Physiological alterations of pineal recess crowding in symptomatic non-hydrocephalic pineal cysts.

Pineal cysts are prevalent in the population. Due to more widespread use of magnetic resonance imaging, an increasing number of symptomatic patients with non-hydrocephalic pineal cysts are referred to neurologists and neurosurgeons. Currently, there is no generally accepted theoretical framework for linking symptoms to a pineal cyst. We have previously suggested that cyst-induced crowding of the pineal recess may affect venous runoff from the deep cerebral veins crossing the cyst. However, evidence underpinning this hypothesis is sparse. In the present study, we asked whether crowding of the pineal recess without imaging signs of hydrocephalus may be accompanied with alterations in blood flow of the internal cerebral veins, cerebrospinal fluid flow in the Sylvian aqueduct and cerebrospinal fluid-mediated tracer clearance from the brain along extravascular pathways (referred to as glymphatic function). This prospective, observational study included symptomatic individuals with non-hydrocephalic pineal cysts who underwent a standardized magnetic resonance imaging protocol (n = 25): Eleven patients were treated surgically with craniotomy and cyst extirpation and 14 individuals were managed conservatively without surgery. Our findings suggest that cyst-induced crowding of the pineal recess may have brain-wide effects: (i) There was a significant negative correlation between degree of crowding within the pineal recess and change in maximum venous flow velocity at the cyst, and a significant positive correlation between maximum venous flow velocity change at the cyst and net cerebrospinal fluid flow in the Sylvian aqueduct; (ii) increased degree of crowding in the pineal recess was accompanied by significantly impaired glymphatic enrichment in the cerebral cortex and subcortical white matter, indicative of a brain-wide effect in this cohort who also reported markedly impaired subjective sleep quality; (iii) there was a significant negative correlation between the apparent diffusion coefficient (suggestive of interstitial water content) within the thalamus and glymphatic enrichment of tracer and (iv) pineal recess crowding associated with symptoms. Comparison of the surgical cases [in whom 10/11 (91%) reported marked clinical improvement at follow-up] and the conservatively managed cases [in whom 1/14 (7%) reported marked clinical improvement at follow-up] showed differences in pre-treatment glymphatic tracer enrichment as well as differences in tracer enrichment in subarachnoid cerebrospinal fluid spaces. Taken together, we interpret these observations to support the hypothesis that cyst-induced crowding of the pineal recess without hydrocephalus may alter blood flow of the internal cerebral veins and cerebrospinal fluid flow and even cause brain-wide impairment of glymphatic transport with possible implications for cerebrospinal fluid transport of trophic factors such as melatonin.

Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases.

BACKGROUND: Several central nervous system diseases are associated with disturbed cerebrospinal fluid (CSF) flow patterns and have typically been characterized in vivo by phase-contrast magnetic resonance imaging (MRI). This technique is, however, limited by its applicability in space and time. Phase-contrast MRI has yet to be compared directly with CSF tracer enhanced imaging, which can be considered gold standard for assessing long-term CSF flow dynamics within the intracranial compartment. METHODS: Here, we studied patients with various CSF disorders and compared MRI biomarkers of CSF space anatomy and phase-contrast MRI at level of the aqueduct and cranio-cervical junction with dynamic intrathecal contrast-enhanced MRI using the contrast agent gadobutrol as CSF tracer. Tracer enrichment of cerebral ventricles was graded 0-4 by visual assessment. An intracranial pressure (ICP) score was used as surrogate marker of intracranial compliance. RESULTS: The study included 94 patients and disclosed marked variation of CSF flow measures across disease categories. The grade of supra-aqueductal reflux of tracer varied, with strong reflux (grades 3-4) in half of patients. Ventricular tracer reflux correlated with stroke volume and aqueductal CSF pressure gradient. CSF flow in the cerebral aqueduct was retrograde (from 4th to 3rd ventricle) in one third of patients, with estimated CSF net flow volume about 1.0 L/24 h. In the cranio-cervical junction, net flow was cranially directed in 78% patients, with estimated CSF net flow volume about 4.7 L/24 h. CONCLUSIONS: The present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients.

Respiratory influence on cerebrospinal fluid flow - a computational study based on long-term intracranial pressure measurements.

