Cerebrospinal Fluid Flow Dynamics Research Articles

Integration of CSF pressure and flow data to further investigate nature of cerebrospinal compliance in hydrocephalus

Intracranial pressure (ICP) monitoring and infusion test are widely used in the diagnosis and management of hydrocephalus. MR neuroimaging allows the quantification of cerebrospinal fluid (CSF) and blood flow dynamics that can be used to calculate intracranial volume changes (IVC) during cardiac cycle and to help diagnose active hydrocephalus which need the placement of a shunt. Since compliance is a function of ICP and IVC changes, the aim of this work is to combine these two techniques to calculate the cerebrospinal system compliance along the cardiac cycle.

Cerebrospinal fluid biomarkers in patients with idiopathic normal pressure hydrocephalus with temporary response to shunt insertion

Obstruction to cerebrospinal fluid (CSF) flow in idiopathic normal pressure hydrocephalus (iNPH) results in reduced CSF total tau (t-tau) and amyloid-β 42 (Aβ42) protein concentrations [1]. Restoration of normal CSF flow dynamics with ventriculoperitoneal (VP) shunt allows these biomarkers to clear from extracellular fluid into the CSF(1). CSF biomarkers in iNPH have been an interesting subject with initials results suggestive of reduced t-tau and amyloid-β. A subgroup of probable iNPH patients responds favorably to VP shunt insertion but for a brief period (temporary responders). In our unit, these patients are further investigated with assessment of the effect of shunt tapping on walking speed. A large proportion underwent shunt revision. In this population, CSF biomarkers were studied over a prolonged period of time.

A novel method to study cerebrospinal fluid dynamics in rats

Cerebrospinal fluid (CSF) flow dynamics play critical roles in both the immature and adult brain, with implications for neurodevelopment and disease processes such as hydrocephalus and neurodegeneration. Remarkably, the only reported method to date for measuring CSF formation in laboratory rats is the indirect tracer dilution method (a.k.a., ventriculocisternal perfusion), which has limitations. Anesthetized rats were mounted in a stereotaxic apparatus, both lateral ventricles were cannulated, and the Sylvian aqueduct was occluded. Fluid exited one ventricle at a rate equal to the rate of CSF formation plus the rate of infusion (if any) into the contralateral ventricle. Pharmacological agents infused at a constant known rate into the contralateral ventricle were tested for their effect on CSF formation in real-time. The measured rate of CSF formation was increased by blockade of the Sylvian aqueduct but was not changed by increasing the outflow pressure (0-3cm of H2O). In male Wistar rats, CSF formation was age-dependent: 0.39±0.06, 0.74±0.05, 1.02±0.04 and 1.40±0.06μL/min at 8, 9, 10 and 12 weeks, respectively. CSF formation was reduced 57% by intraventricular infusion of the carbonic anhydrase inhibitor, acetazolamide. Tracer dilution methods do not permit ongoing real-time determination of the rate of CSF formation, are not readily amenable to pharmacological manipulations, and require critical assumptions. Direct measurement of CSF formation overcomes these limitations. Direct measurement of CSF formation in rats is feasible. Our method should prove useful for studying CSF dynamics in normal physiology and disease models.

Cerebrospinal fluid flow dynamics in multiple sclerosis patients through phase contrast magnetic resonance imaging.

We studied cerebrospinal fluid (CSF) flow dynamics at the cervical level in association with internal jugular veins (IJV) flow for 92 patients with multiple sclerosis (MS). Phase contrast magnetic resonance imaging was used to quantify flow of the CSF and major vessels (including the IJV and the carotid arteries) at the C2-C3 level in the neck. Contrast enhanced MR angiography and time-of-flight MR venography were used to subdivide MS patients into stenotic (ST) and non-stenotic (NST) populations. We evaluated: IJV flow normalized by arterial flow; CSF peaks; CSF outflow duration and its onset from systole. We tested if these variables were statistically different among different MS phenotypes and between ST and NST MS patients. The delay between the beginning of beginning of systole and the CSF outflow was higher in ST compared to NST MS. Less IJV flow was observed in ST vs NST MS. None of the measures was different between the different MS phenotypes. These results suggest that alterations of IJV morphology affect both IJV flow and CSF flow timing but not CSF flow amplitude.

