Infectious meningitis. Why are the leptomeninges preferentially involved? Electron microscopic insights.

In infectious meningitis, pathogens preferentially attack the leptomeninges (pia mater and arachnoid) rather than the pachymeninges (dura mater). This study aims to provide ultra-anatomical insights from our extensive collection of electron microscopy images and propose mechanisms, highlighting structures that favor the introduction, adherence, colonization, and proliferation of microorganisms leading to spinal meningitis. Over several years, we analyzed an extensive collection of transmission and scanning electron microscopy images of human spinal meninges captured in our laboratories. Upon examining 378 of those images, we identified potential sites for the iatrogenic or hematogenic introduction and adherence of microorganisms, as well as sites for their colonization and proliferation. These included the outer surface of the spinal dural sac, structures within the epidural space, and the spinal dural sac itself, which comprises compact dura mater with interwoven collagen fibers and tightly bound arachnoid cells. Also, the subdural (extra-arachnoid) compartment, consisting of fragile neurothelial cells prone to rupture under force, formed an acquired spinal subdural space, a new subarachnoid compartment, limited by arachnoid trabeculae, that surrounded the nerve roots and spinal cord and the pia mater. Macrophages, fibroblasts, mast cells, and plasma cells were also observed within the dura mater, arachnoid layer, arachnoid trabeculae, and pia mater. These images illustrate how the characteristics of the meningeal layers could contribute to bacterial adhesion and proliferation at various locations, inducing selective inflammation during (iatrogenic) spinal meningitis. In addition, the images help to explain why magnetic resonance imaging enhancement appears preferentially at specific sites.

Anatomical study with clinical significance of communicating and visceral branching of the cervical and upper thoracic sympathetic trunk.

Current advances in the management of the autonomic nervous system in various cardiovascular diseases, and in treatments for pain or sympathetic disturbances in the head, neck, or upper limbs, necessitate a thorough understanding of the anatomy of the cervicothoracic sympathetic trunk. Our objective was to enhance our understanding of the origin and distribution of communicating branches and visceral cervicothoracic sympathetic nerves in human fetuses. This was achieved through a comprehensive topographic systematization of the branching patterns observed in the cervical and upper thoracic ganglia, along with the distribution of communicating branches to each cervical spinal nerve. We conducted detailed sub-macroscopic dissections of the cervical and thoracic regions in 20 human fetuses (40 sides). The superior and cervicothoracic ganglia were identified as the cervical sympathetic ganglia that provided the most communicating branches on both sides. The middle and accessory cervical ganglia contributed the fewest branches, with no significant differences between the right and left sides. The cervicothoracic ganglion supplied sympathetic branches to the greatest number of spinal nerves, spanning from C5 to T2. The distribution of communicating branches to spinal nerves was non-uniform. Notably, C3, C4, and C5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C1 and C2 received sympathetic connections exclusively from the superior ganglion. Spinal nerves that received more branches often did so from multiple ganglia. The vertebral nerve provided deep communicating branches primarily to C6, with lesser contributions to C7, C5, and C8. The vagus nerve stood out as the cranial nerve with the most direct sympathetic connections. The autonomic branching pattern and connections of the cervicothoracic sympathetic trunk are significantly variable in the fetus. A comprehensive understanding of the anatomy of the cervical and upper thoracic sympathetic trunk and its branches is valuable during autonomic interventions and neuromodulation. This knowledge is particularly relevant for addressing various autonomic cardiac diseases and for treating pain and vascular dysfunction in the head, neck, and upper limbs.

Refractory primary and secondary headache disorders that dramatically responded to combined treatment of ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks and non-invasive vagus nerve stimulation: a case series.

