Alterations In Cerebrospinal Fluid Flow Research Articles

Abstract Su1201: Alteration in cerebrospinal fluid flow in out-of-hospital cardiac arrest patients who underwent target temperature management.

Background: Various parameters of cerebrospinal fluid (CSF) flow measured through magnetic resonance imaging (MRI) flowmetry are utilized to assess the progression of certain diseases. Our study evaluated changes in CSF flow using MRI flowmetry in survivors of out-of-hospital cardiac arrest (OHCA) who underwent target temperature management (TTM). Methods: This prospective observational cohort study was conducted from May 2023 to April 2024 at a single center. We performed Wilcoxon signed-rank tests to compare maximum velocity (V max ), stroke volume (SV), maximum flow (flow max ), and stroke distance measured immediately after return of spontaneous circulation (ROSC) with those measured at 72 h after ROSC. Results: Of the 20 patients enrolled, 7(35.0%), 1(5.0%), 2(10.0%), 5(25.0%) and 5(25.0%) patients had CPC scores of 1, 2, 3, 4, and 5, respectively. V max , SV, flow max , stroke distance measured immediately after ROSC were 3.41 (2.03~4.96), 14.00 (4.00~23.38), 0.09 (0.06~0.22), -0.07 (-0.17~0.05), respectively. V max , SV, flow max , stroke distance measured at 72h after ROSC were 5.26 (2.76~9.28), 24.00 (10.38~42.25), 0.14 (0.08~0.31), -0.07 (-0.18~0.03), respectively. Although V max , SV, and flow max measured at 72 h after ROSC were statistically significantly higher compared to those measured immediately after ROSC (p = 0.002, 0.02, 0.002), there was no significant difference between the stroke distances measured immediately after ROSC and at 72 h after ROSC (p = 0.43). Additionally, the caudocranial direction of CSF flow was observed in 13 (65.0%) patients immediately after ROSC, and in 14 (70.0%) patients 72h after ROSC. Conclusion: This study demonstrated that alterations in cerebrospinal fluid flow were observed in OHCA patients. However, Further studies are needed to determine whether there are differences in alteration in CSF flow based on neurological prognosis.

Significant individual variation in cardiac-cycle-linked cerebrospinal fluid production following subarachnoid hemorrhage

BackgroundSpontaneous subarachnoid hemorrhage (SAH) often results in altered cerebrospinal fluid (CSF) flow and secondary hydrocephalus, yet the mechanisms behind these phenomena remain poorly understood. This study aimed to elucidate the impact of SAH on individual CSF flow patterns and their association with secondary hydrocephalus.MethodsIn patients who had experienced SAH, changes in CSF flow were assessed using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI) at the Sylvian aqueduct and cranio-cervical junction (CCJ). Within these regions of interest, volumetric CSF flow was determined for every pixel and net CSF flow volume and direction calculated. The presence of acute or chronic hydrocephalus was deemed from ventriculomegaly and need of CSF diversion. For comparison, we included healthy subjects and patients examined for different CSF diseases.ResultsTwenty-four SAH patients were enrolled, revealing a heterogeneous array of CSF flow alterations at the Sylvian aqueduct. The cardiac-cycle-linked CSF net flow in Sylvian aqueduct differed from the traditional figures of ventricular CSF production about 0.30–0.40 mL/min. In 15 out of 24 patients (62.5%), net CSF flow was retrograde from the fourth to the third and lateral ventricles, while it was upward at the cranio-cervical junction in 2 out of 2 patients (100%). The diverse CSF flow metrics did not distinguish between individuals with acute or chronic secondary hydrocephalus. In comparison, 4/4 healthy subjects showed antegrade net CSF flow in the Sylvian aqueduct and net upward CSF flow in CCJ. These net CSF flow measures also showed interindividual variability among other patients with CSF diseases.ConclusionsThere is considerable inter-individual variation in net CSF flow rates following SAH. Net CSF flow in the Sylvian aqueduct differs markedly from the traditional ventricular CSF production rates of 0.30–0.40 mL/min in SAH patients, but less so in healthy subjects. Furthermore, the cardiac-cycle-linked net CSF flow rates in Sylvian aqueduct and CCJ suggest an important role of extra-ventricular CSF production.

Alteration in cerebrospinal fluid flow based on the neurological prognosis of out-of-hospital cardiac arrest patients.

