Our research path toward the restoration of natural sensations in hand prostheses.

The human hand, with its intricate sensory capabilities, plays a pivotal role in our daily interactions with the world. This remarkable organ possesses a wide range of natural sensors that enrich our experiences, enabling us to perceive touch, position, and temperature. These natural sensors work in concert to provide us with a rich sensory experience, enabling us to distinguish between various textures, gauge the force of our grip, determine the position of our fingers without needing to see them, perceive the temperature of objects we come into contact with or detect if a cloth is wet or dry. This complex sensory system is fundamental to our ability to manipulate objects, explore our surroundings, and interact with the world and people around us. In this article, we summarize the research performed in our laboratories over the years and our findings to restore both touch, position, and temperature modalities. The combination of intraneural stimulation, sensory substitution, and wearable technology opens new possibilities for enhancing sensory feedback in prosthetic hands, promising improved functionality and a closer approximation to natural sensory experiences for individuals with limb differences.

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends.

Introduction: Proteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate the molecular patterns underlying a digital nerve injury, focusing on differences in protein expression between the proximal and distal nerve ends. Methods: A total of 26 human injured digital nerve samples (24 men; 2 women; median age 47 [30-66] years), harvested during primary nerve repair within 48 h post-injury from proximal and distal nerve ends, were analyzed using mass spectrometry. Results: A total of 3,914 proteins were identified, with 127 proteins showing significant differences in abundance between the proximal and the distal nerve ends. The downregulation of proteins in the distal nerve end was associated with synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion and migration. Conversely, proteins upregulated in the distal nerve end were implicated in cellular stress response, neuromuscular junction stability and muscle contraction, neuronal excitability and neurotransmitter release, synaptic vesicle recycling and axon guidance and angiogenesis. Discussion: Investigation of proteins, with functional annotations analysis, in proximal and the distal ends of human injured digital nerves, revealed dynamic cellular responses aimed at promoting tissue degeneration and restoration, while suppressing non-essential processes.

Solitary neurofibroma confined to inferior rectus muscle tendon: a case report.

The present study reports a case of solitary neurofibroma attached to the Inferior Rectus (IR) muscle tendon in a 24-year-old healthy woman and reviews the relevant literature regarding the clinical presentation, diagnosis, and management of this uncommon tumor. The patient underwent successful surgical resection of the tumor, leading to the resolution of associated symptoms (left lower eyelid protrusion and redness). Pathological examination confirmed the diagnosis of neurofibroma based on characteristic histopathological and immunohistochemical markers. This case report underscores the rarity of solitary neurofibromas and primary neoplasms of orbit and ocular adnexa. We also discuss the background of solitary neurofibromas originating from orbit and ocular adnexa. The successful management of this case through surgical resection highlights the importance of accurate diagnosis and tailored treatment strategies. To the best of our knowledge, this is the first reported solitary neurofibroma confined solely to the IR tendon.

Rat ventral caudal nerve as a model for long distance regeneration.

In the rat, tail nerves are the longest peripheral nerves in their body. We suggest that ventral caudal nerve (VCN) may serve as a model for studying nerve injury and long distance regeneration. For this purpose, we have studied the anatomy and morphometry of the VCN in control animals. 10 cm long segment of the VCN was removed, and transversal sections were collected at 10 mm distances. The myelinated axons were counted, and the series of data were used to characterize the craniocaudal tapering of the nerve. In a separate group of animals, retrograde tracing with Fluorogold was used to localize and quantitate the spinal neurons projecting their axons into the VCN. After complete nerve transection, the time course of histopathological changes in the distal segment was studied. The primary goal was to define the time needed for axonal disintegration. In later periods, axonal debris removal and rearrangement of tissue elements was documented. After compression injury (axonotmesis), Wallerian degeneration was followed by spontaneous regeneration of axons. We show that the growing axons will span the 10 cm distance within 4-8 weeks. After different survival periods, the numbers of regenerating axons were counted at 10 mm distances. These data were used to characterize the dynamics of axonal regeneration during 4 months' survival period. In the present study we show that axonal regeneration across 10 cm distance can be studied and quantitatively analyzed in a small laboratory animal.

