CSF Dynamics Research Articles

Assessment of disorders of hemodynamics and csf dynamics in idiopathic intracranial hypertension syndrome according to MRI data

Highlights. An increase in the pulsatility index of intracranial venous blood flow and cerebrospinal fluid flow at the foramen magnum level, and a decrease in arteriovenous delay and an intracranial compliance index indicate disturbances in the pulse wave distribution, and a decrease in compliance/extensibility of the brain due to increased intracranial pressure.Aim. To assess the parameters of hemodynamics and cerebrospinal fluid dynamics in patients with idiopathic intracranial hypertension syndrome according to phase-contrast MRI.Methods. The study included 18 patients with idiopathic intracranial hypertension syndrome and 20 controls, all patient were examined using the Ingenia 3,0T MRI scanner. The analysis was performed using phase-contrast MRI to assess quantitative parameters of hemodynamics and cerebrospinal fluid (CSF) dynamics in 14 different structures. The blood and CSF volumes, pulsatility index (PI), arterio-venous delay, and intracranial compliance index were calculated. The Mann-Whitney U-test reliability was used to assess the differences between the controls and patients.Results. The group of patients had an increased CSF systolic peak at the foramen magnum without significant changes in CSF volume, and significantly increased CSF PI at the cervical level by 11.88% (p<0,05). There was a tendency toward an increase in the intracranial venous blood volume, as well as a tendency toward significant increase in PI at the straight and superior sagittal sinuses by 1,3 times (p><0,01, p><0,05). Moreover, there was a reduction of intracranial arterio-venous delay by 1,9 times (p><0,05), and a significant decrease in the intracranial compliance index by 1,2 times (p><0,05). Conclusion We have assessed the parameters of hemodynamics and CSF dynamics in patients with idiopathic intracranial hypertension and revealed disturbances in CSF dynamics and pulse wave propagation in the intracranial regions. Such changes may indicate a decrease in compliance/increase in stiffness of the brain tissue due to an increase in intracranial pressure and a possible diffuse stagnation of interstitial fluid. Keywords Phase-contrast magnetic resonance imaging • Central nervous system • Idiopathic intracranial hypertension • Hemodynamics • Cerebrospinal fluid dynamics • Intracranial compliance index>˂0,05). There was a tendency toward an increase in the intracranial venous blood volume, as well as a tendency toward significant increase in PI at the straight and superior sagittal sinuses by 1,3 times (p˂0,01, p˂0,05). Moreover, there was a reduction of intracranial arterio-venous delay by 1,9 times (p˂0,05), and a significant decrease in the intracranial compliance index by 1,2 times (p˂0,05).Conclusion. We have assessed the parameters of hemodynamics and CSF dynamics in patients with idiopathic intracranial hypertension and revealed disturbances in CSF dynamics and pulse wave propagation in the intracranial regions. Such changes may indicate a decrease in compliance/increase in stiffness of the brain tissue due to an increase in intracranial pressure and a possible diffuse stagnation of interstitial fluid.

MRI as a one-stop destination for evaluation of CSF shunt malfunction

BackgroundDespite the high-frequency rate of cerebrospinal fluid shunt malfunction, radiological evaluation of CSF shunts has remained deficient, focusing mainly on demonstrating secondary signs of shunt failure rather than evaluating the shunt tube itself. We aimed to study the utility of different MR pulse sequences in evaluating the cranial and abdominal ends of CSF shunts in order to identify the potential cause of shunt failure and its impact on patient management.ResultsTwenty-five patients (18 males, 7 females, median age 2.5 years, IQR 0.75–15) were enrolled in the study, having 28 ventriculo-peritoneal shunts and single ventriculo-gallbladder shunt. The catheter lumen and fine intraventricular septae were only demonstrated in 3D-DRIVE sequences (p < 0.001). Except for three patients (having cranial end-related complications), all patients with cranial and/or abdominal end-related complications received surgery (p < 0.001, positive likelihood and negative likelihood ratios = 7.27, 0.3, respectively, sensitivity = 0.7 and specificity = 0.9). MRI findings (luminal occlusion, disconnection, CSF collection, or migration) were consistent with operative data. There is no significant difference between patients who underwent surgery and those with conservative management, or symptomatic and asymptomatic patients in terms of the prevalence of ventricular dilatation or white matter signal abnormality. The results of the abdomino-pelvic fat-suppressed T2-WI showed excellent agreement with ultrasound findings (Cohen’s Kappa 0.9). Quantitative PC could give insights into CSF dynamics, which depend on the site and cause of shunt malfunction.ConclusionsMRI could be a one-stop destination for evaluating patients with suspected non-acute shunt malfunction. It was found to have clinical relevance in terms of accurately locating the exact site and possible cause of shunt-related complications.

