Identification of direct connections between the dura and the brain.

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.

Dimensions of Arachnoid Bulk Ratio: A Superior Optic Nerve Sheath Index for Intracranial Pressure.

Background Discrepancies in the literature regarding optimal optic nerve sheath diameter (ONSD) cutoffs for intracranial pressure (ICP) necessitate alternative neuroimaging parameters to improve clinical management. Purpose To evaluate the diagnostic accuracy of the dimensions of the perineural subarachnoid space to the optic nerve sheath ratio, measured using US, in predicting increased ICP. Materials and Methods In a prospective cohort study from April 2022 to December 2023, patients with suspected increased ICP underwent optic nerve US to determine the dimensions of arachnoid bulk (DAB) ratio and ONSD before invasive ICP measurement. Correlation between the parameters and ICP, as well as diagnostic accuracy, was assessed using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 30 participants were included (mean age, 39 years ± 14 [SD]; 24 female). The DAB ratio and ONSD were significantly larger in participants with increased ICP (38% [0.16 of 0.42] and 14% [0.82 of 6.04 mm], respectively; P < .001). The DAB ratio showed a stronger correlation with ICP than ONSD (rs = 0.87 [P < .001] vs rs = 0.61 [P < .001]). The DAB ratio and ONSD optimal cutoffs for increased ICP were 0.5 and 6.5 mm, respectively, and the ratio had higher sensitivity (100% vs 92%) and specificity (94% vs 83%) compared with ONSD. Moreover, the DAB ratio better predicted increased ICP than ONSD, with a higher AUC (0.98 [95% CI: 0.95, 1.00] vs 0.86 [95% CI: 0.71, 0.95], P = .047). Conclusion An imaging ratio was proposed to predict ICP based on the relative anatomy of the cerebrospinal fluid space, demonstrating more accurate diagnosis of increased ICP and a strong correlation with ICP values, suggesting its potential utility as a neuroimaging marker in clinical settings. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.

Arachnoid granulations in idiopathic intracranial hypertension: Do they have an influence?

OBJECTIVE: The aim of this study was to investigate whether the relative narrowing of the dural venous sinuses by arachnoid granulations (AGs) is more pronounced in patients with idiopathic intracranial hypertension (IIH) compared to healthy controls. BACKGROUND: IIH is characterized by increased intracranial pressure, which is associated with symptoms such as headache and visual disturbances. The role of cerebral venous drainage obstruction in IIH is the subject of ongoing research. MATERIALS AND METHODS: In this retrospective case-control study, 3D contrast-enhanced magnetic resonance images of a cohort of 43 patients with IIH were evaluated for (1) the number of AGs per venous sinus and (2) the diameters of the dural venous sinuses at the site of an AG and at standardized measurement points. In addition, the minimum width of the transverse/sigmoid sinus was measured. All data were compared to the same data from a cohort of 43 control participants. RESULTS: Patients with IIH showed less relative sinus narrowing by AG compared to controls (median: 7%, interquartile range [IQR] 10% vs. 11%, IQR 9% in controls; p = 0.009). In patients with IIH, sinus diameter was larger at the site of an AG (70 ± 25 mm2) compared to its diameter at the standardized measurement point (48 ± 23 mm2; p = 0.010). In the superior sagittal sinus (SSS), patients with IIH had smaller AGs (median: 3 mm2, IQR 2 mm2 vs. 5 mm2, IQR 3 mm2 in controls; p = 0.023) while the respective sinus segment was larger (median: 69 mm2; IQR 21 mm2 vs. 52 mm2, IQR 26 mm2 in controls; p = 0.002). The right transverse sinus was narrower in patients with IIH (41 ± 21 mm vs. 57 ± 20 mm in controls; p < 0.001). CONCLUSIONS: In contrast to our hypothesis, patients with IIH showed less pronounced relative sinus narrowing by AG compared to controls, especially within the SSS, where AGs were smaller and the corresponding sinus segment wider. Smaller AGs could result in lower cerebrospinal fluid resorption, favoring the development of IIH. Conversely, the smaller AGs could also be a consequence of IIH due to backpressure in the SSS because of the narrower transverse/sigmoid sinus, which widens the SSS and compresses the AG.

