Cerebrospinal Fluid Dynamics Research Articles

Calculated Parameters for Assessing the Interaction of Fluids in the Central Nervous System According to Radiation Introscopy (Part I)

The aim of this literature review is to consider the range of different integral characteristics and indices, by which it can be possible to evaluate impaired hemodynamics and cerebrospinal fluid dynamics in the central nervous system according to radiation introscopy, including ultrasound and phase-contrast magnetic resonance imaging. Consideration is given to various volume-velocity and temporal parameters and the possibility of using the described characteristics to study joint blood and cerebrospinal fluid flows. Emphasis is laid on the analysis of the information provided by each of the indices and by the possibility of its clinical application. This expanded study of the interaction of fluids in the central nervous system will be able to give a better insight into the mechanisms involved in maintaining homeostasis in the brain.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Emerging themes in idiopathic intracranial hypertension

PurposeIdiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets.FindingsIIH is becoming more common, with the incidence rising in parallel with the global obesity epidemic. Current medical management remains centred around weight management, which is challenging. Metabolic investigations of patients have identified specific androgen profiles in cerebrospinal fluid (CSF), which suggest an endocrine dysfunction impacting CSF secretion in IIH. Glucagon-like peptide-1 (GLP-1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been found to play a role in CSF dynamics in IIH and have formed the basis of the first clinical trials looking at new treatments.ConclusionsIdentification of novel molecular targets thought to underlie IIH pathology is now being translated to clinical trials.

Compressed-sensing accelerated 4D flow MRI of cerebrospinal fluid dynamics

Background4D flow magnetic resonance imaging (MRI) of CSF can make an important contribution to the understanding of hydrodynamic changes in various neurological diseases but remains limited in clinical application due to long acquisition times. The aim of this study was to evaluate the accuracy of compressed SENSE accelerated MRI measurements of the spinal CSF flow.MethodsIn 20 healthy subjects 4D flow MRI of the CSF in the cervical spine was acquired using compressed sensitivity encoding [CSE, a combination of compressed sensing and parallel imaging (SENSE) provided by the manufacturer] with acceleration factors between 4 and 10. A conventional scan using SENSE was used as reference. Extracted parameters were peak velocity, absolute net flow, forward flow and backward flow. Bland–Altman analysis was performed to determine the scan-rescan reproducibility and the agreement between SENSE and compressed SENSE. Additionally, a time accumulated flow error was calculated. In one additional subject flow of the spinal canal at the level of the entire spinal cord was assessed.ResultsAveraged acquisition times were 10:21 min (SENSE), 9:31 min (CSE4), 6:25 min (CSE6), 4:53 min (CSE8) and 3:51 min (CSE10). Acquisition of the CSF flow surrounding the entire spinal cord took 14:40 min. Bland–Altman analysis showed good agreement for peak velocity, but slight overestimations for absolute net flow, forward flow and backward flow (< 1 ml/min) in CSE4–8. Results of the accumulated flow error were similar for CSE4 to CSE8.ConclusionA quantitative analysis of acceleration factors CSE4–10 showed that CSE with an acceleration factor up to 6 is feasible. This allows a scan time reduction of 40% and enables the acquisition and analysis of the CSF flow dynamics surrounding the entire spinal cord within a clinically acceptable scan time.

Identification of lymphatic endothelium in cranial arachnoid granulation-like dural gap.

The dynamics of cerebrospinal fluid (CSF) are essential for maintaining homeostasis in the central nervous system. Despite insufficiently detailed descriptions of their structural and molecular properties for a century, cranial arachnoid granulations (CAGs) on meninges have been thought to participate in draining CSF from the subarachnoid space into the dural sinuses. However, recent studies have demonstrated the existence of other types of CSF drainage systems, such as lymphatic vessels adjacent to dural sinus and paravascular space in the brain so-called glymphatic system. Therefore, the role of CAGs in CSF drainage has become dubious. To better understand CAG function, we analyzed the ultrastructure and molecular identity of CAG-like structure on meninges adjacent to the superior sagittal sinus of pigs. Transmission electron microscopy analysis revealed that this structure has a reticular conglomerate consisting of endothelial cells that resembles lymphatic linings. Furthermore, immunohistochemistry and immunoelectron microscopy showed that they express molecules specific to lymphatic endothelial cell. We coined a name 'CAG-like dural gap (CAG-LDG)' to this structure and discussed the physiological relevance in terms of CSF drainage.