Potential association among posterior fossa bony volume and crowdedness, tonsillar hernia, syringomyelia, and CSF dynamics at the craniocervical junction in Chiari malformation type I.

The characteristic morphological parameters (bony posterior fossa volume (bony-PFV), posterior fossa crowdness, cerebellar tonsillar hernia, and syringomyelia) and CSF dynamics parameters at the craniocervical junction (CVJ) in Chiari malformation type I (CMI) were measured. The potential association between these characteristic morphologies and CSF dynamics at CVJ was analyzed. A total of 46 cases of control subjects and 48 patients with CMI underwent computed tomography and phase-contrast magnetic resonance imaging. Seven morphovolumetric measures and four CSF dynamics at CVJ measures were performed. The CMI cohort was further divided into "syringomyelia" and "non-syringomyelia" subgroups. All the measured parameters were analyzed by the Pearson correlation. Compared with the control, the posterior cranial fossa (PCF) area, bony-PFV, and CSF net flow were significantly smaller (P < 0.001) in the CMI group. Otherwise, the PCF crowdedness index (PCF CI, P < 0.001) and the peak velocity of CSF (P < 0.05) were significantly larger in the CMI cohort. The mean velocity (MV) was faster in patients with CMI with syringomyelia (P < 0.05). In the correlation analysis, the degree of cerebellar tonsillar hernia was correlated with PCF CI (R = 0.319, P < 0.05), MV (R = -0.303, P < 0.05), and the net flow of CSF (R = -0.300, P < 0.05). The Vaquero index was well correlated with the bony-PFV (R= -0.384, P < 0.05), MV (R = 0.326, P < 0.05), and the net flow of CSF (R = 0.505, P < 0.05). The bony-PFV in patients with CMI was smaller, and the MV was faster in CMI with syringomyelia. Cerebellar subtonsillar hernia and syringomyelia are independent indicators for evaluating CMI. Subcerebellar tonsillar hernia was associated with PCF crowdedness, MV, and the net flow of CSF at CVJ, while syringomyelia was associated with bony-PFV, MV, and the net flow of CSF at the CVJ. Thus, the bony-PFV, PCF crowdedness, and the degree of CSF patency should also be one of the indicators of CMI evaluation.

Decompressive Craniectomy in Severe Traumatic Brain Injury: The Intensivist’s Point of View

Traumatic brain injury (TBI) represents a severe pathology with important social and economic concerns, decompressive craniectomy (DC) represents a life-saving surgical option to treat elevated intracranial hypertension (ICP). The rationale underlying DC is to remove part of the cranial bones and open the dura mater to create space, avoiding secondary parenchymal damage and brain herniations. The scope of this narrative review is to summarize the most relevant literature and to discuss main issues about indication, timing, surgical procedure, outcome, and complications in adult patients involved in severe traumatic brain injury, underwent to the DC. The literature research is made with Medical Subject Headings (MeSH) terms on PubMed/MEDLINE from 2003 to 2022 and we reviewed the most recent and relevant articles using the following keywords alone or matched with each other: decompressive craniectomy; traumatic brain injury; intracranial hypertension; acute subdural hematoma; cranioplasty; cerebral herniation, neuro-critical care, neuro-anesthesiology. The pathogenesis of TBI involves both primary injuries that correlate directly to the external impact of the brain and skull, and secondary injuries due to molecular, chemical, and inflammatory cascade inducing further cerebral damage. The DC can be classified into primary, defined as bone flap removing without its replacement for the treatment of intracerebral mass, and secondary, which indicates for the treatment of elevated intracranial pressure (ICP), refractory to intensive medical management. Briefly, the increased brain compliance following bone removal reflects on CBF and autoregulation inducing an alteration in CSF dynamics and so, eventual complications. The risk of complications is estimated around 40%. The main cause of mortality in DC patients is due to brain swelling. In traumatic brain injury, primary or secondary decompressive craniectomy is a life-saving surgery, and the right indication should be mandatory in multidisciplinary medical-surgical consultation.

