Cribriform Plate Foramina Count in Patients With Acquired and Congenital Anosmia.

BACKGROUND: Cribriform foramina provide the openings for olfactory nerve fibers to cross from the nasal cavity to the olfactory bulb. Disruption of the olfactory nerve fibers is known to affect olfactory function, but little is known about the potential effects on the number of cribriform foramina in congenital anosmia. OBJECTIVE: This pilot study aimed to investigate whether there was a reduction in foramina in patients with acquired and congenital anosmia (including both Kallmann syndrome and isolated congenital anosmia) compared to controls with normal olfactory function. METHODS: Paranasal CT image stacks were analyzed from 20 patients with congenital anosmia (n = 6), acquired anosmia (n = 6), or normal olfactory function (n = 8). Cribriform foramina were counted by three observers from the slice revealing the crista galli and the ethmoidal slits. The two closest values for each subject were analyzed in comparison across the three groups using one-way analysis of variance. RESULTS: Patients with congenital, but not acquired, anosmia had significantly fewer cribriform foramina (x̄ ± SE = 10.17 ± 1.23) compared to healthy, normosmic controls (x̄ ± SE = 19.88 ± 2.01). There was no significant difference in foramina count between congenital and acquired anosmics (x̄ ± SE = 15.83 ± 3.47). CONCLUSION: In this pilot study, a reduced number of cribriform foramina was found in individuals with congenital anosmia. Examination of cribriform foramina could be helpful in counseling patients with olfactory loss. Further investigation in larger studies with additional cohorts is warranted.

Rostral cranial fossa and sinonasal neoplasms with cribriform plate involvement in 32 dogs and 17 cats.

The rostral cranial fossa (RCF) consists of the sphenoid and ethmoid bones, which accommodate the olfactory bulbs and nerves along the recesses of the cribriform plate. Neoplasms located in the vicinities of the RCF can compress and/or invade the cribriform plate. Here we describe the clinical and pathologic findings of neoplasms involving the cribriform plate in 32 dogs and 17 cats autopsied over a 13-y period. The average ages of affected dogs and cats were 9.2 y and 9.7 y, respectively. No sex or breed predisposition was evident in dogs, but 13 of 18 cats were spayed females and 14 of 18 were domestic shorthair cats. The main clinical signs were seizures (10 cases) and epistaxis (5 cases) in dogs, and red-to-brown nasal discharge (5 cases) and seizures (4 cases) in cats. In dogs, the 22 sinonasal neoplasms included adenocarcinoma (14 cases), transitional carcinoma (4), squamous cell carcinoma (2), lymphoma (1), and histiocytic sarcoma (1); the 10 intracranial neoplasms consisted of high-grade gliomas (3 cases), psammomatous meningiomas (2), histiocytic sarcomas (2), olfactory neuroblastomas (2), and a meningeal granular cell tumor (1). In cats, the 14 sinonasal neoplasms included lymphoma (8 cases), adenocarcinoma (4), adenosquamous carcinoma (1), and squamous cell carcinoma (1); the 3 intracranial neoplasms consisted of oligodendroglioma (1), transitional meningioma (1), and olfactory neuroblastoma (1).

Pneumocephalus: A Rare Complication of Sinusitis in a Pediatric Patient.

Pneumocephalus is uncommon, mostly arising as a result of surgery, trauma, infection, or neoplasm. Spontaneous occurrence is extremely rare and few case studies have been published. Pneumocephalus may also present as a complication of sinusitis and is a potential emergency. It is necessary to make a prompt diagnosis in order to direct treatment toward the underlying cause. Although usually asymptomatic, pneumocephalus can lead to tension pneumocephalus or septic meningitis as the result of infection from bacteria. We present a case of spontaneous, non-traumatic pneumocephalus in the setting of pansinusitis in a pediatric patient. Our aim is to briefly discuss the etiology and emergency department evaluation and management of patients with pneumocephalus.

Clearance of erythrocytes from the subarachnoid space through cribriform plate lymphatics in female mice.

BACKGROUND: Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways. METHODS: Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts. FINDINGS: RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis. INTERPRETATION: This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH. FUNDING: Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).

Endoscopic Management of a Case of Spontaneous Cerebrospinal Fluid Leaks in Anterior Skull Base.

