Complete meningioma resolution following endovascular embolization of chronic subdural hematoma.

We present the first reported case that describes the complete resolution of a meningioma following endovascular embolization. A man in his 70s who presented with gait abnormalities and recurrent falls was diagnosed with normal pressure hydrocephalus (NPH) and found to have a small incidental meningioma. Due to ventriculoperitoneal (VP) shunt placement for cerebrospinal fluid diversion, the patient developed a bilateral subdural hematoma (SDH) requiring evacuation and drain placement. The patient also underwent bilateral middle meningeal artery (MMA) embolization. During the embolization, the known right frontal meningioma was embolized as it was supplied by the right MMA. The patient remained neurologically stable after this procedure. His follow-up magnetic resonance imaging (MRI) 1 year and 2 years after the procedure demonstrated complete resolution of the meningioma.

Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review.

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

Biomimetic and Nonbiomimetic Approaches in Dura Substitutes: The Influence of Mechanical Properties.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid (CSF) leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.

Regulatory T cell-derived enkephalin imparts pregnancy-induced analgesia.

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. mTregs are both necessary and sufficient for suppressing mechanical pain sensitivity in female but not male mice. Notably, the mTreg modulation of pain thresholds depends on sex-hormones and expansion of enkephalinergic mTregs during gestation imparts a remarkable pregnancy-induced analgesia in a pre-existing, chronic, unremitting neuropathic pain model. These results uncover a fundamental sex-specific, pregnancy-pronounced, and immunologically-derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology and maternal health.

Successful Implementation of Combined Treatment Methods for a Rare Recurrence of Waldenstrom Macroglobulinemia With Extramedullary Lesions.

A 67-year-old woman was admitted to the Hematology Department in 2014 with complaints of weakness and a low-grade fever. After conducting various tests, it was confirmed that she had Waldenstrom macroglobulinemia. She underwent several rounds of chemotherapy and maintenance therapy with rituximab, which resulted in a good clinical response. However, in 2019, an abnormal growth in the soft tissues of patient's frontal region was discovered, which was diagnosed as lymphoplasmacytic lymphoma. This later progressed to an intracranial lesion. The patient underwent radiation therapy for both the extramedullary and intracranial growths, which had a positive effect. A year later, she developed a lesion in her lymph nodes and soft tissues of her right leg, which was confirmed to be a recurrence of Waldenstrom disease. She underwent further treatment and is currently in complete remission. This case highlights the rare occurrence of relapse in Waldenstrom disease and the challenges in diagnosing extramedullary lesions. It also demonstrates the success of modern treatment approaches using a combination of therapies.

The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.

Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Revascularisation patterns and characteristics after erythropoietin pretreatment and multiple burr holes in patients who had acute stroke with perfusion impairment.

BACKGROUND: Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals. METHODS: We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups. RESULTS: Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform. CONCLUSIONS: Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.

Single-cell analysis of mesenchymal cells in permeable neural vasculature reveals novel diverse subpopulations of fibroblasts.

BACKGROUND: In the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments. METHODS: The Hic1CreERT2 Rosa26LSL-TdTomato mouse model was used in conjunction with a PdgfraH2B-EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra- pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses. RESULTS: We found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34. CONCLUSIONS: Novel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules.

From neural tube to spinal cord: The dynamic journey of the dorsal neuroepithelium.

In a developing embryo, formation of tissues and organs is remarkably precise in both time and space. Through cell-cell interactions, neighboring progenitors coordinate their activities, sequentially generating distinct types of cells. At present, we only have limited knowledge, rather than a systematic understanding, of the underlying logic and mechanisms responsible for cell fate transitions. The formation of the dorsal aspect of the spinal cord is an outstanding model to tackle these dynamics, as it first generates the peripheral nervous system and is later responsible for transmitting sensory information from the periphery to the brain and for coordinating local reflexes. This is reflected first by the ontogeny of neural crest cells, progenitors of the peripheral nervous system, followed by formation of the definitive roof plate of the central nervous system and specification of adjacent interneurons, then a transformation of roof plate into dorsal radial glia and ependyma lining the forming central canal. How do these peripheral and central neural branches segregate from common progenitors? How are dorsal radial glia established concomitant with transformation of the neural tube lumen into a central canal? How do the dorsal radial glia influence neighboring cells? This is only a partial list of questions whose clarification requires the implementation of experimental paradigms in which precise control of timing is crucial. Here, we outline some available answers and still open issues, while highlighting the contributions of avian models and their potential to address mechanisms of neural patterning and function.

Subarachnoid Hemorrhage Depletes Calcitonin Gene-Related Peptide Levels of Trigeminal Neurons in Rat Dura Mater.

Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.

Population-based estimates suggest middle meningeal artery embolization for subdural hematomas could significantly expand the scope of neurovascular therapies.

BACKGROUND: This study quantifies the impact of middle meningeal artery embolization (MMAE) for subdural hematomas (SDHs) by estimating a target population. METHODS: A population-based study at a tertiary hospital, the main SDH facility for a four-county population, used primary ICD-10 codes over 3 years to collate SDH hospitalizations. Clinical and imaging data confirmed traumatic versus non-traumatic and acute versus non-acute (mixed or chronic) SDH. The MMAE-eligible population included patients with non-traumatic, non-acute SDH aged ≥18 years plus patients with 'traumatic' but non-acute SDH aged ≥60 years presenting with a fall. This was contrasted with the rate of large vessel strokes in the same population. RESULTS: 1279 hospitalizations with a primary ICD-10 SDH diagnosis were identified, with 389 from the study population. Excluding repeat admissions, 350 patients were analyzed, 233 (67%) traumatic, and 117 (33%) non-traumatic SDH. Regarding etiology, 'fall ≥60 years' was the most common category in the entire cohort (n=156; 45% (95% CI 39% to 50%)). The SDH rate was 52/100 000 persons/year (95% CI 47 to 57). The rate of all non-traumatic, non-acute SDH in patients aged ≥18 years was 17/100 000 persons/year (95% CI 15 to 20), combining with 'traumatic' but non-acute fall-related SDH in patients aged ≥60 years yielded 41/100 000 persons/year (95% CI 36 to 47). This demographic may represent an MMAE-eligible population, exceeding large vessel stroke rates (31/100 000 persons/year) in the same population, estimating 139 387 potential MMAE cases/year (95% CI 121 517 to 158 168) in the USA. CONCLUSION: MMAE could transform non-acute SDH management, especially in the elderly, potentially surpassing the impact of large vessel stroke. Clinical trials are essential for validation of its efficacy and safety compared with standard management.

Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission.

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.g., migraine), the role of oxytocinergic transmission in modulating nociception at this level has been poorly explored. Hence, in vivo electrophysiological recordings of TCC wide dynamic range (WDR) cells sensitive to stimulation of the periorbital or meningeal region were performed in male Wistar rats. PVN electrical stimulation diminished the neuronal firing evoked by periorbital or meningeal electrical stimulation; this inhibition was reversed by OTR antagonists administered locally. Accordingly, neuronal projections (using Fluoro-Ruby) from the PVN to the WDR cells filled with Neurobiotin were observed. Moreover, colocalization between OTR and calcitonin gene-related peptide (CGRP) or OTR and GABA was found near Neurobiotin-filled WDR cells. Retrograde neuronal tracers deposited at the meningeal (True-Blue, TB) and infraorbital nerves (Fluoro-Gold, FG) showed that at the trigeminal ganglion (TG), some cells were immunopositive to both fluorophores, suggesting that some TG cells send projections via the V1 and V2 trigeminal branches. Together, these data may imply that endogenous oxytocinergic transmission inhibits the nociceptive activity of second-order neurons via OTR activation in CGRPergic (primary afferent fibers) and GABAergic cells.

Nomogram to Predict the Outcome of Ventriculoperitoneal Shunt Among Patients with Non-HIV Cryptococcal Meningitis.

BACKGROUND: The ventriculoperitoneal (VP) shunt is widely acknowledged as a treatment option for managing intracranial hypertension resulting from non-human immunodeficiency virus (HIV) cryptococcal meningitis (CM). Nonetheless, there is currently no consensus on the appropriate surgical indications for this procedure. Therefore, it is crucial to conduct a preoperative evaluation of patient characteristics and predict the outcome of the VP shunt to guide clinical treatment effectively. METHODS: A retrospective analysis was conducted on data from 85 patients with non-HIV CM who underwent VP shunt surgery at our hospital. The analysis involved studying demographic data, preoperative clinical manifestations, cerebrospinal fluid (CSF) characteristics, and surgical outcomes and comparisons between before and after surgery. A nomogram was developed and evaluated. RESULTS: The therapy outcomes of 71 patients improved, whereas 14 cases had worse outcomes. Age, preoperative cryptococcus count, and preoperative CSF protein levels were found to influence the surgical outcome. The nomogram exhibited exceptional predictive performance (area under the curve = 0.896, 95% confidence interval: 0.8292-0.9635). Internal validation confirmed the nomogram's excellent predictive capabilities. Moreover, decision curve analysis demonstrated the nomogram's practical clinical utility. CONCLUSIONS: The surgical outcome of VP shunt procedures patients with non-HIV CM was associated with age, preoperative cryptococcal count, and preoperative CSF protein levels. We developed a nomogram that can be used to predict surgical outcomes in patients with non-HIV CM.

