Abnormal CSF Flow Research Articles

CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow.

Intellectual and developmental disabilities result from abnormal nervous system development. Over a 1,000 genes have been associated with intellectual and developmental disabilities, driving continued efforts toward dissecting variant functionality to enhance our understanding of the disease mechanism. This report identified two novel variants in CC2D1A in a cohort of four patients from two unrelated families. We used multiple model systems for functional analysis, including Xenopus, Drosophila, and patient-derived fibroblasts. Our experiments revealed that cc2d1a is expressed explicitly in a spectrum of ciliated tissues, including the left-right organizer, epidermis, pronephric duct, nephrostomes, and ventricular zone of the brain. In line with this expression pattern, loss of cc2d1a led to cardiac heterotaxy, cystic kidneys, and abnormal CSF circulation via defective ciliogenesis. Interestingly, when we analyzed brain development, mutant tadpoles showed abnormal CSF circulation only in the midbrain region, suggesting abnormal local CSF flow. Furthermore, our analysis of the patient-derived fibroblasts confirmed defective ciliogenesis, further supporting our observations. In summary, we revealed novel insight into the role of CC2D1A by establishing its new critical role in ciliogenesis and CSF circulation.

Cerebrospinal Fluid Dynamics Study: A Unique Tool for Management of Chiari 1 Malformation Patients

Background and Aim: Chiari I malformation(CIM) is defined as descent of cerebellar tonsils 5mm or more below the foramen magnum, with or without associated syrinx. Degree of tonsillar descent has a poor correlation with the progression of disease and symptomatology. Abnormal CSF dynamics at foramen magnum is the main pathophysiological factor responsible for the progression of tonsillar descent, syrinx formation and hence symptomatology. The aim of this study is to correlate CSF dynamic changes with the clinicoradiological profile of CIM patients. Methods and Materials/Patients: A prospective longitudinal study was done in 25 patients of CIM out of which 24 patients underwent standard midline suboccipital craniectomy with augmented duraplasty and 1 patient had ventriculoperitoneal shunt surgery for hydrocephalus. CSF flow study was done in sagittal as well as in axial sections at the level of foramen magnum using cine flow magnetic resonance imaging (MRI). Clinical and radiological assessment in reference to CSF flow parameters was done before and after decompression surgery. Results: After suboccipital decompression 23 out of 24 patients had relief in their symptoms and 1 patient had progressive syringomyelia. Postoperative MRI scan at 3months showed round shaped tonsils in all 24 patients. Ten out of 11 patients with syrinx had reduction in diameter of syrinx cavity. Peak CSF flow velocities reduced significantly (p value < 0.05) in the postoperative period and correlated well with the clinicoradiological improvement. Conclusion: Abnormal CSF flow dynamics is responsible for the progression of disease and symptomatology in CIM patients. Cine flow MRI is a useful tool in the management of CIM patients both for proper selection of surgical candidates and in post-operative follow-up.

SCIDOT-37. ASSESSING CEREBROSPINAL FLUID FLOW DYNAMICS IN PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS

Abstract BACKGROUND The incidence of abnormal CSF flow dynamics in the pediatric population with CNS tumors prior to intraventricular therapy has not been described. METHODS We performed a single-institution, retrospective review of patients with primary or metastatic CNS tumors treated between 2003–2018 (15 years).. Patients underwent 111-indium diethylene triamine pentaacetic acid injection into the CSF intraventricular space followed by nuclear medicine imaging at 90 minutes, 4, 24, and 48 hours (if required). CSF flow was classified as normal, delayed, asymmetric or obstructed. RESULTS 278 CSF flow studies were performed in 224 patients, 202(90%) <18 years of age. 116(52%) patients had metastatic CNS neuroblastoma, 57(25%) had medulloblastoma, and 51(23%) had other CNS histologies. Of the 278 studies, 237(85%) were normal, 9(3%) required neurosurgical intervention, 25(9%) were delayed, and 7(3%) were asymmetric. CONCLUSIONS Abnormal CSF flow and necessity of neurosurgical intervention must be considered when attempting to ensure appropriate intraventricular therapy in the pediatric population.