Efficacy of parasternal peripheral nerve catheters versus no block for median sternotomy: a single-centre retrospective study.

Background: Sternal pain after cardiac surgery results in considerable discomfort. Single-injection parasternal fascial plane blocks have been shown to reduce pain scores and opioid consumption during the first 24 h after surgery, but the efficacy of continuous infusion has not been evaluated. This retrospective cohort study examined the effect of a continuous infusion of local anaesthetic through parasternal catheters on the integrated Pain Intensity and Opioid Consumption (PIOC) score up to 72 h. Methods: We performed a retrospective analysis of patients undergoing cardiac surgery with median sternotomy at a single academic centre before and after the addition of parasternal nerve catheters to a standard multimodal analgesic protocol. Outcomes included PIOC score, total opioid consumption in oral morphine equivalents, and time-weighted area under the curve pain scores up to 72 h after surgery. Results: Continuous infusion of ropivacaine 0.1% through parasternal catheters resulted in a significant reduction in PIOC scores at 24 h (-62, 95% confidence interval -108 to -16; P<0.01) and 48 h (-50, 95% CI -97 to -2.2; P=0.04) compared with no block. A significant reduction in opioid consumption up to 72 h was the primary factor in reduction of PIOC. Conclusions: This study suggests that continuous infusion of local anaesthetic through parasternal catheters may be a useful addition to a multimodal analgesic protocol in patients undergoing cardiac surgery with sternotomy. Further prospective study is warranted to determine the full benefits of continuous infusion compared with single injection or no block.

Cross-Sectional Area and Echogenicity Reference Values for Sonography of Peripheral Nerves in the Lithuanian Population.

OBJECTIVES: We aimed to provide data of nerve sizes and echogenicity reference values of the Lithuanian population. METHODS: High-resolution ultrasound was bilaterally performed according to the Ultrasound Pattern Sum Score and Neuropathy ultrasound protocols for healthy Lithuanian adults. Cross-sectional area (CSA) measurement and echogenicity were used as the main parameters for investigation. Echogenicity was evaluated using ImageJ, and nerves were categorized in classes according to echogenicity. RESULTS: Of 125 subjects enrolled, 63 were males (mean age 47.57 years, range 25-78 years) and 62 were females (mean age 50.50 years, range 25-80 years). Reference values of nerve sizes and values of echogenicity as a fraction of black in percentage of cervical roots, upper and middle trunks of the brachial plexus and the following nerves: vagal, median, ulnar, radial, superficial radial, tibial, fibular, and sural in standard regions were established. Mild to moderate correlations were found between nerves CSA, echogenicity values and anthropometric measurements with the differences according to sex. Inter-rater (ICC 0.93; 95% CI 0.92-0.94) and intra-rater (ICC 0.94; 95% CI 0.93-0.95) reliability was excellent. CONCLUSIONS: Reference values of nerve size and echogenicity of Lithuanians were presented for the first time as a novel such kind of publication from the Baltic countries.

Electrophysiological and histopathological evaluation of the effectiveness of melatonin and glatiramer acetate for traumatic facial nerve injuries.