Nonreflecting Boundary Conditions for a CSF Model of Fourth Ventricle: Spinal SAS Dynamics.

In this paper, we introduce a one-dimensional model for analyzing the cerebrospinal fluid dynamics within the fourth ventricle and the spinal subarachnoid space (SSAS). The model has been derived starting from an original model of Linninger et al. and from the detailed mathematical analysis of two different reformulations. We show the steps of the modelization and the rigorous analysis of the first-order nonlinear hyperbolic system of equations which rules the new CSF model, whose conservative-law form and characteristic form are required for the boundary conditions treatment. By assuming sub-critical flows, for the particular dynamics we are dealing with, the most desirable option is to employ the nonreflecting boundary conditions, that allow the simple wave associated with the outgoing characteristic to exit the computational domain with no reflections. Finally, we carry out some numerical simulations related to different cerebral physiological conditions.

Compressive myelopathy secondary to posthemorragic arachnoiditis: Case report and literature review

BackgroundSpinal arachnoiditis is an arachnoid inflammatory process frequently caused by infection or spinal surgery; there are different degrees of severity, including arachnoid thickening and severe adhesive lesions that can lead to the development of arachnoid cysts. Non-traumatic subarachnoid haemorrhage (ntSAH) is a relatively uncommon cause of arachnoiditis; further complication with spinal cord compression (SCC) is even more unusual. Methodwe describe a 70-year-old female, with SCC caused by arachnoid cysts. Her medical past history was relevant for an episode of ntSAH after rupture of a posterior communicating artery aneurysm, eight months prior to the onset of symptoms. We also present a literature review of previous published cases. Resultswe selected 23 articles with 24 case reports. A noticeable female predominance (11:1) was observed. It is more common between the fourth and fifth decades. The majority of cases (58 %) were secondary to aneurysmal SAH due to rupture of a posterior circulation aneurysm. The most common location of the cyst is in the cervicothoracic spine. The average time between the initial bleeding and symptom development is 3–6 months. The most frequently described treatment is laminectomy and marsupialization of the cyst, but reports show a high recurrence rate. ConclusionsntSAH is an uncommon aetiology of arachnoiditis and arachnoid cysts. SCC from arachnoid cysts secondary to ntSAH is exceptional. Treatment through laminectomy has a relatively high recurrence rate (33 %). We present different hypotheses to try to explain how the alteration of cerebrospinal fluid (CSF) dynamics after ntSAH can lead to arachnoid cyst development and SCC. Although the small number of cases included in the present series precludes us to draw definite conclusions, ventriculoperitoneal shunt (VPS) placement can be considered as an alternative treatment in the management of known ntSAH patients that present recurrent symptomatic arachnoid cysts.

Can early cranioplasty reduce the incidence of hydrocephalus after decompressive craniectomy? A meta-analysis

Background: Do alterations of cerebrospinal fluid dynamics secondary to decompressive craniectomy (DC) lead to hydrocephalus, and can this effect be mitigated by early cranioplasty (CP)? In this meta-analysis, we evaluated whether the timing of CP decreased the incidence of postoperative hydrocephalus.Methods: We performed a systematic search of PubMed/MEDLINE, Scopus, and the Cochrane databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for English language articles (1990–2020). We included case series, case–control, and cohort studies, and clinical trials assessing the incidence of hydrocephalus in adult patients undergoing early CP (within 3 months) versus late CP (after 3 months) after DC.Results: Eleven studies matched the inclusion criteria. The rate of postoperative hydrocephalus was not significantly different between the early (=96/1063; 9.03%) and late CP (=65/966; 6.72%) group (P = 0.09). Only in the three studies specifically reporting on the rate of hydrocephalus after DC performed to address traumatic brain injury (TBI) alone was there a significantly lower incidence of hydrocephalus with early CP (P = 0.01).Conclusion: Early CP (within 90 days) after DC performed in TBI patients alone was associated with a lower incidence of hydrocephalus. However, this finding was not corroborated in the remaining eight studies involving CP for pathology exclusive of TBI.