Impaired Glymphatic Transport in Spontaneously Hypertensive Rats.

The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI to assess the effect of hypertension on glymphatic transport kinetics in male young and adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto rats (WKY). We anesthetized the rats with dexmedetomidine/isoflurane and infused paramagnetic contrast (Gd-DOTA) into the cisterna magna during dynamic contrast-enhanced MRI to quantify glymphatic transport kinetics. Structural MRI analysis showed that cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared with WKY rats, regardless of age. We observed ventricular reflux of Gd-DOTA in SHR rats only, indicating abnormal CSF flow dynamics secondary to innate hydrocephalus. One-tissue compartment analysis revealed impeded glymphatic transport of Gd-DOTA in SHR compared with WKY rats in both age groups, implying that glymphatic transport, including solute clearance from brain parenchyma, is impaired during evolving hypertension in young SHR, an effect that worsens in states of chronic hypertension. The study demonstrates the suppression of glymphatic clearance in SHR rats and thus offers new insight into the coexistence of hypertension and concomitant vascular pathologies in Alzheimer's disease. The study further highlights the importance of considering the distribution of tracers in the CSF compartment in the analysis of the glymphatic system.SIGNIFICANCE STATEMENT The glymphatic system contributes to the removal of amyloid β from the brain and is disrupted in Alzheimer's disease and aging. Using a rat model of hypertension, we measured gross CSF flow and tracked glymphatic influx and efflux rates with dynamic contrast-enhanced MRI, showing that glymphatic transport is compromised in both early and advanced stages of hypertension. The study provides a new perspective on the importance for brain metabolite and fluid homeostasis of maintaining healthy blood vessels, an increasingly pertinent issue in an aging population that in part may explain the link between vascular pathology and Alzheimer's disease.

Unusual Complication of the Foramen Magnum Decompression

The pathophysiology of Chiari-Imalformation lies with the abnormal CSF flow across Foramen magnum and Foramen magnum decompression (FMD) restores this flow. However, recent data suggests that FMD itself can alter the CSF dynamics in an abnormal fashion resulting in raised intracranial pressure. We report such a case where FMD has led to the development of subdural hygroma and hydrocephalus. Patient was managed with VP shunt after a failed trial of re-exploration and burr hole drainage. The mechanism behind this complication is not clearly understood despite several hypotheses being proposed. Once established, management has to be individualized, based upon the clinical condition and location of CSF collection.

Leptomeningeal Metastases.

Treatment options for leptomeningeal metastases are expanding with greater tolerability and efficacy than in the past. Improved knowledge of molecular subtypes of some cancers can guide in choosing more effective therapeutic options; however, physicians should be mindful that these molecular types can be different in the central nervous system compared to the rest of the body. This is particularly true in breast and lung cancer, in which some patients now can live for many months or even years after diagnosis of leptomeningeal metastases. Options for intrathecal therapies are expanding, but physicians should be mindful that this is a passive delivery system that relies on normal CSF flow, so therapies will not penetrate bulky or parenchymal disease sites, especially in the presence of abnormal CSF flow. When chemotherapeutic options are lacking or unsuccessful, focal radiosurgery which can provide symptomatic relief and proton craniospinal radiation remain effective options. Hopefully more formal studies will be conducted in the future to verify which treatments are indeed most effective for particular types of cancer.

Spinal fluid biomechanics and imaging: an update for neuroradiologists.

