Cellular senescence, DNA damage, and neuroinflammation in the aging brain.

Aging may lead to low-level chronic inflammation that increases the susceptibility to age-related conditions, including memory impairment and progressive loss of brain volume. As brain health is essential to promoting healthspan and lifespan, it is vital to understand age-related changes in the immune system and central nervous system (CNS) that drive normal brain aging. However, the relative importance, mechanistic interrelationships, and hierarchical order of such changes and their impact on normal brain aging remain to be clarified. Here, we synthesize accumulating evidence that age-related DNA damage and cellular senescence in the immune system and CNS contribute to the escalation of neuroinflammation and cognitive decline during normal brain aging. Targeting cellular senescence and immune modulation may provide a logical rationale for developing new treatment options to restore immune homeostasis and counteract age-related brain dysfunction and diseases.

The Posterior Auricularis Muscle as Superficial Landmark for the Sigmoid Sinus and Transverse-Sigmoid Sinus Junction: An Anatomical Study.

OBJECTIVE: Neuronavigation systems coupled with previously reported external anatomical landmarks assist neurosurgeons during intracranial procedures. We aimed to verify whether the posterior auricularis muscle (PAM) could be used as an external landmark for identifying the sigmoid sinus (SS) and the transverse-sigmoid sinus junction (TSSJ) during posterior cranial fossa surgery. METHODS: The PAM was dissected in 10 adult cadaveric heads and after drilling the underlying bone, the relationships with the underlying SS and TSSJ were noted. The width and length of the PAM, and the distance between the muscle and reference points (asterion, mastoid tip, and midline), were measured. RESULTS: The PAM was identified in 18 sides (9 left, 9 right). The first 20 mm of the muscle length (mean 28.28 mm) consistently overlay the mastoid process anteriorly and the proximal half of the SS slightly posteriorly on all sides. The superior border was a mean of 2.22 mm inferior to the TSSJ and, especially when the muscle length exceeded 20 mm, this border extended closer to the transverse sinus; it was usually found at a mean of 3.11 mm (range 0.0-13.80 mm) inferior to the distal third of the transverse sinus. CONCLUSIONS: Superficial landmarks give surgeons improved surgical access, avoiding overexposure of deep neurovascular structures and reducing brain retraction. On the basis of our cadaveric study, the PAM is a reliable and accurate direct landmark for identifying the SS and TSSJ. The PAM could potentially be used for guiding the retrosigmoid approach.

Tracing the path of disruption: 13C isotope applications in traumatic brain injury-induced metabolic dysfunction.

Cerebral metabolic dysfunction is a critical pathological hallmark observed in the aftermath of traumatic brain injury (TBI), as extensively documented in clinical investigations and experimental models. An in-depth understanding of the bioenergetic disturbances that occur following TBI promises to reveal novel therapeutic targets, paving the way for the timely development of interventions to improve patient outcomes. The 13C isotope tracing technique represents a robust methodological advance, harnessing biochemical quantification to delineate the metabolic trajectories of isotopically labeled substrates. This nuanced approach enables real-time mapping of metabolic fluxes, providing a window into the cellular energetic state and elucidating the perturbations in key metabolic circuits. By applying this sophisticated tool, researchers can dissect the complexities of bioenergetic networks within the central nervous system, offering insights into the metabolic derangements specific to TBI pathology. Embraced by both animal studies and clinical research, 13C isotope tracing has bolstered our understanding of TBI-induced metabolic dysregulation. This review synthesizes current applications of isotope tracing and its transformative potential in evaluating and addressing the metabolic sequelae of TBI.

The Top 100 Most Cited Journal Articles on Hydrocephalus.