Measuring CSF flow dynamics in spontaneous intracranial hypotension with phase-contrast magnetic resonance imaging: Potential implications for diagnosis and treatment

Certain magnetic resonance (MR) techniques are flow sensitive, and phase-contrast magnetic resonance imaging (PC-MR) has been utilized both qualitatively and quantitatively to evaluate cerebrospinal fluid (CSF) flow in a variety of clinical conditions (1). Although spontaneous intracranial hypotension (SIH) is, by definition, a disorder of CSF homeostasis typically resulting from a spinal CSF leak, PC-MR has been studied very little in this setting. An initial case report in 2004 first documented decreased systolic and diastolic CSF flow volume at the level of the cerebral aqueduct using PC-MR in a patient with SIH (2). Although confined to a single patient, the findings were compelling because normalization was documented following resolution of SIH. A number of years elapsed before a more systematic study of PC-MR in SIH was completed when Hasiloglu et al. showed a change in CSF flow dynamics in 25 SIH patients compared with controls and further related the PC-MR findings to clinical findings and opening pressure (3). The manuscript entitled Usefulness of PhaseContrast Magnetic Resonance Imaging for Diagnosis and Treatment Evaluation in Patients with SIH by Tung et al. is a welcome addition to the existing body of literature (4). The discriminating power of some of the measured CSF flow parameters at the level of the cerebral aqueduct rivals that of the more widely accepted anatomic imaging features of SIH. Moreover, there may be potential for PC-MR to identify SIH patients who lack characteristic MR findings such as dural enhancement. The change in CSF flow witnessed with treatment suggests that PC-MR may also be beneficial for monitoring patient progress during treatment for SIH. The authors point out that results with PC-MR are known to vary in subjects in relation to age, sex, body mass index, cardiac function, and technical parameters (i.e. velocity encoding gradient, anatomic site, MR scanner, etc.). As a result, the impact of these variables will need to be more fully defined in SIH patients, as has been conducted for healthy subjects. Appropriately, the authors also recognize multiple potential technical limitations in their study. However, moving forward, a number of considerations unique to the use of PC-MR in SIH patients will need to be considered. Although correlation of CSF flow dynamics with patient symptoms and validated imaging findings in SIH is useful, a quantifiable relationship with opening pressure would be preferred. No lumbar punctures were performed in the current study to allow for correlation of opening pressure with CSF flow dynamics as measured by PC-MR (4). When patient presentation and imaging findings strongly suggest headache due to SIH, it is increasingly common in clinical practice to forego lumbar puncture for opening pressure measurement. Indeed, this approach is also endorsed in the International Classification of Headache Disorders, 3rd edition (beta version), which states that dural puncture to directly measure CSF pressure is not necessary in patients with positive MR findings (5). However, it would be ideal for future research studies using PC-MR in SIH to report opening pressures as much as possible. Applying PC-MR to SIH is a relatively new application of existing technology. Hasiloglu et al. demonstrated a significant positive correlation between opening pressure and multiple CSF flow parameters (CSF flow

Analysis of cerebrospinal fluid flow dynamics and morphology in Chiari I malformation with cine phase-contrast magnetic resonance imaging

