Intracranial Cerebrospinal Fluid Research Articles

Anesthesia blunts carbon dioxide effects on glymphatic cerebrospinal fluid dynamics in mechanically ventilated rats.

Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid (CSF) flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial CSF-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, we studied the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences - vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane (ISO). End-tidal carbon dioxide (EtCO2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (EtCO2 80 mmHg) or hyperventilation (EtCO2 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 minutes in 1) normoventilated (EtCO2 40 mmHg) K/DEX, 2) normoventilated ISO, 3) hypercapnic K/DEX, and 4) hyperventilated ISO groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging. Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries (MCAs), and intracranial CSF volume were higher under K/DEX compared with ISO (cortical Cmax ratio 2.33 [95% CI 1.35 to 4.04], perivascular size ratio 2.20 [95% CI 1.09 to 4.45], and intracranial CSF volume ratio 1.90 [95% CI 1.33 to 2.71]). Under ISO, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under ISO despite a 28% increase in CSF volume around MCAs. K/DEX and ISO overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia whereas hyperventilation was insufficient to increase cerebral CSF perfusion under ISO.

Effect of spaceflight experience on human brain structure, microstructure, and function: systematic review of neuroimaging studies.

Spaceflight-induced brain changes have been commonly reported in astronauts. The role of microgravity in the alteration of the brain structure, microstructure, and function can be tested with magnetic resonance imaging (MRI) techniques. Here, we aim to provide a comprehensive overview of Spaceflight studies exploring the potential role of brain alterations identified by MRI in astronauts. We conducted a search on PubMed, Web of Science, and Scopus to find neuroimaging correlates of spaceflight experience using MRI. A total of 20 studies (structural MRI n = 8, diffusion-based MRI n = 2, functional MRI n = 1, structural MRI and diffusion-weighted MRI n = 6, structural MRI and functional MRI n = 3) met our inclusion criteria. Overall, the studies showed that regardless of the MRI techniques, mission duration significantly impacts the human brain, prompting the inclusion of various brain regions as features in the analyses. After spaceflight, notable alterations were also observed in the superior occipital gyrus and the precentral gyrus which show alterations in connectivity and activation during spaceflight. The results provided highlight the alterations in brain structure after spaceflight, the unique patterns of brain remodeling, the challenges in drawing unified conclusions, and the impact of microgravity on intracranial cerebrospinal fluid volume.

Factors to predict recurrence after epidural blood patch in patients with spontaneous intracranial hypotension.

This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.

Is foramen magnum decompression for acquired Chiari I malformation like putting a finger in the dyke? - A simplistic overview of artificial intelligence in assessing critical upstream and downstream etiologies