In 1981, Devoghel achieved an 85.6% success rate in treating patients with treatment-refractory cluster headaches with alcoholization of the pterygopalatine ganglion (PPG) via the percutaneous suprazygomatic approach. Devoghel's study led to the theory that interrupting the parasympathetic pathway by blocking its transduction at the PPG could prevent or treat symptoms related to primary headache disorders (PHDs). Furthermore, non-invasive vagus nerve stimulation (nVNS) has proven to treat PHDs and has been approved by national regulatory bodies to treat, among others, cluster headaches and migraines.In this case series, nine desperate patients who presented with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch-resistant postdural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks (PPGB), and seven also received nVNS. The patients were randomly selected and were not part of a research study. They experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report). The report provides the case descriptions, briefly reviews the trigeminovascular and neurogenic inflammatory theories of the pathophysiology, outlines aspects of these PPGB and nVNS interventions, and argues for adopting this treatment regime as a first-line or second-line treatment rather than desperate last-line treatment of PDPH and PHDs.

Identification of spread after deliberated intraneural injection in five mammalian species: not all animal models and needle types are valid for studying the effect of intraneural injections in humans.

INTRODUCTION: This research endeavors to investigate the phenomenon of intraneural spread across distinct locations: subcircumneurium, extrafascicular intraneural, intrafascicular intraneural, and intraperineurium after deliberate intraneural injections across five mammalian species. The study also aims to propose determinants influencing this spread. Furthermore, the investigation strives to ascertain the optimal animal species and needle configuration for extrapolating intraneural injection outcomes to human contexts. METHODS: This study examined 60 sciatic nerves from 30 fresh and untreated cadavers of rats, rabbits, dogs, pigs, and sheep. The specimens were organized into five groups, each comprising an equal number of nerves. Histological assessments were performed on 30 nerves, involving fascicle metrics. The remaining 30 nerves underwent intentional intraneural injections, facilitated by 19G and 23G needles under ultrasound and direct visualization guidance.Heparinized erythrocytes combined with a methylene blue solution were used as a marker to analyze the extent and patterns of intraneural spread. Needle orifice measurements were obtained, and these data were overlaid onto images of both nerves and needles. This enabled a comparative evaluation of sizes and an assessment of marker diffusion. RESULTS: The findings indicated that sciatic nerves in rats, rabbits, and dogs were oligofascicular, characterized by larger fascicles, whereas pigs and sheep exhibited polyfascicular nerves comprised of numerous smaller fascicles. Fascicular diameters were variable across species, with dogs presenting the largest measurements. While intraneural spread was observed and documented, intrafascicular marker spreading was rare, occurring only in one rabbit specimen. Needle orifice attributes were scrutinized and visually depicted. CONCLUSIONS: Despite the formidable challenges associated with the practical realization of intrafascicular injection, the utilization of animal models possessing monofascicular or oligofascicular nerves, such as rats, rabbits, and dogs, in conjunction with needles featuring aperture dimensions surpassing those of the fascicles, likely contributes to the compromised reliability of investigations into intraneural injection outcomes.

The size, number, and distribution of nerve endings around and within the human epiglottis, focusing on tracheal intubation maneuvers.

The aim of this study was to examine the distribution of nerve endings in the mucosa, submucosa, and cartilage of the epiglottis and the vallecula area and to quantify them. The findings could inform the choice of laryngoscope blades for intubation procedures. Fourteen neck slices from seven unembalmed, cryopreserved human cadavers were analyzed. The slices were stained, and cross and longitudinal sections were obtained from each. The nerve endings and cartilage were identified. The primary metrics recorded were the number, area, and circumference of nerve endings located in the mucosa and submucosa of the pharyngeal and laryngeal sides of the epiglottis, epiglottis cartilage, and epiglottic vallecula zone. The length and thickness of the epiglottis and cartilage were also measured. The elastic cartilage of the epiglottis was primarily continuous; however, it contained several fragments. It was covered with dense collagen fibers and surrounded by adipose cells from the pharyngeal and laryngeal submucosa. Nerve endings were found within the submucosa of pharyngeal and laryngeal epiglottis and epiglottic vallecula. There were significantly more nerve endings on the posterior surface of the epiglottis than on the anterior surface. The epiglottic cartilage was twice the length of the epiglottis. The study demonstrated that the distribution of nerve endings in the epiglottis differed significantly between the posterior and anterior sides; there were considerably more in the former. The findings have implications for tracheal intubation and laryngoscope blade selection and design.

