Dural Vessels Research Articles

Penetration of Non-Adhesive Gel-like Embolic Materials During Dural Vessels Embolization According to Characteristics of Tantalum Powder

Tantalum powder is included in the composition of Non-Adhesive Gel-like Embolic Materials (NAGLEMs) for X-ray opacity. The duration of X-ray opacity during embolization is primarily associated with the particle size, which differs in the most used NAGLEMs—ONYX (Medtronic) and SQUID (Balt). NAGLEMs are widely used for the embolization of branches of the middle meningeal artery (MMA) in patients with chronic subdural hematomas (CSDHs). Considering the size (5–15 microns) of the target dural vessels, we assumed that not only the viscosity of NAGLEMs, but also the size and shape of tantalum granules may be important for the penetration of these gel-like embolic agents and determine their behavior. A notable discrepancy in size was observed. The medium-sized granules in the SQUID 18 sample (0.443 ± 0.086 microns, M ± SD) were found to be approximately ten times smaller than the tantalum granules in the ONYX 18 sample (5.2 ± 0.33 microns, M ± SD).Tantalum granules in SQUID 18 have a regular spherical shape; in ONYX 18 they have an irregular angular shape. When comparing the behavior of gel-like embolic agents of the same viscosity during MMA embolization in patients with CSDHs (an average age of 62.2 ± 14.3 years) in the group where SQUID 18 (n = 8) was used, the gel-like embolic agent in dural vessels demonstrated significantly greater penetration ability compared with the group where ONYX 18 (n = 8) was used. Accordingly, not only the viscosity of NAGLEMs, but also the size and shape of tantalum granules can have a significant effect on the penetration ability of gel compositions.

Distribution of the Middle Meningeal Artery Variants in Patients Undergoing Embolization for Chronic Subdural Hematoma

The middle meningeal artery (MMA) is a major dural vessel that plays a significant role in developing chronic subdural hematomas (cSDH). Understanding its variable anatomy is essential for the effective management of cSDH and the prevention of complications. Middle meningeal artery anatomy was retrospectively assessed in a population of 92 patients who underwent digital subtraction angiography of cerebral vessels before middle meningeal artery embolization for chronic subdural hematoma. We assessed 121 middle meningeal arteries in 92 patients who underwent digital subtraction angiography for chronic subdural hematoma treatment from October 2020 to July 2023. The most common type in the extended Adachi classification was IC (19.82%) and the rarest was IB (6.31%). The anterior branch of the MMA was the most frequently dominant, while the most common origin of the posterior branch was observed in the distal segment. We reported 4 cases (3.31%) of the MMA arising from the ophthalmic artery. The most common configuration of MMA was Adachi-type IC. The MMA most often originated from the maxillary artery. The anterior branch of the MMA was typically dominant, and the posterior branch most frequently originated from the distal segment. There was no significant impact of Adachi type on treatment results or fluoroscopy time.

The Impact of VEGF-C-Induced Dural Lymphatic Vessel Growth on Ischemic Stroke Pathology.

Timely relief of edema and clearance of waste products, as well as promotion of anti-inflammatory immune responses, reduce ischemic stroke pathology, and attenuate harmful long-term effects post-stroke. The discovery of an extensive and functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural lymphatic vessel (dLV) growth via a single injection of a vector encoding vascular endothelial growth factor C (VEGF-C). In the present study, we aimed to improve post-stroke outcomes by inducing dLV growth in mice. We injected mice with a single intracerebroventricular dose of adeno-associated viral particles encoding VEGF-C before subjecting them to transient middle cerebral artery occlusion (tMCAo). Behavioral testing, Gadolinium (Gd) contrast agent-enhanced magnetic resonance imaging (MRI), and immunohistochemical analysis were performed to define the impact of VEGF-C on the post-stroke outcome. VEGF-C improved stroke-induced behavioral deficits, such as gait disturbances and neurological deficits, ameliorated post-stroke inflammation, and enhanced an alternative glial immune response. Importantly, VEGF-C treatment increased the drainage of brain interstitial fluid (ISF) and cerebrospinal fluid (CSF), as shown by Gd-enhanced MRI. These outcomes were closely associated with an increase in the growth of dLVs around the region where we observed increased vefgc mRNA expression within the brain, including the olfactory bulb, cortex, and cerebellum. Strikingly, VEGF-C-treated ischemic mice exhibited a faster and stronger Gd-signal accumulation in ischemic core area and an enhanced fluid outflow via the cribriform plate. In conclusion, the VEGF-C-induced dLV growth improved the overall outcome post-stroke, indicating that VEGF-C has potential to be included in the treatment strategies of post-ischemic stroke. However, to maximize the therapeutic potential of VEGF-C treatment, further studies on the impact of an enhanced dural lymphatic system at clinically relevant time points are essential.