The application of integrated MRI CSF flowmetry in the diagnosis and treatment of CSF dynamic changes in hydrocephalus patients: a systematic review

Background: CSF has contributed to the growth of brain development during the time of evolution and later protects against external trauma. Idiopathic normal pressure hydrocephalus (iNPH) is known as an aberration of intracranial hydrodynamics resulting in the accumulation of CSF endo-ventricular. The use of phase-contrast (PC) MRI is proven effective in assessing the communication of arachnoid cyst and subarachnoid CSF spaces. The CSF flow MRI has been found to show efficacy in differentiation between the communicating and non-communicating hydrocephalus for localizing obstruction levels in obstructive hydrocephalus and later providing important information concerning the preoperative evaluation of NPH, along with the differential diagnosis and the prediction of the related advantages from surgery and post-operative follow-up. Hence, the present study aimed for analyzing the role of MRI CSF flowmetry in the evaluation of patients with suspected hydrocephalus. Method: The role of MRI CSF flowmetry in the evaluation of patients with suspected hydrocephalus was undertaken by conducting a systematic literature review. The current review was reported as required reporting features for systematic reviews and meta-analysis statements (PRISMA). The systematic literature review included a total of 22 studies that analyzed the various applications of MRI CSF flowmetry in the medical field, mainly focusing on the use of MRI CSF flowmetry in the evaluation of patients with suspected hydrocephalus. Results: The result mainly included the identification of the CSF flow by integrating the PC MRI technique and the aqueduct-CSF flow rate was detected accurately showing as statistically significant in diagnosis of NPH. Evaluating the peak velocities and aqueductal stroke volume (ASV) showed a significant increase among hydrocephalus patients. Conclusion: The condition of hydrocephalus makes the ventricular size increase and eventually puts pressure on the brain due to excess accumulation of fluid while blocking the CSF flow after it exits ventricles. Currently, many imaging techniques are available for the detection of hydrocephalus that study the CSF flow dynamics and its related parameters. Among them, the MRI technique is the most reliable, rapid, and most importantly, a non-invasive method for the quantitative measurement of CSF flow rate and intracranial pulsations. Keywords: Intracranial pressure, Magnetic resonance imaging (MRI), MRI CSF Flowmetry, Neurological disorder, CSF dynamics

Spinal cord motion assessed by phase-contrast MRI - An inter-center pooled data analysis

BackgroundPhase-contrast MRI of CSF and spinal cord dynamics has evolved among diseases caused by altered CSF volume (spontaneous intracranial hypotension, normal pressure hydrocephalus) and by altered CSF space (degenerative cervical myelopathy (DCM), Chiari malformation). While CSF seems to be an obvious target for possible diagnostic use, craniocaudal spinal cord motion analysis offers the benefit of fast and reliable assessments. It is driven by volume shifts between the intracranial and the intraspinal compartments (Monro-Kellie hypothesis). Despite promising initial reports, comparison of spinal cord motion data across different centers is challenged by reports of varying value, raising questions about the validity of the findings. ObjectiveTo systematically investigate inter-center differences between phase-contrast MRI data. MethodsAge- and gender matched, retrospective, pooled-data analysis across two centers: cardiac-gated, sagittal phase-contrast MRI of the cervical spinal cord (segments C2/C3 to C7/T1) including healthy participants and DCM patients; comparison and analysis of different MRI sequences and processing techniques (manual versus fully automated). ResultsA genuine craniocaudal spinal cord motion pattern and an increased focal spinal cord motion among DCM patients were depicted by both MRI sequences (p < 0.01). Higher time-resolution resolved steeper and larger peaks, causing inter-center differences (p < 0.01). Comparison of different processing methods showed a high level of rating reliability (ICC > 0.86 at segments C2/C3 to C6/C7). DiscussionCraniocaudal spinal cord motion is a genuine finding. Differences between values were attributed to time-resolution of the MRI sequences. Automated processing confers the benefit of unbiased and consistent analysis, while data did not reveal any superiority.