Flow imaging with cardiac-gated phase-contrast MR has applications in the management of neurologic disorders. Together with computational fluid dynamics, phase-contrast MR has advanced our understanding of spinal CSF flow. Phase-contrast MR is used to evaluate patients with Chiari I malformation who are candidates for surgical treatment. In theory, abnormal CSF flow resulting from the abnormal tonsil position causes syringomyelia and other neurologic signs and symptoms in patients with Chiari I. CSF flow imaging also has research applications in syringomyelia and spinal stenosis. To optimize MR acquisition and interpretation, neuroradiologists must have familiarity with healthy and pathologic patterns of CSF flow. The purpose of this review is to update concepts of CSF flow that are important for the practice of flow imaging in the spine.

Prenatal and postnatal evaluation for syringomyelia in patients with spinal dysraphism.

Syringomyelia can be diagnosed in isolation but is more commonly found in the presence of craniocervical junction anomalies or spinal dysraphism. The origin of syringomyelia has been hypothesized to be either congenital or acquired. The purpose of this study was to determine the incidence of syringomyelia within the fetal and postnatal population with neural tube defects (NTDs). A review was performed of the authors' fetal MRI database of pregnancies with imaging between March 2004 and November 2011 for evaluation of an intrauterine anomaly detected via prenatal ultrasonography. Those cases with an NTD were then selected and a chart review was performed of all prenatal and postnatal imaging as well as available clinical history. A total of 2362 fetal MRI examinations were performed, and 109 of these were patients with an NTD. Of the 2362 studies reviewed, 2 cases of fetal syringomyelia were identified. Both fetal syrinxes were identified in fetuses with CSF flow disturbances (1 case each of encephalocele and myelomeningocele). Both fetal MRI examinations were performed late in gestation, at 31 and 38 weeks, respectively. The patient with an encephalocele was excluded from the spinal NTD population; therefore a syrinx was identified in 0.08% (2/2362) of the entire population of fetuses who underwent MRI, or 0.9% (1/109) of fetuses with a spinal NTD. Sixty-three of the 109 patients with an NTD had postnatal clinical data available for review. Twenty-nine (46%) of 63 had a syrinx identified during the follow-up period. Of this group, 50 patients had an open NTD and 27 (54%) of 50 developed a syrinx. Among the patients with an open NTD who developed a syrinx, only 7% did not have or develop hydrocephalus, compared with 35% of the patients who did not develop a syrinx (p < 0.05). There were nonsignificantly more frequent shunt revisions among those patients who developed a syrinx, and a syrinx developed in all patients who required surgical Chiari malformation decompression or tethered cord release. The initial identification of a spinal cord syrinx varied greatly between patients, ranging from 38 weeks gestation to greater than 4 years of age. These data suggest that syringomyelia is not a congenital embryonic condition. A syrinx was not identified in fetuses who underwent imaging for other intrauterine anomalies. In the population of patients with NTDs who are known to be at high risk for developing syringomyelia, the pathology was only identified in 2 third-trimester fetuses or postnatally, typically in the presence of hydrocephalus, shunt placement, Chiari malformation decompression, or tethered cord release. The study supports the authors' hypothesis that a syrinx is an acquired lesion, most likely due to the effects of abnormal CSF flow.

Changes in CSF flow after one-stage posterior vertebral column resection in scoliosis patients with syringomyelia and Chiari malformation Type I