Current theories suggest that waste solutes are cleared from the brain via cerebrospinal fluid (CSF) flow, driven by pressure pulsations of possibly both cardiac and respiratory origin. In this study, we explored the importance of respiratory versus cardiac pressure gradients for CSF flow within one of the main conduits of the brain, the cerebral aqueduct. We obtained overnight intracranial pressure measurements from two different locations in 10 idiopathic normal pressure hydrocephalus (iNPH) patients. The resulting pressure gradients were analyzed with respect to cardiac and respiratory frequencies and amplitudes (182,000 cardiac and 48,000 respiratory cycles). Pressure gradients were used to compute CSF flow in simplified and patient-specific models of the aqueduct. The average ratio between cardiac over respiratory flow volume was 0.21 ± 0.09, even though the corresponding ratio between the pressure gradient amplitudes was 2.85 ± 1.06. The cardiac cycle was 0.25 ± 0.04 times the length of the respiratory cycle, allowing the respiratory pressure gradient to build considerable momentum despite its small magnitude. No significant differences in pressure gradient pulsations were found in the sleeping versus awake state. Pressure gradients underlying CSF flow in the cerebral aqueduct are dominated by cardiac pulsations, but induce CSF flow volumes dominated by respiration.

Magnitude and direction of aqueductal cerebrospinal fluid flow: large variations in patients with intracranial aneurysms with or without a previous subarachnoid hemorrhage.

BACKGROUND: Net cerebrospinal fluid (CSF) flow within the cerebral aqueduct is usually considered to be antegrade, i.e., from the third to the fourth ventricle with volumes ranging between 500 and 600 ml over 24 h. Knowledge of individual CSF flow dynamics, however, is hitherto scarcely investigated. In order to explore individual CSF flow rate and direction, we assessed net aqueductal CSF flow in individuals with intracranial aneurysms with or without a previous subarachnoid hemorrhage (SAH). METHODS: A prospective observational study was performed utilizing phase-contrast magnetic resonance imaging (PC-MRI) to determine the magnitude and direction of aqueductal CSF flow with an in-depth, pixel-by-pixel approach. Estimation of net flow was used to calculate CSF flow volumes over 24 h. PC-MRI provides positive values when flow is retrograde. RESULTS: The study included eight patients with intracranial aneurysms. Four were examined within days after their SAH; three were studied in the chronic stage after SAH while one patient had an unruptured intracranial aneurysm. There was a vast variation in magnitude and direction of aqueductal CSF flow between individuals. Net aqueductal CSF flow was retrograde, i.e., directed towards the third ventricle in 5/8 individuals. For the entire patient cohort, the estimated net aqueductal CSF volumetric flow rate (independent of direction) was median 898 ml/24 h (ranges 69 ml/24 h to 12.9 l/24 h). One of the two individuals who had a very high estimated net aqueductal CSF volumetric flow rate, 8.7 l/24 h retrograde, later needed a permanent CSF shunt. CONCLUSIONS: The magnitude and direction of net aqueductal CSF flow vary extensively in patients with intracranial aneurysms. Following SAH, PC-MRI may offer the possibility to perform individualized assessments of the CSF circulation.

Cerebrospinal fluid volumetric net flow rate and direction in idiopathic normal pressure hydrocephalus.

The aim of the present study was to examine cerebrospinal fluid (CSF) volumetric net flow rate and direction at the cranio-cervical junction (CCJ) and cerebral aqueduct in individuals with idiopathic normal pressure hydrocephalus (iNPH) using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI). An in-depth, pixel-by-pixel analysis of regions of interest from the CCJ and cerebral aqueduct, respectively, was done in 26 iNPH individuals, and in 4 healthy subjects for validation purposes. Results from patients were compared with over-night measurements of static and pulsatile intracranial pressure (ICP). In iNPH, CSF net flow at CCJ was cranially directed in 17/22 as well as in 4/4 healthy subjects. Estimated daily CSF volumetric net flow rate at CCJ was 6.9 ±â€¯9.9 L/24 h in iNPH patients and 4.5 ±â€¯5.0 L/24 h in healthy individuals. Within the cerebral aqueduct, the CSF net flow was antegrade in 7/21 iNPH patients and in 4/4 healthy subjects, while it was retrograde (i.e. towards ventricles) in 14/21 iNPH patients. Estimated daily CSF volumetric net flow rate in cerebral aqueduct was 1.1 ±â€¯2.2 L/24 h in iNPH while 295 ±â€¯53 mL/24 h in healthy individuals. Magnitude of cranially directed CSF net flow in cerebral aqueduct was highest in iNPH individuals with signs of impaired intracranial compliance. The study results indicate CSF flow volumes and direction that are profoundly different from previously assumed. We hypothesize that spinal CSF formation may serve to buffer increased demand for CSF flow through the glymphatic system during sleep and during deep inspiration to compensate for venous outflow.