30 Years of Experience in CSF Dynamics Testing in Adult Hydrocephalus

30 Years of Experience in CSF Dynamics Testing in Adult Hydrocephalus

A chronic post dural puncture syndrome without low opening pressure or altered CSF dynamics

A chronic post dural puncture syndrome without low opening pressure or altered CSF dynamics

Sphenoid dysplasia in patients with neurofibromatosis type 1: Clinical features and imaging findings including cerebrospinal fluid alterations.

Neurofibromatosis Type 1 (NF-1) is a genetic disorder that occurs in 1:2500-3000 live births and may involve multiple organs. An uncommon but well-known phenomena is sphenoid dysplasia, which appears in 3-11% of the patients, and may result in significant lowering of the orbit. Understanding the cause and development of this process might predict its course and its treatment. The records of 29 patients with PNF in the head and neck region were searched for location of the PNF and type of surgery. Photographs were studied for facial disturbances, including vertical dystopia, hypertelorism, ptosis, exophthalmos and enophthalmos. MR and CT scans were studied for the presence of PNF, aspect of the sphenoid bone, alteration in the CSF circulation, and other tumour involvement. Fourteen of 29 patients with PNF in the head and neck presented with sphenoid dysplasia. All 14 patients had their PNF located in the periorbital region. Increased locoregional CSF collections were seen in almost all of these patients. Besides glioma of the optical nerve or hamartomas in the cerebrum and cerebellum, there were no other tumours found. Surgical treatment varies from simple excision to excessive debulking of the PNF, reconstruction of the orbit and even enucleation. Although sphenoid dysplasia is uncommon in NF-1 patients, early recognition is important to prevent facial disfigurement and vision loss. Clinicians should be aware that abnormalities in the periorbital region and especially vertical dystopia might be the first sign of sphenoid dysplasia. Performing a CT or black-bone MR scan would be the next step to confirm or exclude sphenoid dysplasia and abnormal CSF dynamics.

Compromised Cranio-Spinal Suspension in Chiari Malformation Type 1: A Potential Role as Secondary Pathophysiology.

In Chiari Malformation Type I (CM1), low-lying tonsils obstruct the cisterna magna at the foramen magnum, thereby compromising the essential juncture between the cranial and spinal compartments. The anatomical obstruction of the cisterna magna inhibits bi-directional CSF flow as well as CSF pulse pressure equilibration between the intracranial compartment and the intraspinal compartment in response to instances of increased intracranial pressure. Less understood, however, are the roles of the spinal cord suspension structures at the craniocervical junction which lend viscoelastic support to the spinal cord and tonsils, as well as maintain the anatomical integrity of the cisterna magna and the dura. These include extradural ligaments including the myodural bridges (MDBs), as well as intradural dentate ligaments and the arachnoid framework. We propose that when these elements are disrupted by the cisterna magna obstruction, tonsillar pathology, and altered CSF dynamics, there may arise a secondary pathophysiology of compromised and dysfunctional cranio-spinal suspension in CM1. We present intraoperative images and videos captured during surgical exposure of the craniocervical junction in CM1 to illustrate this proposal.

CSF Dynamics: Implications for Hydrocephalus and Glymphatic Clearance.

Beyond its neuroprotective role, CSF functions to rid the brain of toxic waste products through glymphatic clearance. Disturbances in the circulation of CSF and glymphatic exchange are common among those experiencing HCP syndrome, which often results from SAH. Normally, the secretion of CSF follows a two-step process, including filtration of plasma followed by the introduction of ions, bicarbonate, and water. Arachnoid granulations are the main site of CSF absorption, although there are other influencing factors that affect this process. The pathway through which CSF is through to flow is from its site of secretion, at the choroid plexus, to its site of absorption. However, the CSF flow dynamics are influenced by the cardiovascular system and interactions between CSF and CNS anatomy. One, two, and three-dimensional models are currently methods researchers use to predict and describe CSF flow, both under normal and pathological conditions. They are, however, not without their limitations. "Rest-of-body" models, which consider whole-body compartments, may be more effective for understanding the disruption to CSF flow due to hemorrhages and hydrocephalus. Specifically, SAH is thought to prevent CSF flow into the basal cistern and paravascular spaces. It is also more subject to backflow, caused by the presence of coagulation cascade products. In regard to the fluid dynamics of CSF, scar tissue, red blood cells, and protein content resulting from SAH may contribute to increased viscosity, decreased vessel diameter, and increased vessel resistance. Outside of its direct influence on CSF flow, SAH may result in one or both forms of hydrocephalus, including noncommunicating (obstructive) and communicating (nonobstructive) HCP. Imaging modalities such as PC-MRI, Time-SLIP, and CFD model, a mathematical model relying on PC-MRI data, are commonly used to better understand CSF flow. While PC-MRI utilizes phase shift data to ultimately determine CSF speed and flow, Time-SLIP compares signals generated by CSF to background signals to characterizes complex fluid dynamics. Currently, there are gaps in sufficient CSF flow models and imaging modalities. A prospective area of study includes generation of models that consider "rest-of-body" compartments and elements like arterial pulse waves, respiratory waves, posture, and jugular venous posture. Going forward, imaging modalities should work to focus more on patients in nature in order to appropriately assess how CSF flow is disrupted in SAH and HCP.

Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy

BackgroundNarcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls.MethodsIn this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis.ResultsWe find that variance and fractional variance in the very low frequency (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard variance (R = −0.48, p = 0.0249).ConclusionsWe suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1.

The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure.

During mammalian evolution, the Myodural Bridges (MDB) have been shown to be highly conserved anatomical structures. However, the putative physiological function of these structures remains unclear. The MDB functionally connects the suboccipital musculature to the cervical spinal dura mater, while passing through the posterior atlanto-occipital and atlanto-axial interspaces. MDB transmits the tensile forces generated by the suboccipital muscles to the cervical dura mater. Moreover, head movements have been shown to be an important contributor to human CSF circulation. In the present study, a 16-week administration of a Myostatin-specific inhibitor, ACE-031, was injected into the suboccipital musculature of rats to establish an experimental animal model of hyperplasia of the suboccipital musculature. Using an optic fiber pressure measurement instrument, the present authors observed a significant increase in intracranial pressure (ICP) while utilizing the hyperplasia model. In contrast, surgically severing the MDB connections resulted in a significant decrease in intracranial pressure. Thus, these results indicated that muscular activation of the MDB may affect CSF circulation, suggesting a potential functional role of the MDB, and providing a new research perspective on CSF dynamics.

Measurement of CSF pulsation from EPI-based human fMRI

It is recently discovered that the glymphatic system and meningeal lymphatic system are the primary routes for the clearance of brain waste products. The CSF flow is part of these systems, facilitating the clearance procedure. Nonetheless, the relationship between CSF flow and brain functional activity has been underexplored. To investigate CSF dynamics and functional brain activity simultaneously, recent studies have proposed a CSF inflow index measured on edge slices (CSFedge) of echo-planar imaging (EPI) based functional magnetic resonance imaging (fMRI), however, it lacks the quantitative aspect of the CSF pulsation. We proposed a new method for quantifying CSF pulsation (CSFpulse) based on an interslice CSF pulsation model in the 4th ventricle of EPI-based fMRI. The proposed CSFpulse successfully detected the higher CSF flow during the resting state than the typical task states (visual and motor) (p<.05), which is consistent with previous studies based on phase contrast (PC) MRI and CSF volume MRI, while it was not detected in CSFedge based indices or baseline CSF signals in various regions of interest (ROIs). Moreover, CSFpulse demonstrated dynamic functional changes in CSF pulsation: it decreased during the activation-on blocks while it increased during the activation-off blocks. CSFpulse significantly correlated with stroke volume measured using PC MRI, a standard method for CSF pulsation quantification, under the same functional state, while CSFedge based indices or CSF ROIs showed no correlation with the PC MRI stroke volume. Lastly, the correlation of CSFpulse with global BOLD was weaker than that of CSFedge, suggesting that CSFpulse may reflect distinct CSF physiological information that is less affected by global BOLD effects. Based on these results, the proposed CSFpulse provides CSF pulsatility information more accurately in a quantitative manner than CSFedge based indices from the recent CSF studies or the conventional ROI-based analysis. In addition to the high correlation with PC MRI, CSFpulse is much faster than PC MRI and provides information of functional brain activations simultaneously, advantageous over PC MRI or CSF volume MRI. Accordingly, the suggested CSFpulse can be used for investigating intra-subject functional changes in BOLD and CSF pulsation simultaneously and inter-subject CSF pulsation variations based on conventional EPI-based fMRI, which warrants further investigation.

