Biomechanical characterization of cadaveric brachial plexus regions using uniaxial tensile tests.

INTRODUCTION: The proximal regions of the brachial plexus (roots, trunks) are more susceptible to permanent damage due to stretch injuries than the distal regions (cords, terminal branches). A better description of brachial plexus mechanical behavior is necessary to better understand deformation mechanisms in stretch injury. The purpose of this study was to model the biomechanical behavior of each portion of the brachial plexus (roots, trunks, cords, peripheral nerves) in a cadaveric model and report differences in elastic modulus, maximum stress and maximum strain. METHODS: Eight cadaveric plexi, divided into 47 segments according to regions of interest, underwent cyclical uniaxial tensile tests, using a BOSE® Electroforce® 3330 and INSTRON® 5969 material testing machines, to obtain the stress and strain histories of each specimen. Maximum stress, maximum strain and elastic modulus were extracted from the load-displacement and stress-strain curves. Statistical analyses used 1-way ANOVA with post-hoc Tukey HSD (Honestly Significant Difference) and Mann-Whitney tests. RESULTS: Mean elastic modulus was 8.65 MPa for roots, 8.82 MPa for trunks, 22.44 MPa for cords, and 26.43 MPa for peripheral nerves. Differences in elastic modulus and in maximum stress were statistically significant (p < 0.001) between proximal (roots, trunks) and distal (cords, peripheral nerves) specimens. CONCLUSIONS: Proximal structures demonstrated significantly smaller elastic modulus and maximum stress than distal structures. These data confirm the greater fragility of proximal regions of the brachial plexus.

Biomechanical characterization of cadaveric brachial plexus microstructure.

INTRODUCTION: Peripheral nerves consist of axons and connective tissue. The amount of connective tissue in peripheral nerves such as the brachial plexus varies proximally to distally. The proximal regions of the brachial plexus are more susceptible to stretch injuries than the distal regions. A description of the mechanical behavior of the peripheral nerve components is necessary to better understand the deformation mechanisms during stretch injuries. The purpose of this study was to model the biomechanical behavior of each component of the peripheral nerves (fascicles, connective tissue) in a cadaveric model and report differences in elastic modulus, maximum stress and maximum strain. METHODS: Forty-six specimens of fascicles and epi-perineurium were subjected to cyclical uniaxial tensile tests to obtain the stress and strain histories of each specimen, using a BOSE® Electroforce® 3330 and INSTRON® 5969 materials testing machines. Maximum stress, maximum strain and elastic modulus were extracted from the load-displacement and stress-strain curves, and analyzed using Mann-Whitney tests. RESULTS: Mean elastic modulus was 6.34 MPa for fascicles, and 32.1 MPa for connective tissue. The differences in elastic modulus and maximum stress between fascicles and connective tissue were statistically significant (p < 0.001). CONCLUSIONS: Peripheral nerve connective tissue showed significantly higher elastic modulus and maximum stress than fascicles. These data confirm the greater fragility of axons compared to connective tissue, suggesting that the greater susceptibility to stretch injury in proximal regions of the brachial plexus might be related to the smaller amount of connective tissue.

Decellularized porcine peripheral nerve based injectable hydrogels as a Schwann cell carrier for injured spinal cord regeneration.

Objective.To develop a clinically relevant injectable hydrogel derived from decellularized porcine peripheral nerves and with mechanical properties comparable to native central nervous system (CNS) tissue to be used as a delivery vehicle for Schwann cell transplantation to treat spinal cord injury (SCI).Approach.Porcine peripheral nerves (sciatic and peroneal) were decellularized by chemical decellularization using a sodium deoxycholate and DNase (SDD) method previously developed by our group. The decellularized nerves were delipidated using dichloromethane and ethanol solvent and then digested using pepsin enzyme to form injectable hydrogel formulations. Genipin was used as a crosslinker to enhance mechanical properties. The injectability, mechanical properties, and gelation kinetics of the hydrogels were further analyzed using rheology. Schwann cells encapsulated within the injectable hydrogel formulations were passed through a 25-gauge needle and cell viability was assessed using live/dead staining. The ability of the hydrogel to maintain Schwann cell viability against an inflammatory milieu was assessedin vitrousing inflamed astrocytes co-cultured with Schwann cells.Mainresults. The SDD method effectively removes cells and retains extracellular matrix in decellularized tissues. Using rheological studies, we found that delipidation of decellularized porcine peripheral nerves using dichloromethane and ethanol solvent improves gelation kinetics and mechanical strength of hydrogels. The delipidated and decellularized hydrogels crosslinked using genipin mimicked the mechanical strength of CNS tissue. The hydrogels were found to have shear thinning properties desirable for injectable formulations and they also maintained higher Schwann cell viability during injection compared to saline controls. Usingin vitroco-culture experiments, we found that the genipin-crosslinked hydrogels also protected Schwann cells from astrocyte-mediated inflammation.Significance. Injectable hydrogels developed using delipidated and decellularized porcine peripheral nerves are a potential clinically relevant solution to deliver Schwann cells, and possibly other therapeutic cells, at the SCI site by maintaining higher cellular viability and increasing therapeutic efficacy for SCI treatment.