Innervation of the heart: Anatomical study with application to better understanding pathologies of the cardiac autonomics.

Current advances in management of the cardiac neuroaxis in different cardiovascular diseases require a deeper knowledge of cardiac neuroanatomy. The aim of the study was to increase knowledge of the human fetal extrinsic cardiac nervous system. We achieved this by systematizing the origin and formation of the cardiac nerves, branches, and ganglia and their sympathetic/parasympathetic connections. Thirty human fetuses (60 sides) were subjected to detailed sub-macroscopic dissection of the cervical and thoracic regions. Cardiac accessory ganglia lying on a cardiac nerve or in conjunction with two or more (up to four) nerves before entering the mediastinal cardiac plexus were observed in 13 sides. Except for the superior cardiac nerve, the sympathetic cardiac nerves were individually variable and inconstant. In contrast, the cardiac branches of the vagus nerve appeared grossly more constant and invariable, although the individual cardiac branches varied in number and position of origin. Each cervical cardiac nerve or cardiac branch of the vagus nerve could be singular or multiple (up to six) and originated from the sympathetic trunk or the vagus nerve by one, two, or three roots. Sympathetic nerves arose from the cervical-thoracic ganglia or the interganglionic segment of the sympathetic trunk. Connections were found outside the cardiac plexus. Some cardiac nerves were connected to non-cardiac nerves, while others were connected to each other. Common sympathetic/parasympathetic cardiac nerve trunks were more frequent on right (70%) versus left sides (20%). The origin, frequency, and connections of the cardiac nerves and branches are highly variable in the fetus. Detailed knowledge of the normal neuroanatomy of the heart could be useful during cardiac neuromodulation procedures and in better understanding nervous pathologies of the heart.

Human lumbar sympathetic blockade: An anatomical study to address potential block failure.

The lumbar sympathetic block is often used to treat complex regional pain syndrome, but it seems to have a high failure rate. This study seeks anatomical explanations for this apparent failure in order to refine our block procedure. Two simulated sympathetic trunk blocks were carried out on four fresh, cryopreserved unembalmed human cadavers under fluoroscopic control at the L2 vertebral body level, followed by two further simulated blocks at the L4 vertebral body level on the other side. Dye was injected, and the areas were dissected following a specific protocol. We then describe the anatomy and the spread of the dye compared to the spread of the contrast medium on fluoroscopy. The ganglia were differently located at different vertebral levels, and differed among the cadavers. Following this anatomical clarification, we now prefer to perform lumbar sympathetic blocks at the fourth lumbar vertebra level, using an extraforaminal approach at the caudal end of ​​the vertebra, avoiding the anterolateral margin of the vertebral body at the midpoint.

Early reduction in postoperative pain is associated with improved long-term function after shoulder arthroplasty: a retrospective case series.

PURPOSE: Mixed modalities are frequently utilized in total shoulder arthroplasty (TSA) to control pain, improve patient satisfaction, reduce narcotics use and facilitate earlier discharge. We investigate the relationship between early postoperative pain control and long-term functional outcomes after shoulder arthroplasty. METHODS: A retrospective review identified 294 patients (314 shoulders) who underwent anatomic or reverse TSA and received a continuous cervical paravertebral nerve block perioperatively. Opioid and non-opioid analgesics were also available to the patients in an "as needed" capacity to augment perioperative pain control. In addition to demographic and surgical characteristics, the impact on functional outcomes of relative pain (i.e., a patient's subjective pain relative to the entire cohort), pain gradient (i.e., the slope of a patient's subjective pain), and opioid consumption during the first 24 h postoperatively were assessed. Shoulder function was assessed using validated outcome measures collected at 2 year follow-up. Outcomes were measured using American Shoulder and Elbow Surgeons questionnaire (ASES), Shoulder Pain and Disability Index (SPADI), SPADI-130, Raw and Normalized Constant Score, SST-12 and UCLA score. RESULTS: Patients younger than 65, females, reverse TSA, revisions, and preoperative opioid users had worse functional outcomes. On univariate analysis, increased pain perioperatively (> 50% percentile relative pain) was associated with decreased function at 2 years when analyzed with all seven outcome scores (P < .001 for all), reaching minimal clinically important difference (MCID) using the Constant Score. On multivariate analysis, increased pain in the first 24 h postoperatively (assessed on a continuous scale) was independently associated with worse ASES, SPADI, and SPADI-130 scores. Intraoperative ketamine administration and opioid consumption in the 24 h postoperative period did not influence long-term shoulder function. CONCLUSION: Patients reporting reduced pain after TSA demonstrated improved shoulder function with the Constant score at 2 years postoperatively in both univariate and multivariate analysis. Larger-scale investigation may be warranted to see if this is true for other functional outcome measures. LEVEL OF EVIDENCE: III, treatment study.