ABSTRACT Background: Missed diagnosis of evolving or coexisting idiopathic (IIH) and spontaneous intracranial hypotension (SIH) is often the reason for persistent or worsening symptoms after foramen magnum decompression for Chiari malformation (CM) I. We explore the role of artificial intelligence (AI)/convolutional neural networks (CNN) in Chiari I malformation in a combinatorial role for the first time in literature, exploring both upstream and downstream magnetic resonance findings as initial screening profilers in CM-1. We have also put together a review of all existing subtypes of CM and discuss the role of upright (gravity-aided) magnetic resonance imaging (MRI) in evaluating equivocal tonsillar descent on a lying-down MRI. We have formulated a workflow algorithm MaChiP 1.0 (Manjila Chiari Protocol 1.0) using upstream and downstream profilers, that cause de novo or worsening Chiari I malformation, which we plan to implement using AI. Materials and Methods: The PRISMA guidelines were used for “CM and machine learning and CNN” on PubMed database articles, and four articles specific to the topic were encountered. The radiologic criteria for IIH and SIH were applied from neurosurgical literature, and they were applied between primary and secondary (acquired) Chiari I malformations. An upstream etiology such as IIH or SIH and an isolated downstream etiology in the spine were characterized using the existing body of literature. We propose the utility of using four selected criteria for IIH and SIH each, over MRI T2 images of the brain and spine, predominantly sagittal sequences in upstream etiology in the brain and multiplanar MRI in spinal lesions. Results: Using MaChiP 1.0 (patent/ copyright pending) concepts, we have proposed the upstream and downstream profilers implicated in progressive Chiari I malformation. The upstream profilers included findings of brain sagging, slope of the third ventricular floor, pontomesencephalic angle, mamillopontine distance, lateral ventricular angle, internal cerebral vein–vein of Galen angle, and displacement of iter, clivus length, tonsillar descent, etc., suggestive of SIH. The IIH features noted in upstream pathologies were posterior flattening of globe of the eye, partial empty sella, optic nerve sheath distortion, and optic nerve tortuosity in MRI. The downstream etiologies involved spinal cerebrospinal fluid (CSF) leak from dural tear, meningeal diverticula, CSF-venous fistulae, etc. Conclusion: AI would help offer predictive analysis along the spectrum of upstream and downstream etiologies, ensuring safety and efficacy in treating secondary (acquired) Chiari I malformation, especially with coexisting IIH and SIH. The MaChiP 1.0 algorithm can help document worsening of a previously diagnosed CM-1 and find the exact etiology of a secondary CM-I. However, the role of posterior fossa morphometry and cine-flow MRI data for intracranial CSF flow dynamics, along with advanced spinal CSF studies using dynamic myelo-CT scanning in the formation of secondary CM-I is still being evaluated.

The Role of Phase-Contrast MRI in Diagnosing Cerebrospinal Fluid Flow Abnormalities.

Background Cerebrospinal fluid (CSF) dynamics play a crucial role in maintaining the homeostasis of the central nervous system (CNS). Any disruption in CSF flow can lead to various congenital and acquired conditions, impacting neurological function and overall health. This study aims to analyze the significance of phase-contrast MRI in evaluating abnormalities in CSF flow and its diagnostic utility in various CSF-related disorders. Phase contrast MRIhas emerged as a valuable tool for evaluating CSF dynamics non-invasively by examining CSF flow characteristics such as pulsatile flow patterns, hyperdynamic or hypodynamic flow, and disruptions in CSF circulation. Alterations in CSF pulsatility and stroke volume can indicate changes in intracranial compliance, vascular resistance, or CSF production and absorption rates. The findings of this study will advance our understanding of CSF physiology and its relevance in neurological pathologies, potentially leading to improved patient outcomes and management approaches. Materials and methods The study involved 36 patients and was conducted as an observational, prospective study over 18 months (October 2020 to March 2022) at the Department of Radiology, Saveetha Medical College and Hospital, Chennai. We utilized a 1.5 T Philips Multiva MRI scanner by Philips Healthcare in Amsterdam, Netherlands.The study included patients with suspected CSF flow abnormalities and abnormal MRI findings (normal pressure hydrocephalus (NPH), age-related brain atrophy, aqueduct stenosis (AS), Chiari malformation type 1, syringomyelia, or arachnoid cyst), alongside control exhibiting normal neurological symptoms and MRI results. Exclusions involved individuals with febrile seizures, neurological diseases, cerebrovascular accidents, anti-convulsive medication use, cardiac arrhythmia, or MRI contraindications. Post-processing involved analyzing stroke volume (SV), peak systolic velocity (PSV), end diastolic velocity (EDV), and mean flux. Statistical analysis was conducted using the StatisticalPackage for the Social Sciences (IBMSPSSStatisticsforWindows,IBMCorp., Version 24.0, Armonk,NY), employing the χ2-test for categorical variables and nonparametric tests like Mann-Whitney U and Kruskal-Wallis H-tests for quantitative variables. A p-value < 0.05 was considered significant. Results The 36 patients, aged 1 to 80 years, were referred by the neurology department and categorized into four subgroups based on clinical history and conventional MRI findings: NPH, AS, age-related brain atrophy, and a normal control group. MRI CSF flowmetry evaluation focused on PSV, PDV, and SV. We found peak diastolic velocity (PDV), PSV, and average blood velocity (ABV) to be significantly higher in NPH compared to the control group (PSV, EDV, and SV: 9.96 +/- 1.73, 4.72 +/- 0.62, and 63 +/- 12.88 for NPH versus 4.8 +/- 0.39, 3.21 +/- 0.55, and 20.72 +/- 5.7 for control, respectively; p = 0.000). Conversely, patients with age-related brain atrophy and AS exhibited lower values (1.6 +/- 0.44, 1.13 +/- 0.09, and 6.33 +/- 2.08 for AS, and 2.07 +/- 0.09, 1.62 +/- 0.33, and 6.8 +/- 2.16 for age-related brain atrophy versus control; p = 0.002). Conclusion MRI CSF flowmetry emerges as a rapid, accurate, and non-invasive diagnostic tool for various neurological disorders associated with abnormal CSF flow. Additionally, this technique may aid in selecting appropriate treatment strategies.