Predicting the presence of 4th ventricular outlet obstruction in Chiari I Malformation.

INTRODUCTION: A subset of children with Chiari 1 malformation (CM-1) have a 4th ventricle arachnoid veil-a thin membrane covering the outlet of the 4th ventricle. Studies suggest that failure to disrupt this veil during posterior fossa decompression can reduce the likelihood of syringomyelia resolution. However, there is no reliable method for predicting the presence of the veil without direct surgical exploration. This study aims to evaluate the association between pre-operative symptoms, radiographic measurements, and the arachnoid veil. METHODS: A retrospective review of an institutional database of children evaluated for CM-I was conducted. For patients treated with surgery, operative notes were reviewed to determine if an arachnoid veil was present. Logistic regression was used to test for relationship of clinical variables and radiographic measurements with the presence of an arachnoid veil. RESULTS: Out of 997 children with CM-1, 226 surgical patients were included in the analysis after excluding those with inadequate documentation. An arachnoid veil was found in 23 patients (10.2%). Larger syrinx, spinal canal, and thecal sac diameters were significantly associated with the presence of a veil, with odds ratios of 1.23 (95% CI 1.2-1.48; p = 0.03), 1.27 (95% CI 1.02-1.59; p = 0.03), and 1.35 (95% CI 1.03-1.77; p = 0.03), respectively. No significant associations were found with any signs or symptoms. CONCLUSIONS: Arachnoid veil was present in 10% of cases. Radiographic measurements indicating larger syrinx size were the only variables found to be significantly associated with an arachnoid veil. Exploration of the 4th ventricular outlet is recommended for CM-I decompression in the setting of expansile syringomyelia.

To be thorough or tailored: influence of the arachnoid dissection range on the surgical outcomes of microvascular decompression for hemifacial spasm.

BACKGROUND: As one of the most fundamental elements in exposure and decompression, the dissection of arachnoid has been rarely correlated with the surgical results in studies on Microvascular decompression (MVD) procedures for Hemifacial spasm (HFS). MATERIALS AND METHODS: Patients' records of the HFS cases treated with MVD from January 2016 to December 2021 in our center was retrospectively reviewed. The video of the procedures was inspected thoroughly to evaluate the range of dissection of arachnoid. Four areas were defined in order to facilitate the evaluation of the dissection range. The correlation between the arachnoid dissection and the surgical outcomes were analyzed. RESULTS: The arachnoid structures between the nineth cranial nerve and the seventh, eighth cranial nerves were dissected in all cases, other areas were entered based on different consideration. The rate of neurological complications of the extended dissection pattern group was higher than that of the standard pattern group (P < 0.05). The procedures in which the arachnoid structure above the vestibulocochlear nerve was dissected, led to more neurological complications (P < 0.05). CONCLUSION: Thorough dissection as an initial aim for all cases was not recommended in MVD for HFS, arachnoid dissection should be tailored to achieving safety and effectiveness during the procedure.

Extended endoscopic endonasal approach to the chiasmatic cistern: An anatomical study of the arachnoid.

This paper studied the arachnoid of the chiasmatic cistern (CC) and the methods for increasing the exposure of the CC from an endoscopic perspective. Eight anatomical specimens with vascular injection were used for endoscopic endonasal dissection. The anatomical characteristics of the CC were studied and documented, and anatomical measurements were collected. The CC is an unpaired five-walled arachnoid cistern located between the optic nerve, optic chiasm, and the diaphragma sellae. The average exposed area of the CC before the anterior intercavernous sinus (AICS) was transected was 66.67 ± 33.76 mm2 . After the AICS was transected and the pituitary gland (PG) was mobilized, the average exposed area of the CC was 95.90 ± 45.48 mm2 . The CC has five walls and a complex neurovascular structure. It is located in a critical anatomical position. The transection of the AICS and mobilization of the PG or the selective sacrifice of the descending branch of the superior hypophyseal artery can improve the operative field.

