Cerebrospinal fluid velocity amplitudes within the cerebral aqueduct in healthy children and patients with Chiari I malformation.

PURPOSE: To assess the effects of cerebrospinal fluid (CSF) bidirectional motion in Chiari malformation type I (CMI), we monitored CSF velocity amplitudes on phase contrast MRI (PC-MRI) in patients before and after surgery; and in healthy volunteers. MATERIALS AND METHODS: 10 pediatric volunteers and 10 CMI patients participated in this study. CMI patients underwent PC-MRI scans before and approximately 14 months following surgery. Two parameters-amplitude of mean velocity (AMV) and amplitude of peak velocity (APV) of CSF-were derived from the data. Measurements were made at the mid-portion of the cerebral aqueduct, and anterior and posterior compartments of the spinal canal at the craniovertebral junction (CVJ). RESULTS: AMV and APV within the cerebral aqueduct were greater in preoperative assessments of the CMI patients compared to normal volunteers. Statistical significance was noted when comparing aqueductal AMV between the preoperative values and normal controls (P = 0.03), and before and after surgery in the CMI patients (P = 0.02). Lower values of AMV (P = 0.02) were noted in the anterior CVJ compartment in the patients before and after surgery when compared to the normal volunteers. There were no significant correlations (P = 0.06) noted for the APV at the CVJ between the normal control and patients, before or after surgery. CONCLUSION: In pediatric CMI patients, AMV for CSF within the cerebral aqueduct and anterior CVJ subarachnoid space are significantly elevated preoperatively and normalize following surgery. Given the biphasic CSF motion, measuring amplitude accounts for cranial and caudal flow. It may offer an alternative parameter to assess postsurgical outcome. J. Magn. Reson. Imaging 2016;44:463-470.

A computational fluid dynamics study to assess the impact of coughing on cerebrospinal fluid dynamics in Chiari type 1 malformation.

Chiari type 1 malformation is a neurological disorder characterized by an obstruction of the cerebrospinal fluid (CSF) circulation between the brain (intracranial) and spinal cord (spinal) compartments. Actions such as coughing might evoke spinal cord complications in patients with Chiari type 1 malformation, but the underlying mechanisms are not well understood. More insight into the impact of the obstruction on local and overall CSF dynamics can help reveal these mechanisms. Therefore, our previously developed computational fluid dynamics framework was used to establish a subject-specific model of the intracranial and upper spinal CSF space of a healthy control. In this model, we emulated a single cough and introduced porous zones to model a posterior (OBS-1), mild (OBS-2), and severe posterior-anterior (OBS-3) obstruction. OBS-1 and OBS-2 induced minor changes to the overall CSF pressures, while OBS-3 caused significantly larger changes with a decoupling between the intracranial and spinal compartment. Coughing led to a peak in overall CSF pressure. During this peak, pressure differences between the lateral ventricles and the spinal compartment were locally amplified for all degrees of obstruction. These results emphasize the effects of coughing and indicate that severe levels of obstruction lead to distinct changes in intracranial pressure.

Transient Decrease in Cerebrospinal Fluid Motion Is Related to Cough-Associated Headache in Chiari I Malformation.