Automated volumetric evaluation of intracranial compartments and cerebrospinal fluid distribution on emergency trauma head CT scans to quantify mass effect.

Intracranial space is divided into three compartments by the falx cerebri and tentorium cerebelli. We assessed whether cerebrospinal fluid (CSF) distribution evaluated by a specifically developed deep-learning neural network (DLNN) could assist in quantifying mass effect. Head trauma CT scans from a high-volume emergency department between 2018 and 2020 were retrospectively analyzed. Manual segmentations of intracranial compartments and CSF served as the ground truth to develop a DLNN model to automate the segmentation process. Dice Similarity Coefficient (DSC) was used to evaluate the segmentation performance. Supratentorial CSF Ratio was calculated by dividing the volume of CSF on the side with reduced CSF reserve by the volume of CSF on the opposite side. Two hundred and seventy-four patients (mean age, 61 years ± 18.6) after traumatic brain injury (TBI) who had an emergency head CT scan were included. The average DSC for training and validation datasets were respectively: 0.782 and 0.765. Lower DSC were observed in the segmentation of CSF, respectively 0.589, 0.615, and 0.572 for the right supratentorial, left supratentorial, and infratentorial CSF regions in the training dataset, and slightly lower values in the validation dataset, respectively 0.567, 0.574, and 0.556. Twenty-two patients (8%) had midline shift exceeding 5 mm, and 24 (8.8%) presented with high/mixed density lesion exceeding >25 ml. Fifty-five patients (20.1%) exhibited mass effect requiring neurosurgical treatment. They had lower supratentorial CSF volume and lower Supratentorial CSF Ratio (both p < 0.001). A Supratentorial CSF Ratio below 60% had a sensitivity of 74.5% and specificity of 87.7% (AUC 0.88, 95%CI 0.82-0.94) in identifying patients that require neurosurgical treatment for mass effect. On the other hand, patients with CSF constituting 10-20% of the intracranial space, with 80-90% of CSF specifically in the supratentorial compartment, and whose Supratentorial CSF Ratio exceeded 80% had minimal risk. CSF distribution may be presented as quantifiable ratios that help to predict surgery in patients after TBI. Automated segmentation of intracranial compartments using the DLNN model demonstrates a potential of artificial intelligence in quantifying mass effect. Further validation of the described method is necessary to confirm its efficacy in triaging patients and identifying those who require neurosurgical treatment.

Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications

BackgroundIdiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the cerebrospinal fluid reabsorption rate, increasing cerebrospinal fluid volume and pressure at the expense of intracranial compliance and promoting further sinus compression. Intracranial compliance is the ability of the craniospinal space to accept small volumetric increases of one of its compartments without appreciable intracranial pressure rise. In idiopathic intracranial hypertension, a condition associated with a reduced rate of CSF reabsorption leading to its volumetric expansion, a pathologically reduced IC precedes and accompanies the rise of ICP. Syncope is defined as a transient loss of consciousness due to a transient cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. A transient global cerebral hypoperfusion represents the final mechanism of syncope determined by cardiac output and/or total peripheral resistance decrease. There are many causes determining low cardiac output including reflex bradycardia, arrhythmias, cardiac structural disease, inadequate venous return, and chronotropic and inotropic incompetence. Typically, syncopal transient loss of consciousness is mainly referred to an extracranial mechanism triggering a decrease in cardiac output and/or total peripheral resistance. Conversely, the association of syncope with a deranged control of intracranial compliance related to cerebral venous outflow disorders has been only anecdotally reported.Case PresentationWe report on a 57-year-old woman with daily recurrent orthostatic hypotension syncope and idiopathic intracranial hypertension-related headaches, which resolved after lumbar puncture with cerebrospinal fluid subtraction.ConclusionsA novel mechanism underlying the triggering of orthostatic syncope in the presence of intracranial hypertension-dependent reduced intracranial compliance is discussed.

Hydrodynamic and Hemodynamic Interactions in Chronic Hydrocephalus.

During a cardiac cycle, intracranial pressure is related to arterial entry into the cranium and its interaction with intracranial compliance. The arterial inflow is compensated by intracranial compliance and, initially, the flushing of cerebrospinal fluid (CSF) into the cervical subarachnoid spaces. Our objective is to analyze the interactions between intracranial arteriovenous exchange and cerebrospinal fluid oscillations. A total of 23 patients (73 ± 8 years) with suspected chronic hydrocephalus (CH) underwent an infusion test and phase-contrast MRI. Rout is an important factor in the diagnosis of CH. Patients were divided into 2 populations: probableCH (Rout: resistance to CSF outflow) (Rout > 12 mmHg/mL/min, 13 patients) and unlikelyCH (Rout < 12 mmHg/mL/min, 10 patients). We measured the intracranial vascular volume (arteriovenous stroke volume: SVvasc) and CSF (CSF stroke volume at upper cervical level: SVCSF) volume variations during the cardiac cycle. In the whole population, we observed a significant correlation between SVvasc and SVCSF (R2 = 0.43; p = 0.0007). In the population unlikelyCH, this correlation was significant (R2 = 0.76; p = 0.001). In the population probableCH, this correlation was not significant (R2 = 0.17, p = 0.16). These results show that the link between the compliance of the oscillating CSF and the abrupt arterial inflow seems to be altered in CH. CSF oscillations between intracranial and cervical fluid spaces limit the impact of the abrupt arterial inflow.

P14.05.B 2-HYDROXYGLUTARATE IN CEREBROSPINAL FLUID AS A MONITORING BIOMARKER FOR IDH-MUTANT GLIOMAS

Abstract BACKGROUND D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas, no study has evaluated the ability of CSF D-2-HG to quantitatively monitor tumor burden and therapeutic response. Toward this goal, we are routinely obtaining CSF samples from patients prior to, during, and after treatment via intra-operative collection and CSF-access devices. MATERIAL AND METHODS Patients were enrolled into our Ommaya reservoir study (NCT04692337), which enables longitudinal access to CSF. The catheter for the implanted reservoir was placed within the surgical resection cavity following a standard-of-care resection. Intra-operatively collected CSF samples were also biobanked through Mayo Clinic’s Neuro-Oncology biorepository. CSF samples were also acquired via clinically indicated ventriculoperitoneal shunts (VP shunts) or external ventricular drains via our ongoing CSF biomarkers study (NCT04692324). D-and-L-2-HG were assayed from each CSF sample via gas chromatography-mass spectrometry (GC-MS) at Mayo Clinic’s Biochemical Genetics Laboratory. RESULTS CSF was collected prior to and after resection in patients via Ommaya reservoirs or VP shunts, all of whom underwent near gross total resections (&amp;gt;95% of tumor volume). D-2-HG and the D/L ratio fell on average by 57.9% (range: 15.1%-98.6%) and 68.8% (range: 49.3%-98.9%), respectively, following resection. In one patient with a largely intraventricular grade 4 IDH-mutant astrocytoma, D-and-L-2-HG fell by 99.1% and 99.3% by post-operative day 2, consistent with the impact of ventricular contact on baseline CSF D-2-HG levels. In patients for whom CSF was collected throughout chemoradiation, with or without immunotherapy, D-2-HG and the D/L ratio continued to decrease over time, despite concern for pseudoprogression versus progression on imaging. CONCLUSION Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas. Work is ongoing to evaluate the reproducibility of these findings in a larger cohort of patients with low or high-grade gliomas, in addition to the impact of tumor recurrence on 2-HG. Future studies will evaluate the impact of IDH inhibitors and other experimental therapies on CSF 2-HG levels for pharmacodynamic monitoring of treatment response.