Description and clinical relevance of the variable conformation of canine spinal arachnoid diverticula.

The conformation of spinal arachnoid diverticula (SAD) and their clinical implications are poorly characterized in dogs. This retrospective cross-sectional study describes different SAD conformations in dogs and aims to identify if there is an association between SAD conformation and clinical features, localization, syringomyelia (SM) presence, concurrent vertebral condition, treatment option, and short as well as long-term outcome. Sixty-two dogs were included (12 cervical and 50 thoracolumbar SAD). All dogs with a cervical SAD had a cranial tethered conformation and were not included in the statistical analysis. Half of the dogs with a thoracolumbar SAD were cranial tethered, and the other half were caudal tethered. SM associated with SAD had a moderate prevalence in the cervical region (58.3%) and a high prevalence in the thoracolumbar region (82%). All dogs with the presence of SM and caudal tethered SAD had a cranial positioned SM, and all dogs with SM and a cranial tethered SAD had a caudal positioned SM. The SM absolute length and SM length/L2 ratio were significantly higher (P = .018, respectively) in the caudal tethered SAD compared with the cranial tethered SAD. The short-term outcome was statistically different (P = .045) between caudal and cranial tethered thoracolumbar SAD, but not the long-term outcome (P = .062). Multivariable logistic regression identified thoracolumbar caudal tethered SAD conformation had a better short-term outcome (P = 0.017, OR: 0.043, CI: 0.003-0.563), independently of SM length measurements. SAD conformation in dogs can influence SM formation. A possible link between short-term outcome and SAD conformation was found, but further research is warranted.

[Our approach to the treatment of vestibular schwannomas with arachnoid dissection of the facial nerve]. / Nash podkhod k lecheniyu vestibulyarnykh shvannom s primeneniem metodiki arakhnoidal'noi dissektsii litsevogo nerva.

Preserving the function of the facial nerve is extremely important in surgery for vestibular schwannomas. Two methods of arachnoid dissection are described for resection of vestibular schwannoma via retrosigmoid approach (from the brain stem and internal auditory canal). OBJECTIVE: To evaluate the results of arachnoid dissection of the facial nerve from internal auditory canal when resecting the vestibular schwannoma. MATERIAL AND METHODS: We analyzed 61 patients with vestibular schwannomas. Patients were divided into 2 groups depending on surgical technique. We estimated facial nerve function before and after surgery, preoperative dimension of vestibular schwannoma and extent of resection. The influence of various factors on extent of resection and postoperative facial nerve function was studied. RESULTS: Vestibular schwannoma resection from the brain stem was performed in 30 patients, arachnoid dissection - in 31 patients. There was no significant between-group difference. Gross total resection was performed in 78.7% of cases. Both techniques demonstrated similar results regarding extent of resection. Arachnoid dissection showed the advantage regarding facial nerve function immediately after surgery (p=0.012) and 6 months later (p<0.001). Normal facial nerve function in 6 months after arachnoid dissection was observed in 80.7% of patients. Preoperative dimension of tumor influenced facial nerve function in addition to technique of resection (p=0.001). CONCLUSION: We identified the factors influencing facial nerve function after resection of vestibular schwannoma. Surgical technique was the most significant factor. These data expand and popularize arachnoid dissection in surgery of vestibular schwannomas.

A causative role for remote dural puncture and resultant arachnoid bleb in new daily persistent headache: A case report.

