Magnetic Resonance Neurography of the Foot and Ankle.

Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.

[Discussion on the relationship between pathological changes of sciatic nerve and Sarm1 protein expression in rats with n-hexane poisoning].

Objective: To explore the potential evidence of active peripheral nerve necrosis when n-hexane produces toxic effects on peripheral nerves. Methods: In May 2023, 36 SPF grade SD male rats with a body weight of 200-220 g were divided into 4 groups with 9 rats in each group and given normal saline and different doses of n-hexane (168, 675, 2 700 mg/kg) by gavage for 6 consecutive weeks (5 days/week). Three rats in each group were killed at the 2nd, 4th and 6th week, respectively. The spinal cord to sciatic nerve tissue was broken and the supernatant was extracted for SDS-PAGE protein isolation. The expression level of Sarm1 protein was analyzed with the ß-Actin color strip of internal reference protein by Western blot. The expression of Sarm1 protein was analyzed by the gray ratio of the two. At the 6th week, the sciatic nerve sections of the each group were observed by light microscope and electron microscope. Results: The number of axons was obviously reduced by light microscopy. According to electron microscope, myelin lesions were mainly local disintegration, deformation, and different thickness. The deformation of axonal surface became smaller. The axons in the nerve bundle membrane showed degeneration and reduction. The gray ratio of Sarm1 protein and internal reference protein bands in each group had no significant change at the second week of exposure, and the ratio of SARM1 protein to internal reference protein bands was 1.47 in the high dose group at the fourth week, and 1.51 and 1.89 in the middle and high dose group at the sixth week, respectively. Conclusion: Waller's degeneration was observed in sciatic neuropathologic manifestations of n-hexane-poisoned rats, and the expression level of Sarm1 protein increased.

[Peripheral nerves' function recovery by intratissual electric stimulation]. / Vosstanovlenie funktsii perifericheskikh nervov vnutritkanevoi elektrostimulyatsiei.

An intratissual electrical stimulation, accompanied by irritation of their central neurons, is used to recover the function of damaged peripheral nerves. Treatment results exceeded those with the use of cutaneous electrical stimulation, which is confirmed by comparative results of trial animal experiments. The time and quality of peripheral nerves' function recovery in comparison of intratissual and cutaneous electrical stimulation methods remain unknown. OBJECTIVE: To evaluate the time and quality of peripheral nerves' functions recovery after their suturing and conducting two different methods of electrical stimulation, namely intratissual and cutaneous, in projection of central neurons of damaged spinal nerves in the postoperative period. MATERIAL AND METHODS: The basic technical parameters of the method of peripheral nerves' functions recovery in the postoperative period were ptacticed. Postoperative rehabilitation treatment was performed in 77 patients with traumatic peripheral nerves' injuries at the level of the forearm: in 42 with intratissual electrical stimulation, in 35 - using cutaneous one with similar characteristics of electrical current and concomitant pharmacological therapy. The follow-up duration was 2 years. RESULTS: A significant (in 4-6 times) reduction in time of treatment and a greater improvement in qualitative indicators when using intratissual electrical stimulation compared to the use of cutaneous stimulation were obtained. The effectiveness of the restorative therapy was dependent on the number of procedures, and a complete recovery of the damaged peripheral nerves' functions was observed after three courses of intratissual electrical stimulation. CONCLUSION: The time and degree of recovery of peripheral nerves' functions depends on the functional activity of their central neurons at the level of the spinal cord. The activation of these neurons by low-frequency electrical current allows to activate their trophic function. Thus, the cutaneous electrical stimulation does not cause the necessary level of irritation of the neurons due to the fact that the skin is a barrier to electrical current, which reduces its impact in 200-500 times. The intratissual electrical stimulation allows to solve the problem by supplying the needle-electrode much closer to the «target¼. The proposed method of intratissual electrical stimulation has shown its advantage over cutaneous electrical stimulation, significantly reducing the duration of the restorative treatment and increasing its qualitative indicators.

3D fascicular reconstruction of median and ulnar nerve: initial experience and comparison between high-resolution ultrasound and MR microscopy.

BACKGROUND: The complex anatomy of peripheral nerves has been traditionally investigated through histological microsections, with inherent limitations. We aimed to compare three-dimensional (3D) reconstructions of median and ulnar nerves acquired with tomographic high-resolution ultrasound (HRUS) and magnetic resonance microscopy (MRM) and assess their capacity to depict intraneural anatomy. METHODS: Three fresh-frozen human upper extremity specimens were prepared for HRUS imaging by submersion in a water medium. The median and ulnar nerves were pierced with sutures to improve orientation during imaging. Peripheral nerve 3D HRUS scanning was performed on the mid-upper arm using a broadband linear probe (10-22 MHz) equipped with a tomographic 3D HRUS system. Following excision, nerves were cut into 16-mm segments and loaded into the MRM probe of a 9.4-T system (scanning time 27 h). Fascicle and nerve counting was performed to estimate the nerve volume, fascicle volume, fascicle count, and number of interfascicular connections. HRUS reconstructions employed artificial intelligence-based algorithms, while MRM reconstructions were generated using an open-source imaging software 3D slicer. RESULTS: Compared to MRM, 3D HRUS underestimated nerve volume by up to 22% and volume of all fascicles by up to 11%. Additionally, 3D HRUS depicted 6-60% fewer fascicles compared to MRM and visualized approximately half as many interfascicular connections. CONCLUSION: MRM demonstrated a more detailed fascicular depiction compared to 3D HRUS, with a greater capacity for visualizing smaller fascicles. While 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, their limitations in depicting interfascicular connections and small fascicles within clusters necessitate cautious interpretation. CLINICAL RELEVANCE STATEMENT: Although 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, even in intraoperative settings, their limitations in depicting interfascicular branches and small fascicles within clusters require cautious interpretation. KEY POINTS: 3D HRUS was limited in visualizing nerve interfascicular connections. MRM demonstrated better nerve fascicle depiction than 3D HRUS. MRM depicted more nerve interfascicular connections than 3D HRUS.

