Cerebrospinal Fluid Dynamics Research Articles

Microwave Sensing of Brain Water – a Simulation and Experimental Study Using Human Brain Models

This paper introduces a microwave-based approach that aims to non-invasively measure water, particularly cerebrospinal fluid (CSF) dynamics, in the human brain. The microwave measurement technique is well-known in industrial applications. More recently microwave techniques have awakened interest also in biomedical applications. This is the first time it is suggested to be utilized in measurements of brain water, particularly of CSF. Two different head phantoms were built in order to validate the sensitivity of the technique to sense dynamic variations of CSF and water volume inside a human skull. These were comprised of multilayered head phantom, including a real human skull, mimicking the electromagnetic properties of a human head. In addition, the variation of the CSF is evaluated with electromagnetic simulations using a planar layer model and a hemispherical layer model. Moreover, propagation and power flow inside the head model is evaluated using 2D power flow presentations. Reflection sensor principle was selected due to its simplicity and ability to measure relatively thick samples. Importantly, reflection sensor requires only one-port measurement making it very feasible for in vivo brain monitoring. In addition, the measurement setup does not require attachment of the sensor to the head, thus the measurement can be realized also without touching the head. Our experimental study as well as simulation results demonstrated the possibility to non-invasively sense, by microwaves, small dynamic variations in CSF volume in the brain, in particularly in the subarachnoid space.

Normal tension glaucoma in Asia: Epidemiology, pathogenesis, diagnosis, and management.

Normal tension glaucoma (NTG) has similar optic neuropathy as primary open-angle glaucoma (POAG), but intraocular pressure (IOP) is within the normal range. Compared with high-pressure POAG, the development of NTG is possibly a consequence of a complex interaction of several ocular and systemic factors. Recent data have shown higher translaminar pressure gradient due to impaired cerebrospinal fluid dynamics may account for the pathogenic mechanism. Insufficient blood supply and vascular dysregulation may also be the cause of the disease. In clinical evaluation, NTG is a diagnosis by excluding other nonglaucomatous optic neuropathies. NTG is characterized by larger and deeper optic-disc cupping, more central visual field defects and a higher incidence of disc hemorrhage compared with POAG. In clinical practice, controlling IOP as low as possible (with medication, laser trabeculoplasty, or surgery) is the key to manage NTG patients. In addition to IOP reduction, the control of systemic risk factors or improving ocular perfusion may be beneficial therapies. NTG is more prevalent in Asia than in the Western countries. Due to increasing old population and underdiagnoses in the clinical settings, NTG became a great challenge for ophthalmologist in Asia. Therefore, the aim of this article is to focus on the epidemiology, to update pathogenesis, diagnosis, and management for NTG.

Men Are from Mars, Idiopathic Intracranial Hypertension Is from Venous: The Role of Venous Sinus Stenosis and Stenting in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a disease primarily affecting obese women of child-bearing age, typically presenting with positional headaches, diplopia from abducens nerve palsies, pulse-synchronous tinnitus, and visual disturbances related to papilledema, including transient visual obscurations, blurry vision, and visual field defects. Controversy remains regarding the pathophysiology of IIH. Elevated intracranial pressure in IIH is thought to be the result of a dysregulation of cerebrospinal fluid (CSF) dynamics, through excessive secretion, reduced drainage, or both. Passive CSF drainage through the arachnoid granulations depends on a pressure gradient between the subarachnoid space and the cerebral venous system, such that elevations in cerebral venous pressure lead to impaired CSF drainage. Dural venous sinus stenosis (DVSS) at the junction of the transverse and sigmoid sinuses, leading to local venous hypertension and a secondary reduction in CSF drainage through the arachnoid granulations, is increasingly recognized as an important component of the pathophysiology of IIH. A growing number of studies have demonstrated a role for stenting of DVSS as an alternative to CSF shunting and optic nerve sheath fenestration in medically refractory IIH patients with vision loss or debilitating symptoms.