Spontaneous cerebrospinal fluid (sCSF) leaks are rare, and their diagnosis and treatment often present significant challenges. This paper discusses and reports cases experienced at our facility. We retrospectively reviewed three of five cases of sCSF leaks experienced at the Department of Otolaryngology and Head and Neck Surgery, Kyushu University, from December 2020 to December 2022, excluding CSF otorrhea. All three patients were female; their mean age was 56 years (44-71 years). Two of the three patients were obese (first degree), and one was average weight (according to the criteria of the Japan Society for the Study of Obesity). Two patients had hypertension, and one had sleep apnea syndrome as an underlying disease. In all cases, leakage sites, which were all the cribriform plate, can be endoscopically identified, and all could be closed by an endoscopic intranasal approach. We reviewed cases of sCSF leaks. Although some patients had difficulty identifying the leakage site in a narrow and complex nasal cavity, an endoscopic survey was useful in identifying the leakage site. All cases were closed and there were no signs of recurrence. Identifying the site of leakage and selecting the appropriate closure method depending on the extent of the leakage is essential in treating such cases.

The Effects of Nasal Septal Deviation on Anterior Skull Base Parameters.

Introduction Functional endoscopic sinus surgery and endoscopic skull base surgery are frequently performed surgeries today. Nasal septal deviation is a common finding and can affect the surgical area. Therefore, it is important to examine the effect of this deviation on other anatomical structures. Objective The aim of the present study was to determine whether there is a relationship between the degree of nasal septal deviation and anterior skull base structures using computed tomography (CT). Methods A total of 312 patients (aged 18 to 65 years old) whose paranasal sinus CT images were available were included in the study. Measurements were obtained on images retrieved from Picture Archiving and Communication System (PACS) and Horos image archive systems in the bone window in the coronal and axial plane. Results The mean age of 312 patients was 33.00 years old (standard deviation [SD] 11.22 years). The presence of septal deviation was not associated with changes in olfactory fossa (OF) depths, Keros degrees, and the angle between the lateral lamella and the cribriform lamella. However, OF depths and Keros degrees on the deviated side of the septum were found to change at a significant level ( p < 0.05). No significant association was observed between the degree of septal deviation and cribriform lamella-lateral lamella angle. Conclusion The study showed significantly increased OF depth and Keros degree on the deviated side of the nasal septum. Performing CT scans before endoscopic sinus surgery and endoscopic skull base surgery is important to increase the chances of a successful surgical outcome and to reduce complications.

Unmasking the Masquerade: Lessons from a Case of Spontaneous Mid-Clival CSF Leak Mimicking an Ethmoidal Leak.

Spontaneous cerebrospinal fluid (CSF) leaks are an uncommon clinical entity, often challenging to diagnose accurately. We present a unique case of a patient with symptoms suggestive of an ethmoidal CSF leak, initially supported by radiological findings, but ultimately revealed to be a mid-clival CSF leak (from the posterior wall of the sphenoid sinus). This case underscores the complexities of diagnosing CSF leaks and highlights the importance of surgical exploration in cases where radiological evidence appears contradictory. The patient's Computed Tomography scan indicated a CSF leak in the cribriform plate, prompting a surgical approach to address this region. However, intraoperative findings surprisingly revealed no evidence of leak in the cribriform plate but instead a posterior wall of the sphenoid defect as the culprit. This report emphasizes the critical role of interdisciplinary collaboration, meticulous preoperative and intraoperative assessment, and adaptability in managing challenging cases of CSF leaks, ultimately leading to successful surgical repair and improved patient outcomes. It serves as a valuable reminder for clinicians to consider the possibility of a masquerading CSF leak when clinical and radiological findings do not align, thereby facilitating more precise diagnosis and targeted treatment.

[1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects.

BACKGROUND: Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid. METHODS: 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aß+) and 16 Aß- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC. RESULTS: LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aß+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress. CONCLUSION: The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

Distribution of insulin in primate brain following nose-to-brain transport.