AIM: This study aimed to evaluate the effect of systemic/local use of melatonin and glatiramer acetate on regeneration in traumatic nerve injury models. MATERIALS AND METHODS: A total of 42 male Wistar albino rats were randomly divided into 6 groups: healthy control (Group 1), injured control (Group 2), local melatonin (Group 3), systemic melatonin (Group 4), local glatiramer acetate (Group 5), and systemic glatiramer acetate (Group 6). In all groups, electromyography recordings of the facial nerve were obtained after surgery and before sacrifice, and the damaged nerve region was histopathologically examined after sacrifice. RESULTS: In the electrophysiological evaluation, the control group had the greatest decrease in amplitude and extension in latency time following surgery than the treatment groups. Furthermore, a significant decrease in the degenerative axon count, edematous areas, and fibrotic areas as well as a significant increase in axonal surface areas was observed in all the treatment groups compared with the damage control group. CONCLUSIONS: Although both glatiramer acetate and melatonin are beneficial in regeneration in traumatic facial nerve injuries, it can be concluded that systemic use of melatonin can yield more positive results than glatiramer acetate and local use of both two drugs.

Clinical effects of perineural dexmedetomidine or magnesium sulphate as adjuvants to ropivacaine in dogs undergoing tibial plateau leveling osteotomy.

The study aimed to compare the quality of perioperative analgesia, the motor block duration, and the effects on main cardiovascular parameters of dexmedetomidine (1 µg/kg/nerve block) or magnesium sulphate (2 mg/kg/nerve block) as adjuvants to 0.3% ropivacaine for sciatic and saphenous nerves block in dogs undergoing tibial plateau leveling osteotomy (TPLO). Dogs randomly received perineural dexmedetomidine-ropivacaine (D group), magnesium sulphate-ropivacaine (M group), or ropivacaine (C group). Fentanyl was administered in case of intraoperative nociception. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale (SF-GCMPS) and VAS scale. The duration of motor blockade and intra- and postoperative cardiovascular parameters were also recorded. Group M required significantly more fentanyl than D group (p = 0.04). Group M had a significantly higher SF-GCMPS score than group C at 4 (p = 0.002) and 5 h after extubation (p = 0.01), and a significantly higher VAS score than group D at 3 h after extubation (p = 0.03), and at 4 h if compared to group C (p = 0.009). No significant differences regarding the duration of motor blockade were detected between groups (p = 0.07). The heart rate was significantly lower in group D than in M and C groups intraoperatively and during the first 1.5 h post extubation. The addition of dexmedetomidine or magnesium sulphate as adjuvants to perineural ropivacaine did not improve the quality of perioperative analgesia and did not prolong the motor blockade in dogs undergoing sciatic and saphenous nerves block for TPLO surgery.

The Use of Hexokinase 2-Displacing Peptides as an Anti-Neoplastic Approach for Malignant Peripheral Nerve Sheath Tumors.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment.

Fabrication of ECM protein coated hollow collagen channels to study peripheral nerve regeneration.

Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin's superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches.

Redesigned Electrodes for Improved Intraoperative Nerve Conduction Studies during the Treatment of Peripheral Nerve Injuries.

Traumatic peripheral nerve injuries (PNI), present with symptoms ranging from pain to loss of motor and sensory function. Difficulties in intraoperative visual assessment of nerve functional status necessitate intraoperative nerve conduction studies (INCSs) by neurosurgeons and neurologists to determine the presence of functioning axons in the zone of a PNI. This process, also referred to as nerve "inching", uses a set of stimulating and recording electrode hooks to lift the injured nerve from the surrounding surgical field and to determine whether an electrical stimulus can travel through the zone of injury. However, confounding electrical signal artifacts can arise from the current workflow and electrode design, particularly from the mandatory lifting of the nerve, complicating the definitive assessment of nerve function and neurosurgical treatment decision-making. The objective of this study is to describe the design process and verification testing of our group's newly designed stimulating and recording electrodes that do not require the lifting or displacement of the injured nerve during INCSs. Ergonomic in vivo analysis of the device within a porcine model demonstrated successful intraoperative manipulation of the device, while quantitative nerve action potential (NAP) signal analysis with an ex vivo simulated "inching" procedure on healthy non-human primate nerve tissue demonstrated excellent reproducible recorded NAP fidelity and the absence of NAP signal artifacts at all points of recording. Lastly, electrode pullout force testing determined maximum forces of 0.43 N, 1.57 N, and 3.61 N required to remove the device from 2 mm, 5 mm, and 1 cm nerve models, respectively, which are well within established thresholds for nerve safety. These results suggest that these new electrodes can safely and successfully perform accurate PNI assessment without the presence of artifacts, with the potential to improve the INCS standard of care while remaining compatible with currently used neurosurgical technology, infrastructure, and clinical workflows.