Comparison of phase-contrast MR and flow simulations for the study of CSF dynamics in the cervical spine.

Background Investigators use phase-contrast magnetic resonance (PC-MR) and computational fluid dynamics (CFD) to assess cerebrospinal fluid dynamics. We compared qualitative and quantitative results from the two methods. Methods Four volunteers were imaged with a heavily T2-weighted volume gradient echo scan of the brain and cervical spine at 3T and with PC-MR. Velocities were calculated from PC-MR for each phase in the cardiac cycle. Mean pressure gradients in the PC-MR acquisition through the cardiac cycle were calculated with the Navier-Stokes equations. Volumetric MR images of the brain and upper spine were segmented and converted to meshes. Models of the subarachnoid space were created from volume images with the Vascular Modeling Toolkit. CFD simulations were performed with a previously verified flow solver. The flow patterns, velocities and pressures were compared in PC-MR and CFD flow images. Results PC-MR images consistently revealed more inhomogeneous flow patterns than CFD, especially in the anterolateral subarachnoid space where spinal nerve roots are located. On average, peak systolic and diastolic velocities in PC-MR exceeded those in CFD by 31% and 41%, respectively. On average, systolic and diastolic pressure gradients calculated from PC-MR exceeded those of CFD by 11% and 39%, respectively. Conclusions PC-MR shows local flow disturbances that are not evident in typical CFD. The velocities and pressure gradients calculated from PC-MR are systematically larger than those calculated from CFD.

Non-invasive assessment of pulsatile intracranial pressure with phase-contrast magnetic resonance imaging.

Invasive monitoring of pulsatile intracranial pressure can accurately predict shunt response in patients with idiopathic normal pressure hydrocephalus, but may potentially cause complications such as bleeding and infection. We tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of "true" normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43). Pulse pressure gradients were also similar in patients and healthy controls (P = .26), and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97). Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate marker for intracranial pressure pulsations.

The association between the pulse pressure gradient at the cranio-cervical junction derived from phase-contrast magnetic resonance imaging and invasively measured pulsatile intracranial pressure in symptomatic patients with Chiari malformation type 1.

BACKGROUND: In symptomatic Chiari malformation type 1 (CMI), impaired intracranial compliance (ICC) is associated with an increased cranio-spinal pulsatile pressure gradient. Phase-contrast magnetic resonance imaging (MRI) represents a non-invasive modality for the assessment of the pulse pressure gradient at the cranio-cervical junction (CCJ). We wished to explore how the MRI-derived pulse pressure gradient (MRI-dP) compares with invasively measured pulsatile intracranial pressure (ICP) in CMI, and with healthy controls. METHODS: From phase-contrast MRI of CMI patients and healthy controls, we computed cerebrospinal fluid (CSF) flow velocities and MRI-dP at the CCJ. We assessed bidirectional flow and compared the flow between the anterior and the posterior subarachnoid space at the CCJ. We computed total intracranial volume (ICV), ventricular CSF volume (VV), and posterior cranial fossa volume (PCFV). We analyzed the static and pulsatile ICP scores from overnight monitoring in CMI patients. RESULTS: Five CMI patients and four healthy subjects were included. The CMI group had a significantly larger extent of tonsillar ectopia, smaller PCFV, and a smaller area of CSF in the FM. The pulsatile ICP (mean ICP wave amplitude, MWA) was abnormally increased in 4/5 CMI patients and correlated positively with MRI-dP. However, the MRI-dP as well as the CSF flow velocities did not differ significantly between CMI and healthy subjects. Moreover, bidirectional flow was observed in both CMI as well as healthy subjects, with no significant difference. CONCLUSIONS: In symptomatic CMI patients, we found a significant association between the pulse pressure gradient at the CCJ derived from phase-contrast MRI and the pulsatile ICP (MWA) measured invasively. However, the MRI-dP was close to identical in CMI patients and healthy subjects. Moreover, the CSF flow velocities at the CCJ and the occurrence of bidirectional flow were not different in CMI patients and healthy individuals. Further studies are required to determine the diagnostic role of phase-contrast MRI in CMI patients.