Phase contrast-cine MRI (PC-cine MRI) studies in patients with syringomyelia and Chiari malformation Type I (CM-I) have demonstrated abnormal CSF flow across the foramen magnum, which can revert to normal after craniocervical decompression with syrinx shrinkage. In order to investigate the mechanisms leading to postoperative syringomyelia shrinkage, the authors studied the hydrodynamic changes of CSF flow in the craniocervical junction and spinal canal in patients with scoliosis associated with syringomyelia after one-stage deformity correction by posterior vertebral column resection. Preoperative and postoperative CSF flow dynamics at the levels of the foramen magnum, C-7, T-7 (or apex), and L-1 were assessed by electrocardiogram-synchronized cardiac-gated PC-cine MRI in 8 adolescent patients suffering from severe scoliosis with syringomyelia and CM-I (scoliosis group) and undergoing posterior vertebral column resection. An additional 8 patients with syringomyelia and CM-I without spinal deformity (syrinx group) and 8 healthy volunteers (control group) were also enrolled. Mean values were obtained for the following parameters: the duration of a CSF cycle, the duration of caudad CSF flow (CSF downflow [DF]) and cephalad CSF flow (CSF upflow [UF]), the ratio of DF duration to CSF cycle duration (DF%), and the ratio of UF duration to CSF cycle duration (UF%). The ratio of the stationary phase (SP) duration to CSF cycle duration was calculated (SP%). The maximum downflow velocities (VD max) and maximum upflow velocities (VU max) were measured. SPSS (version 14.0) was used for all statistical analysis. Patients in the scoliosis group underwent one-stage posterior vertebral column resection for deformity correction without suboccipital decompression. The mean preoperative coronal Cobb angle was 102.4° (range 76°-138°). The mean postoperative Cobb angle was 41.7° (range 12°-75°), with an average correction rate of 59.3%. During the follow-up, 1 patient with hypermyotonia experienced a significant decrease of muscle tension and 1 patient with reduced anal sphincter tone manifested recovery. A total of 5 patients demonstrated a significant decrease (> 30%) in syrinx size. With respect to changes in CSF flow dynamics, the syrinx group was characterized by slower and shorter downflow than the control group, and the difference was more significant at the foramen magnum and C-7 levels. In patients with scoliosis, CSF downflow at the foramen magnum level was significantly restricted, and a prolonged stationary phase indicated increased obstruction of CSF flow. After posterior vertebral column resection, the peak velocity of CSF flow at the foramen magnum increased, and the downflow phase duration was markedly prolonged. The parameters showed a return to almost normal CSF dynamics at the craniocervical region, and this improvement was maintained for 6-12 months of follow-up. There were distinct abnormalities of CSF flow at the craniocervical junction in patients with syringomyelia. Abnormal dynamics of downflow could be aggravated by associated severe spinal deformity and improved by correction via posterior vertebral column resection.

Pediatric Chiari malformation Type 0: a 12-year institutional experience

In 1998 the authors identified 5 patients with syringomyelia and no evidence of Chiari malformation Type I (CM-I). Magnetic resonance imaging of the entire neuraxis ruled out other causes of a syrinx. Ultimately, abnormal CSF flow at the foramen magnum was the suspected cause. The label "Chiari 0" was used to categorize these unique cases with no tonsillar ectopia. All of the patients underwent posterior fossa decompression and duraplasty identical to the technique used to treat patients with CM-I. Significant syrinx and symptom resolution occurred in these patients. Herein, the authors report on a follow-up study of patients with CM-0 who were derived from over 400 operative cases of pediatric CM-I decompression. The authors present their 12-year experience with this group of patients. Fifteen patients (3.7%) were identified. At surgery, many were found to have physical barriers to CSF flow near the foramen magnum. In most of them, the syringomyelia was greatly diminished postoperatively. The authors stress that this subgroup represents a very small cohort among patients with Chiari malformations. They emphasize that careful patient selection is critical when diagnosing CM-0. Without an obvious CM-I, other etiologies of a spinal syrinx must be conclusively ruled out. Only then can one reasonably expect to ameliorate the clinical course of these patients via posterior fossa decompression.

CSF Flow in Chiari I and Syringomyelia from the Perspective of Computational Fluid Dynamics

Phase contrast MR in patients with the Chiari I malformation demonstrates abnormal CSF flow in the foramen magnum and upper cervical spinal canal, related to abnormal pressure gradients. The purpose of this study was to analyze the role of CSF pressure in the pathogenesis of syringomyelia, with computational models. The spinal cord was modeled as a cylindrical poro-elastic structure with homogenous and isotropic permeability. The permeability was then made heterogeneous and anisotropic to represent the different properties of the central canal, gray and white matter. Fluid with a defined pressure, varying both in time and space, was prescribed in the SAS. Simulations were performed to quantify deformations and fluid movement within the cord. In the simulations with uniform permeability fluid moved into the cord in regions of higher pressure and out of the cord in regions of lower pressure. With permeability differences simulating gray and white matter the pattern was more complex, but similar. Adding the central spinal canal, fluid moved into the cord as in the previous case. However, preferential flow along the central canal hindered fluid from flowing back into the SAS. Pressure gradients in the SAS produce movement of fluid in the spinal cord. Assuming different relative permeability in gray matter, white matter and the central spinal canal, abnormal CSF gradients lead to accumulation of fluid within and adjacent to the spinal cord central canal.