BACKGROUND: Short-lasting cough-associated headache (CAH) in patients with Chiari I malformation (CMI) is believed to be due to transient worsening of cerebrospinal flow (CSF) obstruction at the foramen magnum. We assessed changes in CSF flow in response to coughing in CMI patients with CAH and compared with those without CAH and healthy participants (HPs) using real-time magnetic resonance imaging. METHODS: Seventeen CMI patients (12 with CAH, 5 without CAH) and 6 HPs were prospectively assessed using real-time pencil-beam imaging magnetic resonance sequence. A 64-mm length pencil-beam imaging cylinder was placed at the craniocervical junction. CSF stroke volume (SVCSF) was assessed during resting, postcoughing, and relaxation phases via a 90-second scan. SVCSF was measured at 6 levels at 5-mm intervals between 10 and 35 mm below the foramen magnum. During each phase, SVCSF was compared between CMI with and without CAH and HPs and corrected for multiple comparisons. RESULTS: At multiple consecutive levels, postcoughing SVCSF was significantly lower in CMI with CAH compared with both CMI without CAH and HP (P < 0.05). No differences in postcoughing SVCSF were seen between CMI without CAH and HP. At rest or relaxation phase, no differences in SVCSF were seen between patients with and without CAH but minimal differences were seen between CMI with CAH and HP. CONCLUSIONS: A decrease in CSF flow after coughing in CMI patients with CAH supports the notion that CAH is caused by transient worsening of CSF flow obstruction at the foramen magnum.

Combined Cerebrospinal Fluid Hydrodynamics and Fourth Ventricle Outlet Morphology to Improve Predictive Efficiency of Prognosis for Chiari Malformation Type I Decompression.

OBJECTIVE: To identify the morphological characteristics together with cerebrospinal fluid (CSF) hydrodynamics on preoperative magnetic resonance imaging that improve the prediction of foramen magnum decompression (FMD) treatment outcome for Chiari malformations type I (CM-I) patients compared with the CSF hydrodynamics-based model. METHODS: This retrospective study included CM-I patients who underwent FMD, phase-contrast cine magnetic resonance, and static MR between January 2018 and March 2022. The relationships of the preoperative CSF hydrodynamic quantifications derived from phase-contrast cine magnetic resonance and morphological measurements from static magnetic resonance imaging, clinical indicators with different outcomes, were analyzed with logistic regression analysis. The outcomes were determined using the Chicago Chiari Outcome Scale. The predictive performance was evaluated with receiver operating characteristic, calibration, decision curves and area under the receiver operating characteristic curve, net reclassification index, and integrated discrimination improvement and was compared with CSF hydrodynamics-based model. RESULTS: A total of 27 patients were included. 17 (63%) had improved outcomes and 10 (37%) had poor outcomes. The peak diastolic velocity of the aqueduct midportion (odd ratio, 5.17; 95% confidence interval: 1.08, 24.70; P = 0.039) and the fourth ventricle outlet diameter (odd ratio, 7.17; 95% confidence interval: 1.07, 48.16; P = 0.043) were predictors of different prognoses. The predictive performance improved significantly than the CSF hydrodynamics-based model. CONCLUSIONS: Combined CSF hydrodynamic and static morphologic MR measurements can better predict the response to FMD. A higher peak diastolic velocity of the aqueduct midportion and broader fourth ventricle outlet were associated with satisfying outcomes after decompression in CM-I patients.

Cerebrospinal Fluid Hydrodynamics in Chiari I Malformation and Syringomyelia: Modeling Pathophysiology.

Anatomic MRI, MRI flow studies, and intraoperative ultrasonography demonstrate that the Chiari I malformation obstructs CSF pathways at the foramen magnum and prevents normal CSF movement through the foramen magnum. Impaired CSF displacement across the foramen magnum during the cardiac cycle increases pulsatile hindbrain motion, pressure transmission to the spinal subarachnoid space, and the amplitude of CSF subarachnoid pressure waves driving CSF into the spinal cord. Central canal septations in adults prevent syrinx formation by CSF directly transmitting its pressure wave from the fourth ventricle to the central canal.

Postural control in Chiari I malformation: protocol for a paediatric prospective, observational cohort - potential role of posturography for surgical indication.