Influence of Human Leukocyte Antigen in Susceptibility to Migraine in Patients

Migraine affects more than one billion individuals each year across the world, and is one of the most common neurologic disorders, with a high prevalence and morbidity, especially among young adults and females. Migraine is associated with a wide range of comorbidities, which range from stress and sleep disturbances to suicide. The complex and largely unclear mechanisms of migraine development have resulted in the proposal of various social and biological risk factors, such as hormonal imbalances, genetic and epigenetic influences, as well as cardiovascular, neurological, and autoimmune diseases. Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache (CH) patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine.

The role of surgical disconnection for posterior fossa pial arteriovenous fistulas and dural fistulas with pial supply: an illustrative case series.

Pial arteriovenous fistulas (pAVFs) are rare vascular malformations characterized by high-flow arteriovenous shunting involving a cortical arterial supply directly connecting to venous drainage without an intermediate nidus. Dural arteriovenous fistulas (dAVFs) can infrequently involve additional pial feeders which can introduce higher flow shunting and increase the associated treatment risk. In the posterior fossa, arteriovenous fistula (AVF) angioarchitecture tends to be particularly complex, involving either multiple arterial feeders-sometimes from both dural and pial origins-or small caliber vessels that are difficult to catheterize and tend to be intimately involved with functionally critical brainstem or upper cervical cord structures. Given their rarity, published experience on microsurgical or endovascular treatment strategies for posterior fossa pAVFs and dAVFs with pial supply remains limited. Retrospective chart review from 2019-2023 at a high-volume center identified six adult patients with posterior fossa pAVFs that were unable to be fully treated endovascularly and required microsurgical disconnection. These cases are individually presented with a technical emphasis andsupported by comprehensive angiographic and intraoperative images. One vermian (Case 1), three cerebellopontine angle (Cases 2-4) and two craniovertebral junction (Cases 5-6) posterior fossa pAVFs or dAVFs with pial supply are presented. Three cases involved mixed dural and pial arterial supply (Cases 1, 4, and 6), and one case involved a concomitant microAVM (Case 2). Endovascular embolization was attempted in four cases (Cases 1-4): The small caliber and tortuosity of the main arterial feeder prevented catheterization in two cases (Cases 1 and 3). Partial embolization was achieved in Cases 2 and 4. In Cases 5 and 6, involvement of the lateral spinal artery or anterior spinal artery created a prohibitive risk forendovascular embolization, and surgical clip ligation was pursued as primary management. In all cases, microsurgical disconnection resulted in complete fistula obliteration without evidence of recurrence on follow-up imaging (mean follow-up 27.1 months). Two patients experienced persistent post-treatment sensory deficits without significant functional limitation. This illustrative case series highlights thetechnical difficulties and anatomical limitations of endovascular management for posterior fossa pAVFs and dAVFs with pial supply and emphasizes the relative safety and utility of microsurgical disconnection in this context. A combined approach involving partial preoperative embolization-when the angioarchitecture is permissive-can potentially decrease surgical morbidity. Larger studies are warranted to better define the role for multimodal intervention and to assess associated long-term AVF obliteration rates in the setting of pial arterial involvement.

