The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

The marine microturbellarian Macrostomum lignano (Platyhelminthes, Rhabditophora) is an emerging laboratory model used by a growing community of researchers because it is easy to cultivate, has a fully sequenced genome, and offers multiple molecular tools for its study. M. lignano has a compartmentalized brain that receives sensory information from receptors integrated in the epidermis. Receptors of the head, as well as accompanying glands and specialized epidermal cells, form a compound sensory structure called the frontal glandular complex. In this study, we used semi-serial transmission electron microscopy (TEM) to document the types, ultrastructure, and three-dimensional architecture of the cells of the frontal glandular complex. We distinguish a ventral compartment formed by clusters of type 1 (multiciliated) sensory receptors from a central domain where type 2 (collar) sensory receptors predominate. Six different types of glands (rhammite glands, mucoid glands, glands with aster-like and perimaculate granula, vacuolated glands, and buckle glands) are closely associated with type 1 sensory receptors. Endings of a seventh type of gland (rhabdite gland) define a dorsal domain of the frontal glandular complex. A pair of ciliary photoreceptors is closely associated with the base of the frontal glandular complex. Bundles of dendrites, connecting the receptor endings with their cell bodies which are located in the brain, form the (frontal) peripheral nerves. Nerve fibers show a varicose structure, with thick segments alternating with thin segments, and are devoid of a glial layer. This distinguishes platyhelminths from larger and/or more complex invertebrates whose nerves are embedded in prominent glial sheaths.

In neural prostheses, intensity modulation of a single channel (i.e., through a single stimulating electrode) has been achieved by increasing the magnitude or width of each stimulation pulse, which risks eliciting pain or paraesthesia; and by changing the stimulation rate, which leads to concurrent changes in perceived frequency. In this study, we sought to render a perception of tactile intensity and frequency independently, by means of temporal pulse train patterns of fixed magnitude, delivered non-invasively. Our psychophysical study exploits a previously discovered frequency coding mechanism, where the perceived frequency of stimulus pulses grouped into periodic bursts depends on the duration of the inter-burst interval, rather than the mean pulse rate or periodicity. When electrical stimulus pulses were organised into bursts, perceived intensity was influenced by the number of pulses within a burst, while perceived frequency was determined by the time between the end of one burst envelope and the start of the next. The perceived amplitude was modulated by 1.6× while perceived frequency was varied independently by 2× within the tested range (20-40 Hz). Thus, the sensation of intensity might be controlled independently from frequency through a single stimulation channel without having to vary the injected electrical current. This can form the basis for improving strategies in delivering more complex and natural sensations for prosthetic hand users.

Objective. We intend to chronically restore somatosensation and provide high-fidelity myoelectric control for those with limb loss via a novel, distributed, high-channel-count, implanted system.Approach.We have developed the implanted Somatosensory Electrical Neurostimulation and Sensing (iSens®) system to support peripheral nerve stimulation through up to 64, 96, or 128 electrode contacts with myoelectric recording from 16, 8, or 0 bipolar sites, respectively. The rechargeable central device has Bluetooth® wireless telemetry to communicate to external devices and wired connections for up to four implanted satellite stimulation or recording devices. We characterized the stimulation, recording, battery runtime, and wireless performance and completed safety testing to support its use in human trials.Results.The stimulator operates as expected across a range of parameters and can schedule multiple asynchronous, interleaved pulse trains subject to total charge delivery limits. Recorded signals in saline show negligible stimulus artifact when 10 cm from a 1 mA stimulating source. The wireless telemetry range exceeds 1 m (direction and orientation dependent) in a saline torso phantom. The bandwidth supports 100 Hz bidirectional update rates of stimulation commands and data features or streaming select full bandwidth myoelectric signals. Preliminary first-in-human data validates the bench testing result.Significance.We developed, tested, and clinically implemented an advanced, modular, fully implanted peripheral stimulation and sensing system for somatosensory restoration and myoelectric control. The modularity in electrode type and number, including distributed sensing and stimulation, supports a wide variety of applications; iSens® is a flexible platform to bring peripheral neuromodulation applications to clinical reality. ClinicalTrials.gov ID NCT04430218.

OBJECTIVE: Traumatic brachial plexus injury (BPI) is a high-morbidity condition with an escalating incidence. One of the treatment options is neurotization using the ipsilateral phrenic nerve. Therefore, diagnosis of nerve dysfunction is a crucial step in preoperative planning. This study aimed to assess the accuracy and reliability of the fluoroscopic sniff test for preoperative diagnosis of phrenic nerve injury in patients with traumatic BPI.
METHODS: The study was conducted from June 2019 to August 2023 at a tertiary care hospital. A preoperative fluoroscopic sniff test was performed. During brachial plexus surgery, direct phrenic nerve stimulation was conducted as a gold standard of phrenic nerve function. Two nonoperating orthopedic surgeons interpreted the accuracy and reliability of the test.
RESULTS: Seventy-four patients with traumatic BPI (66 males and 8 females) with a median age of 26 years were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the fluoroscopic sniff test were 90.9% (95% CI 75.7%-98.1%), 100% (95% CI 91.4%-100%), 100% (95% CI 88.4%-100%), 93.2% (95% CI 82.3%-97.6%), and 95.9% (95% CI 88.6%-99.2%), respectively. Interobserver reliability showed excellent agreement (κ = 1, p < 0.001).
CONCLUSIONS: The fluoroscopic sniff test was proven to be an accurate, reliable, and simple tool to evaluate phrenic nerve function in patients with traumatic BPI. Preoperative testing should be performed to reduce operative time to identify the phrenic nerve as a donor for nerve transfer surgery in cases in which no function is detected from the fluoroscopic sniff test.