INTRODUCTION: Chiari I malformation (CM1) is an anatomical abnormality characterised by the cerebellar tonsils descending at least 5 mm below the foramen magnum. CM1 causes obstruction of cerebrospinal fluid (CSF) circulation as well as direct compression on the brainstem, thus causing typical consequences (syringomyelia), and typical clinical features (characteristic headaches and neurological impairment). Surgery is the only available treatment, indicated when symptomatology is present. However, sometimes patients have atypical complaints, which are often suggestive of otolaryngological (ears, nose and throat, ENT) involvement. This may be difficult for a neurosurgeon to explain. Our study aims to investigate the relationship between one of these atypical symptoms, for example, postural instability, in a paediatric population using a Computerised Dynamic Posturography (Equitest, NeuroCom, Clackamas, OR). To our knowledge, there are no previously published studies carried out on children with CM1, using dynamic posturography. METHODS AND ANALYSIS: Forty-five children aged 6-18 years old presenting with radiologically confirmed CM1 and presenting ENT clinical complaints will be included in the study for a duration of 3 years. As primary endpoint, posturographic results will be described in the population study. Second, posturographic results will be compared between patients with and without indication for surgery. Finally, preoperative and postoperative posturographic results, as well as CSF circulation quality at foramen magnum level, syringomyelia, sleep apnoea syndrome, scoliosis and behaviour will be compared in the operated patient group. ETHICS AND DISSEMINATION: This protocol received ethical approval from the Clinical Research Delegation of Nancy University Hospital, in accordance with the National Commission on Informatics and Liberties (Commission Nationale de l'Informatique et des Libertés) (protocol number 2019PI256-107). Our data treatment was in accordance with the Methodology of reference Methodology Reference-004 specification for data policy. The study findings will be disseminated via peer-reviewed publications and conference presentations, especially to the Neurosphynx's rare disease healthcare network. TRIAL REGISTRATION NUMBER: NCT04679792; Pre-results.

In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI.

BACKGROUND: Phase contrast magnetic resonance imaging, PC MRI, is a valuable tool allowing for non-invasive quantification of CSF dynamics, but has lacked adoption in clinical practice for Chiari malformation diagnostics. To improve these diagnostic practices, a better understanding of PC MRI based measurement agreement, repeatability, and reproducibility of CSF dynamics is needed. METHODS: An anatomically realistic in vitro subject specific model of a Chiari malformation patient was scanned three times at five different scanning centers using 2D PC MRI and 4D Flow techniques to quantify intra-scanner repeatability, inter-scanner reproducibility, and agreement between imaging modalities. Peak systolic CSF velocities were measured at nine axial planes using 2D PC MRI, which were then compared to 4D Flow peak systolic velocity measurements extracted at those exact axial positions along the model. RESULTS: Comparison of measurement results showed good overall agreement of CSF velocity detection between 2D PC MRI and 4D Flow (p = 0.86), fair intra-scanner repeatability (confidence intervals ± 1.5 cm/s), and poor inter-scanner reproducibility. On average, 4D Flow measurements had a larger variability than 2D PC MRI measurements (standard deviations 1.83 and 1.04 cm/s, respectively). CONCLUSION: Agreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases.

Spinal subarachnoid space pressure measurements in an in vitro spinal stenosis model: implications on syringomyelia theories.

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted.

Etiopathology of Arnold-Chiari malformation: a fetal rat model of dysraphism.

OBJECTIVES: We report an experimental fetal rat model with the aim of comparing two surgical methods used to check Arnold-Chiari Malformation (ACM) by dysraphism. We also wanted to (1) determine which type(s) of ACM akin to human anatomical findings were generated with the model and (2) study whether a cerebrospinal fluid pressure gradient could be responsible for ACM's etiopathology. MATERIALS AND METHODS: At E20, a mean of two fetuses per pregnant rat underwent an incision at the 2-3 lumbar level, deep into the medulla oblongata central canal, by two different surgical methods. Cesarian section was performed at E22. Dysraphic fetuses were examined clinically. Those born alive and controls without lesions were anatomically and histologically studied. RESULTS: Method 2 was better than method 1 at reproducing the model. 100% of operated fetuses showed no spontaneous motility or sensibility to pressure on the posterior limbs in addition to anatomopathological evidence of type II ACM. CONCLUSIONS: A high rate of ACM could be checked by dysraphism with both methods. The opening of the central canal was demonstrated to generate a cerebrospinal fluid pressure gradient responsible for the herniation of encephalic structures comparable with human ACM. We believe this model may be useful for evaluating further strategies for prenatal treatment.