To determine cerebrospinal fluid (CSF) dynamics and morphology in Chiari I malformation (CMI) and assess the response to surgery of the posterior cranial fossa, we examined midsagittal imaging along with anterior cervical 2-3 (AC2-3), posterior cervical 2-3 (PC2-3), and aqueduct CSF flow hydrodynamics in axial imaging by using cine phase-contrast magnetic resonance imaging (PCMR). We examined 52 patients with CMI, both with and without syringomyelia (SM), pre-/post-surgery, and compared them to 17 healthy volunteers. Statistical analyses included paired t-tests, independent-samples t-tests, binary logistic regression, and crosstab with MedCalc software. Patients with CMI had significantly shorter clivus length and larger tentorial angle than the healthy controls (P = 0.004, P = 0.019, respectively). The AC2-3 cranial/caudal peak velocity (PV), PC2-3 cranial/caudal PV and aqueduct cranial peak PV of patients with CMI were significantly lower than healthy volunteers pre-surgery (P = 0.034 AC2-3 cranial PV, P = 0.000002 AC2-3 caudal PV; P = 0.046 PC2-3 cranial PV, P = 0.015 PC2-3 caudal PV; P = 0.022 aqueduct cranial PV) and increased after surgery (P = 0.024 AC2-3 cranial PV, P = 0.002 AC2-3 caudal PV; P = 0.001 PC2-3 cranial PV, P = 0.032 PC2-3 caudal PV; P = 0.003 aqueduct cranial PV). The aqueduct caudal PV of patients with CMI was higher than that of healthy controls (P = 0.004) and decreased post-surgery (P = 0.012). Patients with pre-surgery PC2-3 cranial PV >2.63 cm/s and aqueduct cranial PV >2.13 cm/s, respectively, experienced primary symptom improvement after surgery. The innate bony dysontogenesis in patients with CMI contributes to tonsilar ectopia and exacerbates CSF flow obstruction. A pressure gradient that existed between SM and SAS supports the perivascular space theory that is used to explain SM formation. Our findings demonstrate that PCMR maybe a useful tool for predicting patient prognosis.

Syringomyelia

Syringomyelia is an etiologically diverse affliction caused by disturbance of normal cerebrospinal fluid flow dynamics. An evaluation by comprehensive imaging, using advanced three-dimensional constructive interference in steady state and four-dimensional phase contrast imaging techniques, should be focused on finding the causative lesion because this determines which surgical strategy could be employed. This review discusses the pathogenesis and various etiologies of syringomyelia, and focuses on the specific surgical approach for each, mentioning aspects of surgical complications and prognosis. Particular attention is given to the "persistent central canal," a normal anatomical variant of the persistent fetal configuration of the central canal, as this is increasingly seen nowadays on routine magnetic resonance imaging.

Intraoperative aneurysmal subarachnoid hemorrhage after rupture of a previously undiagnosed intracranial aneurysm during Chiari decompression

A type I Chiari malformation occurs when caudal displacement of the cerebellar tonsils below the level of the foramen magnum obstructs the normal flow of cerebrospinal fluid (CSF) between the cranial and spinal spaces, a condition that often needs surgical decompression to restore normal CSF circulation. Abrupt changes in CSF flow dynamics after Chiari decompression can affect the intracranial CSF dynamics to the extent that a previously undiagnosed intracranial aneurysm remote from the site can rupture. The authors describe the development of an intraoperative aneurysmal subarachnoid hemorrhage that occurred as a result of spontaneous rupture of a previously undiagnosed right distal posterior inferior cerebellar artery in a 57-year-old woman with type I Chiari malformation who was undergoing surgical decompression. The mechanism of the aneurysmal rupture appears to be related to the changes of CSF flow dynamics during surgical decompression. Normally, pressure equilibrium between the two sides of the aneurysmal wall prevents its rupture, but factors that significantly affect this equilibrium, such as systemic hypertension, can cause the aneurysm to rupture. To our knowledge, the concept of spontaneous intraoperative rupture of intracranial aneurysm remote from the site of surgery has been described twice previously but under different scenarios. This scenario, to our knowledge, has not been previously described.