A 24-year-old woman experienced a postdural puncture headache following a labor epidural, recovered following bedrest, and was then without headache for 12 years. She then experienced sudden onset of daily, holocephalic headache persisting for 6 years prior to presentation. Pain reduced with prolonged recumbency. MRI brain, MRI myelography, and later bilateral decubitus digital subtraction myelography showed no cerebrospinal fluid (CSF) leak or CSF venous fistula, and normal opening pressure. Review of an initial noncontrast MRI myelogram revealed a subcentimeter dural outpouching at L3-L4, suspicious for a posttraumatic arachnoid bleb. Targeted epidural fibrin patch at the bleb resulted in profound but temporary symptom relief, and the patient was offered surgical repair. Intraoperatively, an arachnoid bleb was discovered and repaired followed by remission of headache. We report that a distant dural puncture can play a causative role in the long delayed onset of new daily persistent headache.

Microanatomical study of arachnoid granulations and meningeal architecture around Meckel's cave.

Although the microanatomy of Meckel's cave (MC) has been well studied, there are still controversies regarding the meningeal architecture of the space. Moreover, there are only general mentions of the arachnoid granulations near MC in just a few sources. This study is aimed at determining the frequency, location, and anatomical variability of the main clusters of arachnoid granulations around MC. The dissection involved 26 isolated specimens of MC fixed in formalin (neutral buffered, 10%). This number included five freshly harvested specimens examined histologically. Additional paraffin block with MC horizontal section was taken from our neuroanatomical collection. Carefully selected anatomical and histological techniques were applied to assess the complex relationships between the arachnoid granulations and adjacent structures. Arachnoid granulations were found around MC in all specimens with different anatomical variations. The main clusters of arachnoid granulations were close to the trigeminal ganglion and its divisions. The dorsolateral wall of MC was a thick layer formed by interweaving bundles of collagen fibers arranged in various directions. The entire MC was surrounded by a dural sleeve (envelope). This sleeve separated MC from the lateral sellar compartment. At its anterior (rostral) end, it formed a cribriform area pierced by individual fascicles of the trigeminal nerve's primary divisions. The connective tissue forming the sleeve was not only continuous with the epineurium but also shifted to the perineuria surrounding individual nerve fascicles. The meningeal architecture around MC has a complex and multilayer arrangement with a collagenous sleeve closely related to the trigeminal ganglion. Arachnoid granulations are typically found around MC.

Petroclival Clinoidal Folds and Relationships with Arachnoidal Membranes of Anterior and Middle Incisural Spaces: Old Neuroanatomical Terms for a New Neurosurgical Speech in Cadaver Labs with Limited Resources Era. Part II: Free Edge of the Tentorium, Petroclinoid Folds, and Incisural Spaces.

BACKGROUND Anatomical dissections play an irreplaceable role in the training of new generations of effective neurosurgeons, especially when addressing skull base lesions is required.The Authors describe an inter-laboratory dissection study aimed at improving the knowledge of a complex region of the skull base. The anterior and middle incisural spaces are of remarkable anatomical and surgical interest due to complex relationships between bony, dural, arachnoidal, and neurovascular structures. The primary purposes of this study are to describe the anatomy of this region with particular emphasis on the relationships between the anterior margin of the free edge of the tentorium and the sphenoid and petrous bone; to identify surgical implications in many different types of neurosurgical procedures dealing with this challenging, complex anatomic area.METHODS Thirteen anatomical specimens, including five injected specimens, were dissected in this study. In the formalin-fixed specimens, vessels were injected with colored silicone.RESULTS The anatomical study was focused on the description of the relationships between bony dural, arachnoid, and neurovascular structures. Surgical implications are described accordingly.CONCLUSIONS Detailed anatomical knowledge of this region finds concrete applications in neurosurgical practice since the anterior and middle incisural spaces are often surgically exposed in neoplastic and vascular diseases. The high-definition pictures reported in this study could represent useful support to understand the anatomy of this complex region.Finally, our study could provide guidance to neurosurgical centers in which resources are limited that are either planning to establish their own cadaver dissection laboratory or failed to do so because of the supposed high-costs.