Correlation of a new hydrodynamic index with other effective indexes in Chiari I malformation patients with different associations.

This study aimed to find a new CSF hydrodynamic index to assess Chiari type I malformation (CM-I) patients' conditions and examine the relationship of this new index with morphometric and volumetric changes in these patients and their clinical symptoms. To this end, 58 CM-I patients in four groups and 20 healthy subjects underwent PC-MRI. Ten morphometric and three volumetric parameters were calculated. The CSF hydrodynamic parameters were also analyzed through computational fluid dynamic (CFD) simulation. The maximum CSF pressure was identified as a new hydrodynamic parameter to assess the CM-I patients' conditions. This parameter was similar in patients with the same symptoms regardless of the group to which they belonged. The result showed a weak correlation between the maximum CSF pressure and the morphometric parameters in the patients. Among the volumetric parameters, PCF volume had the highest correlation with the maximum CSF pressure, which its value being higher in patients with CM-I/SM/scoliosis (R2 = 65.6%, P = 0.0022) than in the other patients. PCF volume was the more relevant volumetric parameter to assess the patients' symptoms. The values of PCF volume were greater in patients that headache symptom was more obvious than other symptoms, as compared to the other patients.

Cerebrospinal fluid area and syringogenesis in Chiari malformation type I.

OBJECTIVE: Syringogenesis in Chiari malformation type I (CM-I) is thought to occur secondary to impaction of the cerebellar tonsils within the foramen magnum (FM). However, the correlation between the CSF area and syringogenesis has yet to be elucidated. The authors sought to determine whether the diminution in subarachnoid space is associated with syringogenesis. Further, the authors sought to determine if syrinx resolution was associated with the degree of expansion of subarachnoid spaces after surgery. METHODS: The authors performed a retrospective review of all patients undergoing posterior fossa decompression for CM-I from 2004 to 2016 at the University of Virginia Health System. The subarachnoid spaces at the FM and at the level of the most severe stenosis were measured before and after surgery by manual delineation of the canal and neural tissue area on MRI and verified through automated CSF intensity measurements. Imaging and clinical outcomes were then compared. RESULTS: Of 68 patients, 26 had a syrinx at presentation. Syrinx patients had significantly less subarachnoid space at the FM (13% vs 19%, p = 0.0070) compared to those without syrinx. Following matching based on degree of tonsillar herniation and age, the subarachnoid space was significantly smaller in patients with a syrinx (12% vs 19%, p = 0.0015). Syrinx resolution was associated with an increase in patients' subarachnoid space after surgery compared with those patients without resolution (23% vs 10%, p = 0.0323). CONCLUSIONS: Syrinx development in CM-I patients is correlated with the degree to which the subarachnoid CSF spaces are diminished at the cranial outlet. Successful syrinx reduction is associated with the degree to which the subarachnoid spaces are increased following surgery.

Clinicoradiological study of adult Chiari malformation type 1 patients with emphasis on cerebrospinal fluid peak flow velocity at foramen magnum level.