CGRP Inhibitor Use In Migraine Treatments

Several possible remedies for migraines have been discovered to date, the most prominent ones include various antiepileptic drugs such as divalproex sodium and topiramate, as well as beta (Amiri et al., 2021)blockers such as propranolol and timolol. However many of these treatments are not entirely effective treatments for patients who face chronic migraines due to their somewhat prosaic success rates. In 1985, researchers noticed the presence of Calcitonin Gene-Related Peptide (CGRP) in the plasma increased drastically in its levels during the presence of a migraine attack (Deen et al. 2). CGRP is a neuropeptide that is involved in the dilation of both dural and cerebral blood vessels, and this interaction is believed to be the main cause of migraines. Generally, when migraines are treated with triptans (a common symptom relief medication), CGRP levels in the blood generally reduce. It was further found that certain CGRP inhibitors reduced neurogenic inflammation and lead to an increased reduction of pain during the migraine (Deen et al. 4). When faced with a multitude of treatment options for chronic migraines, one must consider inhibitors of the CGRP pathway as a possible alternative. CGRP inhibitors introduce a possible better treatment option than previous medicinal drugs. A few previously used CGRP inhibitors include erenumab, galcanezumab, and fremanezumab, which have recently been used to treat patients of chronic migraines. In this paper we will consider the various CGRP inhibitors and their advantages and disadvantages in the face of conventional chronic migraine treatment options.

An Intraosseous Pterygopalatine Fossa Dural Arteriovenous Fistula

Intraosseous dural arteriovenous fistulas (DAVFs) are distinct in that the fistula is located within the bone rather than the dura through which the dural vessels pass. It has been stated that only fistulas within marrow should be considered as intraosseous DAVFs rather than DAVFs with traditional angioarchitecture that erode into bone or are located within a bony foramen. The ambiguity in the definition may have contributed to the oversight and scarcity of relevant cases reported in the literature. Three- or four-dimensional digital subtraction angiography is useful for determining the location of the fistula and developing treatment plans. We present an intraosseous DAVF around the pterygopalatine fossa using a transvenous approach.

Abstract 118: Ophtalmic‐ethmoidal dural arteriovenous fistula

Introduction Ophtalmic dural arteriovenous fistula is not a common diagnosis. They usually present as subarachnoid hemorrhage, or parenquimatous hemorrhage as in our patient. Male, 46 years old, electric worker, right‐handed. Family: Diabetes mellitus, gastric cancer, COVID. Tobacco, Marihuana and alcohol positive. Presents SAH on October 2022 posterior to physical activity. Intense cephalea, nausea and vomit, anxiety, with no neurological deficit, and went to sleep. Two days after, he presents somnolence, altered verbal speech, and disorientation, and next day he presents seizure, then he goes to emergency. Physical examination: Normal. Neurological examination: Disorientation, confused and non‐fluent language, altered mental status. No other signs of focalization. No visual affectation. Methods Patient was evaluated at emergency room. CT: SAH and parenquimatous left frontal basal hemorrhage of 2x3.4cm. AngioCT: a dilated orbito frontal vein, and a venous aneurysm at the anterior third of the superior sagittal sinus. Fronto basal fistula was suspected. Angiography was performed, and it was found right fronto‐basal arteriovenous fistula Borden III, Cognard IV. Comunication between righ ophthalmic artery to superior sagittal sinus. Patient was delivered home three days after the event. When patient had recovered clinically, we performed embolization. Results We performed doble access, femoral artery and braquial vein. It was not possible to achieve to the fistula through vein system. We catheterized ophthalmic artery, and did embolization through it, with a successful result, and with no ophthalmic symptoms after embolization. Conclusion Dural arteriovenous fistulas are shunts found from dural vessels. This type of fistulas ophthalmic‐ethmoidal are rare. We performed angiography which is the know gold standard for diagnosis, and we tried to do a combined access which was not possible, so we performed simple embolization through ophthalmic artery. This approach it is performed and it has been reported as an effective and safe treatment.