Comparison of cerebrospinal fluid space between probable normal pressure hydrocephalus and Alzheimer's disease.

Idiopathic normal pressure hydrocephalus (INPH) is a potentially reversible syndrome characterized by complex symptoms, difficulty in diagnosis and a lack of detailed clinical description, and it is difficult to distinguish from Alzheimer's disease (AD). The objective of this study was to design a method for measuring the actual amount of hydrocephalus in patients with INPH and to evaluate INPH. All subjects underwent a 3D T1-weighted MRI. Statistical parametric mapping 12 was used for preprocessing images, statistical analysis, and voxel-based morphometric gray matter (GM) volume, white matter (WM) volume, and cerebrospinal fluid (CSF) volume analysis. The demographic and clinical characteristics of the groups were compared using a t-test for continuous variables and a chi-square test for categorical variables. Pearson's correlation analysis and Bonferroni's statistic-corrected one-way ANOVA were used to determine the relationship among demographic variables. Receiver operating characteristic (ROC) curves were used to assess the accuracy of the callosal angle (CA), WM ratio, and CSF ratio in distinguishing probable INPH from AD. The study included 42 patients with INPH, 32 patients with AD, and 24 healthy control subjects (HCs). There were no differences among the three groups in basic characteristics except for Mini-Mental State Examination (MMSE). There was a correlation between the intracranial CSF ratio and CA. The WM ratio and CSF ratio in patients with INPH and AD were statistically different. Furthermore, the combination of CA, WM ratio, and CSF ratio had a greater differential diagnostic value between INPH and AD patients than CA alone. INPH can be accurately assessed by measuring intracranial CSF ratio, and the addition of WM ratio and CSF ratio significantly improved the differential diagnostic value of probable INPH from AD compared to CA alone.

Fully automated measurement of intracranial CSF and brain parenchyma volumes in pediatric hydrocephalus by segmentation of clinical MRI studies.

Brain parenchyma (BP) and intracranial cerebrospinal fluid (iCSF) volumes measured by fully automated segmentation of clinical brain MRI studies may be useful for the diagnosis and follow-up of pediatric hydrocephalus. However, previously published segmentation techniques either rely on dedicated sequences, not routinely used in clinical practice, or on spatial normalization, which has limited accuracy when severe brain distortions, such as in hydrocephalic patients, are present. We developed a fully automated method to measure BP and iCSF volumes from clinical brain MRI studies of pediatric hydrocephalus patients, exploiting the complementary information contained in T2- and T1-weighted images commonly used in clinical practice. The proposed procedure, following skull-stripping of the combined volumes, performed using a multiparametric method to obtain a reliable definition of the inner skull profile, maximizes the CSF-to-parenchyma contrast by dividing the T2w- by the T1w- volume after full-scale dynamic rescaling, thus allowing separation of iCSF and BP through a simple thresholding routine. Validation against manual tracing on 23 studies (four controls and 19 hydrocephalic patients) showed excellent concordance (ICC>0.98) and spatial overlap (Dice coefficients ranging from 77.2% for iCSF to 96.8% for intracranial volume). Accuracy was comparable to the intra-operator reproducibility of manual segmentation, as measured in 14 studies processed twice by the same experienced neuroradiologist. Results of the application of the algorithm to a dataset of 63 controls and 57 hydrocephalic patients (19 with parenchymal damage), measuring volumes' changes with normal development and in hydrocephalic patients, are also reported for demonstration purposes. The proposed approach allows fully automated segmentation of BP and iCSF in clinical studies, also in severely distorted brains, enabling to assess age- and disease-related changes in intracranial tissue volume with an accuracy comparable to expert manual segmentation.