Characterization of Cyclic CSF Flow in the Foramen Magnum and Upper Cervical Spinal Canal with MR Flow Imaging and Computational Fluid Dynamics

CSF flow has been shown to exhibit complex patterns in MR images in both healthy subjects and in patients with Chiari I. Abnormal CSF flow oscillations, according to prevailing opinion, cause syringomyelia and other clinical manifestations that affect some patients with the Chiari I malformation. For this article, we reviewed the literature on PC MR of CSF flow, collected the published CFD studies relevant to CSF flow, and performed flow simulations. PC MR creates cine and still images of CSF flow and measurements of flow velocities. CFD, a technique used to compute flow and pressure in liquid systems, simulates the CSF flow patterns that occur in a specific geometry or anatomy of the SAS and a specific volume of flow. Published PC MR studies show greater peak CSF velocities and more complex flow patterns in patients with Chiari I than in healthy subjects, with synchronous bidirectional flow one of the characteristic markers of pathologic flow. In mathematic models of the SAS created from high-resolution MR images, CFD displays complex CSF flow patterns similar to those shown in PC MR in patients. CFD shows that the pressure and flow patterns vary from level to level in the upper spinal canal and differ between patients with Chiari and healthy volunteers. In models in which elasticity and motion are incorporated, CFD displays CSF pressure waves in the SAS. PC MR and CFD studies to date demonstrate significant alterations of CSF flow and pressure patterns in patients with Chiari I. CSF flow has nonlaminar complex spatial and temporal variations and associated pressure waves and pressure gradients. Additional simulations of CSF flow supplemented by PC MR will lead to better measures for distinguishing pathologic flow abnormalities that cause syringomyelia, headaches, and other clinical manifestations in Chiari I malformations.

Presyrinx in children with Chiari malformations

Presyrinx is a reversible state of spinal cord edema caused by alterations in CSF flow dynamics. Only three pediatric cases have been reported previously. We describe the clinical and radiologic features of presyrinx in six pediatric patients. We electronically searched pediatric spine MRI reports generated at our institution from January 1995 to April 2007 for the keyword "presyrinx" and identified six patients with this radiologic diagnosis. We reviewed the neuroimaging studies and medical records for information regarding symptoms, treatment, and outcome. Of six patients identified with presyrinx, four had a Chiari I malformation and two had a Chiari II malformation. The MRI characteristics of the presyrinx included T2 prolongation, mild indistinct T1 prolongation, and cord enlargement without frank cavitation. Cine phase-contrast MRI studies were performed in three patients and showed severely diminished or absent CSF flow at the foramen magnum. Five patients underwent surgical decompression. All three patients with postoperative spine imaging showed restoration of CSF flow and resolution of the presyrinx. Symptoms of chronic or acute myelopathy attributable to the presyrinx were present in two patients. These symptoms resolved postoperatively. Chiari I and II malformations obstructing CSF flow at the craniocervical junction may cause presyrinx in children. Presyrinx should be considered in the differential diagnosis of chronic or acute myelopathy in patients at risk for abnormal CSF flow dynamics.

Relationship of Cine Phase-Contrast MRI to Outcome after Decompression for Chiari I Malformation.

