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BioRxiv : the Preprint Server For... Jan 2024The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood....
UNLABELLED
The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-β (Aβ) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4 antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4 B cells and gut-specific IgA cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aβ plaques and overall frailty. These changes corresponded to an expansion of gut IgA cells and rescued peripheral T levels. Our study points to a key glia-gut axis and potential targets against AD.
STUDY HIGHLIGHTS
AD is associated with altered immune parameters in the gut of mice. 5 colon has reduced ASCs, including CXCR4 cells with a migratory gene signature. brain gliosis includes increased CXCL12 expression. CXCR4 B cells and gut-specific IgA ASCs accumulate in the brain and/or dura mater. Inulin diet attenuates AD disease parameters while boosting IgA cell and T levels.
PubMed: 38352325
DOI: 10.1101/2024.01.27.573841 -
International Journal of Computer... Nov 2023In bone surgery specialties, like orthopedics, neurosurgery, and oral and maxillofacial surgery patient safety and treatment success depends on the accurate...
PURPOSE
In bone surgery specialties, like orthopedics, neurosurgery, and oral and maxillofacial surgery patient safety and treatment success depends on the accurate implementation of computer-based surgical plans. Unintentional plan deviations can result in long-term functional damage to the patient. With on-site teleoperation, the surgeon operates a slave robot with a physically-decoupled master device, while being directly present at the operation site. This allows the surgeon to perform surgical tasks with robotic accuracy, while always remaining in the control loop.
METHODS
In this study the master- and slave-side accuracy of an on-site teleoperated miniature cooperative robot (minaroHD) is evaluated. Master-side accuracy is investigated in a user study regarding scale factor, target feed rate, movement direction and haptic guidance stiffness. Scale factors are chosen to correspond to primarily finger, hand, and arm movements. Slave-side accuracy is investigated in autonomous milling trials regarding stepover, feed rate, movement direction, and material density.
RESULTS
Master-side user input errors increase with increasing target feed rate and scale factor, and decrease with increasing haptic guidance stiffness. Resulting slave-side errors decrease with increasing scale factor and are < 0.07 mm for optimal guidance parameters. Slave-side robot position errors correlate with the feed rate but show little correlation with stepover distance. For optimal milling parameters, the 95th percentile of tracked slave-side position error is 0.086 mm with a maximal error of 0.16 mm.
CONCLUSION
For optimal guidance and milling parameters, the combined error of 0.23 mm is in the range of the dura mater thickness (< 0.27 mm) or mandibular canal wall (~ 0.85 mm). This corresponds to safety margins in high-demand surgical procedures like craniotomies, laminectomies, or decortication of the jaw. However, for further clinical translation, the performance and usability of on-site teleoperated milling must be further evaluated for real-life clinical application examples with consideration of all error sources in a computer-assisted surgery workflow.
PubMed: 37454325
DOI: 10.1007/s11548-023-02983-2 -
Finite element modeling of the human cervical spinal cord and its applications: A systematic review.North American Spine Society Journal Sep 2023Finite element modeling (FEM) is an established tool to analyze the biomechanics of complex systems. Advances in computational techniques have led to the increasing use... (Review)
Review
BACKGROUND CONTEXT
Finite element modeling (FEM) is an established tool to analyze the biomechanics of complex systems. Advances in computational techniques have led to the increasing use of spinal cord FEMs to study cervical spinal cord pathology. There is considerable variability in the creation of cervical spinal cord FEMs and to date there has been no systematic review of the technique. The aim of this study was to review the uses, techniques, limitations, and applications of FEMs of the human cervical spinal cord.
METHODS
A literature search was performed through PubMed and Scopus using the words finite element analysis, spinal cord, and biomechanics. Studies were selected based on the following inclusion criteria: (1) use of human spinal cord modeling at the cervical level; (2) model the cervical spinal cord with or without the osteoligamentous spine; and (3) the study should describe an application of the spinal cord FEM.
RESULTS
Our search resulted in 369 total publications, 49 underwent reviews of the abstract and full text, and 23 were included in the study. Spinal cord FEMs are used to study spinal cord injury and trauma, pathologic processes, and spine surgery. Considerable variation exists in the derivation of spinal cord geometries, mathematical models, and material properties. Less than 50% of the FEMs incorporate the dura mater, cerebrospinal fluid, nerve roots, and denticulate ligaments. Von Mises stress, and strain of the spinal cord are the most common outputs studied. FEM offers the opportunity for dynamic simulation, but this has been used in only four studies.
CONCLUSIONS
Spinal cord FEM provides unique insight into the stress and strain of the cervical spinal cord in various pathological conditions and allows for the simulation of surgical procedures. Standardization of modeling parameters, anatomical structures and inclusion of patient-specific data are necessary to improve the clinical translation.