Venous sinus volume in the caudal cranial fossa in Cavalier King Charles spaniels with syringomyelia

Syringomyelia (SM) in Cavalier King Charles spaniels (CKCS) has a complex pathophysiology. Recent studies support a relationship between altered venous drainage and cerebrospinal fluid flow dynamics. The aim of this study was to evaluate the relationship between venous sinus and parenchymal volume within the caudal cranial fossa (CCF) in CKCS with SM (n=22) and without SM (n=12) using magnetic resonance venography (MRV). MRI and MRV images were used to obtain volumetric calculations of CCF volume, as well as the percentage of this volume occupied by parenchyma (CCFP%) and venous sinuses (CCFV%). In CKCS with SM, CCFP% was significantly higher (P<0.001), whilst CCFV% was significantly lower (P=0.001) than in CKCS without SM. These results support a role for reduced venous drainage and parenchymal ‘overcrowding’ of the CCF in the pathophysiology of SM.

Caudal cranial fossa partitioning in Cavalier King Charles spaniels

Cavalier King Charles spaniels (CKCS) are notable among dog breeds for their high rate of Chiari-like malformation (CM-characterised by indentation of the cerebellum by the supraoccipital bone and/or herniation of...

Patients with a History of Spine Surgery or Spinal Injury may have a Higher Chance of Intrathecal Catheter Granuloma Formation

Intrathecal drug delivery is an effective method to treat intractable pain. However, intrathecal catheter tip granuloma (ICTG) is a devastating complication of intrathecal drug delivery systems. It typically occurs in the thoracic region; particularly, in patients receiving high doses or high concentrations of intrathecal drug infusions. The PUBMED/MEDLINE and Cochrane databases were also systematically searched for all reports on ICTG published in any language. The key words included "intrathecal," "granuloma," and "spine surgery," and all related publications between the earliest available date (the first granuloma-related chronic complication of intrathecal infusion reported in PUBMED/MEDLINE in 1996) and June (week 1) of 2012 were searched. This case report is unique because it describes the formation of an intrathecal granuloma in the lumbar region of a patient who received a low-dose intrathecal infusion. Cerebrospinal fluid flow dynamics within the spinal canal along with the physical, chemical, and immunological properties of intrathecal medications have been suggested to be responsible for the growth of inflammatory mass lesions at the tips of intrathecal drug delivery catheters. Our literature review supports the possible role of certain factors, specifically previous spine surgery or spinal injury, in granuloma formation. The rate of development of ICTG appears to be higher in patients who have had previous spine surgery or spinal injury (68%) than in a general cohort of patients (48%), with an intrathecal pump. Therefore patients with a history of spine surgery or injury may be at increased risk of ICTG when receiving chronic intrathecal analgesia.

Cine cerebrospinal fluid imaging in multiple sclerosis

To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age- and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes. Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 μL/beat, P = 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P = 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05). CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

CSF flow dynamics in motor neuron disease

Objective: To assess cerebrospinal fluid (CSF) flow dynamics involvement in the pathogenesis of amyotrophic lateral sclerosis (ALS), we conducted CSF flow studies on 40 individuals with motor neuron diseases (MNDs) including ALS, and 28 age-matched normal and disease [cervical spondylosis (CS)] controls.Methods: The CSF pulsatile velocity anterior to the cervical cord at level C5 during one heart beat was determined non-invasively by phase-contrast electrocardiography-triggered magnetic resonance imaging.Results: In MND, caudal CSF velocity peaked at 25% of the cardiac cycle after the R wave (UTc/RR), showing an increased delay in comparison to normal controls, while amplitude Hc was significantly larger than that in CS.Discussion: We conclude that CSF flow dynamics of MND differ from those of controls and may thus facilitate differentiation of MND from CS.

Assessment of CSF Flow Dynamics Using PC‐MRI in Spontaneous Intracranial Hypotension