Hydrocephalus represents a significant burden of disease, with more than 383,000 new cases annually worldwide. When the magnitude of this condition is considered, a centralized archive of pertinent literature is of great clinical value. From a neurosurgical standpoint, hydrocephalus is one of the most frequently treated conditions in the field. The focus of this study was to identify the top 100 journal articles specific to hydrocephalus using bibliometric analysis. Using the Journal of Citation Report database, 10 journals were identified. The Web of Science Core Collection was then searched using each journal name and the search term "hydrocephalus." The results were ordered by "Times Cited" and searched by the number of citations. The database contained journal articles from 1976 to 2021, and the following variables were collected for analysis: journal, article type, year of publication, and the number of citations. Journal articles were excluded if they had no relation to hydrocephalus, mostly involved basic science research, or included animal studies. Ten journals were identified using the above criteria, and a catalog of the 100 most cited publications in the hydrocephalus literature was created. Articles were arranged from highest to lowest citation number, with further classification by journal, article type, and publication year. Of the 100 articles referenced, 38 were review articles, 24 were original articles, 15 were comparative studies, 11 were clinical trials, six were multi-center studies, three were cross-sectional, and three were case reports with reviews. Articles were also sorted by study type and further stratified by etiology. If the etiology was not specified, studies were instead subcategorized by treatment type. Etiologies such as aqueductal stenosis, tumors, and other obstructive causes of hydrocephalus were classified as obstructive (n=6). Communicating (n=15) included idiopathic, normal pressure hydrocephalus, and other non-obstructive etiologies. The category "other" (n=3) was assigned to studies that included etiologies, populations, and/or treatments that did not fit into the classifications previously outlined. Through our analysis of highly cited journal articles focusing on different etiologies and the surgical or medical management of hydrocephalus, we hope to elucidate important trends. By establishing the 100 most cited hydrocephalus articles, we contribute one source, stratified for efficient referencing, to facilitate clinical care and future research on hydrocephalus.

Angulation of the dural venous sinuses of the posterior cranial fossa: Anatomical study with clinical and surgical applications.

Cerebral vein and dural venous sinus thromboses (CVST) account for 0.5%-1% of all strokes. Some structural factors associated with a potentially higher risk for developing CVST have been described. However, angulation of the dural venous sinuses (DVS) has yet to be studied as a structural factor. The current study was performed because this variable could be related to alterations in venous flow, thus predisposing to a greater risk of CVST development. Additionally, such information could help shed light on venous sinus stenosis (VSS) at or near the transverse-sigmoid junction. The angulations formed in the different segments of the grooves of the transverse (TS), sigmoid (SS), and superior sagittal sinuses (SSS) were measured in 52 skulls (104 sides). The overall angulation of the TS groove was measured using two reference points. Other variables were examined, such as the communication pattern at the sinuses' confluence and the sinus grooves' lengths and widths. The patterns of communication between sides were compared statistically. The most typical communication pattern at the sinuses' confluence was a right-dominant TS groove (82.98%). The mean angulations of the entire left TS groove at two different points (A and B) were 46° and 43°. Those of the right TS groove were 44° and 45°. The median angulations of the left and right SSS-transverse sinus junction grooves were 127° and 124°. The mean angulations of the left and right TS-SSJsv grooves were 111° (range 82°-152°) and 103° (range 79°-130°). Differentiating normal and abnormal angulations of the DVSs of the posterior cranial fossa can help to explain why some patients are more susceptible to pathologies affecting the DVSs, such as CVST and VSS. Future application of these findings to patients with such pathologies is now necessary to extrapolate our results.

Immune cells: potential carriers or agents for drug delivery to the central nervous system.

Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood-brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.

Unreported variant foramen of the frontal bone: the latero-orbital foramen.

Variant foramina of the skull can lead to misdiagnosis on medical imaging and potentially, intraoperative complications if not appreciated. Here, we report an unusual foramen found superior to the frontozygomatic suture. The foramen was located on the left side at the superolateral rim of the orbit, 2.36 cm inferolateral to the supraorbital foramen. It was positioned 2.5 mm superior to the frontozygomatic suture. The foramen had a length of 3.1 mm and a width of 1.3 mm. The internal opening of the foramen was located 1.45 cm superolateral to the zygomaticotemporal foramen. We suggest that this foramen is a pathway for either a branch of the zygomatic nerve or lacrimal nerve and/or their vascular bundles. Although the prevalence of such a finding cannot be confirmed, such a case is of archival value as a comparison for future similar cases.

Are the Ethmoidal Foramina Through the Frontal Bone, Ethmoid Bone, or Frontoethmoidal Suture?