Oligoclonal bands and levels of interleukin 4, interleukin 10, and tumor necrosis factor alpha in idiopathic intracranial hypertension Egyptian patients

BackgroundIdiopathic intracranial hypertension (IIH) is a neurological disorder of unknown pathophysiology with many proposed theories that involve CSF dynamics but recently, involvement of inflammatory and autoimmune processes has been postulated.ObjectivesTo investigate presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and serum cytokine level in patients with IIH.MethodsThis study was conducted on 27 IIH female patients and 21 age- and sex-matched control groups. Patient and control groups were subjected to measurement of interleukin-4 (IL-4), IL-10, and tumor necrosis factor α (TNF-α) levels in serum, and CSF oligoclonal bands was measured in the IIH patient group. Body mass index (BMI) was measured to both patients and control.ResultsSerum levels of IL-4, IL-10, and TNF alpha were significantly higher in IIH patients than controls (p < 0.001); 22% of IIH patients had positive OCB in CSF. There was a statistically significant difference regarding TNF-α level in OCB-positive and OCB-negative patients being higher in positive patients. No statistically significant correlation was found between serum levels of IL-4, IL-10, TNF-α, and BMI.ConclusionAutoimmune inflammatory process may play a role in pathophysiology of IIH.

Cerebrospinal Fluid Flowmetry in Pediatric Patients with Chiari Malformation I with Surgical Implications

Chiari malformations include a large spectrum of anomalies of hindbrain formation that appear at different stages of development of the central nervous system. Chiari described these malformations as congenital anomalies of the hindbrain characterized by downward elongation of the brain stem and cerebellum into the cervical portion of spinal cord. Much research regarding Chiari malformation I (CMI) has focused on the cerebrospinal fluid (CSF) dynamics rather than the anatomic relationships of the tonsils and brainstem. The aim of the present study was to measure the peak CSF velocity at the foramen magnum and record the changes after foramen magnum decompression in patients with CMI aged <18years. A total of 39 patients with CMI were included during a 2-year period and were analyzed for peak CSF flow velocity with respect to surgical intervention using predefined magnetic resonance imaging protocols and surgical technique. After foramen magnum decompression, the postoperative mean CSF peak flow velocity showed a statistically significant difference compared with the preoperative value. Decompression of the foramen magnum was associated with decreased CSF peak velocity in patients with CMI.

A Novel Porcine Model for the Study of Cerebrospinal Fluid Dynamics: Development and Preliminary Results.

Idiopathic intracranial hypertension, space-flight associated neuro-ocular syndrome (SANS), and glaucoma are conditions that are among a spectrum of cerebrospinal fluid (CSF)-related ophthalmologic disease. This implies that local CSF pressures at the level of the optic nerve are involved to variable extent in these disease processes. However, CSF pressure measurements are problematic due to invasiveness and interpretation. The pressure measured by a lumbar puncture is likely not the same as the orbital CSF pressure. It is believed this is at least in part due to the flow restrictive properties of the optic canal. To investigate CSF flow within the orbit, a model for CSF dynamics was created using three medium-sized pigs. Contrast was administered through a lumbar subarachnoid space access. The contrast front was imaged with repeated computed tomographic (CT) imaging. Once contrast entered the orbit, rapid, sequential CT imaging was performed until the contrast reached the posterior globe. Head tilting was performed to highlight the role of gravitational dependence within the subarachnoid space.

Lymphatic outflow of cerebrospinal fluid is reduced in glioma

Glioblastoma is a malignant brain tumor with mean overall survival of less than 15 months. Blood vessel leakage and peritumoral edema lead to increased intracranial pressure and augment neurological deficits which profoundly decrease the quality of life of glioblastoma patients. It is unknown how the dynamics of cerebrospinal fluid (CSF) turnover are affected during this process. By monitoring the transport of CSF tracers to the systemic blood circulation after infusion into the cisterna magna, we demonstrate that the outflow of CSF is dramatically reduced in glioma-bearing mice. Using a combination of magnetic resonance imaging (MRI) and near-infrared (NIR) imaging, we found that the circulation of CSF tracers was hindered after cisterna magna injection with reduced signals along the exiting cranial nerves and downstream lymph nodes, which represent the major CSF outflow route in mice. Due to blockage of the normal routes of CSF bulk flow within and from the cranial cavity, CSF tracers were redirected into the spinal space. In some mice, impaired CSF clearance from the cranium was compensated by a lymphatic outflow from the sacral spine.