BACKGROUND Many patients with symptomatic Chiari I malformation experience symptom recurrence after surgical decompression. Identification of predictors of outcome is needed to better select patients most likely to benefit from surgical intervention. We examined whether CSF flow dynamics assessed by cine phase-contrast MRI could independently predict response to posterior fossa decompression for Chiari I malformation. METHODS Pre and postoperative CSF flow dynamics were assessed by cine phase contrast magnetic resonance imaging in 130 consecutive patients receiving posterior fossa decompression for Chiari I malformation between 1997 and 2003. CSF flow was classified as “abnormal CSF flow” if biphasic flow was either absent or decreased through the aqueduct, fourth ventricle and its outlets, the foramen magnum, or ventral or dorsal to the cervical spinal cord. If no evidence of decreased flow was noted CSF flow was classified as “normal.” The association between pre-operative CSF flow dynamics, all recorded variables, and long-term outcome was assessed utilizing multivariate proportional hazards regression analysis. RESULTS All patients had tonsil herniation > 5mm below the foramen magnum (average 11 ± 5mm). Abnormal hindbrain CSF flow was observed in 81% of patients (43% complete obstruction, 38% reduced flow). Normal CSF flow was observed in 19% of patients. In multivariate analysis, patients with normal preoperative hindbrain CSF flow were 4.8-fold more likely to experience symptom recurrence following surgery (RR, 4.85; 95%CI, 1.88–12.5, P < 0.001) regardless of degree of tonsillar ectopia or presence of syringomyelia. Isolated frontal headache (RR, 4.16; 95%CI, 1.7–9.8, P < 0.05) and scoliosis (RR, 9.2; 95% CI, 1.7–10.5, P < 0.001) were also independent risk factors for symptom recurrence. CONCLUSIONS Normal preoperative hindbrain CSF flow was an independent risk factor for treatment failure after decompression for Chiari I malformation regardless of the degree of tonsilar ectopia. Cine phase-contrast MRI may be a valuable tool in identifying patients less likely to respond to surgical decompression for Chiari I malformation.

Normal pressure hydrocephalus in diabetic patients with recurrent episodes of hypoglycemic coma

The pathophysiology of brain damage induced by severe hypoglycemia is still unknown. We experienced a case with type l diabetes and recurrent severe hypoglycemic coma who showed a central brain atrophy and an abnormal cerebrospinal fluid flow, suggesting normal pressure hydrocephalus. Following this case, the CSF flow was studied using 111In-DTPA cisternography in six consecutive diabetic patients admitted for repeated episodes of hypoglycemic coma. All the patients showed the central brain atrophy on computed tomography and four of them (67%) had the ventricular reflux, with delayed clearance of 111In-DTPA. Two patients with abnormal CSF flow showed cognitive dysfunction by WAIS or WAIS-R. In contrast, none of five randomly selected diabetic patients, without hypoglycemic coma showed abnormal CSF flow.Our results suggest the presence of normal pressure hydrocephalus in diabetic patients with recurrent hypoglycemic coma. It may associate with the cognitive dysfunction.

111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases.

Abnormal CSF flow can impair the distribution of intrathecally administered drugs. We examined the relationship between 111indium-diethylenetriamine pentaacetic acid (111In-DTPA) CSF flow studies and methotrexate levels in ventricular and lumbar CSF and correlated these findings with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) received 12 mg methotrexate and 0.5 mCi 111In-DTPA by intra-Ommaya injection; images were obtained immediately and after 4, 24, and 48 hours. Ventricular and lumbar CSF methotrexate and radioactivity levels were measured 6 hours after injection. Thirteen patients had abnormal CSF flow studies, 9 with multiple sites of obstruction. CSF flow obstruction was observed at ventricular outlets in 13 patients, cerebral convexities in 9 and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricular and lumbar methotrexate and radioactivity levels correlated closely. Three patients with a normal CSF flow study are alive at 15+, 7.5+, and 3.9+ months from treatment. Of 12 with abnormal CSF flow studies, 11 are dead a median of 2 months from diagnosis. Two patients had diffusely delayed flow studies and both developed methotrexate leukoencephalopathy. CSF flow studies using 111In-DTPA reliably predict distribution of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and may predict intrathecal chemotherapy toxicity.