INTRODUCTION: To investigate the locations of the anterior, middle, and posterior ethmoidal foramina and their relationships to the frontoethmoidal suture. METHODS: One hundred twenty sides from sixty adult human skulls were used. Specimens with significant damage to the medial orbit wall were excluded. The number of ethmoidal foramina (anterior, middle, and posterior) on the medial orbital wall and the relationship of each foramen to the frontoethmoidal suture were recorded and classified as follows: Type I: superior to the frontoethmoidal suture; Type II: on the frontoethmoidal suture; Type III: inferior to the frontoethmoidal suture. RESULTS: Of the ninety-four sides, fourteen (14.9%) had one foramen, sixty-two (66.0%) had two , and eighteen (19.1%) had three. In total, 192 ethmoidal foramina were observed. Among the fourteen sides with one foramen, eight foramina were anterior and six were posterior. Among the 192 ethmoidal foramina, 162 were eligible for fur ther classification (74 anterior, 14 middle, and 74 posterior). Types I, II, and III ethmoidal foramina were found in 38.3% (62/162), 61.7% (100/162), and 0% (0/162), respectively. CONCLUSIONS: Our current study found a higher incidence of type I than previously reported. It is important to be aware of the significant incidence of foramen variations when the medial orbit wall is manipulated during surgery. Unless caution is observed, an inadvertent surgical injury can occur and lead to life-threatening complications. Therefore, a good understanding of orbital anatomy and its potential variations is critical for improving patient out comes.

Assessing the clinical reasoning of ChatGPT for mechanical thrombectomy in patients with stroke.

BACKGROUND: Artificial intelligence (AI) has become a promising tool in medicine. ChatGPT, a large language model AI Chatbot, shows promise in supporting clinical practice. We assess the potential of ChatGPT as a clinical reasoning tool for mechanical thrombectomy in patients with stroke. METHODS: An internal validation of the abilities of ChatGPT was first performed using artificially created patient scenarios before assessment of real patient scenarios from the medical center's stroke database. All patients with large vessel occlusions who underwent mechanical thrombectomy at Tulane Medical Center between January 1, 2022 and December 31, 2022 were included in the study. The performance of ChatGPT in evaluating which patients should undergo mechanical thrombectomy was compared with the decisions made by board-certified stroke neurologists and neurointerventionalists. The interpretation skills, clinical reasoning, and accuracy of ChatGPT were analyzed. RESULTS: 102 patients with large vessel occlusions underwent mechanical thrombectomy. ChatGPT agreed with the physician's decision whether or not to pursue thrombectomy in 54.3% of the cases. ChatGPT had mistakes in 8.8% of the cases, consisting of mathematics, logic, and misinterpretation errors. In the internal validation phase, ChatGPT was able to provide nuanced clinical reasoning and was able to perform multi-step thinking, although with an increased rate of making mistakes. CONCLUSION: ChatGPT shows promise in clinical reasoning, including the ability to factor a patient's underlying comorbidities when considering mechanical thrombectomy. However, ChatGPT is prone to errors as well and should not be relied on as a sole decision-making tool in its present form, but it has potential to assist clinicians with more efficient work flow.

L5 spondylolysis: Anatomical study comparing healed and unhealed lesions.

The anatomy and pathogenesis of spondylolysis has been widely studied; however, the microanatomy of spondylolysis of the lumbar vertebra has not been well described. Therefore, we aim to better elucidate this anatomy. Twenty dry bone specimens of healed and unhealed spondylolysis of the L5 vertebra were collected from human skeletal remains. Twelve L5 vertebrae were examples of unhealed spondylolysis and eight specimens exhibited a healed (i.e., bony fusion of the lesion) spondylolysis lesion. The specimens underwent macro and microanatomical analysis followed by CT and microCT imaging. Finally, selected healed and unhealed lesions were submitted for histological analysis using Mason Trichrome staining. The pars interarticularis of two L5 vertebrae without signs of healed/unhealed spondylolysis were evaluated histologically as controls. Of the 12 unhealed L5 pars defects, three were unilateral on left side. Of the eight healed pars defects, all were unilateral and seven of these were on left sides. One unilateral pars defect also had spina bifida occulta. Both on imaging and histological analysis, healed pars defects were only so superficially and not at deeper levels. Histologically, unhealed edges were made up of dense cortical bone while healed edges were made up primarily of trabecular bone. Based on our anatomical findings, the so-called healed spondylolysis lesions, although externally fused, are not thoroughly fused internally. Moreover, the anterior and posterior edges of the unhealed spondylosysis lesions are irregular and show signs of long-term disarticulation. Taken together, these data suggest that such 'healed' lesions might not be as stable as the normal L5 pars interarticularis.

Transcription factor support for the dual embryological origin of the sternocleidomastoid and trapezius muscles.