Moyamoya disease-specific extracellular vesicle-derived microRNAs in the cerebrospinal fluid revealed by comprehensive expression analysis through microRNA sequencing.

To examine the specific changes that occur in the expression levels of extracellular vesicle-derived microRNAs (miRNAs) in intracranial cerebrospinal fluid (CSF) in moyamoya disease. Patients with arteriosclerotic cerebral ischemia were used as controls to eliminate the effects of cerebral ischemia. Intracranial CSF was collected from moyamoya disease and control patients during bypass surgery. Extracellular vesicles (EVs) were extracted from the CSF. Comprehensive expression analysis of miRNAs extracted from EVs by next-generation sequencing (NGS) and validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed. Experiments were conducted on eight cases of moyamoya disease and four control cases. In the comprehensive miRNA expression analysis, 153 miRNAs were upregulated, and 98 miRNAs were downregulated in moyamoya disease compared to the control cases (q-value < 0.05 and |log2 fold change|> 1). qRT-PCR performed on the four most variable miRNAs (hsa-miR-421, hsa-miR-361-5p, hsa-miR-320a, and hsa-miR-29b-3p) associated with vascular lesions among the differentially expressed miRNAs gave the same results as miRNA sequencing. On gene ontology (GO) analysis for the target genes, cytoplasmic stress granule was the most significant GO term. This study is the first comprehensive expression analysis of EV-derived miRNAs in the CSF of moyamoya disease patients using NGS. The miRNAs identified here may be related to the etiology and pathophysiology of moyamoya disease.

Cerebrospinal Fluid Production and Absorption and Ventricular Enlargement Mechanisms in Hydrocephalus.

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

Cavernous Malformations: What They Have Taught Us.

Cavernous Malformations: What They Have Taught Us.

Voxel-based morphometric magnetic resonance imaging evaluation of small head fetus: A comparative study with normal developmental fetus.

To explore the application value of voxel-based morphometric (VBM) in prenatal diagnosis of microcephaly. A retrospective study of magnetic resonance imaging of fetuses with microcephaly was performed using a single-shot fast spin echo sequence; semiautomatic segmentation of grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF); calculation of their volumes; and VBM analysis of their GM. Two independent samples t-test was used to statistically analyse the fetal GM volume in the microcephaly and normal control groups. Total intracranial volume (TIV), GM volume, WM volume, and CSF volume were linearly regressed against gestational age and compared between the two groups. In the fetus with microcephaly, GM volume of frontal lobe, temporal lobe, cuneus, anterior central gyrus, and posterior central gyrus decreased significantly (P < 0.001, corrected by family-wise error at mass level). The GM volume of microcephaly was significantly lower than that of the control group (except for 28 weeks of gestation) (P < 0.05). TIV, GM volume, WM volume, and CSF volume were all positively correlated with gestational age, and the curves in the microcephaly group were all lower than those in the control group. Compared with the normal control group, the GM volume of microcephaly fetuses decreased, and there were significant differences in many brain regions through VBM analysis.

Usefulness of intravoxel incoherent motion MRI for visualizing slow cerebrospinal fluid motion