INTRODUCTION: The aim of this study was to determine the peak cerebrospinal fluid (CSF) flow velocity at the foramen magnum level in adult patients with Chiari type 1 malformation (CM1) and to determine the changes in velocity after posterior fossa decompression. An attempt was also made to determine whether or not CSF flow velocity can be a significant predictor in patients who need surgical intervention. MATERIALS AND METHODS: A prospective longitudinal study was conducted in 32 symptomatic patients of CM1 treated with craniocervical decompression. Only adult patients with age ≥18 years and tonsillar herniation ≥5 mm were included in this study. Clinical and radiological assessment of patients with reference to their CSF flow characteristics was done both preoperatively and after suboccipital decompression. RESULTS: Out of the 32 patients, 30 patients underwent a suboccipital decompression and two patients were treated with a venriculoperitoneal shunt procedure due to gross hydrocephalus. The preoperative mean tonsillar herniation was 10.4 ± 4.64 mm that reduced to 7.35 ± 3.10 mm in the follow up period. Postoperatively, there was also a substantial decrease in the peak CSF velocity at the foramen magnum along with reduction in the extent and size of the syrinx. These changes in CSF velocity correlated with a more normal appearing foramen magnum and an improvement in symptoms. CONCLUSION: Although the selection criteria for surgery are based mainly on the degree of tonsillar ectopia and presenting symptoms, the degree of CSF flow obstruction rather than the degree of tonsillar herniation can better select patients who are most responsive to surgery. An improved CSF velocity profile following surgery in such patients is a useful guide to anticipate a symptomatic improvement.

Novel Assessment of Cerebrospinal Fluid Dynamics by Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging in Patients with Chiari Malformation Type I.

OBJECTIVE: We investigated cerebrospinal fluid (CSF) dynamics at the craniocervical junction (CCJ) using Time-SLIP magnetic resonance imaging to demonstrate the significance of ventral and dorsal combined CSF dynamics in assessing CSF flow disturbance in patients with Chiari malformation type I. METHODS: Fifteen examinations were performed in 9 cases of CM-I (3 female patients; mean age, 24.7 years; age range, 11-46 years) before or after craniocervical decompression. The longitudinal maximum movement of the caudal edge of tagged midsagittal CSF at the CCJ was measured as length of motion (LOM), and total on the ventral and dorsal sides was defined as total LOM. RESULTS: In 8 conditions, where it was concluded that no craniocervical decompression was necessary or where symptoms improved following craniocervical decompression based on the clinical symptoms, total LOM was 49.8 ± 13.1 mm. In contrast, in the 7 cases where craniocervical decompression was mandatory, total LOM was 23.2 ± 9.2 mm. Significant differences were identified between the 2 groups. Total LOM <35.0 mm resulted to indicate the insufficiency of CSF dynamics, because it corresponded to the necessity of craniocervical decompression based on patients' symptoms. CONCLUSIONS: Time-SLIP MRI enabled clinicians to use novel dynamic indices, such as CSF motions, in addition to the conventional findings acquired by MRI. In particular, it was essential to examine combined ventral and dorsal CSF dynamics in assessing CSF patency at the CCJ in patients with CM-I.

Relationship of Morphologic Changes in the Brain and Spinal Cord and Disease Symptoms with Cerebrospinal Fluid Hydrodynamic Changes in Patients with Chiari Malformation Type I.

BACKGROUND: Morphometric analysis or examination of symptoms in patients with Chiari malformation type I (CM-I) with various associations does not suffice for evaluation of surgical outcome of these patients. We assessed the relationship of morphologic changes in brain and spinal cord and disease symptoms with changes in cerebrospinal fluid (CSF) hydrodynamic parameters in patients with CM-I. METHODS: The study included 41 patients in 3 groups of CM-I, CM-I/occipitoatlantoaxial joint instability, and CM-I/tethered cord syndrome and 18 normal subjects. Phase-contrast magnetic resonance imaging and computational fluid dynamics analysis were done for all samples. RESULTS: Maximum CSF velocities and pressures in patients had an increase of 17.1%-23.2% and 41.5%-56.8%, respectively, compared with normal subjects. The data dispersion of maximum CSF velocity was >3.1 times that of the maximum pressure. Results showed that maximum CSF pressure is a more appropriate hydrodynamic parameter than maximum CSF velocity for assessing the condition of patients. Results also showed that CSF and PCF volumes had declined 57% and 11.3%, respectively, in CM-I. These declines were greater in CM-I than in the other 2 groups. CONCLUSIONS: Maximum CSF pressure regardless of the group the patients belonged to was similar in patients with symptoms of similar intensity. The correlation between maximum CSF pressure with CSF and PCF volumes decreased secondary to the disease. PCF volume was more favorable than CSF volume for assessing intensity of disease symptoms. Furthermore, in a constant pressure change, sensitivity of PCF volume in CM-I/occipitoatlantoaxial joint instability and CM-I/tethered cord syndrome groups was more than in the CM-I group.

