, sustained by efflux/influx of water between brain capillaries and interstitial fluid. Moreover, our results suggest the participation of AQPs in structural functions also related with CSF homeostasis such as the distensibility capacity of the ventricular system.

C.03 Surgical complications with and without image guidance: meta-analysis of Ommaya reservoir insertions

Background: There remains an important role for consolidating evidence on the utility of image guidance (IG) in neurosurgery. In 1963, Ayub Ommaya proposed a surgical technique for the -placement of a subcutaneous reservoir and pump to allow access to intraventricular cerebrospinal fluid. In this study, we sought to compile evidence from the literature about surgical outcome in ORI with and without IG. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Overall surgical complication rate was considered a primary outcome and further classified into specific complication categories. Results: 40 studies were identified, including our own series, for a total of 1947 independent ORI procedures. Pooled rates of outcome for IG compared to non-IG were 6.0% versus 13.6% for overall complications; 2.0% versus 2.8% for catheter malfunction; 1.9% versus 2.3% for catheter malposition; 0.5% versus 4.0% for early infection; 4.3% versus 9.4% for any infection; and 0.4% versus 1.4% for mortality. Conclusions: We observed that IG ORI resulted in improved accuracy and decreased complications compared to non-IG. To our knowledge, this study comprises the largest observational analysis of operative outcomes demonstrating evidence for the utility of IG.

Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series.

Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement in 1963 to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion (ORI) in adults is for patients with hematologic or leptomeningeal disorders requiring repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to examine short-term complication rates with ORI with image guidance (IG) and without image guidance (non-IG). We retrospectively evaluated all operative cases of ORI from 2000 to 2014 by the senior author. Patient demographic data, surgical outcomes, and peri-operative complications were collected. Accurate placement and early (30-day) morbidity or mortality were considered primary outcomes. Fifty-five consecutive patients underwent ORI by the senior author over the study period (43.5 ± 16.6years; 40.0% female). Indications for placement included acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There were seven (12.7%) total complications: three (37.5%) with no-IG versus four (8.5%) with IG. Catheter malpositions were significantly higher in the non-IG group at 37.5% compared to 2.1%. Catheters were also more likely to require multiple passes with non-IG at 25% compare to 0% with IG. There were no early infections in either group. We demonstrate improved accuracy and decreased complications using an image-guided approach compared with a traditional approach. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective ORI for intraventricular chemotherapy.