We evaluated alterations in cerebrospinal fluid (CSF) flow based on the neurological prognosis of out-of-hospital cardiac arrest (OHCA) patients. This prospective observational study was conducted from May 2023 to June 2024. Stroke distance was measured using magnetic resonance imaging flowmetry immediately and at 72h after return of spontaneous circulation (ROSC), with negative values indicating caudocranial direction. The caudocranial direction of CSF flow was observed in 17 (56.7%) patients immediately after ROSC, and in 20 (66.7%) patients at 72h after ROSC. There was no significant difference in the occurrence of caudocranial CSF flow immediately after ROSC between the groups with good and poor neurological prognosis [6 (50.0%) vs. 11 (61.1%); p = 0.55]. However, the occurrence of caudocranial CSF flow at 72h after ROSC was significantly higher in the group with poor neurological prognosis compared to the group with good neurological prognosis [3 (25.0%) vs. 17 (94.4%); p < 0.001]. This study demonstrated that the occurrence of caudocranial CSF flow at 72h after ROSC was significantly higher in the group with poor neurological prognosis compared to the group with good neurological prognosis.

The Anatomy and Physiology of the Glymphatic System and Its Role in Craniectomies and Syndrome of the Trephined

Background: The glymphatic system, a relatively recently discovered system for transport of cerebrospinal fluid (CSF) and waste products in the central nervous system, has been implicated in several neurologic disorders. Altered CSF dynamics are seen after decompressive craniectomy, suggesting this procedure may impact glymphatic function. We aimed to systematically review the current literature to understand the effect of the glymphatic system on patients with decompressive craniectomies and Syndrome of the Trephined (SoT). Methods: PubMed and Embase were searched for preclinical and clinical studies investigating the glymphatic system and craniectomy, cranioplasty, or SoT in years 2012 to 2023. Results: Sixty-three studies were identified for review. Intracranial oscillations, cerebral perfusion, and arterial pulsations have been identified as major drivers of glymphatic influx. Each of these processes are diminished following craniectomy, suggesting craniectomy may impair glymphatic function. Reductions in brain pulsatility and alterations in glymphatic drainage after craniectomy were accompanied by impaired functional outcomes, as seen in SoT. Radiologically, CSF flow alterations are seen after craniectomies, which improve with cranioplasty. Conclusions: Glymphatic system dysfunction after craniectomy and in SoT may be a potential therapeutic target for patients with iatrogenically altered cranial vault anatomy.

Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters

BackgroundCervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype.MethodsThirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration.ResultsThe frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one.ConclusionsThe spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape.

Decreased Cerebrospinal Fluid Flow Is Associated With Cognitive Deficit in Elderly Patients.

Background: Disruptions in cerebrospinal fluid (CSF) flow during aging could compromise protein clearance from the brain and contribute to the etiology of Alzheimer’s Disease (AD).Objective: To determine whether CSF flow is associated with cognitive deficit in elderly patients (>70 years).Methods: We studied 92 patients admitted to our geriatric unit for non-acute reasons using phase-contrast magnetic resonance imaging (PC-MRI) to calculate their ventricular and spinal CSF flow, and assessed their global cognitive status, memory, executive functions, and praxis. Multivariable regressions with backward selection (criterion p < 0.15) were performed to determine associations between cognitive tests and ventricular and spinal CSF flow, adjusting for depression, anxiety, and cardiovascular risk factors.Results: The cohort comprised 71 women (77%) and 21 (33%) men, aged 84.1 ± 5.2 years (range, 73–96). Net ventricular CSF flow was 52 ± 40 μL/cc (range, 0–210), and net spinal CSF flow was 500 ± 295 μL/cc (range, 0–1420). Ventricular CSF flow was associated with the number of BEC96 figures recognized (β = 0.18, CI, 0.02–0.33; p = 0.025). Spinal CSF flow was associated with the WAIS Digit Span Backward test (β = 0.06, CI, 0.01–0.12; p = 0.034), and categoric verbal fluency (β = 0.53, CI, 0.07–0.98; p = 0.024) and semantic verbal fluency (β = 0.55, CI, 0.07–1.02; p = 0.024).Conclusion: Patients with lower CSF flow had significantly worse memory, visuo-constructive capacities, and verbal fluency. Alterations in CSF flow could contribute to some of the cognitive deficit observed in patients with AD. Diagnosis and treatment of CSF flow alterations in geriatric patients with neurocognitive disorders could contribute to the prevention of their cognitive decline.

An MRI-Compatible Hydrodynamic Simulator of Cerebrospinal Fluid Motion in the Cervical Spine.