The embryological origin of the trapezius and sternocleidomastoid muscles has been debated for over a century. To shed light on this issue, the present anatomical study was performed. Five fresh frozen human cadavers, three males and two females, were used for this study. Samples from each specimen's trapezius and sternocleidomastoid were fixed in 10% formalin and placed in paraffin blocks. As Paired like homeodomain 2 (Pitx2) and T-box factor 1(Tbx1) have been implicated in the region and muscle type regulation, we performed Tbx1 and Pitx2 Immunohistochemistry (IHC) on these muscle tissue samples to identify the origin of the trapezius and sternocleidomastoid muscles. We have used the latest version of QuPath, v0.4.3, software to quantify the Tbx and Pitx2 staining. For the sternocleidomastoid muscle, for evaluated samples, the average amount of positively stained Tbx1 and Pitx2 was 25% (range 16%-30%) and 18% (range 12%-23%), respectively. For the trapezius muscles, for evaluated samples, the average amount of positively stained Tbx1 and Pitx2 parts of the samples was 17% (range 15%-20%) and 15% (14%-17%), respectively. Our anatomical findings suggest dual origins of both the trapezius and sternocleidomastoid muscles. Additionally, as neither Pitx2 nor Tbx1 made up all the staining observed for each muscle, other contributions to these structures are likely. Future studies with larger samples are now necessary to confirm these findings.

A Highly Unusual Source and Course of the Inferior Gluteal Nerve With Related Variations: A Case Report.

The gluteal region is rich in neurovasculature that divides in predictable ways. Though these characteristic relationships can be helpful when orienting oneself to the gluteal region, it is especially useful to be aware of anatomical variations in this region. Knowledge of such differences allows for a better appreciation of nerve entrapments and neuropathies, and such awareness is critical during surgeries. In this case report, we explore an uncharacteristic relationship among the piriformis muscle, the sciatic nerve and its components, and the inferior gluteal and posterior femoral cutaneous nerves.

An anatomical study of the sigmoid sinus artery: Application to the transmastoid approach.

INTRODUCTION: We aimed to investigate the morphological features of the artery that traverse the sigmoid sinus's lateral surface and to discuss this structure's clinical relevance. METHODS: Ten sides from five cadaveric Caucasian heads were used for gross anatomical dissection to investigate the morphological features of the sigmoid sinus artery (SSA), and additional five sides were used for histological observation. RESULTS: The SSA was found on eight out of ten sides (80%). The mean diameter of the SSA was 0.3 mm. The mean distance from the tip of the mastoid process to the artery was 20.3 mm. Histological observation identified extradural and intradural courses of SSA. The intradural course was further categorized into protruding and non-protruding types. In the protruding type, the SSA traveled within the dura but indented into the bone, making it more or less an intraosseous artery. In the non-protruding type, the SSA traveled within the dura but did not protrude into the bone but rather indented into the lumen of the SS. In all sections, both intradural and extradural courses were identified simultaneously. CONCLUSIONS: When the mastoid foramen is observed, it does not always only carry an emissary vein but also an artery. The SSA could be considered a "warning landmark" during bone drilling for the transmastoid approach.

Trabeculae in the basilar venous plexus: anatomical and histological study with application to intravascular procedures.

Few studies have examined the basilar venous plexus (BVP) and to our knowledge, no previous study has described its histology. The present anatomical study was performed to better elucidate these structures. In ten cadavers, the BVP was dissected. The anatomical and histological evaluation of the intraluminal trabeculae within this sinus were evaluated. Once all gross measurements were made, the clivus and overlying BVP were harvested and submitted for histological analysis. A BVP was identified in all specimens and in each of these, intraluminal trabeculae were identified. The mean number of trabeculae per plexus was five. These were most concentrated in the upper half of the clivus and were more often centrally located. These septations traveled in a posterior to anterior direction and usually, from inferiorly to superiorly however some were noted to travel horizontally. In a few specimens the trabeculae had wider bases, especially on the posterior attachment to the meningeal layer of dura mater. More commonly, the trabeculae ended in a denticulate form at their two terminal ends. The trabeculae were on average were 0.85 mm in length. The mean width of the trabeculae was 0.35 mm. These septations were consistent with the cords of Willis as are found in the lumen of some of the other intradural venous sinuses. An understanding of the internal anatomy of the BVP can aid in our understanding of venous pathology. Furthermore, this knowledge will benefit patients undergoing interventional treatments that involve the BVP.

Dural sinus septum as an underlying cause of intrinsic venous sinus stenosis: Anatomical, clinical, and stent placement considerations.