Impact of Neurapheresis System on Intrathecal Cerebrospinal Fluid Dynamics: A Computational Fluid Dynamics Study.

It has been hypothesized that early and rapid filtration of blood from cerebrospinal fluid (CSF) in postsubarachnoid hemorrhage patients may reduce hospital stay and related adverse events. In this study, we formulated a subject-specific computational fluid dynamics (CFD) model to parametrically investigate the impact of a novel dual-lumen catheter-based CSF filtration system, the Neurapheresis™ system (Minnetronix Neuro, Inc., St. Paul, MN), on intrathecal CSF dynamics. The operating principle of this system is to remove CSF from one location along the spine (aspiration port), externally filter the CSF routing the retentate to a waste bag, and return permeate (uncontaminated CSF) to another location along the spine (return port). The CFD model allowed parametric simulation of how the Neurapheresis system impacts intrathecal CSF velocities and steady-steady streaming under various Neurapheresis flow settings ranging from 0.5 to 2.0 ml/min and with a constant retentate removal rate of 0.2 ml/min simulation of the Neurapheresis system were compared to a lumbar drain simulation with a typical CSF removal rate setting of 0.2 ml/min. Results showed that the Neurapheresis system at a maximum flow of 2.0 ml/min increased average steady streaming CSF velocity 2× in comparison to lumbar drain (0.190 ± 0.133 versus 0.093 ± 0.107 mm/s, respectively). This affect was localized to the region within the Neurapheresis flow loop. The mean velocities introduced by the flow loop were relatively small in comparison to normal cardiac-induced CSF velocities.

Form follows function: estimation of CSF flow in the third ventricle-aqueduct-fourth ventricle complex modeled as a diffuser/nozzle pump.

In the last 20 years, researchers have debated cerebrospinal fluid (CSF) dynamics theories, commonly based on the classic bulk flow perspective. New hypotheses do not consider a possible hydraulic impact of the ventricular morphology. The present study investigates, by means of a mathematical model, the eventual role played by the geometric shape of the "third ventricle-aqueduct-fourth ventricle" complex in CSF circulation under the assumption that the complex behaves like a diffuser/nozzle (DN) pump. DN pumps are quite recent devices introduced as valveless micropumps in various industrial applications given their property of driving net flow when subjected to rhythmic pulsations. A novel peculiar DN pump configuration was adopted in this study to mimic the ventricular complex, with two reservoirs (the ventricles) and one tube provided with a conical reach (the aqueduct-proximal fourth ventricle). The flow was modeled according to the classic equations of laminar flow, and the external rhythmic pulsations forcing the system were reproduced as a pulsatile pressure gradient between the chambers. Several physiological scenarios were implemented with the integration of data acquired by MRI in 10 patients with no known pathology of CSF dynamics, and a quantitative analysis of the effect of geometric and hydraulic parameters (diverging angle, sizes, frequency of pulsations) on the CSF net flow was performed. The results showed a craniocaudal net flow in all the given values, consistent with the findings of cine MRI studies. Moreover, the net flow estimated for the analyzed cohort of patients ranged from 0.221 to 0.505 ml/min, remarkably close to the values found on phase contrast cine MRI in healthy subjects. Sensitivity analysis underlines the pivotal role of the DN configuration, as well as of the frequency of forcing pressure, which promotes a relevant net flow considering both the heart and respiration rate. This work suggests that the geometry of the third ventricle-aqueduct-fourth ventricle complex, which resembles a diverter, appears to be functional in the generation of a net craniocaudal flow and potentially has an impact on CSF dynamics. These conclusions can be drawn by observing the analogies between the shape of the ventricles and the geometry of DN pumps and by recognizing the basis of the mathematical model of the simplified third ventricle-aqueduct-fourth ventricle complex proposed.

Current understanding of the effects of inspiratory resistance on the interactions between systemic blood pressure, cerebral perfusion, intracranial pressure, and cerebrospinal fluid dynamics.