Develop and test an MRI-compatible hydrodynamic simulator of cerebrospinal fluid (CSF) motion in the cervical spinal subarachnoid space. Four anatomically realistic subject-specific models were created based on a 22-year-old healthy volunteer and a five-year-old patient diagnosed with Chiari I malformation. The in vitro models were based on manual segmentation of high-resolution T2-weighted MRI of the cervical spine. Anatomically realistic dorsal and ventral spinal cord nerve rootlets (NR) were added. Models were three dimensional (3-D) printed by stereolithography with 50-μm layer thickness. A computer controlled pump system was used to replicate the shape of the subject specific in vivo CSF flow measured by phase-contrast MRI. Each model was then scanned by T2-weighted and 4-D phase contrast MRI (4D flow). Cross-sectional area, wetted perimeter, and hydraulic diameter were quantified for each model. The oscillatory CSF velocity field (flow jets near NR, velocity profile shape, and magnitude) had similar characteristics to previously reported studies in the literature measured by in vivo MRI. This study describes the first MRI-compatible hydrodynamic simulator of CSF motion in the cervical spine with anatomically realistic NR. NR were found to impact CSF velocity profiles to a great degree. CSF hydrodynamics are thought to be altered in craniospinal disorders such as Chiari I malformation. MRI scanning techniques and protocols can be used to quantify CSF flow alterations in disease states. The provided in vitro models can be used to test the reliability of these protocols across MRI scanner manufacturers and machines.

Cervical compressive myelopathy: flow analysis of cerebrospinal fluid using phase-contrast magnetic resonance imaging.

To evaluate cerebrospinal fluid (CSF) flow in cervical compressive myelopathy (CCM), by both quantitative and qualitative analyses, using 3T cine phase-contrast magnetic resonance imaging (cine MRI). From September, 2014 to June, 2015, we enrolled 45 subjects (18 women and 27 men, mean age, 61.7±13.4years) to undergo cervical cine MRI. The subjects were divided into three groups: no stenosis and cervical stenosis with and without intramedullary T2 hyperintensity. We measured maximal CSF velocity, and 12 CSF velocity waveforms were plotted per subject. Two readers independently assessed the CSF waveform shape (0 absent; 1 serrated; 2 bi-directional with small amplitude; and 3 normal bi-directional waveform) and the CSF motion pattern (0 absent; 1 interrupted; and 2 intact). The numbers of 12 waveform shapes were summed to yield a CSF waveform score. Linear mixed model and ROC curve analyses were used for statistical analyses. Maximal CSF velocity was significantly lower in CCM (marginal mean, 2.72cm/s) than in stenosis without intramedullary T2 hyperintensity (3.27cm/s, p=0.027) and no stenosis (3.80cm/s, p<0.001). Bi-phasic CSF motion was lost in cervical stenosis. CSF waveform scores of 17 (area under curve (AUC), 0.797; p=0.003) and 16.5 (AUC, 0.790; p=0.004) could predict Japanese Orthopedic Association (JOA) score corresponding to CCM. Maximal CSF velocity and CSF waveform score on cine MRI decreased in CCM and was correlated with the JOA score. Thus, both quantitative and qualitative analyses using cine MRI could effectively demonstrate CSF flow alterations in CCM.

Interactions between Flow Oscillations and Biochemical Parameters in the Cerebrospinal Fluid.

The equilibrium between the ventricular and lumbar cerebrospinal fluid (CSF) compartments may be disturbed (in terms of flow and biochemistry) in patients with chronic hydrocephalus (CH). Using flow magnetic resonance imaging (MRI) and CSF assays, we sought to determine whether changes in CSF were associated with biochemical alterations. Nine elderly patients with CH underwent phase-contrast MRI. An index of CSF dynamics (Idyn) was defined as the product of the lumbar and ventricular CSF flows. During surgery, samples of CSF were collected from the lumbar and ventricular compartments and assayed for chloride, glucose and total protein. The lumbar/ventricular (L/V) ratio was calculated for each analyte. The ratio between measured and expected levels (Ibioch) was calculated for each analyte and compared with Idyn. Idyn varied from 0 to 100.103μl2.s2. In contrast to the L/V ratios for chloride and glucose, the L/V ratio for total protein varied markedly from one patient to another (mean ± standard deviation (SD): 2.63 ± 1.24). The Ibioch for total protein was strongly correlated with the corresponding Idyn (Spearman’s R: 0.98; p < 5 × 10−5).We observed correlated alterations in CSF flow and biochemical parameters in patients with CH. Our findings also highlight the value of dynamic flow analysis in the interpretation of data on CSF biochemistry.