Detailed Analysis of Hydrocephalus and Hindbrain Herniation After Prenatal and Postnatal Myelomeningocele Closure: Report From a Single Institution.

The Management of Myelomeningocele Study (MOMS) demonstrated that fetal myelomeningocele (fMMC) closure results in improved hydrocephalus and hindbrain herniation when compared to postnatal closure. To report on the outcomes of a single institution's experience in the post-MOMS era, with regard to hydrocephalus absence and hindbrain herniation resolution. A single-center retrospective study of a subset of post-MOMS patients who underwent fetal/postnatal myelomeningocele closure was performed. Primary outcomes included cerebrospinal fluid (CSF) diversion status and hindbrain herniation resolution. Families were contacted via telephone for outcome information if care was transitioned to outside institutions. Univariate/multivariable analyses were performed using several prenatal and postnatal variables. From January 2011 to May 2016, data were reviewed from families of 62 postnatal and 119 fMMC closure patients. In the postnatal group, 80.6% required CSF diversion compared to 38.7% fetal cases (P<.01). Hindbrain herniation resolution occurred in 81.5% fetal repairs compared to 32.6% postnatal (P<.01). In the fetal group, fetal/premature neonatal demise occurred in 6/119 (5.0%) patients. There was a 42.0% decrease (95% CI -55.2 to -28.8) and 48.9% increase (95% CI 33.7 to 64.1) in risk difference for CSF diversion and hindbrain herniation resolution, respectively, in the fetal group. On univariate analysis for both groups, prenatal atrial diameter, frontal-occipital horn ratio, and hindbrain herniation resolution were significantly associated with the absence of clinical hydrocephalus. The treatment of hydrocephalus was significantly delayed in the fetal group compared to the postnatal group (10 mo vs 13.8 d). This study demonstrates the benefits of fMMC closure with regard to CSF dynamics.

Cerebrospinal fluid leak presented with the C1-C2 sign caused by spinal canal stenosis: a case report

BackgroundIntracranial hypotension is a disorder characterized by low cerebrospinal fluid (CSF) pressure typically caused by loss of CSF. Although some mechanisms account for the CSF leakage have been elucidated, spinal canal stenosis has never been reported as a pathological cause of intracranial hypotension.C1-C2 sign is a characteristic imaging feature, which indicates CSF collection between the spinous processes of C1 and C2, occasionally observed on magnetic resonance imaging (MRI) in patients with intracranial hypotension.Case presentationA 58-year-old man was presented to our institute with complaints of posterior cervical pain persisting for 3 months, along with numbness and muscle weakness of extremities. A fat suppression T2-weighted image of MRI illustrated fluid collection in the retrospinal region at C1-C2 level, and an 111In-DTPA cisternoscintigram clearly revealed the presence of CSF leakage into the same region. The MRI also showed stenosis in spinal canal at C3/4 level, and a computed tomography (CT) myelogram suggested a blockage at the same level. We gave a diagnosis as intracranial hypotension due to the CSF leakage, which might be caused by the spinal canal stenosis at C3/4 level. Despite 72 h of conservative therapy, a brain CT showed the development of bilateral subdural hematomas. We, therefore, performed burr-hole drainage of the subdural hematoma, blood-patch therapy at C1/2 level, and laminoplasty at C3–4 at the same time. Improvement of symptoms and imaging features which suggested the CSF leak and subdural hematoma were obtained post-operatively.ConclusionThe present case suggested the mechanism where the CSF leakage was revealed as fluid collection in the retrospinal region at C1-C2 level. Increased intradural pressure due to the spinal canal stenosis resulted in dural tear. CSF leaked into the epidural space and subsequently to the retrospinal region at C1-C2 level, due to the presence of spinal canal stenosis caudally as well as the vulnerability of the tissue structure in the retrospinal region at C1-C2 level. Thus, our theory supports the mechanisms of previously reported CSF dynamics associated to C1-C2 sign, and also, we suggest spinal canal stenosis as a novel etiology of intracranial hypotension.