Histopathological changes of the dural myeloid cells and lymphatic vessels in a mouse model of sepsis-associated encephalopathy

As a common diffuse encephalopathy caused by sepsis, sepsis-associated encephalopathy (SAE) is closely associated with increased mortality, severe cognition dysfunction and increased cost of health care in patients of sepsis. Accumulating evidence suggests that the dura mater, the outermost meninges of the central nervous system (CNS), plays an important role in CNS immunity, especially with the discovery of meningeal lymphatic vessels (mLVs), as well as a plentiful array of resident or infiltrating immune cells harbored in the dura. Although these findings have significantly enhanced our understanding of the immune function of dura under both steady-state and pathological condition of CNS, whether and how the immune cells and mLVs within dura response to SAE still remains largely unexplored. Here, we established lipopolysaccharide (LPS) intraperitoneal injection-induced SAE model and examined the dural resident immune cells and mLVs. We analysed the histological change in dura by performing hematoxylin and eosin (H&E) and immunofluorescence staining. Results showed that systemic exposure to LPS induced neutrophils recruitment, exudation and gathering around the dural blood vessels. Moreover, resident macrophage altered its shape as well as location, and downregulated major histocompatibility (MHC) class II expression following LPS injection. We also found that LPS exposure induced dorsal meningeal lymphangiogenesis. Together, these findings collectively demonstrated that LPS-induced SAE can stimulate immune cells and mLVs within dura and provided more information about the immune response of the dura in sepsis.

Transverse Canal Foramen and Pericarotid Venous Network in Metatheria and Other Mammals

Transverse Canal Foramen and Pericarotid Venous Network in Metatheria and Other Mammals

Functional assessment of the dural lymphatic vessels using dynamic contrast MRI in multiple sclerosis.

The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance. This prospective study included 20 patients with MS (17 women; age=46.4 [27, 65] years; disease duration=13.6 [2.1, 38.0] years, expanded disability status score (EDSS)=2.0 [0, 6.5]). Patients were scanned on a 3.0T MRI system using intravenous contrast-enhanced fluid-attenuated inversion recovery MRI. Signal in the dural lymphatic vessel along the superior sagittal sinus was measured to calculate peak enhancement, time to maximum enhancement, wash-in and washout slopes, and the area under the time-intensity curve (AUC). Correlation analysis was performed to examine the relationship between the lymphatic dynamic parameters and the demographic and clinical characteristics, including the lesion load and the brain parenchymal fraction (BPF). Contrast enhancement was detected in the dural lymphatics in most patients 2-3min after contrast administration. BPF had a significant correlation with AUC (p<.03), peak enhancement (p<.01), and wash-in slope (p=.01). Lymphatic dynamic parameters did not correlate with age, BMI, disease duration, EDSS, or lesion load. Moderate trends were observed for correlation between patient age and AUC (p=.062), BMI and peak enhancement (p=.059), and BMI and AUC (p=.093). Intravenous dynamic contrast MRI of the dural lymphatics is feasible and may be useful in characterizing its hydrodynamics in neurological diseases.

Cerebral Vasculitis in a patient receiving Risankizumab, an Inhibitor of Interleukin-23: First Case Report (P12-3.013)