Disruption of cerebrospinal fluid flow through the olfactory system may contribute to Alzheimer's disease pathogenesis.

Plaques and tangles may be manifestations of a more substantial underlying cause of Alzheimer's disease (AD). Disease-related changes in the clearance of amyloid-β (Aβ) and other metabolites suggest this cause may involve cerebrospinal fluid (CSF) flow through the interstitial spaces of the brain, including an archaic route through the olfactory system that predates neocortical expansion by three hundred million years. This olfactory CSF conduit (OCC) runs from the medial temporal lobe (MTL) along the lateral olfactory stria, through the olfactory trigone, and down the olfactory tract to the olfactory bulb, where CSF seeps through the cribriform plate to the nasal submucosa. Olfactory dysfunction is common in AD and could be related to alterations in CSF flow along the OCC. Further, reductions in OCC flow may impact CSF hydrodynamics upstream in the MTL and basal forebrain, resulting in less efficient Aβ removal from those areas-among the first affected by neuritic plaques in AD. Factors that reduce CSF drainage across the cribriform plate and slow the clearance of metabolite-laden CSF could include aging-related bone changes, head trauma, inflammation of the nasal epithelium, and toxins that affect olfactory neuron survival and renewal, as well as vascular effects related to diabetes, obesity, and atherosclerosis-all of which have been linked to AD risk. Problems with CSF-mediated clearance could also provide a link between these seemingly disparate factors and familial AD mutations that induce plaque and tangle formation. I hypothesize that disruptions of CSF flow across the cribriform plate are important early events in AD, and I propose that restoring this flow will enhance the drainage of Aβ oligomers and other metabolites from the MTL.

Presyrinx in a child with acquired Chiari I malformation

Spinal cord signal abnormality resulting from alterations in cerebrospinal fluid flow at the craniocervical junction has been termed a presyrinx state. This condition has been described in the adult literature in association with a variety of conditions that cause obstruction to normal cerebrospinal fluid flow. We present a case of presyrinx in a child in the setting of acquired Chiari I malformation caused by lumboperitoneal overshunting. Awareness of the potentially reversible nature of this condition might allow for intervention before irreversible neurological damage has occurred.

Neuraxial Blockade in Patients with Preexisting Spinal Stenosis, Lumbar Disk Disease, or Prior Spine Surgery

Patients with spinal canal pathology, including spinal stenosis and lumbar disk disease, are often not considered candidates for neuraxial blockade because of the risk of exacerbating preexisting neurologic deficits or developing new neurologic dysfunction. In contrast, a history of spine surgery is thought to increase the likelihood of difficult or unsuccessful block. In this retrospective study we investigated the risk of neurologic complications and block efficacy in patients with preexisting spinal canal pathology, with or without a history of spine surgery, after neuraxial anesthesia. During the 15-year study period, all patients with a history of spinal stenosis or lumbar radiculopathy undergoing a neuraxial technique were studied. Patient demographics, preoperative neurologic diagnoses and neurologic findings at the time of surgery/neuraxial block, details of the neuraxial block including technique (spinal vs. epidural, single injection vs. continuous), injectate, technical complications (paresthesia elicitation, bloody needle/catheter placement, inability to advance catheter, accidental dural puncture), and block success were noted. New or progressive neurologic deficits were identified. All patients were followed until resolution or last date of evaluation. There were 937 patients included, 207 (22%) of whom had undergone spinal surgery. A history of spinal stenosis was present in 187 (20%), lumbar radiculopathy in 570 (61%), and peripheral neuropathy in 210 (22%) patients; 180 patients (19%) had multiple neurologic diagnoses. A majority of patients had active but stable neurologic symptoms at the time of surgery. Overall block success was 97.2%. A history of spine surgery did not affect the success rate or frequency of technical complications. Ten (1.1%; 95% confidence interval [CI] 0.5%-2.0%) patients experienced new deficits or worsening of existing symptoms. Three (1.4%) complications occurred in patients with a history of spinal surgery, and the remaining 7 (1.0%) in patients without prior surgical decompression or stabilization (P = NS). Although an orthopedic procedure was not a risk factor, in 5 of the 6 patients in which the surgery was a unilateral lower extremity procedure, the postoperative deficit involved the operative side. Likewise, in both patients undergoing bilateral orthopedic procedures who developed bilateral deficits, the outcome was worse on the previously affected side. A surgical cause was presumed to be the primary etiology in 4 (40%) of 10 patients. The primary etiology of the remaining 6 (60%) complications was judged to be nonsurgical (including anesthetic-related factors). The presence of a preoperative diagnosis of compressive radiculopathy (P = 0.0495) or multiple neurologic diagnoses (P = 0.005) increased the risk of neurologic complications postoperatively. We conclude that patients with preexisting spinal canal pathology have a higher incidence of neurologic complications after neuraxial blockade (1.1%; 95% CI 0.5%-2.0%) than that previously reported for patients without such underlying pathology. However, in the absence of a control group of surgical patients with similar anatomic pathology undergoing general anesthesia, we cannot determine whether the higher incidence of neurologic injury is secondary to the surgical procedure, the anesthetic technique, the natural history of spinal pathology, or a combination of factors and the relative contributions of each.