Recently, an interesting study regarding "Dural sinus septum: an underlying cause of cerebral venous sinus stenting failure and complications." was published, to our knowledge, being the launching point of the clinical/interventional applications of this intraluminal variation. Herein, we wish to highlight paramount anatomical, clinical, and stent placement considerations related to DSS located in the dural venous sinus at the posterior cranial fossa and the interventional complications caused by the presence of this variation during stenting procedures.

Revisiting the transorbital approach for emergency external ventricular drainage: an anatomical study of relevant parameters and their effect on the effectiveness of using Tubbs' point.

The transorbital approach (TOA) can provide immediate access to the lateral ventricles by piercing the roof of the orbit (ROO) with a spinal needle and without the need of a drill. Reliable external landmarks for the TOA ventriculostomy have been described, however, the necessary spinal needle gauge and other relevant parameters such as the thickness of the ROO have not been evaluated. Nineteen formalin-fixed adult cadaveric heads underwent the TOA. Spinal needles of different gauges were consecutively used in each specimen beginning with the smallest gauge until the ROO was successfully pierced. The thickness of the ROO at the puncture site and around its margins was measured. Other parameters were also measured. The TOA was successfully performed in 14 cases (73.68%), where the most suitable needle gauge was 13 (47.37%), followed by a 10-gauge needle (36.84%). The mean thickness of the ROO at the puncture site, and the mean length of the needle to the puncture site were 1.7 mm (range 0.2-3.4 mm) and 15.5 mm (range 9.2-23.4 mm), respectively. A ROO thickness of greater than 2.0 mm required a 10-gauge needle in seven cases, and in five cases, a 10-gauge needle was not sufficient for piercing the ROO. The presence of hyperostosis frontalis interna (HFI) (21.05%) was related to the failure of this procedure (80%; p < 0.00). Using a 13/10-gauge spinal needle at Tubbs' point for TOA ventriculostomy allowed for external ventricular access in most adult specimens. The presence of HFI can hinder this procedure. These findings are important when TOA ventriculostomy is considered.

Histology and immunohistochemistry of the human carotid sinus nerve.

The carotid sinus nerve (CSN) is well known as mediating baroreflexes. However, studies of its detailed histological analysis are scant in the literature. Therefore, the current anatomical study sought to better elucidate the microanatomy of the CSN. Ten fresh frozen adult cadavers underwent dissection of the CSN. Then, it was harvested and submitted for histological and immunohistochemical staining. Specimens were all shown to be nerve fibers on histology and immunohistochemistry. We identified tyrosine hydroxylase positive fibers in all CSN specimens. These fibers were always found to be within the CSN and not on its surface i.e., epineurium. Based on our findings, the majority of fibers contained in the CSN are tyrosine positive in nature. Further studies are necessary to understand the true function of this autonomic nerve fibers.

Review of the caroticotympanic nerves: Anatomy, function and pathology.

The caroticotympanic nerves provide postganglionic sympathetic fibres to the tympanic plexus. However, there are scant reports in the literature detailing with these nerves in great depth. As the caroticotympanic plexus lies near the often-operated tympanic nerve, it is important for the surgeon to understand the anatomy, pathology and surgical implications of it. Here, we present a review of the available literature regarding the caroticotympanic nerves.

Fenestrated popliteal vein pierced by a branch of the tibial nerve.

Knowledge of anatomical variations is important so as to avoid potential iatrogenic injury or misdiagnosis on imaging. Here we report an unusual finding and relationship between the tibial nerve and popliteal vein. During the routine dissection of an adult cadaver, it was noted that a branch of the tibial nerve in the popliteal fossa pierced the most distal part of the popliteal vein. This unusual finding is described and relevant reports in the literature discussed. Our hopes are that such a report might help surgeons avoid injury to such a fenestrated popliteal vein and the tibial nerve branch traveling through it therefore decreasing patient morbidity.

Innervation of pineal gland by the nervus conarii: a review of this almost forgotten structure.

The nervus conarii provides sympathetic nerve innervation to the pineal gland, which is thought to be the primary type of stimulus to this gland. This underreported nerve has been mostly studied in animals. One function of the nervus conarii may be to activate pinealocytes to produce melatonin. Others have also found substance P and calcitonin gene-related peptide from the nervus conarii ending in the pineal gland. The following paper reviews the extant medical literature on the nervus conarii including its anatomy and potential function.