Negative intrathoracic pressure (nITP) is generated by the respiratory muscles during inspiration to overcome inspiratory resistance, thus enabling lung ventilation. Recently developed noninvasive techniques have made it possible to assess the effects of nITP in real time in several physiological aspects such as systemic blood pressure (BP), intracranial pressure (ICP), and cerebral blood flow (CBF). It has been shown that nITP from 0 to -20 cmH2O elevates BP and diminishes ICP, which facilitates brain perfusion. The effects of nITP from -20 to -40 cmH2O on BP, ICP, and CBF remain largely unrecognized, yet even nITP at -40 cmH2O may facilitate CBF by diminishing ICP. Importantly, nITP from -20 to -40 cmH2O has been documented in adults in commonly encountered obstructive sleep apnea, which justifies research in this area. Recent revelations about interactions between ICP and BP have opened up new fields of research in physiological regulation and the pathophysiology of common diseases, such as hypertension, brain injury, and respiratory disorders. A better understanding of these interactions may translate directly into new therapies in various fields of clinical medicine.

In Vivo Imaging of Cerebrospinal Fluid Transport through the Intact Mouse Skull using Fluorescence Macroscopy.

Cerebrospinal fluid (CSF) flow in rodents has largely been studied using ex vivo quantification of tracers. Techniques such as two-photon microscopy and magnetic resonance imaging (MRI) have enabled in vivo quantification of CSF flow but they are limited by reduced imaging volumes and low spatial resolution, respectively. Recent work has found that CSF enters the brain parenchyma through a network of perivascular spaces surrounding the pial and penetrating arteries of the rodent cortex. This perivascular entry of CSF is a primary driver of the glymphatic system, a pathway implicated in the clearance of toxic metabolic solutes (e.g., amyloid-β). Here, we illustrate a new macroscopic imaging technique that allows real-time, mesoscopic imaging of fluorescent CSF tracers through the intact skull of live mice. This minimally-invasive method facilitates a multitude of experimental designs and enables single or repeated testing of CSF dynamics. Macroscopes have high spatial and temporal resolution and their large gantry and working distance allow for imaging while performing tasks on behavioral devices. This imaging approach has been validated using two-photon imaging and fluorescence measurements obtained from this technique strongly correlate with ex vivo fluorescence and quantification of radio-labeled tracers. In this protocol, we describe how transcranial macroscopic imaging can be used to evaluate glymphatic transport in live mice, offering an accessible alternative to more costly imaging modalities.

Identifying the Critical Factors Governing Translaminar Pressure Differential Through a Compartmental Model.

PurposeThe effective management of glaucoma is hindered by an incomplete understanding of its pathologic mechanism. While important, intraocular pressure (IOP) alone is inadequate in explaining glaucoma. Non-IOP–mediated risk factors such as cerebrospinal fluid (CSF) pressure have been reported to contribute to glaucomatous optic neuropathy. Due to the difficulty associated with experimental measurement of the salient variables, such as the retrobulbar CSF pressure, porosity of the subarachnoid space (SAS), and especially those concerned with the perioptic SAS, there remains a limited understanding of the CSF behavior contributing to the translaminar pressure gradient (TLPG), hypothesized to be a critical factor in the development of glaucoma.MethodAn integrated compartmental model describing the intracranial and orbital CSF dynamics, coupled with intraocular dynamics, is developed based on first principles of fluid mechanics. A sensitivity analysis is performed to identify anatomic characteristics that significantly affect the retrobulbar subarachnoid space (RSAS) pressure and, consequently, the TLPG.ResultsOf the 28 parameters considered, the RSAS pressure is most sensitive to CSF flow resistance in the optic nerve SAS and the potential lymphatic outflow from the optic nerve SAS into the orbital space. A parametric study demonstrates that a combination of resistance in the range of 1.600 × 1012 − 1.930 × 1012 Pa s/m3 (200.0 − 241.3 mm Hg min/mL) with 5% to 10% lymphatic CSF outflow yields RSAS pressures that are consistent with the limited number of studies in the literature.ConclusionsThe results suggest that a small percentage of lymphatic CSF outflow through the optic nerve SAS is likely. In addition, flow resistance in the orbital CSF space, hypothesized to be a function of patient-specific optic nerve SAS architecture and optic canal geometry, is a critical parameter in regulating the RSAS pressure and TLPG.