Petroclival Clinoidal Folds and Relationships with Arachnoidal Membranes of Medial Incisural Space: Old Neuroanatomical Terms for a New Neurosurgical Speech in Cadaver Labs with Limited Resources Era. Part III: Arachnoid Membranes, Cranial Nerves, and Surgical Implications.

BACKGROUND Anatomical dissections play an irreplaceable role in the training of new generations of effective neurosurgeons, especially when addressing skull base lesions is required.The Authors describe an inter-laboratory dissection study aimed at improving the knowledge of a complex region of the skull base. The anterior and middle incisural spaces are of remarkable anatomical and surgical interest due to complex relationships between bony, dural, arachnoidal, and neurovascular structures. The primary purposes of this study are to describe the anatomy of this region with particular emphasis on the relationships between the anterior margin of the free edge of the tentorium and the sphenoid and petrous bone; to identify surgical implications in many different types of neurosurgical procedures dealing with this challenging complex anatomic area.METHODS Thirteen anatomical specimens, including five injected specimens, were dissected in this study. In the formalin-fixed specimens, vessels were injected with colored silicone.RESULTS The anatomical study focused on the description of the relationships between bony dural, arachnoid, and neurovascular structures. Surgical implications are described accordingly.CONCLUSIONS Detailed anatomical knowledge of this region finds concrete applications in neurosurgical practice since the anterior and middle incisural spaces are often surgically exposed in neoplastic and vascular diseases. The high-definition pictures reported in this study could represent useful support to understand the anatomy of this complex region.Finally, our study could provide guidance to neurosurgical centers in which resources are limited that are either planning to establish their own cadaver dissection laboratory or failed to do so because of the supposed high-costs.

Petroclival Clinoidal Folds and Relationships with Arachnoidal Membranes and Neural Structures of Anterior and Middle Incisural Spaces: Old Neuroanatomical Terms for a New Neurosurgical Speech in Cadaver Labs with Limited Resources Era. Part I: Osteology and Structural Anatomy of Dura Mater.

Purpose The role of cadaver labs in preparing new generations of effective neurosurgeons is of paramount importance. The Authors describe a personal cadaver lab experience aimed at improving the knowledge of a difficult region of the central skull base. The anterior and middle incisural spaces are regions of remarkable anatomical, and surgical interest due to complex relationships between bony, dural, arachnoidal, and neurovascular structures. The primary purpose of this study is (1) to describe the anatomy of this region with particular emphasis on the relationships between the anterior margin of the free edge of the tentorium and the sphenoid and petrous bone; (2) to identify surgical implications in many different types of neurosurgical procedures dealing with this challenging complex anatomic area.Methods Eight fresh, non-formalin-fixed non-silicon-injected adult cadaver heads and five injected formalin-fixed adult cadaver heads were analyzed in this study.Results The anatomical study was focused on the description of the relationships between bony, dural, arachnoid, and neurovascular structures. Surgical implications are described accordingly.Conclusions Detailed anatomical knowledge of this region finds concrete applications in neurosurgical practice since the anterior and middle incisural spaces are often surgically exposed in neoplastic and vascular diseases.

Microsurgical anatomy and pathoanatomy of the outer arachnoid membranes in the cerebellopontine angle: cadaveric and intraoperative observations.