NerveTracker: a Python-based software toolkit for visualizing and tracking groups of nerve fibers in serial block-face microscopy with ultraviolet surface excitation images.

Significance: Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A serial block-face microscopy method [three-dimensional microscopy with ultraviolet surface excitation (3D-MUSE)] has been developed to image nerves over extended depths ex vivo. To routinely visualize and track nerve fibers in these datasets, a dedicated and customizable software tool is required. Aim: Our objective was to develop custom software that includes image processing and visualization methods to perform microscopic tractography along the length of a peripheral nerve sample. Approach: We modified common computer vision algorithms (optic flow and structure tensor) to track groups of peripheral nerve fibers along the length of the nerve. Interactive streamline visualization and manual editing tools are provided. Optionally, deep learning segmentation of fascicles (fiber bundles) can be applied to constrain the tracts from inadvertently crossing into the epineurium. As an example, we performed tractography on vagus and tibial nerve datasets and assessed accuracy by comparing the resulting nerve tracts with segmentations of fascicles as they split and merge with each other in the nerve sample stack. Results: We found that a normalized Dice overlap ( Dice norm ) metric had a mean value above 0.75 across several millimeters along the nerve. We also found that the tractograms were robust to changes in certain image properties (e.g., downsampling in-plane and out-of-plane), which resulted in only a 2% to 9% change to the mean Dice norm values. In a vagus nerve sample, tractography allowed us to readily identify that subsets of fibers from four distinct fascicles merge into a single fascicle as we move ∼ 5 mm along the nerve's length. Conclusions: Overall, we demonstrated the feasibility of performing automated microscopic tractography on 3D-MUSE datasets of peripheral nerves. The software should be applicable to other imaging approaches. The code is available at https://github.com/ckolluru/NerveTracker.

Nonalcoholic Fatty Liver Disease in Shift Workers and Its Effect on Peripheral Nerve Conduction: A Cross-Sectional Study.

Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Occupation emerges as a significant factor influencing the occurrence of NAFLD. Research indicates that individuals engaged in shift work face an elevated risk of NAFLD, alongside obesity and T2DM, attributed to disruptions in their circadian rhythm, which precipitate hepatic steatosis and inflammation. Remarkably, peripheral neuropathy has been observed in conjunction with advanced liver disorders and NAFLD in the general population. However, the correlation between NAFLD and peripheral neuropathy remains unestablished in shift workers. Objective To identify NAFLD in seemingly healthy rotating shift workers and assess any potential impact of NAFLD on nerve function in this demographic. Methods This cross-sectional study involved 73 apparently healthy nonalcoholic security guards (aged 35 to 60 years) working in rotating shifts. The study included a comprehensive assessment, beginning with a medical history, an evaluation of physical activity, and anthropometric measurements. Confirmation of NAFLD was achieved through abdominal ultrasonography (USG), followed by the analysis of biochemical parameters. Motor and sensory nerve conduction studies (NCS) were conducted on participants with normal vitamin B12 levels using the Aleron electromyograph (EMG) machine (Recorders and Medicare Systems Private Ltd, Budanpur, India). The evaluation encompassed the Median and Common Peroneal motor nerves, as well as Median and Sural sensory nerves. Recorded parameters for motor nerves included distal motor latency (DML), compound muscle action potential (CMAP) amplitude, conduction velocity (CV), and F-wave minimum latency (F-wave), while sensory nerve parameters comprised sensory onset latency (SOL), sensory nerve action potential (SNAP) amplitude, and CV. Results Among 73 healthy security guards working in rotating shifts, 76.1% were diagnosed with NAFLD through abdominal ultrasound. Following participant withdrawals and exclusions due to vitamin B12 deficiency, a comparison of NCS parameters between NAFLD (n=24) and Non-NAFLD (n=12) groups revealed no significant disparities in motor or sensory parameters, except for a slightly diminished CMAP amplitude in the peroneal nerve of NAFLD subjects (8.21±2.83mV vs ±10.22±2.30 mV, p< 0.040). However, these differences fell within normal ranges, indicating no notable impact on peripheral nerve conduction in the presence of NAFLD. Conclusion The results indicate a high prevalence of NAFLD among individuals working rotating shifts. Moreover, the investigation suggests that despite the presence of NAFLD, there is no discernible influence on motor and sensory peripheral nerve conduction, particularly in common peroneal, median, and sural nerves.