Middle meningeal artery arising from the petrous internal carotid artery: Outcome of unusual stapedial artery regression.

Background: The internal and external carotid arterial systems are generally separate regarding branching patterns. However, these two systems do form collateral circulations with their terminal parts. On rare occasions, branches that belong to one arterial system may arise from the other. Case Description: We present a rare variant of a middle meningeal artery, generally derived from the external carotid artery, arising from the internal carotid artery and entering the floor of the middle cranial fossa by traveling through a small unnamed foramen. This anatomy and embryology and other variants of the middle meningeal and petrous carotid systems are discussed. Conclusion: Embryologically, this variant anatomy signifies an atypical regression of the distal stapedial artery and its connection to the external carotid artery. Surgeons who operate on the skull base, vascular interventionalists, and radiologists should be aware of this potential anatomical variation of the skull base.

Absence of meningeal mast cells in the Mitf mutant mouse.

Mast cells (MCs) are located in the meninges of the central nervous system (CNS), where they play key roles in the immune response. MC-deficient mice are advantageous in delineating the role of MCs in the immune response in vivo. In this study, we illustrate that a mutation in microphthalmia-associated transcription factor (Mitf) affects meningeal MC number in a dosage-dependent manner. C57BL/6J Mitf null mice lack meningeal MCs completely, whereas heterozygous mice have on average 25% fewer MCs. Mitf heterozygous mice might be a valuable tool to study the role of MCs in the meninges.

Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model.

Migraine headache is hypothesized to involve the activation and sensitization of trigeminal sensory afferents that innervate the cranial meninges. To better understand migraine pathophysiology and improve clinical translation, we used two-photon calcium imaging via a closed cranial window in awake mice to investigate changes in the responses of meningeal afferent fibers using a preclinical model of migraine involving cortical spreading depolarization (CSD). A single CSD episode caused a seconds-long wave of calcium activation that propagated across afferents and along the length of individual afferents. Surprisingly, unlike previous studies in anesthetized animals with exposed meninges, only a very small afferent population was persistently activated in our awake mouse preparation, questioning the relevance of this neuronal response to the onset of migraine pain. In contrast, we identified a larger subset of meningeal afferents that developed augmented responses to acute three-dimensional meningeal deformations that occur in response to locomotion bouts. We observed increased responsiveness in a subset of afferents that were already somewhat sensitive to meningeal deformation before CSD. Furthermore, another subset of previously insensitive afferents also became sensitive to meningeal deformation following CSD. Our data provides new insights into the mechanisms underlying migraine, including the emergence of enhanced meningeal afferent responses to movement-related meningeal deformations as a potential neural substrate underlying the worsening of migraine headache during physical activity.

Primary leptomeningeal CD30 positive diffuse large B cell lymphoma disguise as meningioma in a young adult: a case report.

BACKGROUND: Primary leptomeningeal lymphoma (PLML) without brain parenchymal involvement or systemic disease is very rare, comprising of approximately 7% of all primary central nervous system lymphomas (PCNSL). PLML is a diagnosis of exclusion which should be confirmed on biopsy after ruling out metastasis from systemic lymphomas and dissemination from PCNSL. CASE DESCRIPTION: A 21-year-old patient presented with the chief complaints of headache, diplopia, decreased vision for five months, and a swelling on the left side of the forehead for four months. On radiology, a large, lobulated, extra-axial mass lesion along the left frontal region with its base towards dura noted. No parenchymal or subependymal CNS lesions were found on CT/MRI. Histopathology was reported as primary leptomeningeal CD30 positive diffuse large B cell lymphoma. CONCLUSIONS: PLML is a very rare meningeal tumor that requires a very high index of suspicion and is always a diagnosis of exclusion.

Role of meningeal immunity in brain function and protection against pathogens.

The brain and spinal cord collectively referred to as the Central Nervous System (CNS) are protected by the blood-brain barrier that limits molecular, microbial and immunological trafficking. However, in the last decade, many studies have emphasized the protective role of 'border regions' at the surface of the CNS which are highly immunologically active, in contrast with the CNS parenchyma. In the steady-state, lymphoid and myeloid cells residing in the cranial meninges can affect brain function and behavior. Upon infection, they provide a first layer of protection against microbial neuroinvasion. The maturation of border sites over time enables more effective brain protection in adults as compared to neonates. Here, we provide a comprehensive update on the meningeal immune system and its role in physiological brain function and protection against infectious agents.