Algorithmic Multimodality Approach to Diagnosis and Treatment of Spinal CSF Leak and Venous Fistula in Patients With Spontaneous Intracranial Hypotension.

Spontaneous intracranial hypotension (SIH) is a disorder of CSF dynamics that causes a complex clinical syndrome and severe disability. SIH is challenging to diagnose because of the variability of its presenting clinical symptoms, the potential for subtle imaging findings to be easily overlooked, and the need for specialized diagnostic testing. Once SIH is suggested by clinical history and/or supported by initial neuroim-aging, many patients may undergo initial nontargeted epidural blood patching with variable and indefinite benefit. However, data suggest that precise localization of the CSF leak or CSF-venous fistula (CVF) can lead to more effective and durable treatment strategies. Leak localization can be achieved using a variety of advanced diagnostic imaging techniques, although these may not be widely performed at nontertiary medical centers, leaving many patients with the potential for inadequate workup or treatment. This review describes imaging techniques including dynamic fluoroscopic and CT myelography as well as delayed MR myelography and treatment options including percutaneous, endovascular, and surgical approaches for SIH. These are summarized by an algorithmic framework for radiologists to approach the workup and treatment of patients with suspected SIH. The importance of a multidisciplinary approach is emphasized.

Statistical shape models of the posterior cranial fossa and hindbrain volumes may provide a more robust clinical metric for Chiari malformation

Chiari malformation is characterised by the herniation of the cerebellar tonsils through the foramen magnum. However, tonsillar herniation and other 2D morphometric measurements of the posterior cranial fossa (PCF) have a weak association with patients’ symptoms and clinical outcomes. This study aimed to contrast current 2D metrics with a novel 3D shape analysis of the PCF and the hindbrain, to determine if 3D measurements provides further insight into the pathophysiology of Chiari. The cranium of 12 controls and 21 Chiari malformation patients with (N = 9) and without (N = 12) a syrinx were scanned. The morphology of the PCF was quantified with typical 2D measurements. Additionally, a correspondence-based shape model that normalised the PCF volume, was used to find 3D differences in the shape of the PCF, and the distance of the hindbrain from the inner surfaces of the PCF. Shape analysis showed that, compared to controls, the caudal (p = 0.007; 2.3 mm, IQR: 1.6–3.3 mm) and anterior (p = 0.027; 1.3 mm,IQR: 1.1–1.6 mm) surfaces of the hindbrain were closer to the PCF in patients with and without a syrinx, respectively. However, there were negligible differences in the shape of the PCF between patient groups (p > 0.39). Current morphometric measures should be normalised for variation in PCF volume, so that shape measures are not biased. The reduced CSF space between the hindbrain and PCF will alter CSF dynamics, which may compress cerebellar vasculature and contribute to patient symptomatology.

Cervical cerebrospinal fluid venous fistula with syringomyelia treated with suboccipital decompression: illustrative case.

BACKGROUNDCerebrospinal fluid (CSF) venous fistulas are a recently discovered and underdiagnosed cause of spontaneous spinal CSF leak, which may lead to spontaneous intracranial hypotension. Most cases occur in the thoracic spine, and only 2 cases were reported in the cervical spine. Treatments include the epidural blood patch, fibrin glue injection, and surgical ligation of the fistula.OBSERVATIONSThe authors report the treatment of a C6–7 CSF venous fistula, for which direct ligation was not feasible, with suboccipital decompression, leading to the complete resolution of the symptoms. Based on the clinical course and outcome in our patient, the authors summarize the previous theory and propose a hypothesis for the pathophysiology of headache and other symptoms in patients with CSF venous fistulas.LESSONSThe symptoms of CSF venous fistulas may be linked not only to intracranial hypotension but also to the altered CSF dynamics induced by tonsillar herniation. Suboccipital decompression should be considered as a potential treatment option, especially in patients with Valsalva-induced headache who show a poor response to surgical ligation, patients in whom surgical ligation is not feasible, and patients with foramen magnum obstruction. Further investigation of the pathophysiology of CSF venous fistulas is warranted and should be performed in the future.