The Role of Flexible Neuroendoscopy in Spinal Neurocysticercosis: Technical Note and Report of 3 Cases

Neurocysticercosis, caused by the larval form of the tapeworm Taenia solium, is the most common parasitic disease affecting the human central nervous system. The incidence of spinal neurocysticercosis in endemic regions ranges from 0.25% to 5.85%. Surgery is preferred when medical treatment fails to achieve control of the symptoms or when multiple cysts are present. We describe the use of spinal flexible endoscopy for patients with spinal neurocysticercosis who failed to achieve control with standard treatment. Three patients with limb weakness and pain underwent a midline interspinous approach at the L5-S1 level to access the lumbar cistern. The flexible endoscope was introduced, the subarachnoid space was inspected, and the cysticerci were extracted. In 1 patient with cervical subarachnoid blockage, a 3-cm suboccipital craniotomy and removal of the posterior arch of C1 were performed to place a subarachnoid-to-subarachnoid catheter going from the craniocervical junction to the thoracic region. Removal of the cysticerci was possible in all cases. No complications related to the surgery were observed. All patients received medical treatment for 2-3 months, and all symptoms were solved. Flexible spinal endoscopy is a feasible and valuable tool in patients with spinal neurocysticercosis that do not respond adequately to standard treatment. It helps restore cerebrospinal fluid dynamics and can be used to place shunt catheters under guided vision. Longer endoscopes are needed to explore the entire spinal subarachnoid space with a single approach, and more research in this area is needed.

Pisa syndrome in Idiopathic Normal Pressure Hydrocephalus

IntroductionIdiopathic Normal Pressure Hydrocephalus (iNPH) is a complex syndrome of ventriculomegaly that can include parkinsonian-like features besides the classical triad of cognitive decline, urinary incontinence, and gait/balance disturbances. Pisa syndrome (PS) is a postural abnormality often associated with parkinsonism and defined as lateral trunk flexion greater than 10° while standing that resolves in the supine position. We reported a case series of classical “fixed” PS and one case of “Metronome” recurrent side-alternating PS in iNPH, displaying opposite electromyographic patterns of paraspinal muscles. MethodsEighty-five iNPH patients were followed longitudinally for at least one year through scheduled clinical and neuropsychological visits. ResultsFive (5.9%) subjects revealed PS. None of them had nigrostriatal dopaminergic involvement detected by [123I]FP-CIT SPECT. Among these patients, four had “fixed” PS, whereas one showed a recurrent side-alternating PS which repeatedly improved after ventriculo-peritoneal shunt and following adjustments of the valve-opening pressure of the shunt system. DiscussionThis is the first case series of PS in iNPH and the first report of “Metronome” PS in iNPH. The prompt response of the abnormal trunk postures through cerebrospinal fluid (CSF) shunt surgery suggests a causative role of an altered CSF dynamics. PS and gait disorders in iNPH could be explained by a direct involvement of cortico-subcortical pathways and subsequent secondary brainstem involvement, with also a possible direct functional damage of the basal ganglia at the postsynaptic level, due to enlargement of the ventricular system and impaired CSF dynamics. The early detection of these cases supports a proper surgical management.

Chiari I malformation and altered cerebrospinal fluid dynamics-the highs and the lows.

This paper reviews the altered cerebrospinal fluid dynamics that can be associated with paediatric Chiari I malformation and we present our own institutional experience. We conducted a thorough review of the literature and retrospectively analyzed all cases of operatively managed paediatric Chiari 1 malformation at our institution between February 2006 and February 2019. Acquired Chiari malformation (ACM) can radiologically mimic Chiari I and has been associated with both intracranial hypotension (either secondary to lumboperitoneal shunting or spontaneous CSF hypotension) and idiopathic intracranial hypertension (IIH). At our institution, 61 paediatric cases (range, 2-15years) underwent foramen magnum decompression (FMD) for Chiari I malformation. Whilst 80% (50/61) of cases underwent FMD with no preceding or post-operative problems of CSF dynamics, 8% (5/61) of cases had hydrocephalus at initial presentation requiring CSF diversion followed by FMD for persistent Chiari, and 10% (6/61) developed hydrocephalus following FMD and required long-term CSF diversion. In paediatric ACM, the management of intracranial hypotension involves thorough radiological assessment and inclusion/adjustment of a valve in the case of lumboperitoneal shunting or epidural blood patch or interventional techniques in the case of spontaneous CSF leak. Thereby, unwarranted posterior fossa decompression surgery is avoided. In the case of IIH and Chiari I malformation, children who have recurrent symptoms despite adequate posterior fossa decompression surgery (failed Chiari), there is a strong role for intracranial pressure monitoring as raised intracranial pressure may indicate long-term CSF diversion.