Neurocutaneous melanosis concurrent with a posterior cranial fossa cyst (Dandy–Walker complex) and an intradural arachnoid cyst of the spinal canal

The paper describes a female patient with neurocutaneous melanosis (NCM) concurrent with Dandy–Walker malformation and a spinal arachnoid cyst, who has been treated in the A.Ya. Kozhevnikov Clinic of Nervous System Diseases. Over the course of one year, the patient had progressive neurological symptoms as central lower paraparesis and coordination disorders; her medical treatment was ineffective. Neuroimaging revealed Dandy–Walker malformation and a spinal arachnoid cyst. Surgical intervention (fenestration of the upper and lower poles of the arachnoid cyst at the C VI-VII and T IX-X level) was performed. After one month, reoperation (commissure resection in the arachnoid cyst cavity at the T V-VI level; implantation of a cystoperitoneal shunt) was made because of the absence of a clinical result. Reversal of neurological disorders was noted postoperatively. The described clinical case is unique, since NCM is an extremely rare abnormality, especially when concurrent with Dandy–Walker malformation and an arachnoid cyst. In addition, it is of interest that the manifestation of neurological symptoms and verification of the diagnosis occurred just in adulthood, although NCM is most commonly diagnosed in children. The present case shows that an operation aimed at improving cerebrospinal fluid dynamics in patients with arachnoid cysts and Dandy–Walker complex in the presence of NCM can lead to a significant reversal of neurological symptoms and improvement in the quality of life despite gross brain structural changes detected by magnetic resonance imaging.

Cerebrospinal fluid dynamics in idiopathic normal pressure hydrocephalus on four-dimensional flow imaging.

To evaluate complex CSF movements and shear stress in patients with idiopathic normal pressure hydrocephalus (iNPH) on four-dimensional (4D) flow MRI. Three-dimensional velocities and volumes of the reciprocating CSF movements through 12 ROIs from the foramen of Monro to the upper cervical spine were measured in 41 patients with iNPH, 23 patients with co-occurrence of iNPH and Alzheimer's disease (AD), and 9 age-matched controls, using 4D flow imaging and application. Stroke volume, reversed-flow rate, and shear stress were automatically calculated. Relationships between flow-related parameters and morphological measurements were also assessed. Stroke volumes, reversed-flow rates, and shear stress at the cerebral aqueduct were significantly higher in patients with iNPH than in controls. Patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD. The stroke volume at the upper end of the cerebral aqueduct had the strongest association with the anteroposterior diameter of the lower end of the cerebral aqueduct (r =0.52). The stroke volume at the foramen of Monro had significant associations with the indices specific to iNPH. The shear stress at the dorsal aspect of the cerebral aqueduct had the strongest association with the diameter of the foramen of Magendie (r = 0.52). Stroke volumes, reversed-flow rates, and shear stress through the cerebral aqueduct on 4D flow MRI are useful parameters for iNPH diagnosis. These findings can aid in elucidating the mechanism of ventricular enlargement in iNPH. • The CSF stroke volume and bimodal shear stress at the cerebral aqueduct were considerably higher in patients with iNPH. • The patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD. • The shear stress at the cerebral aqueduct was significantly associated with the diameter of the foramen of Magendie.

Three-Dimensionally Printed Microelectromechanical-System Hydrogel Valve for Communicating Hydrocephalus.

Hydrocephalus (HCP) is a chronic neurological brain disorder caused by a malfunction of the cerebrospinal fluid (CSF) drainage mechanism in the brain. The current standard method to treat HCP is a shunt system. Unfortunately, the shunt system suffers from complications including mechanical malfunctions, obstructions, infections, blockage, breakage, overdrainage, and/or underdrainage. Some of these complications may be attributed to the shunts' physically large and lengthy course making them susceptible to external forces, siphoning effects, and risks of infection. Additionally, intracranial catheters artificially traverse the brain and drain the ventricle rather than the subarachnoid space. We report a 3D-printed microelectromechanical system-based implantable valve to improve HCP treatment. This device provides an alternative approach targeting restoration of near-natural CSF dynamics by artificial arachnoid granulations (AGs), natural components for CSF drainage in the brain. The valve, made of hydrogel, aims to regulate the CSF flow between the subarachnoid space and the superior sagittal sinus, in essence, substituting for the obstructed arachnoid granulations. The valve, operating in a fully passive manner, utilizes the hydrogel swelling feature to create nonzero cracking pressure, PT ≈ 47.4 ± 6.8 mmH2O, as well as minimize reverse flow leakage, QO ≈ 0.7 μL/min on benchtop experiments. The additional measurements performed in realistic experimental setups using a fixed sheep brain also deliver comparable results, PT ≈ 113.0 ± 9.8 mmH2O and QO ≈ 3.7 μL/min. In automated loop functional tests, the valve maintains functionality for a maximum of 1536 cycles with the PT variance of 44.5 mmH2O < PT < 61.1 mmH2O and negligible average reverse flow leakage rates of ∼0.3 μL/min.