<h3>Objective:</h3> NA <h3>Background:</h3> Iatrogenic neuroinflammation has been frequently reported in recent years owing to expanding biologic therapies for the treatment of a wide range of disorders including Psoriasis. Here we report a case of Central Nervous System (CNS) vasculitis after initiation of Risankizumab, a monoclonal antibody against Interleukin-23 (IL23) used to treat Psoriasis. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 29-year-old female with moderate psoriasis who was started on Risankizumab about one month prior, presented with encephalopathy and left temporal lobe focal seizures with refractory status epilepticus. Her MRI showed punctate infarcts and areas of enhancement in the left temporal lobe and leptomeninges overlying the left convexity. Extensive work up revealed increased Erythrocyte Sedimentation Rate (72 mm/hr) and positive Cardiolipin (IgM and IgG) and Beta-2 Glycoprotein (IgM and IgG) antibodies suggesting antiphospholipid syndrome (APS) for which she was started on anticoagulation. Lumbar puncture revealed normal opening pressure, glucose, protein and five nucleated cells. Oligoclonal bands, meningitis/encephalitis and autoimmune encephalitis panels were negative. Subsequent brain MRI showed new areas of ischemic lesions. Cerebral angiogram was unremarkable. Biopsy revealed focal perivascular lymphocytes (CD45 and CD3 immunohistochemical stained) infiltration in dural vessels consistent with small-vessel vasculitis. She was treated with high dose steroids with clinical improvement and subsequently planned to treat with Cyclophosphamide. Risankizumab was discontinued due to possible association. <h3>Conclusions:</h3> Iatrogenic neuroinflammation has been increasingly recognized during the new era of biological molecules and monoclonal antibodies for systemic inflammatory disorders and malignancies. Tumor necrosis factor inhibitors and immune checkpoint inhibitors are more commonly associated with neuroinflammation. To the best of our knowledge, this is the first reported case of APS and CNS vasculitis possibly associated with the initiation of IL23 inhibitor Risankizumab. Although causality cannot be established with a single case, it suggests a possible association. <b>Disclosure:</b> Dr. Cabrera Pulla has nothing to disclose. Dr. Amirjanyan has nothing to disclose. Qian Wu has nothing to disclose. Dr. Mui has nothing to disclose. Dr. Imitola has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Dr. Imitola has received research support from biogen. Dr. Imitola has a non-compensated relationship as a Board Member with National MS Society that is relevant to AAN interests or activities. Dr. Imitola has a non-compensated relationship as a Committee Member with International Society for Stem Cell Research that is relevant to AAN interests or activities. Dr. Coban has nothing to disclose.

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.

Blockade of VEGFR3 signaling leads to functional impairment of dural lymphatic vessels without affecting autoimmune neuroinflammation.

The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its significance in mediating dural lymphatic function in CNS autoimmunity is unclear. We show that inhibition of the VEGF-C/VEGFR3 signaling pathway using a monoclonal VEGFR3-blocking antibody, a soluble VEGF-C/D trap, or deletion of the Vegfr3 gene in adult lymphatic endothelium causes notable regression and functional impairment of dural LVs but has no effect on the development of CNS autoimmunity in mice. During autoimmune neuroinflammation, the dura mater was only minimally affected, and neuroinflammation-induced helper T (TH) cell recruitment, activation, and polarization were significantly less pronounced in the dura mater than in the CNS. In support of this notion, during autoimmune neuroinflammation, blood vascular endothelial cells in the cranial and spinal dura expressed lower levels of cell adhesion molecules and chemokines, and antigen-presenting cells (i.e., macrophages and dendritic cells) had lower expression of chemokines, MHC class II-associated molecules, and costimulatory molecules than their counterparts in the brain and spinal cord, respectively. The significantly weaker TH cell responses in the dura mater may explain why dural LVs do not contribute directly to CNS autoimmunity.

γδ T cells recruitment and local proliferation in brain parenchyma benefit anti-neuroinflammation after cerebral microbleeds.

Cerebral microbleeds (CMBs) are an early sign of many neurological disorders and accompanied by local neuroinflammation and brain damage. As important regulators of immune response and neuroinflammation, the biological behavior and role of γδ T cells after CMBs remain largely unknown. We made a spot injury of microvessel in the somatosensory cortex to mimic the model of CMBs by two-photon laser and in vivo tracked dynamical behaviors of γδ T cells induced by CMBs using TCR-δGFP transgenic mice. Biological features of γδ T cells in the peri-CMBs parenchyma were decoded by flow cytometry and Raman spectra. In wildtype and γδ T cell-deficient mice, neuroinflammation and neurite degeneration in the peri-CMBs cortex were studied by RNAseq, immunostaining and in vivo imaging respectively. After CMBs, γδ T cells in the dural vessels were tracked to cross the meningeal structure and invade the brain parenchyma in a few days, where the division process of γδ T cells were captured. Parenchymal γδ T cells were highly expressed by CXCR6 and CCR6, similar to meningeal γδ T cells, positive for IL-17A and Ki67 (more than 98%), and they contained abundant substances for energy metabolism and nucleic acid synthesis. In γδ T cell-deficient mice, cortical samples showed the upregulation of neuroinflammatory signaling pathways, enhanced glial response and M1 microglial polarization, and earlier neuronal degeneration in the peri-CMBs brain parenchyma compared with wildtype mice. CMBs induce the accumulation and local proliferation of γδ T cells in the brain parenchyma, and γδ T cells exert anti-neuroinflammatory and neuroprotective effects at the early stage of CMBs.