Spinal subarachnoid space tapering in patients with syringomyelia.

Cervical spine tapering affects cerebrospinal fluid dynamics. Cervical spine taper ratios derived from anteroposterior diameters reportedly differ between patients with syringomyelia and controls. We attempted to verify the differences in diameter and to show differences in cross-sectional area between syringomyelia and controls. Cervical spine magnetic resonance images in syringomyelia patients (idiopathic or Chiari I related) and control patients were examined. In each subject, the anteroposterior diameter of the spinal canal was measured at each cervical level, and C1-C4, C4-C7, and C1-C7 taper ratios were calculated. Differences in taper ratio between groups were tested for statistical significance with the t-test. Cross-sectional areas of the spinal canal were measured at each cervical spinal level, and tapering was calculated. Eighteen patients with idiopathic syringomyelia, 28 with Chiari I, and 29 controls were studied. Chiari and syringomyelia patients had significantly steeper diameter-based taper ratios than controls. The dural sac areas tapered proportionally with the diameter-based taper ratio in all groups. Cervical spine anteroposterior diameter tapering and dural sac cross-sectional areas tapering differ between syringomyelia patients and controls.

Rheologically Essential Surfactant Proteins of the CSF Interacting with Periventricular White Matter Changes in Hydrocephalus Patients - Implications for CSF Dynamics and the Glymphatic System.