Pathogenesis of posthemorrhagic hydrocephalus of prematurity: New horizons

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a vexing problem for patients, their families, and the healthcare system. The complexity of the pathogenesis of PHHP also presents a unique challenge within the fields of neonatology, neurology and neurosurgery. Here we focus on pathogenesis of PHHP and its impact on the development of CSF dynamics including choroid plexus, ependymal motile cilia and glymphatic system. PHHP is contrasted with infantile hydrocephalus from other etiologies, and with other types of posthemorrhagic hydrocephalus that occur later in life. The important concept that distinguishing ventricular volume from brain health and function is highlighted. The influence of the pathogenesis of PHHP on current interventions is reviewed, with particular emphasis on how the unique pathogenesis of PHHP contributes to the high rate of failure of current existing interventions. Finally, we discuss emerging interventions. A thorough understanding of the pathogenesis of PHHP is essential to developing effective non-surgical therapeutics to prevent the transformation from severe IVH to PHHP

Sustained glymphatic transport and impaired drainage to the nasal cavity observed in multiciliated cell ciliopathies with hydrocephalus

BackgroundHydrocephalus (increased ventricular size due to CSF accumulation) is a common finding in human ciliopathies and in mouse models with genetic depletion of the multiciliated cell (MCC) cilia machinery. However, the contribution of MCC to CSF dynamics and, the mechanism by which impaired MCC function leads to hydrocephalus remains poorly understood. The aim of our study was to examine if defects in MCC ciliogenesis and cilia-generated CSF flow impact central nervous system (CNS) fluid homeostasis including glymphatic transport and solute waste drainage.MethodsWe used two distinct mouse models of MCC ciliopathy: MCC-specific CEP164 conditional knockout mice (FOXJ1-Cre;CEP164fl/fl (N = 10), 3-month-old) and p73 knock-out (p73−/− (N = 8), 5-month-old) mice. Age-matched, wild-type littermates for each of the mutants served as controls. Glymphatic transport and solute drainage was quantified using in vivo T1 mapping by magnetic resonance imaging (MRI) after CSF infusion of gadoteric acid. Brain morphometry and aquaporin 4 expression (AQP4) was also assessed. Intracranial pressure (ICP) was measured in separate cohorts.ResultsIn both of the two models of MCC ciliopathy we found the ventriculomegaly to be associated with normal ICP. We showed that FOXJ1-Cre;CEP164fl/fl mice with hydrocephalus still demonstrated sustained glymphatic transport and normal AQP4 expression along capillaries. In p73−/− mice glymphatic transport was even increased, and this was paralleled by an increase in AQP4 polarization around capillaries. Further, solute drainage via the cribriform plate to the nasal cavity was severely impaired in both ciliopathy models and associated with chronic rhinitis and olfactory bulb hypoplasia.ConclusionsThe combination of sustained glymphatic transport, impaired solute drainage via the cribriform plate to the nasal cavity and hydrocephalus has not previously been reported in models of MCC ciliopathy. Our data enhance our understanding of how different types of ciliopathies contribute to disruption of CNS fluid homeostasis, manifested in pathologies such as hydrocephalus.

Deep breathing couples CSF and venous flow dynamics

Venous system pathologies have increasingly been linked to clinically relevant disorders of CSF circulation whereas the exact coupling mechanisms still remain unknown. In this work, flow dynamics of both systems were studied using real-time phase-contrast flow MRI in 16 healthy subjects during normal and forced breathing. Flow evaluations in the aqueduct, at cervical level C3 and lumbar level L3 for both the CSF and venous fluid systems reveal temporal modulations by forced respiration. During normal breathing cardiac-related flow modulations prevailed, while forced breathing shifted the dominant frequency of both CSF and venous flow spectra towards the respiratory component and prompted a correlation between CSF and venous flow in the large vessels. The average of flow magnitude of CSF was increased during forced breathing at all spinal and intracranial positions. Venous flow in the large vessels of the upper body decreased and in the lower body increased during forced breathing. Deep respiration couples interdependent venous and brain fluid flow—most likely mediated by intrathoracic and intraabdominal pressure changes. Further insights into the driving forces of CSF and venous circulation and their correlation will facilitate our understanding how the venous system links to intracranial pressure regulation and of related forms of hydrocephalus.