BackgroundIn the cerebrospinal fluid (CSF) dynamics, the pulsations of cerebral arteries and brain is considered the main driving force for the reciprocating bidirectional CSF movements. However, measuring these complex CSF movements on conventional flow-related MRI methods is difficult. We tried to visualize and quantify the CSF motion by using intravoxel incoherent motion (IVIM) MRI with low multi-b diffusion-weighted imaging.MethodsDiffusion-weighted sequence with six b values (0, 50, 100, 250, 500, and 1000 s/mm2) was performed on 132 healthy volunteers aged ≥ 20 years and 36 patients with idiopathic normal pressure hydrocephalus (iNPH). The healthy volunteers were divided into three age groups (< 40, 40 to < 60, and ≥ 60 years). In the IVIM analysis, the bi-exponential IVIM fitting method using the Levenberg–Marquardt algorithm was adapted. The average, maximum, and minimum values of ADC, D, D*, and fraction of incoherent perfusion (f) calculated by IVIM were quantitatively measured in 45 regions of interests in the whole ventricles and subarachnoid spaces.ResultsCompared with healthy controls aged ≥ 60 years, the iNPH group had significantly lower mean f values in all the parts of the lateral and 3rd ventricles, whereas significantly higher mean f value in the bilateral foramina of Luschka. In the bilateral Sylvian fossa, which contain the middle cerebral bifurcation, the mean f values increased gradually with increasing age, whereas those were significantly lower in the iNPH group. In the 45 regions of interests, the f values in the bilateral foramina of Luschka were the most positively correlated with the ventricular size and indices specific to iNPH, whereas that in the anterior part of the 3rd ventricle was the most negatively correlated with the ventricular size and indices specific to iNPH. Other parameters of ADC, D, and D* were not significantly different between the two groups in any locations.ConclusionsThe f value on IVIM MRI is useful for evaluating small pulsatile complex motion of CSF throughout the intracranial CSF spaces. Patients with iNPH had significantly lower mean f values in the whole lateral ventricles and 3rd ventricles and significantly higher mean f value in the bilateral foramina of Luschka, compared with healthy controls aged ≥ 60 years.

Temperature measurement of intracranial cerebrospinal fluid using diffusion tensor imaging after revascularization surgery in Moyamoya disease

ObjectiveBrain temperature monitoring using a catheter thermometer has been reported to be a useful technique to predict prognosis in neurosurgery. To investigate the possibility of measuring intracranial cerebrospinal fluid temperature for postoperative monitoring in patients with Moyamoya disease (MMD) after bypass surgery. Materials and methodsThis study evaluated fifteen patients with MMD who were indicated for bypass surgery. Diffusion tensor imaging for brain thermometry were performed on a 1.5-T MR scanner. Intracranial cerebrospinal fluid temperature with/without considering the fractional anisotropy component, body temperature, C-reactive protein levels, white blood cell count, and cerebral blood flow measured by 123I-IMP single-photon emission computed tomography were obtained before surgery and 1–3 days after surgery. Pixel values considered to be signal outliers in fractional anisotropy processing were defined as cerebrospinal fluid noise index and calculated. Wilcoxon signed-rank test and effect size were performed to compare the changes before and after revascularization. Spearman's rho correlation coefficient was used to analyze the correlations between each parameter. Statistical significance was defined as p < 0.05. ResultsAll parameter values became significantly higher compared to those measured before revascularization (p < 0.01 in all cases). The effect sizes were largest for the cerebrospinal fluid temperature with fractional anisotropy processing and for C-reactive protein levels (Rank-biserial correlation = 1.0). The cerebrospinal fluid noise index and cerebrospinal fluid temperatures with fractional anisotropy processing (r = 0.84, p < 0.0001) or without fractional anisotropy processing (r = 0.95, p < 0.0001) showed highly significant positive correlations. Although no significant correlation was observed, cerebrospinal fluid temperatures with fractional anisotropy had small or moderately positive correlations with cerebral blood flow, body temperature, C-reactive protein levels, and white blood cell count (r = 0.37, 0.42, 0.41, and 0.44, respectively; p > 0.05). ConclusionOur findings suggest the possibility of postoperative monitoring for MMD patients by measuring intracranial cerebrospinal fluid temperature with fractional anisotropy processing. Intracranial cerebrospinal fluid temperature might be considered as combined response since cerebrospinal fluid, body temperature, and inflammation are equally correlated.

Blockage of CSF Outflow in Rats after Deep Cervical Lymph Node Ligation Observed Using Gd-based MR Imaging.