Introduction: Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([18F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery. Methods: [18F]FB-insulin was prepared by reacting A1,B29-di(tert-butyloxycarbonyl)insulin with [18F]-N-succinimidyl-4-fluorobenzoate. Three methods of N2B delivery for [18F]FB-insulin were compared - delivery as aerosol via tubing (rhesus macaque, n = 2), as aerosol via preplaced catheter (rhesus macaque, n = 3), and as solution via preplaced catheter (cynomolgus macaque, n = 3). Following dosing, dynamic PET imaging (120 min) quantified delivery efficiency to the nasal cavity and whole brain. Area under the time-activity curve was calculated for 46 regions of the cynomolgus macaque brain to determine regional [18F]FB-insulin levels. Results: Liquid instillation of [18F]FB-insulin by catheter outperformed aerosol methods for delivery to the subject (39.89% injected dose vs 10.03% for aerosol via tubing, 0.17% for aerosol by catheter) and subsequently to brain (0.34% injected dose vs 0.00020% for aerosol via tubing, 0.05% for aerosol by catheter). [18F]FB-insulin was rapidly transferred across the cribriform plate to limbic and frontotemporal areas responsible for emotional and memory processing. [18F]FB-insulin half-life was longer in olfactory nerve projection sites with high insulin receptor density compared to the whole brain. Discussion: The catheter-based liquid delivery approach combined with PET imaging successfully tracked the fate of N2B [18F]FB-insulin and is thought to be broadly applicable for assessments of other therapeutic agents. This method can be rapidly applied in humans to advance clinical evaluation of N2B insulin as an AD therapeutic. Highlights for: [18F]FB-insulin passage across the cribriform plate was detected by PET.Intranasal [18F]FB-insulin reached the brain within 13 min.[18F]FB-insulin activity was highest in emotional and memory processing regions.Aerosol delivery was less efficient than liquid instillation by preplaced catheter.Insulin delivery to the cribriform plate was critical for arrival in the brain.

Photon Counting Computed Tomography for Accurate Cribriform Plate (Lamina Cribrosa) Imaging in Adult Patients.

Detailed visualization of the cribriform plate is challenging due to its intricate structure. This study investigates how computed tomography (CT) with a novel photon counting (PC) detector enhance cribriform plate visualization compared to traditionally used energy-integrated detectors in patients. A total of 40 patients were included in a retrospective analysis, with half of them undergoing PC CT (Naeotom Alpha Siemens Healthineers, Forchheim, Germany) and the other half undergoing CT scans using an energy-integrated detector (Somatom Sensation 64, Siemens, Forchheim, Germany) in which the cribriform plate was visualized with a temporal bone protocol. Both groups of scans were evaluated for signal-to-noise ratio, radiation dose, the imaging quality of the whole scan overall, and, separately, the cribriform plate and the clarity of volume rendering reconstructions. Two independent observers conducted a qualitative analysis using a Likert scale. The results consistently demonstrated excellent imaging of the cribriform plate with the PC CT scanner, surpassing traditional technology. The visualization provided by PC CT allowed for precise anatomical assessment of the cribriform plate on multiplanar reconstructions and volume rendering imaging with reduced radiation dose (by approximately 50% per slice) and higher signal-to-noise ratio (by approximately 75%). In conclusion, photon-counting technology provides the possibility of better imaging of the cribriform plate in adult patients. This enhanced imaging could be utilized in skull base-associated pathologies, such as cerebrospinal fluid leaks, to visualize them more reliably for precise treatment.

"Sealing the Gap" : CSF Leakage Demystified-A Comprehensive Analysis of our Experience in CSF Rhinorrhea Management.

CSF (Cerebro Spinal Fluid) rhinorrhoea occurs when the fluid leaks from subarachnoid space into the nasal cavity. The study aims to find out the prevalence and demographic distribution of CSF leak and to describe the site of the CSF leak along with the management. We did a prospective study on 180 patients admitted with head injury in neurosurgery department, along with the patients who came to ENT department with unilateral nasal discharge during the time period from March 2017 to March 2021. A total of 36 cases of CSF leak were obtained during the time period. The etiology in 18 cases was head injury & the other 18 cases were either due to infectious or nontraumatic causes. In our study, 26(72.22%) patients were aged less than 50 years. Incidence was more among males compared to females. The most common etiology was head injury - 18(50%) patients followed by the spontaneous leak- 16 (44.44%) patients with the most common site as the cribriform plate. Endoscopic repair using a hadad flap was done in most of the patients. Trauma due to head injury is the most common etiology in CSF rhinorrhea with more number of patients aged less than 50 years. Most of the leaks can be repaired successfully with the use of endoscope with excellent illumination & localizing the exact site of the leak.

The nasal lymphatic route of CSF outflow: implications for neurodegenerative disease diagnosis and monitoring.

Cerebrospinal fluid (CSF) plays a crucial role in the brain's lymphatics as it traverses the central nervous system (CNS). Its primary function is to facilitate the outward transport of waste. Among the various CSF outflow pathways, the route through the cribriform plate along the olfactory nerves stands out as the most predominant. This review describes the outflow pathway of CSF into the nasal lymphatics. Additionally, we examine existing studies to describe mutual influences observed between the brain and extracranial regions due to this outflow pathway. Notably, pathological conditions in the CNS often influence CSF outflow, leading to observable changes in extracranial regions. The established connection between the brain and the nose is significant, and our review underscores its potential relevance in monitoring CNS ailments, including neurodegenerative diseases. Considering that aging - the most significant risk factor for the onset of neurodegeneration - is also a principal factor in CSF turnover alterations, we suggest a novel approach to studying neurodegenerative diseases in therapeutic terms.