Study on the relationship between peripheral nerve fiber types and levodopa usage in Parkinson's disease.

Background and purpose:

The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.

This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale. 

Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups. 

The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).

Development of a major histocompatibility complex class II conditional knockout mouse to study cell-specific and time-dependent adaptive immune responses in peripheral nerves.

INTRODUCTION/AIMS: The precise relationship between molecular mimicry and tissue-specific autoimmunity is unknown. Major histocompatibility complex (MHC) class II antigen presenting cell-CD4+ T-cell receptor complex interactions are necessary for adaptive immunity. This study aimed to determine the role of endoneurial endothelial cell MHC class II in autoimmune polyneuropathy. METHODS: Cryopreserved Guillain-Barré syndrome (GBS) patient sural nerve biopsies and sciatic nerves from the severe murine experimental autoimmune neuritis (sm-EAN) GBS model were studied. Cultured conditional ready MHC Class II antigen A-alpha chain (H2-Aa) embryonic stem cells were used to generate H2-Aaflox/+ C57BL/6 mice. Mice were backcrossed and intercrossed to the SJL background to generate H2-Aaflox/flox SJL mice, bred with hemizygous Tamoxifen-inducible von Willebrand factor Cre recombinase (vWF-iCre/+) SJL mice to generate H2-Aaflox/flox; vWF-iCre/+ mice to study microvascular endothelial cell adaptive immune responses. Sm-EAN was induced in Tamoxifen-treated H2-Aaflox/flox; vWF-iCre/+, H2-Aaflox/flox; +/+, H2-Aa+/+; vWF-iCre/+ and untreated H2-Aaflox/flox; vWF-iCre/+ adult female SJL mice. Neurobehavioral, electrophysiological and histopathological assessments were performed at predefined time points. RESULTS: Endoneurial endothelial cell MHC class II expression was observed in normal and inflamed human and mouse peripheral nerves. Tamoxifen-treated H2-Aaflox/flox; vWF-iCre/+ mice were resistant to sm-EAN despite extensive MHC class II expression in lymphoid and non-lymphoid tissues. DISCUSSION: A conditional MHC class II knockout mouse to study cell- and time-dependent adaptive immune responses in vivo was developed. Initial studies show microvascular endothelial cell MHC class II expression is necessary for peripheral nerve specific autoimmunity, as advocated by human in vitro adaptive immunity and ex vivo transplant rejection studies.

Central and Peripheral Motor Conduction Studies by Single-Pulse Magnetic Stimulation.

Single-pulse magnetic stimulation is the simplest type of transcranial magnetic stimulation (TMS). Muscle action potentials induced by applying TMS over the primary motor cortex are recorded with surface electromyography electrodes, and they are called motor-evoked potentials (MEPs). The amplitude and latency of MEPs are used for various analyses in clinical practice and research. The most commonly used parameter is the central motor conduction time (CMCT), which is measured using motor cortical and spinal nerve stimulation. In addition, stimulation at the foramen magnum or the conus medullaris can be combined with conventional CMCT measurements to evaluate various conduction parameters in the corticospinal tract more precisely, including the cortical-brainstem conduction time, brainstem-root conduction time, cortical-conus motor conduction time, and cauda equina conduction time. The cortical silent period is also a useful parameter for evaluating cortical excitability. Single-pulse magnetic stimulation is further used to analyze not only the central nervous system but also the peripheral nervous system, such as for detecting lesions in the proximal parts of peripheral nerves. In this review article we introduce four types of single-pulse magnetic stimulation-of the motor cortex, spinal nerve, foramen magnum, and conus medullaris-that are useful for the diagnosis, elucidation of pathophysiology, and evaluation of clinical conditions and therapeutic effects. Single-pulse magnetic stimulation is a clinically useful technique that all neurologists should learn.