Radioisotope CSF flow studies in leptomeningeal metastases.

Leptomeningeal metastases is a frequent neuro-oncologic complication in patients with cancer. Radionuclide CSF flow studies provide a unique method of evaluating CSF compartments in patients with leptomeningeal metastases. Radionuclide CSF flow studies are performed by injecting (111)Indium-DTPA into either the ventricular or lumbar CSF compartment. (111)Indium-DTPA is entrained by CSF and flows through CSF compartments based on normal CSF physiology. Normal times to appearance of (111)Indium-DTPA following intraventricular injection in either adults or children are as follows: ventricles (median 1 minute); cisterna magna/basal cisterns (5); cervical (15); thoracic (20); and lumbar (30) spinal subarachnoid spaces; and sylvian cisterns (50). Normal times to appearance of (111)Indium-DTPA following intralumbar injection are as follows: lumbar (1); thoracic (22.5); cervical (32.5) spinal subarachnoid spaces; cisterna magna/basal cisterns (37.5); sylvian cisterns (65); ventricles (1,440); and cerebral convexities (1,440). In 30 consecutive patients, 47% of patients had documented compartmentalization of CSF by (111)Indium-DTPA CSF flow studies. 13% had base of brain obstruction of whom 50% responded with re-establishment of normal CSF flow and 33% had spinal subarachnoid space block of whom 40% following therapy had re-establishment of normal CSF flow. In 61 consecutive patients, 33% of patients had abnormal spinal CSF flow studies which better demonstrated interruption of CSF flow when compared to CT myelography and spine MR. In 40 patients, all with CSF block, 20 of whom responded to therapy with re-establishment of normal CSF flow as compared to 20 with refractory CSF block, significant differences were seen in median survival and cause of death favoring patients with normal or restored CSF flow. Radioisotope CSF flow studies in patients with leptomeningeal metastasis appear to have two practical uses. First, radioisotope CSF flow studies by documenting normal CSF flow predict for homogeneous distribution of intra-CSF chemotherapy. Secondly, in patients with CSF flow obstruction refractory to site of obstruction therapy, limited survival, rapid leptomeningeal disease progression and death due to progressive CNS disease is predicted.

Quantification of low-velocity motion using a navigator-echo supported MR velocity-mapping technique: Application to intracranial dynamics in volunteers and patients with brain tumours

Gradient-echo pulse sequences with velocity-encoding gradients of 22.5–25 mT/m, were used for brainmotion and CSF-flow studies. To reduce motion artifacts, a phase-correction technique based on navigator echoes was evaluated. Three patients with right-sided parietal tumours were investigated; one astrocytoma grade III–IV, one astrocytoma grade I–II and one benign meningioma. In healthy volunteers, a maximal brain-tissue velocity of (0.94 ± 0.26) mm/s (mean ± 1SD) was observed, which is consistent with previously presented results. The phase correction was proven useful for reduction of artifacts due to external head movements in modulus and phase images, without loss of phase information related to internal motion. The tissue velocity within the astrocytomas was low during the entire cardiac cycle. An abnormally high rostral velocity component was, however, observed in the brain tissue frontal to the astrocytomas. In all patients, an abnormal CSF flow pattern was observed. The study of brain motion may provide further understanding of the effects of tumours and other pathological conditions in the brain. When considering intracranial motion as a source of error in diffusion/perfusion MRI, the present study suggests that a pathology can alter the properties of brain motion and CSF flow considerably, leading to a more complex impact on diffusion/perfusion images.