PURPOSE: The cerebellopontine angle (CPA) is a frequent region of skull base pathologies and therefore a target for neurosurgical operations. The outer arachnoid is the key structure to approach the here located lesions. The goal of our study was to describe the microsurgical anatomy of the outer arachnoid of the CPA and its pathoanatomy in case of space-occupying lesions. METHODS: Our examinations were performed on 35 fresh human cadaveric specimens. Macroscopic dissections and microsurgical and endoscopic examinations were performed. Retrospective analysis of the video documentations of 35 CPA operations was performed to describe the pathoanatomical behavior of the outer arachnoid. RESULTS: The outer arachnoid cover is loosely attached to the inner surface of the dura of the CPA. At the petrosal surface of the cerebellum the pia mater is strongly adhered to the outer arachnoid. At the level of the dural penetration of the cranial nerves, the outer arachnoid forms sheath-like structures around the nerves. In the midline, the outer arachnoid became detached from the pial surface and forms the base of the posterior fossa cisterns. In pathological cases, the outer arachnoid became displaced. The way of displacement depends on the origin of the lesion. The most characteristic patterns of changes of the outer arachnoid were described in case of meningiomas, vestibular schwannomas, and epidermoid cysts of the CPA. CONCLUSION: The knowledge of the anatomy of the outer arachnoid of the cerebellopontine region is essential to safely perform microsurgical approaches as well as of dissections during resection of pathological lesions.

Controlled arachnoid opening to aid endoscopic trans-sphenoidal extrarachnoidal dissection of pituitary macroadenoma.

OBJECTIVES: The arachnoid often bulges prematurely during surgical excision of large pituitary tumors obscuring the deeper regions and crevices preventing total excision. Pushing the arachnoid may not be helpful and may tear it inadvertently and extensively leading to complications. We have described controlled arachnoid opening in large pituitary macroadenomas during the final stages of excision to gain access to the hidden portions and compared our results to the conventional technique. PATIENTS AND METHODS: Patients with pituitary macroadenoma of Hardy's III and KNOSP II in whom arachnoid had bulged prematurely were considered for study. They were grouped temporally. In first group (n = 12), the arachnoid was pushed to retrieve the tumor and in the second group (n = 10) it was punctured to aid resection. The extent of resection was assessed on postoperative scans, and complications in both groups, were noted. RESULTS: In the first group where arachnoid was pushed to retrieve tumor, Gross Total Resection (GTR) could be achieved in 5 patients. Inadvertent large arachnoid tear occurred in 3 patients of which, 2 developed CSF Rhinorrhoea. No patient had neurovascular injury.In the second group, GTR could be achieved in all without any added complications. CONCLUSION: Deliberate needle puncture and controlled drainage of CSF from arachnoid that bulges prematurely while endoscopic Transsphenoidal surgery for large pituitary tumors is a safe and effective method to gain access to the hidden portions of tumor to achieve GTR.

Arachnoid prolapse in endoscopic transsphenoidal surgery of pituitary adenoma, technical note.

PURPOSE: An arachnoid prolapse after endoscopic transsphenoidal surgery for a pituitary adenoma is an uncommon, but important, phenomenon which should be managed. We have evaluated the efficacy of a new simple technique to correct the prolapsed arachnoid following endoscopic surgery of pituitary adenomas. METHODS: A total of 1352 patients with pituitary adenomas, 24-76 years old, who underwent full endoscopic transsphenoidal surgeries between February 2014 and February 2019 in Erfan and Loghman Hakim hospitals. 46 patients with arachnoid prolapse participated in this study and41 patients completed the study. Arachnoid prolapse was repaired by bipolar cauterization with either autologous fat grafts (36 patients) or without autologous fat grafts (5patients). RESULTS: Of 41 patients who completed the study, all except one, had large adenomas with significant suprasellar extension and enlarged diaphragma sellae. All patients had arachnoid prolapse at the end of the tumor removal stage and 13 patients had very minor intraoperative CSF leakage. Prolapsed arachnoid was repaired using a bipolar cautery with or without the autologous fat graft. During the postoperative follow-up period, none of the patient experienced early or delayed postoperative CSF leakage, meningitis, visual deterioration, delayed epistaxis, cranial nerve palsy, recurrence, or death. CONCLUSION: Bipolar cauterization is a safe, effective technique to repair a suprasellar arachnoid prolapse during reconstruction of the sellar floor following endoscopic transsphenoidal pituitary surgery.