SQUID magnetoneurography: an old-fashioned yet new tool for noninvasive functional imaging of spinal cords and peripheral nerves.

We are engaged in the development and clinical application of a neural magnetic field measurement system that utilizes biomagnetic measurements to observe the activity of the spinal cord and peripheral nerves. Unlike conventional surface potential measurements, biomagnetic measurements are not affected by the conductivity distribution within the body, making them less influenced by the anatomical structure of body tissues. Consequently, functional testing using biomagnetic measurements can achieve higher spatial resolution compared to surface potential measurements. The neural magnetic field measurement, referred to as magnetoneurography, takes advantage of these benefits to enable functional testing of the spinal cord and peripheral nerves, while maintaining high spatial resolution and noninvasiveness. Our magnetoneurograph system is based on superconducting quantum interference devices (SQUIDs) similar to the conventional biomagnetic measurement systems. Various design considerations have been incorporated into the SQUID sensor array structure and signal processing software to make it suitable for detecting neural signal propagation along spinal cord and peripheral nerve. The technical validation of this system began in 1999 with a 3-channel SQUID system. Over the course of more than 20 years, we have continued technological development through medical-engineering collaboration, and in the latest prototype released in 2020, neural function imaging of the spinal cord and peripheral nerves, which could also be applied for the diagnosis of neurological disorders, has become possible. This paper provides an overview of the technical aspects of the magnetoneurograph system, covering the measurement hardware and software perspectives for providing diagnostic information, and its applications. Additionally, we discuss the integration with a helium recondensing system, which is a key factor in reducing running costs and achieving practicality in hospitals.

Peripheral nervous system lymphatic vessels: A simple delivery route to promote nerve regeneration.

The structural and functional features of lymphatic vessels in the peripheral nervous system (pLVs) is still unclear. Here, we clarify the existence of pLVs in rats, PROX1-EGFP transgenic mice and human, and exhibit a clear three-dimensional structure for helping understand its structural features. Moreover, two specific phenotypes of lymphatics endothelial cells (Rnd1Hi LECs and Ccl21Hi LECs) in peripheral nerves are well characterized by single-cell sequencing. Subsequently, the ability of trans-lymphatic delivery to peripheral nerves via pLVs has been dynamically demonstrated. After peripheral nerve injury (PNI), extensive lymphangiogenesis occurs in the lesion area and further enhances the efficiency of retrograde lymphatic-nerve transport. In PNI animal models, subcutaneously footpad-injected exosomes are efficiently delivered to sciatic nerve via pLVs which can promote nerve regeneration. The trans-lymphatic delivery to peripheral nerves via pLVs can subtly bypass BNB which provides an easy and alternative delivery route for PNI treatment.

Applications of Tissue Clearing in Central and Peripheral Nerves.

The techniques of tissue clearing have been proposed and applied in anatomical and biomedical research since the 19th century. As we all know, the original study of the nervous system relied on serial ultrathin sections and stereoscopic techniques. The 3D visualization of the nervous system was established by software splicing and reconstruction. With the development of science and technology, microscope equipment had constantly been upgraded. Despite the great progress that has been made in this field, the workload is too complex, and it needs high technical requirements. Abundant mistakes due to manual sections were inescapable and structural integrity remained questionable. According to the classification of tissue transparency methods, we introduced the latest application of transparency methods in central and peripheral nerve research from optical imaging, molecular markers and data analysis. This review summarizes the application of transparent technology in neural pathways. We hope to provide some inspiration for the continuous optimization of tissue clearing methods.

Nerve Preparation and Recordings for Pharmacological Tests of Sensory and Nociceptive Fiber Conduction Ex Vivo.

Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides a valuable model to investigate nerve function ex vivo; however, it requires specific knowledge to ensure successful and stable measurements. Although the methodology for sciatic nerve recordings has long existed, a method for reliable and long-lasting recordings from myelinated and non-myelinated (nociceptive) fibers still needs to be adapted for pharmacological testing. This protocol takes benefits from epineurium sheath removal for pharmacological tests and provides a detailed description of how to make accurate nerve preparations, from the dissection and handling of nerves to epineurium cleaning, fabrication of adaptable suction electrodes for appropriate fiber stimulation and recordings, setting of electrophysiological protocols for compound action potential (CAP) recordings to distinguish between myelinated and non-myelinated (nociceptive) fibers, and finally to the analysis of the datasets of CAP components. We also demonstrate the feasibility of CAP recordings from individual branches in epineurium-free nerve preparations and provide clues to help retain nerve viability and maintain stable recordings over time. Although a sciatic nerve preparation was used here, the methodology can be applied to other nerve-type preparations. Key features • Detailed and simplified protocol for peripheral nerve preparation for recording sensory inputs ex vivo. • Recordings from myelinated and non-myelinated (nociceptive) fibers can be performed hours after nerve preparation. • The protocol involves the epineurium removal to facilitate drug permeability into nerve tissue for pharmacological tests. • The protocol allows physiological and pathological studies (pain/chronic pain conditions).

Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves.

BACKGROUND: In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI. METHODS: Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis. RESULTS: Simplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847-0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy. CONCLUSIONS: In peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner's main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction. RELEVANCE STATEMENT: DTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction. KEY POINTS: • In peripheral nerves, DTI parameters can be approximated using only three gradient vectors. • The simplified model achieves a similar diagnostic performance as a standard DTI. • The simplified model allows for a significant acceleration of image acquisition. • This can help to introduce multi-b-value DTI techniques into clinical practice.

Sanford Larson, MD, PhD: a pioneering neurosurgeon, scientist, and educator.

Dr. Sanford Larson, MD, PhD (1929-2012), was an influential figure in spinal neurosurgery. Dr. Larson played a pivotal role in establishing neurosurgery's foothold in spinal surgery by serving as the inaugural chair of the Joint Section on Disorders of the Spine and Peripheral Nerves and as a president of the Cervical Spine Research Society. He made many advances in spine care, most notably the modification and popularization of the lateral extracavitary approach to the thoracolumbar spine. Dr. Larson established the neurosurgery residency program at the Medical College of Wisconsin; he also instituted the program's spine fellowship, the first in the United States for neurological surgeons. His mentorship produced numerous leaders in organized neurosurgery and neurosurgical education, including Edward Benzel, MD, Dennis Maiman, MD, PhD, Joseph Cheng, MD, Shekar Kurpad, MD, PhD, and Christopher Wolfla, MD. Dr. Larson was a prominent leader in spinal neurosurgery and his legacy carries on today through his contributions to research, education, and surgical technique.

The paraneurium and the tumefactive appearance of peripheral nerve neurolymphomatosis: illustrative case.

BACKGROUND: Peripheral neurolymphomatosis (NL) is an often-misdiagnosed condition characterized by lymphomatous infiltration within the peripheral nerves. Its rarity and complexity frequently result in delayed diagnosis and suboptimal patient outcomes. This study aims to elucidate the role of the paraneurium (circumneurium) in NL, emphasizing its diagnostic and therapeutic significance. OBSERVATIONS: A 72-year-old man presented with lesions on his right lower eyelid. Initial diagnostics were inconclusive until an excisional biopsy confirmed extranodal marginal zone lymphoma. Following a complete metabolic response to rituximab treatment, the patient relapsed 14 months later with progressive lymphoma and bilateral sciatic nerve involvement, as confirmed by positron emission tomography-computed tomography and magnetic resonance imaging. LESSONS: This paper underscores the critical role of the paraneurium in NL, enhancing understanding of its pathophysiology. Integrating advanced imaging techniques have proved essential in accurately identifying neurolymphomatous involvement within the paraneurium. This study paves the way for more effective management strategies in NL and similar conditions, focusing on improving patient care and outcomes.

Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient.

Background: Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm. Methods: We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment. Results: MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control. Conclusion: Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.

Histological and morphological development of the prepuce from birth to prepubertal age.

PURPOSE: To study the histological changes of the preputial tissue from birth to prepubertal age in order to define unnoticed morphological changes. MATERIALS AND METHODS: Prepuce samples were obtained from 79 healthy boys who underwent routine ritual circumcision. Specimens were divided into six groups according to the boys' age: newborn, 0-1 year of age, 2-3 years of age, 4-5 years of age, 6-7 years of age, and 8-9 years of age. Histologic analysis of the specimens was performed by H&E, Masson's trichrome, Verhoeff-Von Gieson, immunohistochemical staining. RESULTS: Microscopic examinations showed that average epithelial thickness increased after the neonatal period (p=0.001). When collagen fiber density was evaluated, no significant differences between groups were found (p=0.083). When the elastic fibers in the dermis were evaluated, it was determined that the number and thickness of elastic fibers increased with age. Immunohistochemical examinations showed that the number of peripheral nerves marked with S100 was lower in the neonatal period than at other ages (p=0.048). When the vessels marked with CD105 antibody were counted, there was no significant difference between the groups (p=0.078). CONCLUSIONS: This is the first study to examine the age-related structure of connective tissue elements in the foreskin. Our results showed that the prepuce's prepubertal maturation process is continuous, and the first 2 years of life are appropriate not only in relation to the physiological effects of age but also the optimum structural changes for wound healing, such as vessel diameter, epithelium thickness, peripheral nerve count.