Assessing Olfactory Fossa Depth and Its Relationship with the Variations in Adjacent Anatomical Structures by Using Cone Beam Computed Tomography (CBCT).

This study aimed to investigate the olfactory fossa anatomy (Keros types) and its relationship with changes in adjacent anatomical structures using cone-beam computed tomography (CBCT). In this descriptive-analytical study, the paranasal CBCT of 120 healthy adults over 18 years of age were evaluated. The olfactory fossa depth on both sides and the degree of asymmetry on both sides were reported. Correlation of olfactory fossa depth with the size of adjacent anatomical structures such as middle concha length, maximum orbital height and distance from ethmoid roof to nasal floor and ethmoid roof height to the palate in the anterior and posterior, length, and lateral angle of the lamella and cribriform plate distance. The lower concha junction was examined. The most common olfactory fossae on both sides of the Keros classification were Type II, Type I, and Type III, respectively. The mean dimensions of adjacent anatomical structures on the right and left did not differ significantly. The length and lateral angle of the lamella and the height of the ethmoid roof to the floor of the nose, and the height of the ethmoid roof to the palate in the back, on the right, and left in Type III were greater. The lateral angle of the left lamella was greater in Type III. The relationship between olfactory fossa depth and changes in anatomical structures were not significantly correlated with increasing olfactory fossa depth. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03538-2.

A retrospective study of sinonasal tumors in 182 dogs treated with stereotactic radiotherapy (3 × 10 Gy) (2010-2015).

BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging treatment for sinonasal tumors in dogs. Reported results regarding tumor control and incidence of acute and late radiation morbidities are inconsistent. OBJECTIVES: To determine treatment efficacy and prognostic indicators of SRT in dogs with sinonasal tumors and to quantify acute and late radiation morbidities. ANIMALS: One hundred and eighty-two client-owned dogs with sinonasal tumors diagnosed cytologically, histologically, or radiographically that underwent SRT. METHODS: Single-arm retrospective study by reviewing medical records of dogs treated with SRT (10 Gy × 3) between 2010 and 2015. Kaplan-Meier analysis was used to determine overall survival (OST; from the first day of SRT to death by any cause) and disease-specific survival times (DSST; OST but censoring tumor/treatment-unrelated death). Tumors were staged using modified Adams criteria. RESULTS: Median OST and DSST of dogs treated with 1 course of SRT was 441 (95% CI: 389-493 days) and 482 (428-536 days) days, respectively with skin/oral cavity acute morbidities observed in 3% of dogs. DSST in dogs with stage 4 disease showed no statistical difference compared to other stages (P = .64). Oro-nasal (n = 2) or naso-cutaneous (n = 11) fistula development occurred in 7.1% of dogs with median time of 425 days (range: 83-1733 days). Possible chronic rhinitis after SRT was recorded in 54 of 88 dogs (61%) where information was available. CONCLUSIONS AND CLINICAL IMPORTANCE: Results are comparable to other reports of treatment of SRT. Acute morbidities were minimal. Modified Adams stage scheme appeared to be inappropriate for prognostication for dogs with sinonasal tumors treated with SRT.

Immune cells as messengers from the CNS to the periphery: the role of the meningeal lymphatic system in immune cell migration from the CNS.

In recent decades there has been a large focus on understanding the mechanisms of peripheral immune cell infiltration into the central nervous system (CNS) in neuroinflammatory diseases. This intense research led to several immunomodulatory therapies to attempt to regulate immune cell infiltration at the blood brain barrier (BBB), the choroid plexus (ChP) epithelium, and the glial barrier. The fate of these infiltrating immune cells depends on both the neuroinflammatory environment and their type-specific interactions with innate cells of the CNS. Although the fate of the majority of tissue infiltrating immune cells is death, a percentage of these cells could become tissue resident immune cells. Additionally, key populations of immune cells can possess the ability to "drain" out of the CNS and act as messengers reporting signals from the CNS toward peripheral lymphatics. Recent data supports that the meningeal lymphatic system is involved not just in fluid homeostatic functions in the CNS but also in facilitating immune cell migration, most notably dendritic cell migration from the CNS to the meningeal borders and to the draining cervical lymph nodes. Similar to the peripheral sites, draining immune cells from the CNS during neuroinflammation have the potential to coordinate immunity in the lymph nodes and thus influence disease. Here in this review, we will evaluate evidence of immune cell drainage from the brain via the meningeal lymphatics and establish the importance of this in animal models and humans. We will discuss how targeting immune cells at sites like the meningeal lymphatics could provide a new mechanism to better provide treatment for a variety of neurological conditions.