Prone Position MRI of the Lumbar Spine in Patients With Low Back Pain and/or Radiculopathy Refractory to Treatment.

BACKGROUND: There are patients with limiting low back pain (LBP) with or without radicular pain in whom conventional supine magnetic resonance imaging (MRI) show no causative pathology. Despite the limitations of dynamic axially loaded MRI examinations, these imaging studies have shown a striking ability to diagnose pathology unrecognized by conventional MRI. The difference in findings between supine and prone MRI with patient symptom correlation has not been studied. METHODS: Nineteen patients suffering from chronic moderate-to-severe LBP and/or radicular pain nonresponsive to conventional therapy or interventional treatment, were included in this study. Both supine and prone MRIs were performed and analyzed by a neuroradiologist. Specific supine and prone measurements were registered, including spinal canal area, lateral recess diameter, foraminal area, and ligamentum flavum thickness. Three-dimensional  MRI reconstructions of varying pathology patterns were created. RESULTS: The mean patient age was 48.7 years (range [R]: 30-69), 63% of patients were women. The mean numeric pain score  was 6.5 (R: 4-8). In 52.6% of cases, disc pathology/increased disc pathology was seen only on prone imaging. We observed significant buckling and increased thickness of the ligamentum flavum in 52.6 % of cases in the prone position that was absent from the supine MRIs. We also documented varying grades of spondylolisthesis and facet joint subluxation resulting in significant foraminal stenosis in 26.3% of prone cases not seen from supine MRIs. CONCLUSIONS: Four patterns of pathological findings have been identified by MRI performed in the prone position. These findings were not observed in the supine position. Prone MRI can be a significant and useful tool in the diagnosis and treatment of patients with back pain refractory to treatment whose conventional supine MRIs appeared unremarkable.

Microscopy of structures surrounding typical acupoints used in clinical practice and electron microscopic evaluation of acupuncture needles.

Although the general functionality and structures of acupoints have been studied, there has been little insight into their underlying morphology and physical characteristics. We describe the microanatomical structures surrounding acupoints, the electron microscopic appearance of the needles, and the physical effects of acupuncture needling on the fascia. We injected heparinized blood solution through thin needles at seven known and commonly used "sweat acupoints" in eight fresh, unembalmed, cryopreserved human cadavers to mark the needle positions, and later, during histological examination, to identify them. After the solution was injected, samples were dissected and prepared for histological examination. We examined 350 cross-sections of five different paraffin wax sections from each acupoint microscopically. Acupuncture needles were photographed and superimposed on the cross-sectioned tissues at similar magnifications. Needles were also examined under a scanning electron microscope to judge the roughness or smoothness of their surfaces. A greater conglomeration of nerve endings surrounded the acupoints than in tissues more than 1-3 cm distant from them. Nerve endings and blood vessels were in close contact with a complex network of membranes formed by interlacing collagen fibers, and were always enclosed within those collagen membranes. Nerve endings were found within hypodermis, muscles, or both. Scanning electron microscopy demonstrated the three-dimensional shapes and sizes of the needles, and the degree of roughness or smoothness of their polished external surfaces. We demonstrate a delicate arrangement of nerve endings and blood vessels enclosed within complex collagen membrane networks at acupoints within the hypodermis and muscle. This arrangement could explain why needling is an essential step in the acupuncture process that provides favorable outcomes in clinical practice.