Popliteal Cyst Compressive Tibial Neuropathy and Venous Insufficiency: A Case Report.

Popliteal cysts are a collection of synovial fluid found in the popliteal fossa that typically form in adults in association with traumatic injuries, degenerative conditions, or inflammatory arthritis of the knee. While often asymptomatic, popliteal cysts may become problematic as enlarging and ruptured cysts may compress surrounding neurovascular structures, resulting in lower extremity edema or peripheral neuropathy. We report a unique case of a symptomatic popliteal cyst in a patient with both compressive neuropathy and venous congestion in the setting of a non-ruptured popliteal cyst after a surgically repaired intraarticular injury. Magnetic resonance imaging (MRI) showed a synovial cyst abutting the posterior neurovascular bundle and evidence of avascular necrosis. An open posterior cyst decompression was done, and the patient was able to report significant symptomatic improvement over the course of two weeks postoperatively. The previously noted varicose veins also demonstrated noticeable resolution. While relatively common, popliteal cysts may require prompt surgical decompression in order to provide effective symptomatic relief.

Subcutaneous injection of lidocaine around ischemic ankle provides safe and effective foot analgesia in patients with critical limb ischemia.

OBJECTIVE: It is often difficult to alleviate foot pain associated with critical limb ischemia (CLI) using common analgesics. Neuraxial block is contraindicated in anticoagulant therapy. This study was designed to determine the response to subcutaneous injection of lidocaine around the network of peripheral nerves around the ankle in patients with CLI pain on anticoagulants and antiplatelets. METHODS: Sixteen patients with CLI pain in the foot were enrolled in this double-blind placebo-controlled crossover study. Patients were randomized to receive either 2% lidocaine or saline via catheters inserted into the subcutaneous area around the ankle. After recurrence of pain, the patients were crossed over to receive the alternative treatment. Pain was assessed with a numerical rating scale (NRS) before and 15 min after injection. Patients used a descriptive scale to grade pain control and were asked to determine the duration of analgesia in each arm of the study. RESULTS: No serious complications including protracted bleeding occurred. Lidocaine significantly decreased the NRS on movement from 10 (6, 10) [median (range)] to 2 (0, 10) (p < .001), and the differences in the Δ change in NRS between lidocaine and placebo were significant (p = .009). Of the 16 patients, 14 patients were very satisfied after lidocaine but only one described the same after saline. The effect of lidocaine and placebo lasted 11 (0, 28) and 1 (0, 22) h, respectively. CONCLUSION: Subcutaneous injection of lidocaine around the ischemic ankle affectively alleviated pain in patients with CLI without serious adverse effects under anticoagulant therapy.

Peripheral nerve decompression for pain relief in the setting of previous obstetrical brachial plexus injury: a retrospective case series.

PURPOSE: In children with previous obstetrical brachial plexus injury (OBPI), upper extremity pain is present in 45 to 66% of patients. Recent literature reports this as musculoskeletal or neuropathic in nature. The purpose of the study is to demonstrate that peripheral nerve decompression, and neurolysis may be an effective treatment for patients with upper extremity pain in the context of previous OBPI. METHODS: A retrospective chart review was performed on patients undergoing peripheral nerve decompression and neurolysis after OBPI by senior author. The primary outcome assessed was pain, and secondary outcome measure was range of motion of the wrist and elbow. Outcome measures were assessed preoperatively as well as at their subsequent follow-up. RESULTS: Six patients were included, with a mean age of 14 years old at time of decompression. Three patients underwent median nerve, two patients underwent ulnar nerve, and one patient underwent posterior interosseous nerve decompression. There was a substantial improvement in pain post-operatively, demonstrated by reduction or resolution of subjective pain in all patients and resolution of Tinel's sign. There was a modest improvement in range of motion. CONCLUSION: This study demonstrates an improvement in subjective pain and range of motion after decompression and neurolysis in small subset of OBPI patients. It generates the hypothesis that peripheral nerve compression is a source of pain that can be addressed in this population. Future research should focus on confirming this hypothesis and assessing treatment options on a larger scale.