Peripheral Nerve Stimulation for Treating Acute Pain Following Traumatic Fracture: A Case Report of Rapid-Onset Analgesia Without Motor Blockade.

Analgesia following acute traumatic fracture remains a clinical challenge. Pain relief via peripheral nerve stimulation (PNS) is a promising treatment modality due to its opioid-sparing effects and rapid, reversible sensory blockade without motor blockade. We present the case of a patient who suffered a traumatic tibial plateau fracture. A popliteal sciatic PNS device was placed on postoperative day 1 following inadequate pain control. The patient reported marked pain relief, a significant reduction in morphine milligram equivalent (MME) utilization, and improved early functional recovery. The PNS lead was removed at the patient's 2-month follow-up visit without any adverse events.

Lower Extremity Peripheral Nerve Blocks for Post-operative Pain Control in a Multi-trauma Patient With Brugada Syndrome: A Literature Review and Case Report.

We describe the case of a 28-year-old man with Brugada syndrome who received single-shot adductor canal and sciatic nerve blocks for the management of post-operative pain related to extensive orthopedic injuries. Low-dose ropivacaine with glucocorticoid additives was administered without any EKG changes, arrhythmias, or syncopal sensations. The patient experienced pain relief for over 24 h and was monitored on telemetry with defibrillator pads as a cardiac precaution. This case adds a valuable data point in the limited canon of information on the safety and efficacy of regional anesthesia in Brugada syndrome for the perioperative physician.

Efficacy of 3D printed anatomically equivalent thermoplastic polyurethane guide conduits in promoting the regeneration of critical-sized peripheral nerve defects.

Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e., fused deposition modeling) technique. Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO 10993-6. To perform in vivo efficacy studies, nerve conduits equivalent to rat's sciatic nerve were fabricated and bridged in a 10 mm sciatic nerve transection model. After four months of implantation, the sensorimotor function and histological assessments revealed that the 3D printed TPU conduits promoted the regeneration in critical-sized peripheral nerve defects equivalent to autografts. This study proved that TPU-based 3D printed nerve guidance conduits can be created to replicate the complicated features of natural nerves that can promote the regeneration of peripheral nerve defects and also show the potential to be extended to several other tissues for regenerative medicine applications. .

Therapeutically Fine-Tuning Autonomic Nervous System to Treat Sepsis: A New Perspective on the Immunomodulatory Effects of Acupuncture.

Recent studies have highlighted the immunomodulatory effects of acupuncture on sepsis and proposed novel non-pharmacological or bioelectronic approaches to managing inflammatory illnesses. Establishing rules for selectively activating sympathetic or vagal nerve-mediated anti-inflammatory pathways using acupuncture has valuable clinical applications. Over the years, studies have revealed the segmental modulatory role of acupuncture in regulating visceral function by targeting the autonomic nervous system (ANS). In this review, we aim to summarize recent findings on acupuncture in treating sepsis, focusing on the underlying ANS mechanism, as well as the rules of acupoint specificity, intensity, frequency, and other parameters utilized in these studies. Mechanistically, the immunomodulatory properties of the sympathetic nervous system have been highlighted. Furthermore, we explore the immunotherapeutic benefits of acupuncture in treating sepsis. A better understanding of the immunoregulatory mechanism of sympathetic nervous system may offer novel approaches for the development of therapeutics to treat or prevent a variety of inflammatory diseases.

Neurological improvement following revision of vascular graft remnants in the upper extremity.