Visceral versus somatic pain: an educational review of anatomy and clinical implications.

Somatic and visceral nociceptive signals travel via different pathways to reach the spinal cord. Additionally, signals regulating visceral blood flow and gastrointestinal tract (GIT) motility travel via efferent sympathetic nerves. To offer optimal pain relief and increase GIT motility and blood flow, we should interfere with all these pathways. These include the afferent nerves that travel with the sympathetic trunks, the somatic fibers that innervate the abdominal wall and part of the parietal peritoneum, and the sympathetic efferent fibers. All somatic and visceral afferent neural and sympathetic efferent pathways are effectively blocked by appropriately placed segmental thoracic epidural blocks (TEBs), whereas well-placed truncal fascial plane blocks evidently do not consistently block the afferent visceral neural pathways nor the sympathetic efferent nerves. It is generally accepted that it would be beneficial to counter the effects of the stress response on the GIT, therefore most enhanced recovery after surgery protocols involve TEB. The TEB failure rate, however, can be high, enticing practitioners to resort to truncal fascial plane blocks. In this educational article, we discuss the differences between visceral and somatic pain, their management and the clinical implications of these differences.

Spinal arachnoid sleeves and their possible causative role in cauda equina syndrome and transient radicular irritation syndrome.

INTRODUCTION: We have previously described arachnoid sleeves around cauda equina nerve roots, but at that time we did not determine whether injections could be performed within those sleeves. The purpose of this observational study was to establish whether the entire distal orifice of a spinal needle can be accommodated within an arachnoid sleeve. MATERIALS AND METHODS: We carefully dissected the entire dural sacs off four fresh cadavers, opened them by longitudinal incision, and immersed them in saline. Under direct vision, we penetrated the cauda equina roots nerves traveling almost vertically downward at 30 locations each with a 27- and a 25-G pencil-point needle (60 punctures total). We captured the images with a stereoscopic camera. RESULTS: The nerve root offered no noticeable resistance to needle entry. Although the arachnoid sleeves could not be identified with the naked eye, they were translucent but visible under microscopy. In 21 of 30 attempts with a 27-gauge needle, and in 20 of 30 attempts with a 25-gauge needle, the distal orifice of the spinal needle was completely within the arachnoid sleeve. CONCLUSION: It seems possible to accommodate the distal orifice of a 25- or a 27-gauge pencil-point spinal needle completely within the space of the arachnoid sleeve. An injection within this sleeve could potentially lead to a neurological syndrome, as we have previously proposed.

A reliable septum exists between the lateral cord and medial and posterior cords in the costoclavicular region: Clinical and microanatomical considerations in brachial plexus anesthetic blockade.

BACKGROUND AND OBJECTIVES: The ultrasound-guided proximal infraclavicular costoclavicular block (PICB) appears popular but its results are inconsistent. We sought an accurate demonstration of septae formed between the brachial plexus cords. METHODS: We performed in-plane, lateral-to-medial PICBs on 120 patients and recorded images. Once the most superficial lateral cord component was entered, a 0.4-0.6 mA current was applied to confirm needle placement; 5 ml of local anesthetic (LA) solution was then injected and its spread was observed and recorded. As the needle was advanced, the presence or absence of a hyperechoic linear structure was noted before the deeper compartment was reached, specifically looking for the possible displacement of such a septum. RESULTS: Upon initial scanning, a septum was observed in 67 of the 120 patients (46.2%). However, there was clear displacement of a linear septum between the lateral cord compartment and the medial and posterior cord compartments that prevented spread between the compartments in 94.16% of patients. Piercing the septum evoked motor responses from the medial or posterior cord. The same anatomical regions were studied microanatomically by analyzing cross-sections obtained with the same approach angle as the ultrasound probe. CONCLUSIONS: Intraplexus fascial septae that bundled the medial and posterior cords into one compartment and separated them from the lateral cord were demonstrated and confirmed microanatomically. This suggests the need for two separate injections (or two separate catheter placements for continuous peripheral nerve blockade) into the superficial and deep compartments to ensure LA spread around all three cords of the brachial plexus at this level.