Glioma with cribriform plate involvement in 6 dogs.

Distinct patterns of local infiltration are a common feature of canine oligodendroglioma and astrocytoma, and typically involve the surrounding neuroparenchyma, ventricles, or leptomeninges. Infiltration of adjacent extraneural sites is rare and has not been well documented in veterinary medicine. Here we describe 6 canine gliomas with cribriform plate involvement (compression or infiltration) and caudal nasal invasion confirmed by neuroimaging, autopsy, and/or histology. All affected dogs were adults (9-12-y-old), and 3 were brachycephalic. Clinical signs were associated with the brain tumor, with no respiratory signs reported. Magnetic resonance imaging in 2 patients revealed a rostral intraparenchymal telencephalic mass with extension into the cribriform plate. All dogs were euthanized. Gross changes consisted of poorly demarcated, white or pale-yellow, soft, and, in oligodendrogliomas, gelatinous, intraparenchymal masses that expanded the rostral portions of the telencephalon and adhered firmly to the ethmoid bone and cribriform plate. Gliomas were classified as high-grade oligodendrogliomas (4 cases) and high-grade astrocytomas (2 cases) based on histology and immunohistochemistry for OLIG2 and GFAP. In all cases, there was evidence of cribriform plate invasion and, in one case, additional invasion of the caudal nasal cavity.

A comparative analysis of the CP and CG using 2D and 3D visualisation approaches.

Investigations on the structural variations in the cribriform plate (CP), olfactory foramina and the Crista Galli showcase the benefits of using 3D imaging on smaller structures. These techniques reveal accurate details about bone morphology and density. Comparing different techniques, this project aims to examine the correlation between the CP, olfactory foramina, and Crista Galli. Computed tomography was used to translate and apply the findings acquired from the samples in radiographic studies on CPs for potential clinical significance. The findings show that the surface area measurements were significantly larger when using 3D imaging techniques in comparison with the 2D counterpart. Using 2D imaging, the maximum surface area of the CPs was 239.54 mm2, however, paired 3D samples showed the maximum surface area was 355.51 mm2. The findings show that Crista Galli's dimensions varied greatly, with length ranging from 15 to 26 mm, height ranging from 5 to 18 mm, and width ranging from 2 to 7 mm. The 3D imaging allowed for surface area measurements on the Crista Galli, and the surface area ranged from 130 to 390 mm2. When 3D imaging was used, significant correlations were found between the surface area of the CP and the length of the Crista Galli (p = 0.001). The findings show that measurements on the Crista Galli using 2D and 3D reconstructed radiographic imaging reflect similar ranges of dimensions to 3D imaging measurements. The findings also suggest that the Crista Galli may increase in length with the CP to support the latter and olfactory bulb during trauma which may be used by clinicians alongside 2D CT scans for optimal diagnosis.

Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice.

BACKGROUND: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. METHODS: Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. RESULTS: At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. CONCLUSIONS: Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.

Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves.

BACKGROUND: Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice. METHODS: PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region. FINDINGS: We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse. INTERPRETATION: Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice. FUNDING: This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.

Study of frontal and ethmoid sinus of sinonasal complex along with olfactory fossa: anatomical considerations for endoscopic sinus surgery.

The Functional endoscopic sinus surgery through transnasal approach is a common modality of treatment for disorders of the nasal cavity, paranasal air sinuses as well as cranial cavity. The olfactory fossa (OF) is located along the superior aspect of cribriform plate which varies in shape and depth. This variable measurement of the depth of OF is mostly responsible for greater risk of intracranial infiltration during endoscopic procedures in and around the nasal cavity. The morphology of frontal and ethmoid sinus (ES) vary from simple to complex. This cadaveric study is planned to improve the ability of the otolaryngologist, radiologist to understand the possible morphological variations and plan steps of less invasive "precision surgery" to have a safe and complication free procedures. A total of 37 human head regions were included in the study. For classification of OF, Modified Kero's classification was used. The size, shape and cells of frontal and ES were noted. We found, type II (60.8%) OF was more common followed by type I (29.7%) than type III (9.5%). The shape of frontal sinus was comma shaped (55.4%) followed by oval (18.9%) than irregular (16.2%). Most common two cells type of ES was seen in 50.0% of both anterior and posterior ES. Out of 74 ES, 8.1% of Onodi cells and 14.9% of agger nasi cells were seen.