Spontaneous intracranial hypotension (SIH) is caused by spontaneous cerebrospinal fluid (CSF) leaks and is known to cause orthostatic headaches. Phase-contrast magnetic resonance imaging (PC-MRI) is a non-invasive technique that can be used to quantify variation in CSF flow. The aim of this study was to assess CSF flow dynamics using PC-MRI in SIH. Twenty-five patients with a definitive diagnosis of SIH and 25 healthy subjects were evaluated with PC-MRI. Magnetic resonance (MR) images were acquired using a 1.5-T unit with an 8-channel head coil. Differences between SIH patients and control subjects were assessed statistically using Wilcoxon's rank sum test, Spearman's rho test, or Pearson's chi-square test, as appropriate. CSF flow volumes toward the third ventricle, CSF flow volumes toward the fourth ventricle, the absolute stroke volume, the peak systolic velocity, and the peak diastolic velocity in SIH patients were significantly smaller than those in control subjects (P < .0001). On the other hand, the net CSF flow volume (P = .9227) and the net CSF flow direction (P = .2472) for SIH patients and control subjects were not significantly different. The results obtained by CSF flow analysis were directly related to values of CSF opening pressure, determined by lumbar puncture, and clinical findings, such as headache scores. Thus, CSF flow analysis with PC-MRI, which has a short performance time and is non-invasive, may contribute to assessment of SIH patients.

Resolution of isolated syringomyelia after treatment of cervical disc herniation: Association or coincidence?

Syringomyelia is a fluid-filled tubular cavity within the spinal cord. The exact pathophysiology of syringomyelia remains complex and uncertain. We present a case of resolution of cervical syringomyelia after cervical disc operation in a follow-up time of 6 months. Restoration of cerebrospinal fluid flow dynamics between the syrinx and the subarachnoid space via removing the main pathology such as in our reported case, may contribute in resolution of the syrinx cavity (Fig. 3, Ref. 22).

Anatomy and physiology of cerebrospinal fluid

The cerebrospinal fluid (CSF) is contained in the brain ventricles and the cranial and spinal subarachnoid spaces. The mean CSF volume is 150 ml, with 25 ml in the ventricles and 125 ml in subarachnoid spaces. CSF is predominantly, but not exclusively, secreted by the choroid plexuses. Brain interstitial fluid, ependyma and capillaries may also play a poorly defined role in CSF secretion. CSF circulation from sites of secretion to sites of absorption largely depends on the arterial pulse wave. Additional factors such as respiratory waves, the subject's posture, jugular venous pressure and physical effort also modulate CSF flow dynamics and pressure. Cranial and spinal arachnoid villi have been considered for a long time to be the predominant sites of CSF absorption into the venous outflow system. Experimental data suggest that cranial and spinal nerve sheaths, the cribriform plate and the adventitia of cerebral arteries constitute substantial pathways of CSF drainage into the lymphatic outflow system. CSF is renewed about four times every 24 hours. Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases. The CSF space is a dynamic pressure system. CSF pressure determines intracranial pressure with physiological values ranging between 3 and 4 mmHg before the age of one year, and between 10 and 15 mmHg in adults. Apart from its function of hydromechanical protection of the central nervous system, CSF also plays a prominent role in brain development and regulation of brain interstitial fluid homeostasis, which influences neuronal functioning.

Magnetic resonance velocity mapping of 3D cerebrospinal fluid flow dynamics in hydrocephalus: preliminary results

To investigate the detectability of CSF flow alterations in the ventricular system of patients with hydrocephalus using time-resolved 3D MR velocity mapping. MR velocity mapping was performed in 21 consecutive hydrocephalus patients and 21 age-matched volunteers using a 3D phase-contrast (PC) sequence. Velocity vectors and particle path lines were calculated for visualisation of flow dynamics. CSF flow was classified as "hypomotile flow" if it showed attenuated dynamics and as "hypermotile flow" if it showed increased dynamics compared with volunteers. Diagnostic efficacy was compared with routine 2D cine PC-MRI. Seven patients showed hypomotile CSF flow: six had non-communicating hydrocephalus due to aqueductal stenosis. One showed oscillating flow between the lateral ventricles after craniotomy for intracranial haemorrhage. Seven patients showed normal flow: six had hydrocephalus ex vacuo due to brain atrophy. One patient who underwent ventriculostomy 10 years ago showed a flow path through the opening. Seven patients showed hypermotile flow: three had normal pressure hydrocephalus, three had dementia, and in one the diagnosis remained unclear. The diagnostic efficacy of velocity mapping was significantly higher except for that of aqueductal stenosis. Our approach may be useful for diagnosis, therapy planning, and follow-up of different kinds of hydrocephalus.