OBJECTIVE: The traditional treatment of sellar Rathke cleft cysts (RCCs) generally involves transsellar drainage; however, suprasellar RCCs present unique challenges to appropriate management and technical complexity. Reports on overall outcomes for the endoscopic endonasal approach (EEA) for this pathology are limited. The EEA for RCCs allows three surgical techniques: marsupialization, fenestration, and fenestration with cyst wall resection.
METHODS: The authors performed a retrospective review of consecutive patients with RCCs that had been treated via an EEA at a single institution between January 2004 and May 2021. Marsupialization entailed the removal of cyst contents while maintaining a drainage pathway into the sphenoid sinus. Fenestration involved the removal of cyst contents, followed by separation from the sphenoid sinus, often with a free mucosal graft or vascularized nasoseptal flap. Cyst wall resection, either partial or complete, was added to select cases.
RESULTS: A total of 148 patients underwent an EEA for RCC. Marsupialization or fenestration was performed in 88 cases (59.5%) and cyst wall resection in 60 (40.5%). Cysts were classified as having a purely sellar origin (43.2%), sellar origin with suprasellar extension (37.8%), and purely suprasellar origin (18.9%). Radiological recurrence was demonstrated in 22 cases (14.9%) at an average 39.7 months\' follow-up (median 45 months, range 0.5-99 months), including 13 symptomatic cases (8.8%). Cases with cyst wall resection had no significantly different rate of recurrence (11.7% vs 15.9%, p = 0.48) or postoperative permanent anterior pituitary dysfunction (21.6% vs 12.5%, p = 0.29) compared to those of fenestrated and marsupialized cases. There was no significant difference in postoperative permanent posterior pituitary dysfunction based on technique, although such dysfunction tended to worsen with cyst wall resection (13.6% vs 4.0%, p = 0.09). Based on cyst location, purely suprasellar cysts were more likely to have a radiological recurrence (28.6%) than sellar cysts with suprasellar extension (12.5%) and purely sellar cysts (9.4%; p = 0.008). Most notably, of the 28 purely suprasellar cysts, selective cyst wall resection significantly improved the long-term (10-year) recurrence risk compared to fenestration alone (17.4% vs 80.0%, p = 0.0005) without any significant added risk of endocrinopathy.
CONCLUSIONS: Endoscopic endonasal marsupialization or fenestration of sellar RCCs may be the ideal treatment strategy, whereas purely suprasellar cysts benefit from partial cyst wall resection to prevent recurrence. Selective cyst wall resection reduced long-term recurrence rates without significantly increasing rates of hypopituitarism.

Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of the immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rats. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.

UNASSIGNED: Traumatic injury to the long thoracic nerve causes paralysis of the serratus muscle, clinically expressed as winged scapula and functional impairment of the shoulder girdle. Treatment varies according to the severity of the injury, with a focus on early intervention for best results; however, the therapeutic approach remains a challenge at present.
UNASSIGNED: We present the case of a 32-year-old male patient, athlete, right-handed, presented with bilateral paresis predominantly in the right arm, associated with paresthesia and changes in the coloring of the upper limbs. After being diagnosed with Thoracic Outlet Syndrome and undergoing surgery, vascular symptoms persisted with a significant loss of strength in the right shoulder. Winged scapula was observed and structural lesions were excluded on magnetic resonance imaging. Electromyographic studies confirmed the presumption of traumatic nerve involvement of the long thoracic nerve. Notwithstanding 6 months of physical therapy, there was no improvement, so a nerve transfer from the thoracodorsal nerve to the right long thoracic nerve was chosen. At 12 months, complete resolution of the winged scapula and functional recovery were observed. The patient also experienced a decrease in preoperative pain from 5/10 to 2/10 on the visual analog scale.
UNASSIGNED: Nerve transfer from the thoracodorsal nerve to the long thoracic nerve is a safe and effective technique to treat winged scapula due to long thoracic nerve injury.

OBJECTIVE: Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors.
METHODS: This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients\' medical and surgical records as well as radiological and pathological findings were analyzed.
RESULTS: During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner\'s syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome.
CONCLUSIONS: RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.

Addressing peripheral nerve disorders with electronic medicine poses significant challenges, especially in replicating the dynamic mechanical properties of nerves and understanding their functionality. In the field of electronic medicine, it is crucial to design a system that thoroughly understands the functions of the nervous system and ensures a stable interface with nervous tissue, facilitating autonomous neural adaptation. Herein, we present a novel neural interface platform that modulates the peripheral nervous system using flexible nerve electrodes and advanced neuromodulation techniques. Specifically, we have developed a surface-based inverse recruitment model for effective joint position control via direct electrical nerve stimulation. Utilizing barycentric coordinates, this model constructs a three-dimensional framework that accurately interpolates inverse isometric recruitment values across various joint positions, thereby enhancing control stability during stimulation. Experimental results from rabbit ankle joint control trials demonstrate our model\'s effectiveness. In combination with a proportional-integral-derivative (PID) controller, it shows superior performance by achieving reduced settling time (less than 1.63 s), faster rising time (less than 0.39 s), and smaller steady-state error (less than 3 degrees) compared to the legacy model. Moreover, the model\'s compatibility with recent advances in flexible interfacing technologies and its integration into a closed-loop controlled functional neuromuscular stimulation (FNS) system highlight its potential for precise neuroprosthetic applications in joint position control. This approach marks a significant advancement in the management of neurological disorders with advanced neuroprosthetic solutions.