Relationship between Cough-Associated Changes in CSF Flow and Disease Severity in Chiari I Malformation: An Exploratory Study Using Real-Time MRI.

BACKGROUND AND PURPOSE: Currently no quantitative objective test exists to determine disease severity in a patient with Chiari I malformation. Our aim was to correlate disease severity in symptomatic patients with Chiari I malformation with cough-associated changes in CSF flow as measured with real-time MR imaging. MATERIALS AND METHODS: Thirteen symptomatic patients with Chiari I malformation (tonsillar herniation of ≥5 mm) were prospectively studied. A real-time, flow-sensitized pencil-beam MR imaging scan was used to measure CSF stroke volume during rest and immediately following coughing and relaxation periods (total scan time, 90 seconds). Multiple posterior fossa and craniocervical anatomic measurements were also obtained. Patients were classified into 2 groups by neurosurgeons blinded to MR imaging measurements: 1) nonspecific Chiari I malformation (5/13)-Chiari I malformation with nonspecific symptoms like non-cough-related or mild occasional cough-related headache, neck pain, dizziness, paresthesias, and/or trouble swallowing; 2) specific Chiari I malformation (8/13)-patients with Chiari I malformation with specific symptoms and/or objective findings like severe cough-related headache, myelopathy, syringomyelia, and muscle atrophy. The Spearman correlation was used to determine correlations between MR imaging measurements and disease severity, and both groups were also compared using a Mann-Whitney U test. RESULTS: There was a significant negative correlation between the percentage change in CSF stroke volume (resting to postcoughing) and Chiari I malformation disease severity (R = 0.59; P = .03). Mann-Whitney comparisons showed the percentage change in CSF stroke volume (resting to postcoughing) to be significantly different between patient groups (P = .04). No other CSF flow measurement or anatomic measure was significantly different between the groups. CONCLUSIONS: Our exploratory study suggests that assessment of CSF flow response to a coughing challenge has the potential to become a valuable objective noninvasive test for clinical assessment of disease severity in patients with Chiari I malformation.

How Should Syringomyelia be Defined and Diagnosed?

OBJECTIVE: Syringomyelia is considered as a fluid-filled cavitation inside the spinal cord. However, there is no agreement whether a dilated central canal should be included under this heading or how glioependymal cysts, myelomalacias, or cystic tumors should be distinguished from syringomyelia. This article provides a definition of syringomyelia and guidelines for its diagnosis. METHODS: Between 1991 and 2015, of 3206 patients with spinal cord pathologies 2276 demonstrated cystic features. All patients underwent magnetic resonance imaging. Syringomyelia was differentiated from cystic intramedullary tumors, glioependymal cysts, myelomalacias, and dilatations of the central canal by clinical and radiologic criteria. RESULTS: A total of 1535 patients were diagnosed with syringomyelia, 635 with dilatations of the central canal, 52 with glioependymal cysts, 52 with mylomalacias, and 2 with cystic intramedullary spinal cord tumors. Additional neuroradiologic studies revealed the causes of syringomyelia. As a result 604 patients showed pathologies at the craniocervical junction leading to disturbances of cerebrospinal fluid (CSF) flow. The commonest was a Chiari I malformation in 543 patients. Nine hundred thirty-one patients presented with pathologies in the spinal canal. The commonest causes were spinal arachnopathies, leading to CSF flow obstructions in 533 patients, intramedullary tumors in 152 patients, and tethered cord syndromes in 69 patients. CONCLUSIONS: The diagnosis of syringomyelia should be reserved for patients with a fluid-filled cavity in the spinal cord related to either a disturbance of CSF flow, spinal cord tethering, or an intramedullary tumor. For patients in whom such a relation cannot be established, the diagnosis of syringomyelia should be withheld.

Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECT: Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be evoked by the decreased availability of nitric oxide (NO). Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO synthase (NOS), have been associated with the course and degree of cerebral vasospasm in a primate model of SAH. In this study, the authors sought to determine if similar changes in CSF ADMA levels are observed in patients with SAH, and whether these changes are associated with NO and NOS metabolite levels in the CSF and the presence of cerebral vasospasm. METHODS: Asymmetric dimethyl-L-arginine, L-arginine, L-citrulline, and nitrite levels were measured in CSF and serum samples collected during the 21-day period after a single aneurysmal SAH in 18 consecutive patients. Samples were also obtained in a control group consisting of seven patients with Chiari malformation Type I and five patients with spontaneous intracerebral hemorrhage without SAH. Vasospasm, defined as a greater than 11% reduction in the anterior circulation vessel diameter ratio compared with the ratio calculated from the initial arteriogram, was assessed on cerebral arteriography performed around Day 7. RESULTS: In 13 patients with SAH, arteriographic cerebral vasospasm developed. Cerebrospinal fluid ADMA levels in patients with SAH were higher than in those in the control group (p < 0.001). The CSF ADMA level remained unchanged in the five patients with SAH without vasospasm, but was significantly increased in patients with vasospasm after Day 3 (6.2 +/- 1.7 microM) peaking during Days 7 through 9 (13.3 +/- 6.7 microM; p < 0.001) and then gradually decreasing between Days 12 and 21 (8.8 +/- 3.2 microM; p < 0.05). Nitrite levels in the CSF were lower in patients with vasospasm compared to patients without vasospasm (p < 0.03). Cerebrospinal fluid ADMA levels positively correlated with the degree of vasospasm (correlation coefficient [CC] = 0.88, p = 0.0001; 95% confidence interval [CI] 0.74-0.95) and negatively correlated with CSF nitrite levels (CC = -0.55; p = 0.017; 95% CI -0.81 to -0.12). CONCLUSIONS: These results support the hypothesis that ADMA is involved in the progression of cerebral vasospasm. Asymmetric dimethyl-L-arginine and its metabolizing enzymes may be a future target for treatment of cerebral vasospasm after SAH.

Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia.

BACKGROUND: About 50% - 70% of patients with Chiari malformation I (CMI) presented with syringomyelia (SM), which is supposed to be related to abnormal cerebrospinal fluid (CSF) flow around the foramen magnum. The aim of this study was to investigate the cerebrospinal fluid dynamics at levels of the aqueduct and upper cervical spine in patients with CMI associated with SM, and to discuss the possible mechanism of formation of SM. METHODS: From January to April 2004, we examined 10 adult patients with symptomatic CMI associated with SM and 10 healthy volunteers by phase-contrast MRI. CSF flow patterns were evaluated at seven regions of interest (ROI): the aqueduct and ventral and dorsal subarachnoid spaces of the spine at levels of the cerebellar tonsil, C2 - 3, and C5 - 6. The CSF flow waveforms were analyzed by measuring CSF circulation time, durations and maximum velocities of cranial- and caudal-directed flows, and the ratio between the two maximum velocities. Data were analyzed by t test using SPSS 11.5. RESULTS: We found no definite communication between the fourth ventricle and syringomyelia by MRI in the 10 patients. In both the groups, we observed cranial-directed flow of CSF in the early cardiac systolic phase, which changed the direction from cranial to caudal from the middle systolic phase to the early diastolic phase, and then turned back in cranial direction in the late diastolic phase. The CSF flow disappeared at the dorsal ROI at the level of C2 - 3 in 3 patients and 1 volunteer, and at the level of C5 - 6 in 6 patients and 3 volunteers. The durations of CSF circulation at all the ROIs were significantly shorter in the patients than those in the healthy volunteers (P = 0.014 at the midbrain aqueduct, P = 0.019 at the inferior margin of the cerebellar tonsil, P = 0.014 at the level of C2 - 3, and P = 0.022 at the level of C5 - 6). No significant difference existed between the two groups in the initial point and duration of the caudal-directed CSF flow during a cardiac cycle at all the ROIs. The maximum velocities of both cranial- and caudal-directed CSF flows were significantly higher in the patients than those in the volunteers at the aqueduct (P = 0.018 and P = 0.007) and ventral ROI at the inferior margin of the cerebellar tonsil (P < 0.001 and P = 0.002), as so did the maximum velocities of the caudal-directed flow in the ventral and dorsal ROIs at the level of C2 - 3 (P = 0.004; P = 0.007). CONCLUSIONS: The direction of CSF flow changes in accordance with cardiac cycle. The syringomyelia in patients with CMI may be due to the decreased circulation time and abnormal dynamics of the CSF in the upper cervical segment. The decompression of the foramen magnum with dural plasty is an alternative for patients with CMI associated with SM.