Giant Arachnoid Granulations: A Systematic Literature Review.

Giant arachnoid granulations (GAGs) are minimally investigated. Here, we systematically review the available data in published reports to better understand their etiologies, nomenclature, and clinical significance. In the literature, 195 GAGs have been documented in 169 persons of varied ages (range, 0.33 to 91 years; mean, 43 ± 20 years; 54% female). Prior reports depict intrasinus (i.e., dural venous sinus, DVS) (84%), extrasinus (i.e., diploic or calvarial) (15%), and mixed (1%) GAG types that exhibit pedunculated, sessile, or vermiform morphologies. GAG size ranged from 0.4 to 6 cm in maximum dimension (mean, 1.9 ± 1.1 cm) and encompassed symptomatic or non-symptomatic enlarged arachnoid granulations (≥1 cm) as well as symptomatic subcentimeter arachnoid granulations. A significant difference was identified in mean GAG size between sex (females, 1.78 cm; males, 3.39 cm; p < 0.05). The signs and symptoms associated with GAGs varied and include headache (19%), sensory change(s) (11%), and intracranial hypertension (2%), among diverse and potentially serious sequelae. Notably, brain herniation was present within 38 GAGs (22%). Among treated individuals, subsets were managed medically (19 persons, 11%), surgically (15 persons, 9%), and/or by endovascular DVS stenting (7 persons, 4%). Histologic workup of 53 (27%) GAG cases depicted internal inflammation (3%), cystic change consistent with fluid accumulation (2%), venous thrombosis (1%), hemorrhage (1%), meningothelial hyperplasia (1%), lymphatic vascular proliferation (1%), and lymphatic vessel obliteration (1%). This review emphasizes heterogeneity in GAG subtypes, morphology, composite, location, symptomatology, and imaging presentations. Additional systematic investigations are needed to better elucidate the pathobiology, clinical effects, and optimal diagnostic and management strategies for enlarged and symptomatic arachnoid granulation subtypes, as different strategies and size thresholds are likely applicable for medical, interventional, and/or surgical treatment of these structures in distinct brain locations.

Giant Arachnoid Granulations: Diagnostic Workup and Characterization in Three Symptomatic Adults.

Giant arachnoid granulations (GAGs) are poorly investigated. Here, we document clinical findings associated with five new GAGs and illustrate the anatomical composition of these structures as well as diagnostic considerations in three symptomatic adults. The GAGs ranged from 1.1 to 3.6 cm (mean, 2.2 cm) in maximum dimension and manifested in middle-aged individuals who presented with long-standing brain mass and/or chronic headache. On imaging examinations, the tissues appeared as irregular parasagittal and/or perisinus structures that demonstrated heterogeneous internal elements. The GAGs abutted dura, extended through calvarial marrow spaces, and impinged on dural venous sinuses, causing their stenosis. The histologic workup of two GAG specimens resected from separate individuals revealed central collagen with pronounced internal vascular proliferation. One specimen additionally exhibited reactive changes within the lesion, including venous thrombosis, hemorrhage, and conspicuous inflammation. The salient immune component consisted of a foam cell-rich infiltrate that obstructed subcapsular and internal sinusoidal GAG spaces. Within this specimen, meningothelial hyperplasia was also appreciated. Notably, proliferated lymphatic vascular elements were additionally observed within the structure, extending into deep central collagen regions and engulfing many extravasated erythrocytes in the subcapsular space. In both surgically treated patients, symptoms resolved completely following resection. This report is the first to definitively depict reactive vascular and immunological changes within GAGs that were clinically associated with headache. The frequency of reactive changes within these meningeal structures is unclear in the literature, as GAGs are rarely sampled and investigated. Further systematic analyses are warranted to elucidate the causes and consequences of GAG genesis and their roles in physiology and disease states.