Impact of tethered cord release on symptoms of Chiari II malformation in children born with a myelomeningocele

PurposeThe role of distal traction in the form of a tethered spinal cord in exacerbating anatomical findings or symptoms of Chiari II malformation (CIIM) has been debated for decades. Despite the association of Chiari II malformation with myelomeningocele, the impact of tethered cord release on CIIM symptoms in patients has not been explored.MethodsA retrospective review of 59 patients born with a myelomeningocele was performed. A total of 92 untethering procedures were performed in which symptoms of CIIM were present in 29 cases. In 57 out of 92 cases, the patients did not have symptoms of CIIM prior to untethering. Six cases were excluded because cervicomedullary decompression was performed prior to untethering. The response of CIIM symptoms, syrinx size, and cerebellar tonsil position were examined before and after spinal cord untethering.ResultsForty-four characteristic signs and symptoms of CIIM were present prior to 29 untetherings. Thirty-three of 44 (75%) symptoms improved following spinal cord untethering, though no symptom resolved completely. Syrinx size and cerebellar tonsil position were unchanged following untethering.ConclusionThe authors conclude that mild to moderate symptoms of CIIM may respond positively to spinal cord untethering, potentially by normalization cerebrospinal fluid flow dynamics. Symptom improvement occurs despite the lack of radiographic evidence of CIIM resolution.

Insight into the patterns of cerebrospinal fluid flow in the human ventricular system using MR velocity mapping

The patterns of cerebrospinal fluid (CSF) flow within the human ventricular system are still not fully understood in all their complexity. Knowledge is based on either the interpretation of CSF flow curves or computational simulations. Both approaches only provide an incomplete insight into the spatial and temporal dynamics of CSF flow. Time-resolved three-dimensional magnetic resonance velocity mapping has previously been used to investigate normal and pathologic blood flow patterns in the human vascular system. Here we used this technique to study the spatial and temporal dynamics of CSF flow in the ventricular system of 40 normal volunteers. Classification of the patterns of CSF flow based on calculation of three-dimensional particle path lines over the cardiac cycle revealed one uniform flow pattern for the lateral ventricles, three categories for the third and two categories for the fourth ventricle. We found no significant aging effects on either the presence of a specific CSF flow pattern or on CSF flow velocities. Our results provide the first detailed demonstration of the patterns of CSF flow within the human ventricular system.

Apport de l’IRM de flux dans les hydrocéphalies à pression normale de l’adulte : intérêt prédictif dans les indications chirurgicales

The diagnosis and management of patients with idiopathic normal-pressure hydrocephalus (NPH) remain somewhat controversial and there is no clear guideline for assessing the post-shunt outcome. The objective of this study was to investigate whether cerebrospinal fluid (CSF) flow dynamics is linked to post-shunt improvement. Fourteen NPH patients (nine males and five females; mean age, 68 years) investigated by magnetic resonance imaging (MRI) before surgical diversion of CSF were retrospectively reviewed. Phase-contrast sequences were added to the morphological clinical protocol for quantification of CSF oscillations, which were recorded at the level of the cerebral aqueduct and the C2 and C3 subarachnoid spaces (SAS). The phase-contrast images were analysed with custom-designed dedicated flow segmentation software. The oscillations measured in this hydrocephalus population were compared to a previously studied healthy population. A difference of at least two standard deviations was used to define a hyperdynamic or hypodynamic state of CSF flow. The cervical CSF flow of the hydrocephalus patients was not significantly different from those of the volunteer population. Of the 14 hydrocephalus patients, 12 had a good response to the shunt. Of these, 10 presented an increased ventricular CSF flow, one a low ventricular CSF flow, and the last one had a normal ventricular CSF flow. Phase-contrast MRI can help develop guidelines for surgical management of NPH. The shunt responders appear to be the patients with hyperdynamic ventricular CSF flow and normal cervical CSF flow.