Posture related in-vitro characterization of a flow regulated MEMS CSF valve.

Overdrainage in upright position is one of the most prevalent issues in treating hydrocephalus with a cerebrospinal fluid (CSF) shunt. Anti-siphon devices (ASDs) are employed to reduce this problem. A novel microelectromechanical system (MEMS)-based valve, termed Chronoflow device, aims to regulate CSF drainage indifferently of the body posture. With this study, the suitability of this MEMS-based valve is evaluated regarding its use for the treatment of hydrocephalus, particularly for the prevention of overdrainage and blockage. In total, four Chronoflow devices were tested. An established in-vitro hardware-in-the-loop (HIL) test bed was used to investigate the valves regarding their pressure-flow characteristics, their behaviors towards CSF dynamics, and their capabilities to prevent CSF overdrainage in upright position. Additionally, a contamination test was conducted to evaluate the susceptibility of the device to blockage due to particles. All valves tested regulated the drainage rate at similar nominal flows and independently of posture. The pressure-flow relation measured, however, was notably higher than numerically calculated. Regarding the CSF dynamics, the first three valves tested led to a decreased steady-state intracranial pressure in supine position and showed stable drainage rate in upright position. During the transitional phase from supine to upright and vice versa, the valves continuously adjusted the outflow resistance, which resulted in a stable transitional phase preventing overdrainage. Yet, the fourth valve showed continuous overdrainage in upright position due to an increased nominal flow. However, after several test iterations the nominal flow decreased and stabilized at a level similar to that of the first three valves tested. The contamination test showed that most particles initially adhere to the pillars and spread throughout the cavity of the valve as the concentration of particles increases, thereby affecting the displacement of the membrane. The devices generally provide a stable flow regulation and prevent overdrainage in upright position. Specifically, their drainage behaviors during the posture changes are very effective. However, they also showed high hysteresis and sensitivity towards particle contamination, which resulted in initial increased and altering nominal flows after many test iterations. This result suggests that the MEMS design presented lacks robustness. Yet, an upstream filter and specific coatings on the fluid pathway may increase significantly its reliability.

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats

BackgroundIdiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined.MethodsIn vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C–C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC).ResultsFemale rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/μl controls, and 7.09 ± 0.26 mmH2O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage.ConclusionsWeight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

Longitudinal analysis of cerebral aqueduct flow measures: multiple sclerosis flow changes driven by brain atrophy

BackgroundSeveral small cross-sectional studies have investigated cerebrospinal fluid (CSF) flow dynamics in multiple sclerosis (MS) patients and have reported mixed results. Currently, there are no longitudinal studies that investigate CSF dynamics in MS patients.ObjectiveTo determine longitudinal changes in CSF dynamics measured at the level of aqueduct of Sylvius (AoS) in MS patients and matched healthy controls (HCs).Materials and methodsForty (40) MS patients and 20 HCs underwent 3T MRI cine phase contrast imaging with velocity-encoded pulse-gated sequence at baseline and 5-year follow-up. For atrophy determination, MS patients underwent additional high-resolution 3D T1-weighted imaging. Measures of AoS cross-sectional area (CSA), average systolic and diastolic velocity peaks, maximal systolic and diastolic velocity peaks and average CSF flow rates were determined. Brain atrophy and ventricular CSF (vCSF) expansion rates were determined. Cross-sectional and longitudinal changes were derived by analysis of covariance (ANCOVA) and paired repeated tests. Confirmatory general linear models were also performed. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant.ResultsThe MS population demonstrated significant increase in maximal diastolic peak (from 7.23 to 7.86 cm/s, non-adjusted p = 0.037), diastolic peak flow rate (7.76 ml/min to 9.33 ml/min, non-adjusted p = 0.023) and AoS CSA (from 3.12 to 3.69 mm2, adjusted p = 0.001). The only differentiator between MS patients and HCs was the greater AoS CSA (3.58 mm2 vs. 2.57 mm2, age- and sex-adjusted ANCOVA, p = 0.045). The AoS CSA change was associated with vCSF expansion rate (age- and sex-adjusted Spearman’s correlation r = 0.496, p = 0.019) and not with baseline nor change in maximal velocity. The expansion rate of the vCSF space explained an additional 23.8% of variance in change of AoS CSA variance when compared to age and sex alone (R2 = 0.273, t = 2.557, standardized β = 0.51, and p = 0.019).ConclusionMS patients present with significant longitudinal AoS enlargement, potentially due to regional atrophy changes and ex-vacuo expansion of the aqueduct.