Remnant vascular grafts may result in significant neurological deficits owing to compression of adjacent neural structures. We report this finding in two cases after extracorporeal membrane oxygenation decannulation and removal of an arteriovenous fistula in the upper extremity. In both cases, removal of the graft, patch arteriotomy, and external neurolysis resulted in significant recovery of neurological function. We review the preoperative workup, diagnostic studies, and technical approach to treatment in an effort to increase recognition among vascular and cardiovascular surgeons and to demonstrate a safe and effective management option through a multidisciplinary approach.

Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.

The outcomes of peripheral nerve surgeries in Africa: Narrative synthesis from existing literature.

BACKGROUND: In Africa, peripheral nerve pathologies are a major source of disability, and the results of surgical therapies differ greatly among countries. The goal of this narrative review is to compile the most recent data on peripheral nerve surgery results in Africa, pinpoint critical variables that affect surgical outcomes, and offer suggestions for enhancing patient care. METHODS: A comprehensive literature review was conducted, focusing on studies published over the past four decades. The sources included peer-reviewed journals, hospital records, and reports from healthcare organizations. The review examined outcomes related to functional recovery, quality of life, and postoperative complications. RESULTS: The outcomes of peripheral nerve surgeries in Africa are influenced by the availability of medical infrastructure, the level of surgeon expertise, and the timeliness of the intervention. Urban centers with better resources tend to report more favorable outcomes, whereas rural areas face significant challenges. Common barriers include limited access to advanced surgical tools, a shortage of specialized surgeons, and inadequate postoperative care and rehabilitation services. Despite these challenges, successful interventions have been reported, particularly in settings where targeted training programs and international collaborations are in place. CONCLUSION: Enhancing surgeon training programs, building comprehensive postoperative care and rehabilitation facilities, and investing in healthcare infrastructure are critical to improving peripheral nerve surgery results in Africa. International and regional collaborations can be extremely helpful in advancing these initiatives by enabling the sharing of knowledge and granting access to cutting-edge methods. Patients with peripheral nerve injuries across the continent may experience improved functional recovery and overall quality of life if these criteria are met.

Ultrasound-Based Multi-Planar Bilateral Comparisons as a Diagnostic and Treatment-Definition Method for Unilateral Peripheral Nerve Entrapment.

OBJECTIVE: The primary goal was to determine the performance of the cross-section area swelling rate (CSASR) for diagnostic and therapeutic purposes based on the reference standard of electrodiagnosis examination (EDX) in this diagnostic test study. METHODS: First, patients with symptoms like unilateral carpal tunnel syndrome (CTS), cubital tunnel syndrome (CuTS), and radial nerve compression (RNC) underwent EDX and ultrasound examination. Second, patients with positive ultrasound were calculated for the CSASR of diseased nerve. Based on previously established CSASR criteria, each patient was categorized as having or not having peripheral nerve entrapment, and for those meeting diagnostic criteria, non-surgical or surgical treatment was recommended. Then, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate (ACC) of ultrasound diagnosis and therapeutic decision-making were calculated based on the reference standard of EDX that had been historically used in the practice. RESULTS: The total sensitivity, specificity, PPV, NPV, and ACC of ultrasound diagnosis are respectively 93.4, 85.2, 94.7, 82.1, and 91.3%. Which of therapeutic decision-making by ultrasound are, respectively, 83.3, 52.2, 78.4, 60.0, and 73.2%. CONCLUSION: The sensitivity and Youden's index of CSASR diagnostic threshold for CuTS is higher than other ultrasound methods. The CSASR diagnostic threshold for CuTS has a potential diagnostic role, but the current date is still not enough to support the potential diagnostic role for CTS or RNS. There is insufficient evidence to suggest that CSASR for CuTS can be used in isolation for diagnosis. Additional research is needed to confirm the diagnostic role of CSASR. The current results suggest that this ultrasound examination method is not suitable for therapeutic decision-making.