In Reply: Angioarchitectural Analysis of Arteriovenous Shunts in Dural Arteriovenous Fistulas and Its Clinical Implications.

To the Editor: We would like to thank Dr Su et al1 for sharing their insights on dural arteriovenous fistulas (DAVFs) and thoughtful and duly comments on our recent article “Angioarchitectural analysis of arteriovenous shunts in dural arteriovenous fistulas and its clinical implications.”2 Based on the histopathological studies and their experience of DAVFs, Dr Su et al point out that fistulas are not formed directly at the dural sinuses but between the dural artery and the dural vein (in the dural sinus wall) before draining into the sinus or the bridging vein.1,3,4 We agree with these classic histopathological finding; however, the main focus of our study was to describe and discriminate the “angiographic” shunt patterns in light of the connections between the shunt, the sinus, and the cortical veins to unveil their practical implications. In this regard, there were specific patients in whom the targetable fistulous channel—regarding the branching patterns and the caliber changes of the vessels—could not be identified but showed functionally direct connections with the sinus. The histopathological basis for these kinds of shunt remains speculative. The variations in the anatomy of the dural vessels (length, location, etc), secondary changes associated with venous hypertension, thrombosis, inflammation, angiogenesis, and dural wall alterations alongside the temporal changes may have manifested as this pattern.3-8 Interestingly in our series, multiple shunt types were noted in several patients (n = 7), more frequently as the coexistence of the direct sinus fistulae and mural channel-type shunts (n = 5), suggesting the dynamic nature of this disease. Extensive histopathological studies are crucial to shed light on these compelling questions but are extremely limited. Meanwhile, angiographic discrimination of the different characteristics of the shunts, such as the diffuse direct connections or channel-like structures or bridging vein type shunts, and their connection patterns with the sinus and the cortical vein are paramount for effectively targeting the lesion and predicting the behavior of the liquid embolic agents. The presence of pial arterial supply to the DAVF has gained much interest. There are concerns that these patients may be associated with postprocedural rupture of the fragile neovascularized vessels after venous outflow obstruction and inadvertent reflux of the embolic agent into the pial arteries.9,10 The presence of the pial feeders are known to be strongly associated with the tentorial DAVFs.9,10 Our series included only the superior sagittal and transverse sigmoid sinus DAVFs; thus, analyzing the implications of pial supplies was considered beyond the scope of our study. However, this is an interesting topic that deserves further scrutinization. We greatly appreciate the comments and insights by Dr Su et al. DAVFs are fascinating but also complex and challenging diseases. We wish for further technological progress and the power of collective intelligence in understanding and overcoming this intriguing disease.

Distinct roles of the meningeal layers in CNS autoimmunity

The meninges, comprising the leptomeninges (pia and arachnoid layers) and the pachymeninx (dura layer), participate in central nervous system (CNS) autoimmunity, but their relative contributions remain unclear. Here we report on findings in animal models of CNS autoimmunity and in patients with multiple sclerosis, where, in acute and chronic disease, the leptomeninges were highly inflamed and showed structural changes, while the dura mater was only marginally affected. Although dural vessels were leakier than leptomeningeal vessels, effector T cells adhered more weakly to the dural endothelium. Furthermore, local antigen-presenting cells presented myelin and neuronal autoantigens less efficiently, and the activation of autoreactive T cells was lower in dural than leptomeningeal layers, preventing local inflammatory processes. Direct antigen application was required to evoke a local inflammatory response in the dura. Together, our data demonstrate an uneven involvement of the meningeal layers in CNS autoimmunity, in which effector T cell trafficking and activation are functionally confined to the leptomeninges, while the dura remains largely excluded from CNS autoimmune processes.

Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier.

.Brain barriers are crucial sites for cerebral energy supply, waste removal, immune cell migration, and solute exchange, all of which maintain an appropriate environment for neuronal activity. At the capillary level, where the largest area of brain–vascular interface occurs, pericytes adjust cerebral blood flow (CBF) by regulating capillary diameter and maintain the blood–brain barrier (BBB) by suppressing endothelial cell (EC) transcytosis and inducing tight junction expression between ECs. Pericytes also limit the infiltration of circulating leukocytes into the brain where resident microglia confine brain injury and provide the first line of defence against invading pathogens. Brain “waste” is cleared across the BBB into the blood, phagocytosed by microglia and astrocytes, or removed by the flow of cerebrospinal fluid (CSF) through perivascular routes—a process driven by respiratory motion and the pulsation of the heart, arteriolar smooth muscle, and possibly pericytes. “Dirty” CSF exits the brain and is probably drained around olfactory nerve rootlets and via the dural meningeal lymphatic vessels and possibly the skull bone marrow. The brain is widely regarded as an immune-privileged organ because it is accessible to few antigen-primed leukocytes. Leukocytes enter the brain via the meninges, the BBB, and the blood-CSF barrier. Advances in genetic and imaging tools have revealed that neurological diseases significantly alter immune–brain barrier interactions in at least three ways: (1) the brain’s immune-privileged status is compromised when pericytes are lost or lymphatic vessels are dysregulated; (2) immune cells release vasoactive molecules to regulate CBF, modulate arteriole stiffness, and can plug and eliminate capillaries which impairs CBF and possibly waste clearance; and (3) immune–vascular interactions can make the BBB leaky via multiple mechanisms, thus aggravating the influx of undesirable substances and cells. Here, we review developments in these three areas and briefly discuss potential therapeutic avenues for restoring brain barrier functions.

Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis.

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues facilitate intersystem communication. Cerebrospinal fluid (CSF), which interfaces with the glymphatic system and thereby drains the brain's interstitial and perivascular spaces, facilitates outward signaling beyond the blood-brain barrier. In the present study, we report that CSF can exit into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice migrate along perivascular spaces of dural blood vessels and then travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria hijack this route to invade the skull's hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. As skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in CSF by regional marrow may have broad implications for inflammatory neurological disorders.

Mechanisms of Cerebrospinal Fluid Production and Absorption and Ventricular Dilatation in Hydrocephalus

The concept of cerebrospinal fluid(CSF)production and absorption changed significantly in the early 2010s from "third circulation theory" and "classical bulk flow theory" as follows. First, CSF is mainly produced from the interstitial fluid excreted from the brain; CSF produced by the choroid plexus is important in maintaining homeostasis of the brain. Next, CSF is not absorbed in the venous sinus via the arachnoid granules, but rather in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways around the attachment of the choroid plexus other than the foramina of Luschka and Magendie. Because of the compensatory direct CSF pathways, the lateral ventricles and the basal cistern are enlarged simultaneously in idiopathic normal pressure hydrocephalus(iNPH). Due to the decrease in brain volume with aging, the average total intracranial CSF volume increases from approximately 150 mL at 20 years to approximately 350 mL at 70 years, and further increases by approximately 50-100 mL to above 400 mL in patients with iNPH. CSF movement is composed of a steady flow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and the dynamic pulsatile flow produced by the pulsation of the cerebral arteries or brain, respiration, and head movement. In general, this pulsatile CSF flow decreases with aging but increases at the opening of the foramen of Magendie and causes the ventricles to expand in iNPH.