Cranioplasty Following Decompressive Craniectomy.

Cranioplasty (CP) after decompressive craniectomy (DC) for trauma is a neurosurgical procedure that aims to restore esthesis, improve cerebrospinal fluid (CSF) dynamics, and provide cerebral protection. In turn, this can facilitate neurological rehabilitation and potentially enhance neurological recovery. However, CP can be associated with significant morbidity. Multiple aspects of CP must be considered to optimize its outcomes. Those aspects range from the intricacies of the surgical dissection/reconstruction during the procedure of CP, the types of materials used for the reconstruction, as well as the timing of the CP in relation to the DC. This article is a narrative mini-review that discusses the current evidence base and suggests that no consensus has been reached about several issues, such as an agreement on the best material for use in CP, the appropriate timing of CP after DC, and the optimal management of hydrocephalus in patients who need cranial reconstruction. Moreover, the protocol-driven standards of care for traumatic brain injury (TBI) patients in high-resource settings are virtually out of reach for low-income countries, including those pertaining to CP. Thus, there is a need to design appropriate prospective studies to provide context-specific solid recommendations regarding this topic.

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients

BackgroundDeveloping novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed.MethodsComplete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then generated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed.ResultsComparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of variability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal.ConclusionWhile our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about the hydrodynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states.

Myelographic CT, A Check-Valve Mechanism, and Microsurgical Treatment of Sacral Perineural Tarlov Cysts

There is currently no consensus regarding surgical indications for symptomatic sacral perineural cysts. Nine patients with symptomatic sacral perineural cysts underwent microsurgery. All patients fulfilled the following criteria: (1) cyst sizes larger than 15 mm; (2)cysts show the "delayed inflow" and/or "delayed outflow" of contrast on myelographic computed tomography (CT), and (3)neurological symptoms correlate with the primary cyst. On myelographic CT, all primary cysts showed the "delayed inflow" of contrast; the average cyst/thecal sac Hounsfield units (HU) ratio was 0.17. In 7 patients, the primary cyst showed "delayed outflow"; the average cyst/thecal sac HU ratio increased to 3.12 on images obtained 24hours after contrast injection. Regarding the modified Rankin Scale, 67% of patients reported that their overall symptoms improved to normal activities after surgery. The most improved symptom was coccydynia (75% improvement, P= 0.017), followed by leg radiation pain (67% improvement, P= 0.027) and buttock pain (50% improvement, P= 0.068). Bowel/bladder dysfunction improved in 100% of patients, but newly developed in 1 patient (P= 0.32). Perineal pain only decreased in 33% (P= 0.41). To the best of our knowledge, this is the first study to have performed a quantitative analysis of the dynamics of cerebrospinal fluid in sacral perineural cysts using myelographic CT. Sixty-seven percent of patients benefited from surgery; however, our criteria may not be a necessary and sufficient condition for patient selection because 33% did not respond to surgery despite the successful elimination of the check-valve.

Is stagnant cerebrospinal fluid involved in the pathophysiology of normal tension glaucoma.

Current concepts of the pathophysiology of normal tension glaucoma (NTG) include intraocular pressure, vascular dysregulation and the concept of a translaminar pressure gradient. Studies on NTG performed with cisternography demonstrated an impaired cerebrospinal fluid (CSF) dynamics in the subarachnoid space of the optic nerve sheath, most pronounced behind the lamina cribrosa. Stagnant CSF might be another risk factor for NTG.