PubMed: 37636342
DOI: 10.1016/j.xnsj.2023.100246 -
Neurologia Medico-chirurgica Aug 2023Chronic subdural hematoma (CSDH) is a common pathology that typically affects the elderly in Japan, an aging society. Burr-hole irrigation is the standard treatment, but... (Review)
Review
Chronic subdural hematoma (CSDH) is a common pathology that typically affects the elderly in Japan, an aging society. Burr-hole irrigation is the standard treatment, but middle meningeal artery (MMA) embolization is a minimally invasive alternative. MMA embolization for CSDH has frequently been reported in recent years, and many technical innovations to improve clinical outcomes have been described. Embolic materials reaching more distally are found to avoid recurrences after MMA embolization. As a result, various studies have described the superiority of embolizing the anterior and posterior branches of the MMA, the advantages of embolic materials reaching beyond the midline, and a high degree of distal penetration using a "sugar rush technique" in which 5% soluble glucose is injected through an intermediate catheter during MMA embolization. Radiographically, reports have described the importance of a "bright falx" sign obtained by infiltrating embolic material beyond the midline and post-embolization enhancement of the dura, capsular membrane, septations, and subdural hematoma fluid as indicators of the spread of embolic materials. This review provides an overview of the current status and future challenges in MMA embolization for CSDH, focusing on technical aspects to improve clinical outcomes.
Topics: Humans; Aged; Hematoma, Subdural, Chronic; Meningeal Arteries; Embolization, Therapeutic; Trephining; Dura Mater
PubMed: 37286481
DOI: 10.2176/jns-nmc.2023-0017 -
Inflammation Jun 2024Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through...
Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845-33,237) and significantly higher than the median systemic blood level of 789 pg/L (465-2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54-44.8) and significantly higher than the dural uPAR level of 0.81 (0.3-1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane.
Topics: Humans; Hematoma, Subdural, Chronic; Receptors, Urokinase Plasminogen Activator; Male; Female; Aged; Aged, 80 and over; Middle Aged; Dura Mater; Recurrence
PubMed: 38236383
DOI: 10.1007/s10753-023-01957-5 -
Stem Cell Research & Therapy Feb 2024Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain...
BACKGROUND
Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined.
METHOD
Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools.
RESULTS
Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups.
CONCLUSION
Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Stromal Vascular Fraction; Autografts; Spinal Cord Injuries; Spinal Cord; Adipose Tissue; Recovery of Function
PubMed: 38303017
DOI: 10.1186/s13287-024-03645-z -
Surgical Neurology International 2023Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain's arachnoid and dura...
BACKGROUND
Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain's arachnoid and dura mater coverings. While steroids have been explored as a potential treatment option, their efficacy and safety remain uncertain. This meta-analysis and systematic review aimed to assess the impact of steroids on CSDH management, including mortality, recurrence, complications, and functional outcomes.
METHODS
We conducted a comprehensive literature search in major electronic databases up to June 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Handbook for Systematic Reviews and Interventions. Inclusion criteria encompassed adult patients with CSDH, the use of steroids as monotherapy or adjuvant therapy, and clearly defined outcomes. Randomized controlled trials and cohort studies meeting these criteria were included in the study.
RESULTS
The initial search yielded 4315 articles, with 12 studies meeting the inclusion criteria. Our findings indicate a non-significant trend toward reduced mortality with steroids in combination with standard care (Odds ratios [OR] = 0.66, 95% confidence interval [CI] 0.20-2.18). However, substantial heterogeneity was observed (I = 70%). Sensitivity analysis, excluding influential studies, suggested a potential increased mortality risk associated with steroids (OR = 1.47, 95% CI 0.87-2.48). Steroids showed a possible benefit in reducing the recurrence of CSDH (OR = 0.58, 95% CI 0.20-1.67), but with significant heterogeneity (I = 89%). No clear advantage of steroids was observed in terms of functional outcomes at three months (modified Rankin scale scores). Furthermore, steroids were associated with a significantly higher incidence of adverse effects and complications (OR = 2.17, 95% CI 1.48-3.17).
CONCLUSION
Steroids may have a potential role in reducing CSDH recurrence but do not appear to confer significant advantages in terms of mortality or functional outcomes. However, their use is associated with a higher risk of adverse effects and complications. Given the limitations of existing studies, further research is needed to refine the role of steroids in CSDH management, considering patient-specific factors and treatment protocols.
PubMed: 38213424
DOI: 10.25259/SNI_771_2023 -
Cureus Feb 2024Hypertrophic pachymeningitis (HP) is a rare condition characterized by inflammation and thickening of the dura mater. It can be idiopathic or secondary to various...