Radical resection of locally advanced and recurrent colorectal carcinoma involving major nerve resection: a systematic review of surgical, oncological and functional outcomes.

BACKGROUND: The aim of this study was to explore the surgical, oncological and quality of life outcomes in the setting of radical resection of colorectal carcinoma involving major nerve resection. METHODS: A systematic review of the literature was registered with the International Prospective Register for Systematic Reviews (PROSPERO) and performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify papers relating to outcomes in radical resection of colorectal cancer where major nerve resection was undertaken. Papers were identified from OVID Medline, EMBASE Classic and Web of Science encompassing all publications in English from January 2010 to June 2023. A total of 1357 nonduplicate studies were identified and screened for relevance, with six studies included in the final review. RESULTS: A total of 354 major nerve resections were undertaken across the six included studies. Overall postoperative morbidity was reported at rates of up to 82%. Two studies considered nerve-resection-specific oncological outcomes, with complete pathological resection achieved at rates comparable to the wider pelvic exenteration cohort (65-68%) and without any overall survival disadvantage being conveyed by major nerve resection (p = 0.78). Two studies considered functional outcomes and noted a transient decrease in physical quality of life over the first 6 months postoperatively (p = 0.041) with significant loss to follow-up. One study considered postoperative pain in nerve resection and noted no significant increase in patient-reported pain scores associated with nerve resection (p = 0.184-0.618). CONCLUSIONS: Major nerve resections in locally advanced and recurrent colorectal cancer remain understudied but with encouraging initial oncological and functional outcomes. Multicentre collaborative prospective reviews are needed to better elucidate contributors to postoperative morbidity and functional deficits and further establish interventions to ameliorate them.

Long-term outcomes of patients affected by Guillain-Barré syndrome in Colombia after the Zika virus epidemic.

BACKGROUND: Guillain-Barré Syndrome (GBS) can lead to significant functional impairments, yet little is understood about the recovery phase and long-term consequences for patients in low- and medium-income countries. OBJECTIVE: To evaluate the functional status and identify factors influencing outcomes among patients with GBS in Colombia. METHODS: Telephone interviews were conducted with GBS patients enrolled in the Neuroviruses Emerging in the Americas Study between 2016 and 2020. The investigation encompassed access to health services and functional status assessments, utilizing the modified Rankin Scale (mRS), GBS Disability Score (GDS), Barthel Index (BI), and International Classification of Functioning (ICF). Univariate analysis, principal component analysis, linear discriminant analysis, and linear regression were employed to explore factors influencing functional status. RESULTS: Forty-five patients (mean age = 50[±22] years) with a median time from diagnosis of 28 months (IQR = 9-34) were included. Notably, 22% and 16% of patients did not receive rehabilitation services during the acute episode and post-discharge, respectively. Most patients demonstrated independence in basic daily activities (median BI = 100, IQR = 77.5-100), improvement in disability as the median mRS at follow-up was lower than at onset (1 [IQR = 0-3] vs. 4.5 [IQR = 4-5], p < 0.001), and most were able to walk without assistance (median GDS = 2, IQR = 0-2). A shorter period from disease onset to interview was associated with worse mRS (p = 0.015) and ICF (p = 0.019). Negative outcomes on GDS and ICF were linked to low socioeconomic status, ICF to the severity of weakness at onset, and BI to an older age. CONCLUSIONS: This study underscores that the functional recovery of GBS patients in Colombia is influenced not only by the natural course of the disease but also by socioeconomic factors, emphasizing the crucial role of social determinants of health.

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.

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.

Ultrasonographic abnormalities in clinically unaffected nerves of patients with nonvasculitic motor and sensorimotor mononeuropathies.

INTRODUCTION/AIMS: Diagnostic criteria for multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensorimotor neuropathy (MADSAM) require the involvement of at least two peripheral nerves. However, many patients with very similar features have clinical involvement of only a single peripheral nerve, which may preclude their correct diagnosis and treatment. The present study aimed to present a cohort of such patients and discuss the role of ultrasonography (US) in their diagnosis. METHODS: Patients with nonvasculitic immune-mediated motor mononeuropathies (MM) and sensorimotor mononeuropathies (SMM) were recruited prospectively or identified from the electronic records. They were invited to comprehensive follow-up visits consisting of clinical examination, electrodiagnostic (EDx), and US studies. RESULTS: Twenty-four patients (13 men) were studied (11 with MM). The characteristics of MM and SMM patients were very similar to MMN and MADSAM, respectively. The US, in addition to a long-swollen segment (average length, 20 cm) in the clinically affected nerve, revealed nerve swelling in, on average, six additional sites in clinically unaffected nerves. DISCUSSION: In patients with clinical and EDx involvement of only a single nerve, an US demonstration of multifocal peripheral nerve swelling points to a more widespread, probably dysimmune mechanism. Further studies are needed to evaluate the value of US as a supplementary method for the diagnosis of MADSAM and MMN in patients with clinical involvement of a single nerve.

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.

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.

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.

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.

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).

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.

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.