To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI. Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF_C1), CSF between the olfactory bulbs (CSF_OB), CSF at the pituitary recess (CSF_PitR), and CSF at the pineal recess (CSF_PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared. Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF_C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF_OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF_PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021). The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.

Deep Grey Matter Volume is Reduced in Amateur Boxers as Compared to Healthy Age-matched Controls

PurposeMild traumatic brain injuries (mTBI) sustained during contact sports like amateur boxing are found to have long-term sequelae, being linked to an increased risk of developing neurological conditions like Parkinson’s disease. The aim of this study was to assess differences in volume of anatomical brain structures between amateur boxers and control subjects with a special interest in the affection of deep grey matter structures.MethodsA total of 19 amateur boxers and 19 healthy controls (HC), matched for age and intelligence quotient (IQ), underwent 3T magnetic resonance imaging (MRI) as well as neuropsychological testing. Body mass index (BMI) was evaluated for every subject and data about years of boxing training and number of fights were collected for each boxer. The acquired 3D high resolution T1 weighted MR images were analyzed to measure the volumes of cortical grey matter (GM), white matter (WM), cerebrospinal fluid (CSF) and deep grey matter structures. Multivariate analysis was applied to reveal differences between groups referencing deep grey matter structures to normalized brain volume (NBV) to adjust for differences in head size and brain volume as well as adding BMI as cofactor.ResultsTotal intracranial volume (TIV), comprising GM, WM and CSF, was lower in boxers compared to controls (by 7.1%, P = 0.009). Accordingly, GM (by 5.5%, P = 0.038) and WM (by 8.4%, P = 0.009) were reduced in boxers. Deep grey matter showed statistically lower volumes of the thalamus (by 8.1%, P = 0.006), caudate nucleus (by 11.1%, P = 0.004), putamen (by 8.1%, P = 0.011), globus pallidus (by 9.6%, P = 0.017) and nucleus accumbens (by 13.9%, P = 0.007) but not the amygdala (by 5.5%, P = 0.221), in boxers compared to HC.ConclusionSeveral deep grey matter structures were reduced in volume in the amateur boxer group. Furthermore, longitudinal studies are needed to determine the damage pattern affecting deep grey matter structures and its neuropsychological relevance.

Leukocyte-Rich and Platelet-Rich Fibrin for Skull Base Reconstruction After Endoscopic Endonasal Skull Base Surgery.

Postoperative cerebrospinal fluid (CSF) leak is one of the most common complications after endoscopic endonasal approach to the skull base. To analyze the effect of leukocyte-rich and platelet-rich fibrin (L-PRF) as part of a standardized endonasal skull base repair protocol on postoperative infection and CSF leak rate. One hundred three patients who underwent an endoscopic endonasal approach and were reconstructed using a standard technique (Group A) were compared with 139 patients using the same protocol with the addition of L-PRF (Group B). Postoperative intracranial infection and CSF leak at 6 months were analyzed. In patients with intraoperative CSF leak, postoperative leak occurred in 10.8% in Group A and 2.6% in Group B ( P .024), and in patients with intraoperative high-flow leaks, the incidences were 11.7% and 3.1%, respectively ( P .048). L-PRF reduced postoperative CSF leak by 76% in cases with intraoperative CSF leak (relative risk 0.24, 95% CI 0.06-0.87) and by 73% of patients with high-flow leak (relative risk 0.27, 95% CI 0.07-0.99). In patients undergoing surgery for diagnoses other than adenomas, there were no cases of postoperative leak in Group B, whereas in Group A occurred in 13.4% of those with intraoperative leaks ( P .047) and 15.8% with high-flow intraoperative leaks ( P .033). No significant differences were found in patients with pituitary adenoma. Meningitis occurred in 0.97% in Group A vs 2.16% in Group B ( P .639), without differences between subgroups. L-PRF reduced the rate of postoperative CSF leaks in patients with intraoperative leaks, without differences on postoperative meningitis.