Direct numerical simulation of transitional hydrodynamics of the cerebrospinal fluid in Chiari I malformation: The role of cranio-vertebral junction.

Obstruction to the cerebrospinal fluid (CSF) outflow caused by the herniation of cerebellar tonsils as a result of Chiari malformation type I leads to altered CSF hydrodynamics. This contribution explores the minutest characteristics of the CSF hydrodynamics in cervical subarachnoid space (SAS) of a healthy subject and 2 Chiari patients by performing highly resolved direct numerical simulation. The lattice Boltzmann method is used for the simulations because of its scalability on modern supercomputers that allow us to simulate up to approximately 109 cells while resolving the Kolmogorov microscales. The results depict that whereas the complex CSF flow remains largely laminar in the SAS of a healthy subject, constriction of the cranio-vertebral junction in Chiari I patients causes manifold fluctuations in the hydrodynamics of the CSF. These fluctuations resemble a flow that is in a transitional regime rather than laminar or fully developed turbulence. The fluctuations confine near the cranio-vertebral junction and are triggered due to the tonsillar herniation, which perturbs the flow as a result of altered anatomy of the SAS.

Chiari malformation may increase perivascular cerebrospinal fluid flow into the spinal cord: A subject-specific computational modelling study.

Syringomyelia is associated with Chiari I malformation, although the mechanistic link is unclear. Studies have suggested that cerebrospinal fluid enters the spinal cord via the perivascular spaces, and that changes in the timing of the subarachnoid pressures may increase flow into the spinal cord. This study aims to determine how Chiari malformation and syringomyelia alter the subarachnoid space pressures and hence perivascular flow. Subject-specific models of healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia, were developed from magnetic resonance imaging (MRI), to simulate the subarachnoid pressures. These pressures were input to an idealised model of the perivascular space to evaluate potential differences in perivascular flow. Peak pressures in Chiari patients without a syrinx were higher than in controls (46% increase; p = .029) and arrived earlier in the cardiac cycle than both controls (2.58% earlier; p = .045) and syrinx patients (2.85% earlier; p = .045). The perivascular model predicted Chiari patients without a syrinx would have the greatest flow into the cord (p < .05) if the arterial pulse delay was between 4 and 10% of the cardiac cycle. Using phase-contrast MRI the mean arterial delay for all subjects was similar, and was estimated as 4.7 ±â€¯0.2%. The perivascular pumping rate showed a strong positive correlation (RAdj2=0.85; p < .0001) with extended periods of high pressure that arrived earlier in the cardiac cycle, suggesting these pressure characteristics may play a role in syrinx development.