Case series of fluoroscopic findings and 3D reconstruction of human spinal MRIs of the space of Okada.

OBJECTIVE: To better understand the unexpected spread of contrast medium observed by conventional fluoroscopic X-ray images during standard neuraxial techniques used in the treatment of pain. The support of 3D reconstruction of MRI images of structures within the lumbar spine was used to better understand the space of Okada. METHODS: Lumbar facet joint and epidural corticosteroid injections in five patients under fluoroscopic guidance with loss of resistance to air or saline to identify the facet joints or epidural space. Next, in a retrospective study, the authors examined the retrodural space of Okada and the neighboring tissues with 3D reconstruction of spinal MRIs of seven patients without any demonstrable spinal pathology to better understand the characteristics of the space of Okada. RESULTS: Contrast medium spread to the ipsilateral and contralateral sides was observed in five patients. The contralateral spread was thought to be through the retrodural space of Okada, which is a potential space between the anterior surface of the vertebral lamina and the posterior surface of the ligamentum flavum. It facilitates communication between the contralateral articular facet joints of the spine. CONCLUSIONS: This study provides new evidence for the existence of the space of Okada where an unexpected contralateral spread occurred following facet joint and attempted epidural injection. The 3D reconstructions of MRIs may help us better understand the nature of the retrodural space of Okada and its clinical implications.

A Simple, Personalized Opioid Stratification Pathway Dramatically Reduces Opioid Utilization.

Orthopaedic surgeons account for the largest proportion of opioid prescriptions in the United States among surgical specialties. In total joint arthroplasty, increased opioid use has been associated with poorer clinical and functional outcomes. Despite an abundance of literature on opioid mitigation strategies, most fail to provide personalized prescriptions. Typically, most protocols prescribe the same opioid regimen regardless of patient factors or the extent of the planned procedure. We present a simple opioid stratification pathway that can be used by physicians and office staff as they prepare patients for arthroplasty. We have found this to be easy to implement, effective, and sustainable at a tertiary academic institution and allows for iterative improvements over time.

Revision Arthroplasty Does Not Require More Opioids Than Primaries: A Review of Prescribing Practices After Implementation of a Structured Perioperative Pain Management Strategy.

BACKGROUND: There is a growing body of literature on opioid mitigation strategies following total joint arthroplasty. However, these have almost exclusively been studied in populations undergoing primary procedures, with revision arthroplasty historically thought to be more resistant due to procedural variability and complexity. We report on opioid utilization for revision arthroplasty following implementation of a structured, standardized opioid reduction strategy. METHODS: Beginning January 2015, a comprehensive multidisciplinary pain protocol was developed and applied universally to all patients undergoing hip and knee arthroplasty, including revisions, without exclusion. We performed a retrospective review of opioid prescription trends for the revision arthroplasty subgroup between January 2014 and July 2018, with the first year serving as a baseline for comparison. Inpatient and outpatient opioid prescription data, inpatient satisfaction scores, and quality metrics were also reviewed. RESULTS: We identified 1273 revision arthroplasty cases in the study period. There was a significant reduction in average oral morphine equivalents utilized per procedure when comparing preintervention and postimplementation values. Overall, inpatient prescriptions decreased 24.1% and outpatient utilization decreased 62.4% over the study period. Significant reductions were seen in both the total hip (60.6%) and total knee (64.0%) subgroups. Although revision arthroplasty patients were prescribed 32.5% more oral morphine equivalents at baseline, at year 5 there was no significant difference in outpatient prescriptions between primary and revision subgroups. CONCLUSION: At our institution, a standardized opioid reduction strategy has resulted in marked reduction in opioid prescriptions for revision arthroplasty patients in line with generally successful reductions for primary arthroplasty. More importantly, with this approach, revision arthroplasty patients required no more outpatient opioids than their primary counterparts. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.