Surfactant proteins (SP) are multi-systemic proteins playing crucial roles in the regulation of rheological properties of physiological fluids, host defense, and the clearance of potentially harmful metabolites. Hydrocephalus patients suffer from disturbed central nervous system (CNS) fluid homeostasis and exhibit remarkably altered SP concentrations within the cerebrospinal fluid (CSF). A connection between CSF-SPs, CSF flow, and ventricular dilatation, a morphological hallmark of hydrocephalus, has been reported previously. However, currently there are no studies investigating the link between rheologically active SPs and periventricular white matter changes caused by impaired CSF microcirculation in hydrocephalic conditions. Thus, the aim of this study was to assess their possible relationships. The present study included 47 individuals (27 healthy subjects and 20 hydrocephalus patients). CSF specimens were analyzed for concentrations of SP-A, SP-C, and SP-D by using enzyme-linked immunosorbent assays (ELISAs). Axial T2w turbo inversion recovery magnitude (TIRM) magnetic resonance imaging was employed in all cases. Using a custom-made MATLAB-based tool for quantification of magnetic resonance signal intensities in the brain, parameters related to disturbed deep white matter CSF microcirculation were estimated (TIRM signal intensity (SI)-mean, minimum, maximum, median, mode, standard deviation, and percentiles, p10th, p25th, p75th, p90th, as well as kurtosis, skewness, and entropy of the SI distribution). Subsequently, statistical analysis was performed (IBM SPSS 24™) to identify differences between hydrocephalic patients and healthy individuals and to further investigate the connections between CSF-SP changes and deep white matter signal intensities. SP-A (0.38 ± 0.23 vs. 0.76 ± 0.49ng/ml) and SP-C (0.54 ± 0.28 vs. 1.27 ± 1.09ng/ml) differed between healthy controls and hydrocephalus patients in a statistically significant manner. Also, corresponding quantification of white matter signal intensities revealed statistically significant differences between hydrocephalus patients and healthy individuals: SImean (370.41 ± 188.15 vs. 222.27 ± 99.86, p = 0.001), SImax (1115.30 ± 700.12 vs. 617.00 ± 459.34, p = 0.005), SImedian (321.40 ± 153.17 vs. 209.52 ± 84.86, p = 0.001), SImode (276.55 ± 125.63 vs. 197.26 ± 78.51, p = 0.011), SIstd (157.09 ± 110.07 vs. 81.71 ± 64.94, p = 0.005), SIp10 (229.10 ± 104.22 vs. 140.00 ± 63.12, p = 0.001), SIp25 (266.95 ± 122.62 vs. 175.63 ± 71.42, p = 0.002), SIp75 (428.80 ± 226.88 vs. 252.19 ± 110.91, p = 0.001), SIp90 (596.47 ± 345.61 vs. 322.06 ± 176.00, p = 0.001), skewness (1.19 ± 0.68 vs. 0.43 ± 1.19, p = 0.014), and entropy (5.36 ± 0.37 vs. 4.92 ± 0.51, p = 0.002). There were no differences regarding SP-D levels in hydrocephalus patients vs. healthy controls. In the acute hydrocephalic subgroup, correlations were as follows: SP-A showed a statistically significant correlation with SImax (r = 0.670, p = 0.024), SIstd (r = 0.697, p = 0.017), SIp90 (r = 0.621, p = 0.041), and inverse correlation with entropy (r = - 0.700, p = 0.016). SP-C correlated inversely with entropy (r = - 0.686, p = 0.020). For the chronic hydrocephalus subgroup, the following correlations were identified: SP-A correlated with kurtosis of the TIRM histogram (r = - 0.746, p = 0.021). SP-C correlated with SImean (r = - 0.688, p = 0.041), SImax (r = - 0.741, p = 0.022), SImedian (r = - 0.716, p = 0.030), SImode (r = - 0.765, p = 0.016), SIstd (r = - 0.671, p = 0.048), SIp25 (r = - 0.740, p = 0.023), SIp75 (r = - 0.672, p = 0.048), and SIp90 (r = - 0.667, p = 0.050). SP-D apparently does not play a major role in CSF fluid physiology. SP-A and SP-C are involved in different aspects of CNS fluid physiology. SP-A appears to play an essential compensatory role in acute hydrocephalus and seems less involved in chronic hydrocephalus. In contrary, SP-C profile and white matter changes are remarkably connected in CSF of chronic hydrocephalus patients. Considering the association between CSF flow phenomena, white matter changes, and SP-C profiles, the latter may especially contribute to the regulation of paravascular glymphatic physiology.

Aqueductal Cerebrospinal Fluid Stroke Volume Flow in a Rodent Model of Chronic Communicating Hydrocephalus: Establishing a Homogeneous Study Population for Cerebrospinal Fluid Dynamics Exploration

Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts. To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus. Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days. Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P= 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P= 0.015), 60 (P= 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days. An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.

Advances in diagnosis and treatment of syndrome of trephined and paradoxical herniation after decompressive craniectomy

The efficacy of decompressive craniectomy (DC) in reducing traumatic brain injury mortality has been affirmed, but there are also many serious complications. Syndrome of the trephined (ST) and paradoxical herniation (PH) are rare complications. ST is characterized by a series of neurological deterioration due to skin flaps subsidence from weeks to months after DC. These neurological impairments are closely related to the subsequent repair of skull defects. PH shows progressive decrease in consciousness on the basis of ST, changes in pupils on the side of skull defects, low touch pressure at the defect window, and obvious midline shift and brain stem compression on CT. ST and PH have common inducements in pathophysiology, including cerebrospinal fluid dynamics, atmospheric pressure, cerebral blood flow and brain material metabolism. There is no consensus on the diagnosis of ST and PH, and early cranioplasty is suggested in terms of treatment. This article reviews the clinical manifestations, pathophysiological changes, diagnosis and treatment of ST and PH after DC operation, so as to provide references for clinicians to further understand ST and PH. Key words: Encephalocele; Decompressive craniectomy; Syndrome of the trephined

Power and limit of MRI to investigate blood and cerebro spinal fluid dynamics in the cranio spinal system

Power and limit of MRI to investigate blood and cerebro spinal fluid dynamics in the cranio spinal system