Acute ventriculoperitoneal shunt malfunction following opening of the spinal subarachnoid space: a case series

Malfunction of cerebrospinal shunts is common and due to multiple etiologies. We hypothesize that opening of the spinal dura may prompt shunt failure in select individuals with previously unrecognized tenuous shunt function. The authors describe five patients with shunted hydrocephalus who underwent procedures in which the spinal dura mater was opened. All patients had acute dysfunction of their ventriculoperitoneal shunt that required shunt revision. All shunt valves were functioning properly at operative inspection but all patients were found to have adherent intracranial catheters with ingrowth of choroid plexus. We theorize that the siphoning effect caused from cerebrospinal fluid egress from the opened spinal subarachnoid space resulted in acute shunt failure. Such alterations in cerebrospinal fluid flow may precipitate complete failure of a shunt that is functioning suboptimally. Clinicians should be aware that spinal procedures that violate the subarachnoid space in shunted hydrocephalic patients may result in acute shunt failure. These patients may warrant more careful observation in the early postoperative period, particularly as shunt failure may compromise spinal wound closures.

Evaluation of CSF flow patterns of posterior fossa cystic malformations using CSF flow MR imaging

Differential radiologic diagnosis of cystic malformations of the posterior fossa is often difficult with conventional imaging techniques because of overlapping features of these entities. Posterior fossa cystic malformations occupy the cerebrospinal fluid (CSF) spaces. They may create secondary dynamic effects on the movements of CSF. The aim of this study was to investigate CSF flow alterations in posterior fossa cystic malformations with CSF flow MR imaging. The study included 40 patients with cystic malformations of the posterior fossa. The patients underwent cardiac-gated phase-contrast cine MR imaging. CSF flow was qualitatively evaluated using an in-plane phase-contrast sequence in the midsagittal plane. The MR images were displayed in a closed-loop cine format. Twelve of the patients had communicating arachnoid cyst, seven had non-communicating arachnoid cyst, ten had mega cisterna magna, six had Dandy-Walker malformation, two had Dandy-Walker variant, and three had Blake's pouch cyst. CSF flow MR imaging indicated the regions of no, slow or higher flow, direction of flow, and abnormal cystic fluid motion. Each malformation displayed a distinct CSF flow pattern. Phase-contrast cine MR imaging for CSF flow evaluation may be a useful adjunct to routine MR imaging in the evaluation of the cystic malformations of the posterior fossa because it can improve the specificity in differentiating such malformations.

Evolution of diagnostic neuroradiology from 1904 to 1999.

Neuroradiology began in the early 1900s soon after Roentgen discovered x rays, with the use of skull radiographs to evaluate brain tumors. This was followed by the development of ventriculography in 1918, pneumoencephalography in 1919, and arteriography in 1927. In the beginning, air studies were the primary modality, but this technique was supplanted by angiography in the 1950s and 1960s. The first full-time neuroradiologist in the United States was Cornelius G. Dyke at the New York Neurological Institute in 1930. Neuroradiology took a firm hold as a specialty in the early 1960s when Dr Juan M. Taveras brought together fourteen neuroradiologists from the United States and Canada to establish the nucleus of what was to become the American Society of Neuroradiology, or ASNR. This society's initial goals were to perform research and to advance knowledge within the specialty. Neuroradiologists initially were able to diagnose vascular disease, infections, tumors, trauma, and alterations in cerebrospinal fluid flow, because the brain structure was invisible. Neuroradiology was forever changed with computed tomography (CT) because the brain structure became visible. Soon thereafter, magnetic resonance (MR) imaging was developed, and it not only provided anatomic but also made possible vascular and physiologic functional imaging.

Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics.

Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

Cerebrospinal fluid flow alterations in the dog with chemical meningitis.

Cerebrospinal fluid flow alterations in the dog with chemical meningitis.