Differentiation of Fibroblasts Into Myofibroblasts in the Arachnoid Membrane of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a very specific disorder in terms of spontaneous development of extracranial-to-intracranial collateral circulation through the dura mater, but the underlying mechanisms are unclear. This study aimed to investigate the role of the arachnoid membrane in this unique angiogenesis in MMD. METHODS: A piece of arachnoid membrane and 1- to 2-mL cerebrospinal fluid were simultaneously harvested during surgery from 26 patients with MMD. The specimens were also collected during surgery as the controls from 6 patients with atherosclerotic carotid artery diseases. The arachnoid membrane was subjected to immunohistochemistry and the cerebrospinal fluid was used to measure the concentration of cytokines using ELISA. RESULTS: The number of cells positive for PDGFR (platelet-derived growth factor receptor) α was significantly higher in MMD than in the controls (5.4±3.1 versus 2.3±2.1 cells/field; P=0.02). The results were same in PDGFRß-positive cells (10.1±4.6 versus 4.8±2.8; P=0.01) and α-SMA (alpha-smooth muscle actin)-positive cells (8.8±3.1 versus 2.0±2.5; P<0.01). On multicolor immunofluorescence, 80.5±15.6% of cells positive for PDGFRα in MMD also expressed α-SMA, being significantly higher than 14.6±7.2% in the controls (P<0.01). The density of collagen in the arachnoid membrane was significantly higher in MMD than in the controls (60.3±15.0% versus 40.1±15.3%; P<0.01). In MMD, advanced disease stage was significantly associated with a larger number of α-SMA-positive cells in the arachnoid membrane (P=0.04). On ELISA, the cerebrospinal fluid concentrations of bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), and TGF (transforming growth factor)-ß1 were significantly higher in MMD than in the controls. CONCLUSIONS: Based on these findings, MMD may elevate the concentrations of angiogenic factors in the cerebrospinal fluid and then promote the proliferation of fibroblasts in the arachnoid membrane and their differentiation into myofibroblasts, which may, in turn, enhance the production of collagen essential for spontaneous collateral formation across the arachnoid membrane.

A human blood-arachnoid barrier atlas of transporters, receptors, enzymes, and tight junction and marker proteins: Comparison with dog and pig in absolute abundance.

The purpose of this study was to elucidate the absolute abundance of transporters, enzymes, receptors, and tight junction and marker proteins at human blood-arachnoid barrier (BAB) and compare with those of dogs and pigs. Protein expression levels in plasma membrane fractions of brain leptomeninges were determined by quantitative targeted absolute proteomics. To realistically compare the absolute abundance of target molecules at the BAB among humans, dogs, and pigs, the unit was converted from fmol/µg-protein to pmol/cm2 -leptomeninges. Of a total of 70 proteins, 52 were detected. OAT1, OAT3, GLUT1, 4F2hc, EAAT1, EAAT2, MCT8, SMVT, CTL2, GFAP, Claudin-5, Na+ /K+ -ATPase, COMT, GSTP1, and CES1 were abundantly expressed at the human BAB (>1 pmol/cm2 ). The protein expression levels were within a 3-fold difference for 16 out of 33 proteins between humans and dogs and for 13 out of 28 proteins between humans and pigs. Both human-dog and human-pig differences in protein expression levels were within 3-fold for OAT1, OAT3, 4F2hc, xCT, OCT2, MDR1, BCRP, PEPT2, SYP, and MCT1. In contrast, OCT3, MCT4, and OATP1A2 were detected in humans but not in dogs or pigs. MRP3 was detected in dogs and pigs but not in humans. The absolute level of GLUT1 in humans was nearly the same as that in dogs but was 6.14-fold greater in pigs. No significant differences in the levels were observed between male and female dogs for nearly all molecules. These results should be helpful in understanding the physiological roles of BAB and cerebrospinal fluid pharmacokinetics in humans and their differences from dogs and pigs.