Hypertrophic pachymeningitis (HP) is a rare condition characterized by inflammation and thickening of the dura mater. It can be idiopathic or secondary to various causes, including infections, tumors, or systemic inflammatory diseases. Diagnosis is challenging due to its rarity and the overlap of symptoms with other conditions. We present the case of a 42-year-old Hispanic woman with diabetes mellitus type 2 and end-stage kidney disease who presented with chest pain, dry cough, mild dyspnea, and chronic occipital headaches. Physical examination revealed cranial VI nerve palsy. Imaging showed pulmonary cavitary lesions and mediastinal lymphadenopathy. Elevated inflammatory markers and positive autoimmune tests, including rheumatoid factor and antineutrophil cytoplasmic antibody (ANCA), led to further investigation. Brain imaging revealed dural thickening, confirming HP. The patient's medical history revealed double ANCA positivity and a lung biopsy confirmed granulomatous pneumonitis. A diagnosis of ANCA-associated vasculitis (granulomatosis with polyangiitis (GPA)) was established, and treatment with rituximab and high-dose corticosteroids led to symptom improvement. GPA rarely involves meningeal inflammation, but severe and persistent headaches are common early symptoms. Inflammatory markers are often elevated, and around two-thirds of HP cases related to GPA have positive serum ANCA. MRI is the primary diagnostic tool, with characteristic findings of dural thickening and contrast enhancement. This case highlights HP as a rare cause of chronic headaches and the importance of a comprehensive medical history in diagnosis. Early recognition and treatment are crucial for improving outcomes in GPA-related HP.
PubMed: 38445136
DOI: 10.7759/cureus.53576 -
Surgical Neurology International 2023Spinal infections are associated with a wide variety of clinical conditions, including osteomyelitis, spondylitis, diskitis, septic facet joints, and abscesses. Based on...
BACKGROUND
Spinal infections are associated with a wide variety of clinical conditions, including osteomyelitis, spondylitis, diskitis, septic facet joints, and abscesses. Based on its anatomical relationship with the dura mater, the abscess can be epidural (extradural) or subdural (intrathecal). Subdural intramedullary abscesses of the lumbar spinal canal are more common than subdural extramedullary abscesses. Here, we present a rare case of a patient with a mixed pyogenic and tuberculous epidural abscess in the lumbar spine, which perforated the dura and extended to the subdural space.
CASE DESCRIPTION
A 29-year-old male presented with progressively worsening back pain and lower-limb weakness over a period of 3 months, with an associated inability to walk, intermittent radicular pain primarily on the left side, intermittent incontinence, and a history of low-grade fever and night sweats. The patient had a history of intravenous (IV) drug abuse and reported practicing unprotected sexual intercourse. Furthermore, the patient had recently came into contact with a person diagnosed with tuberculosis (TB). The patient was administered empirical broad-spectrum antibiotics and underwent emergent L4-L5 laminectomy and spinal abscess decompression. IV antibiotics were selected based on culture results, and anti-TB medications were started. Postoperatively, the patient demonstrated a remarkable lower-limb power improvement and radicular pain alleviation.
CONCLUSION
Spinal epidural abscess perforation of the dura and extension into the subdural space is extremely rare. Distinguishing between epidural and subdural abscesses radiologically is challenging. Multiple risk factors, such as unprotected sexual contact and IV drug misuse, may be associated with the development of polymicrobial abscesses in the lumbar spine. Careful anticipation, identification, and isolation of the causative micro-organisms can ensure effective antibacterial treatment. Early diagnosis, expeditious surgical decompression, and antibiotic treatment are associated with promising outcomes.
PubMed: 37810309
DOI: 10.25259/SNI_536_2023 -
Spine Surgery and Related Research May 2024Idiopathic spinal cord herniation (ISCH) is a rare condition that is characterized by ventral herniation of the spinal cord through a defect in the dura mater into the... (Review)
Review
BACKGROUND
Idiopathic spinal cord herniation (ISCH) is a rare condition that is characterized by ventral herniation of the spinal cord through a defect in the dura mater into the epidural space, with no identifiable cause. ISCH is frequently underdiagnosed, and the information available in case reports is limited. To provide an overview of the clinical manifestations and diagnosis of this condition, this study aims to conduct a review of reported cases of ISCH.
METHODS
A literature review was carried out using seven databases. The search was conducted using the keywords "Idiopathic spinal cord herniation" OR "Idiopathic Ventral Spinal Cord Herniation" AND "Case report" OR "case series."
RESULTS
A total of 92 relevant papers reporting 224 cases, besides the index case, were determined. Of the cases, 58.5% were females and the mean age was 50.7 (SD 13.2) years. Symptoms, diagnoses, and outcomes were similar between genders. The most common clinical signs included motor symptoms (82.6%), instability (61.3%), hypoesthesia (59.2%), and disturbance of thermal sensitivity (47.3%). Brown-Séquard syndrome was observed in 27.2% of the cases, and surgical treatment was employed in 89.7% of the cases.
CONCLUSIONS
ISCH is a pathology that is principally treated with surgical approach. This study provides valuable insights into the clinical manifestations and diagnosis of ISCH, which can aid in the early recognition and treatment of this rare condition.
PubMed: 38868787
DOI: 10.22603/ssrr.2023-0102