Cine MR in the evaluation of normal and abnormal CSF flow: intracranial and intraspinal studies

Evaluation of intracranial and intraspinal CSF flow was accomplished by the use of cardiac gated gradient echo magnetic resonance (MR) technique. Normal patterns of pulsatile flow within the ventricles, cisterns and cervical subarachnoid space were established by this technique and these observations were compared to prior description of CSF flow. With systole there is downward (caudal) flow of CSF in the aqueduct of Sylvius, the foramen of Magendie, the basal cisterns and the dorsal and ventral subarachnoid spaces while during diastole, upward (cranial) flow of CSF in these same structures is seen. The relationships between the cardiac cycle and the CSF pulsations are demonstrated on both magnitude reconstruction and phase reconstruction MR images. Calculations of actual fluid velocity within CSF containing spaces can be obtained from the phase reconstruction images and holds promise for a more accurate analysis of CSF flow. In conditions which result in alterations of flow, cine MR dramatically shows either obstruction or excessively turbulent flow within the CSF pathways. The site of obstructed flow whether in the third ventricle, aqueduct, fourth ventricle, or subarachnoid space can be appreciated by changes in or absence of the normal hypointense signal. Cystic cord lesions such as congenital syringohydromyelia and posttraumatic spinal cord cysts may show pulsatile flow of CSF, a fact which can relate to progressive enlargement of these cysts. The distinction between myelomalacia and cyst formation in the cord is facilitated by the technique. Although the use of cine MR for the analysis of CSF flow is in its infancy, our experience indicates that this technique is useful in a wide range of pathological conditions including, but not limited to, conditions resulting in hydrocephalus or cystic cord lesions.

Diagnostic value of CT cisternography with intrathecal metrizamide enhancement (author's transl)

We have studied the diagnostic value of computed tomography cisternography in the evaluation of altered CSF dynamics and lesions which affects the morphology of the basal cisterns, such as extraaxial tumors in 35 patients. Twenty-two patients received metrizamide for the evaluation of CSF dynamics, mainly of communicating hydrocephalus, 9 for skull base tumors such as pituitary adenomas and CP angle tumors, and 4 for congenital cystic lesions such as porencephaly or arachnoid cyst. Diazepam or phenobarbital was used before intrathecal injection of metrizamide. In most cases, metrizamide was introduced through the lumbar intrathecal route, except for 2 cases which were through cisterna magna puncture and 2 cases into the lateral ventricles via Ommaya's reservoir. Two to 10 ml of metrizamide solution with a concentration of 170 mgI/ml was used. The patients were kept in 30 degrees Trendelenburg position, or kept in the horizontal supine position. Computed tomography with EMI scanner (CT1010) was performed 1, 3, 6, 24, 48 hours and occasionally 72 hours after the injection. In normal CSF dynamics, basal cisterns are clearly visualized one hour after injection. At 3 hours, cisterns are more clearly opacified with metrizamide. At 6 hours, the amount of metrizamide is slightly decreased from basal cisterns. Sylvian and interhemispheric fissures and convexity subarachnoid spaces and sulci become more distinctly opacified. At 24 hours, basal cisterns become almost free of metrizamide and diffuse increased absorption of the cerebral surface and possible cerebral parenchyma are noted. At 48 hours, no metrizamide is detected by CT. The fourth ventricular filling is sometimes seen in normal cases. In abnormal CSF flow pattern, ventricular reflux of metrizamide, persistent or transient, is noted. In such cases, periventricular low density area is often observed on plain CT. In a case shown at Fig. 6, periventricular low density area shows statistically significant increase in Hounsfield units at 6 and 24 hours after metrizamide injection. This suggests periventricular resorption of metrizamide. The site of cisternal block is clearly visualized. Delayed convexity flow is also noted. Detailed morphology of the subarachnoid cisterns can be analysed with the use of CSF enhancement with metrizamide, especially by the 320 × 320 matrix high definition picture. The presence or absence of suprasellar extension of a tumor is exactly diagnosed. A CP angle tumor is also diagnosed as a filling defect. An arachnoid cyst and porencephalic cyst can be diagnosed in relation with CSF flow pattern. The side effects we have observed are headache (10/35), nausea (9/35) and vomiting (6/35). No convulsion has appeared.