Breast sensation plays a significant role in the safety and quality of life of women who undergo mastectomy and reconstruction. In 1992, Slezak et al. introduced the concept of abdominal flap neurotization to improve sensation of the reconstructed breast. Over the next 30 years, numerous studies iterated on Slezak\'s technique, suggesting technical modifications and new methodologies for assessing sensory recovery. Despite evidence that reinnervation increases patient satisfaction following autologous breast reconstruction, abdominal flap neurotization remains a rarely performed procedure. In this article, we review the evolution of flap neurotization in breast reconstruction and describe our approach to facilitating sensory recovery of the breast while limiting donor site morbidity.

OBJECTIVE: This paper reviews the current literature about epidemiology, etiologies, diagnosis, and management of pediatric bilateral vocal fold paralysis (PBVFP).
METHODS: According to PRISMA statements, a narrative review of the current literature was conducted through the PubMed, Scopus, and Cochrane Library databases about the epidemiology, etiologies, diagnosis, and management of PBVFP.
RESULTS: PBVCP is the second most common congenital laryngeal anomaly in the pediatric population, accounting for 10% to 20% of pediatric laryngeal conditions. PBVCP is related to idiopathic (42.2%), congenital (19.7%), and neurological (16.9%) conditions. A tracheotomy is required in 60% of cases regarding stridor and dyspnea, which are the most prevalent symptoms. The diagnosis is based on the etiological features, clinical presentation, laryngoscopic findings, and objective examinations. Laryngeal electromyography may be used to support the diagnosis in difficult cases, but its reliability depends on the practitioner\'s experience. The primary differential diagnosis is posterior glottis stenosis, which needs to be excluded regarding therapeutic and management differences with PBVCP. Transient surgical procedures consist of tracheotomy or laterofixation of the vocal fold. Current permanent procedures include uni- or bilateral partial arytenoidectomy, posterior transverse cordotomy, cricoid splits, and laryngeal selective reinnervation. There is no evidence of the superiority of some procedures over others.
CONCLUSIONS: PBVCP is the second most common laryngeal disorder in the pediatric population. Diagnosis is based on etiological and clinical findings and may require the use of laryngeal electromyography. Therapeutic management may involve several transient or permanent surgical procedures that are associated with overall subjective improvements in symptoms, laryngeal findings, and low complication rates.

UNASSIGNED: Although many different treatments were developed for facial palsy, only a few therapeutic options are available for facial synkinesis. Electrical stimulation of specific muscles via implants could be useful in restoring facial symmetry in synkinetic patients. A challenge in developing stimulation devices is finding the right stimulation location, type, and amplitude. This work assesses the ability to selectively stimulate the zygomaticus muscle (ZYG) in patients with oral-ocular synkinesis to elicit a visually detectable response of the ipsilateral corner of the mouth (COM), without causing a reaction of the orbicularis oculi muscle (OOM). We aimed to assess how close to the COM the stimulation should be delivered in order to be selective.
UNASSIGNED: A total of 10 patients (eight females, two males) were enrolled. Facial function was graded according to the Sunnybrook facial grading system. Needle EMG was used to test the activities of the muscles, during volitional and \"unintended\" movements, and the degree of synkinesis of the ZYG and OOM. Two ball electrodes connected to an external stimulator were placed on the paretic ZYG, as close as possible to the COM.
UNASSIGNED: Independent of the waveform with which the stimulation was presented, a selective ZYG response was observed within 4.5 cm of the horizontal plane and 3 cm of the vertical plane of the COM. When the distance between the electrodes was kept to ≤2 cm, the amplitude necessary to trigger a response ranged between 3 and 6 mA when the stimulation was delivered with triangular pulses and between 2.5 and 3.5 mA for rectangular pulses. The required amplitude did not seem to be dependent on the applied phase duration (PD), as long as the PD was ≥5 ms.
UNASSIGNED: Our results show that selective stimulation of the ZYG presenting synkinetic ZYG-OOM reinnervation can be achieved using a broad PD range (25-1,000 ms) and an average amplitude ≤6 mA, which may be further decreased to 3.5 mA if the stimulation is delivered via rectangular rather than triangular waves. The most comfortable and effective results were observed with PDs between 50 and 250 ms, suggesting that this range should be selected in future studies.
UNASSIGNED: [https://drks.de/search/de/trial/DRKS00019992], identifier (DRKS00019992).

Human pluripotent stem cell (hPSCs) derived-pancreatic islets (hSC-islets) are good candidates for cell replacement therapy for patients with diabetes as substitutes for deceased donor-derived islets, because they are pluripotent and have infinite proliferation potential. Grafted hSC-islets ameliorate hyperglycemia in diabetic mice; however, several weeks are needed to normalize the hyperglycemia. These data suggest hSC-islets require maturation, but their maturation process in vivo is not yet fully understood. In this study, we utilized two kinds of streptozotocin (STZ)-induced diabetes model mice by changing the administration timing in order to examine the time course of maturation of hSC-islets and the effects of hyperglycemia on their maturation. We found no hyperglycemia in immune-compromised mice when hSC-islets had been transplanted under their kidney capsules in advance, and STZ was administered 4 weeks after transplantation. Of note, the blood glucose levels of those mice were stably maintained under 100 mg/dl 10 weeks after transplantation; this is lower than the mouse glycemic set point (120-150 mg/dl), suggesting that hSC-islets control blood glucose levels to the human glycemic set point. We confirmed that gene expression of maturation markers of pancreatic beta cells tended to upregulate during 4 weeks after transplantation. Periodical histological analysis revealed that revascularization was observed as early as 1 week after transplantation, but reinnervation in the grafted hSC-islets was not detected at all, even 15 weeks after transplantation. In conclusion, our hSC-islets need at least 4 weeks to mature, and the human glycemic set point is a good index for evaluating ultimate maturity for hSC-islets in vivo.

Selander emphatically said, \"Handle these nerves with care,\" and those words still echo, conveying a loud and clear message that, however rare, peripheral nerve injury (PNI) remains a perturbing possibility that cannot be ignored. The unprecedented nerve injuries associated with peripheral nerve blocks (PNBs) can be most tormenting for the unfortunate patient and a nightmare for the anesthetist. Possible justifications for the seemingly infrequent occurrences of PNB-related PNIs include a lack of documentation/reporting, improper aftercare, or associated legal implications. Although they make up only a small portion of medicolegal claims, they are sometimes difficult to defend. The most common allegations are attributed to insufficient informed consent; preventable damage to a nerve(s); delay in diagnosis, referral, or treatment; misdiagnosis, and inappropriate treatment and follow-up care. Also, sufficient prospective studies or randomized trials have not been conducted, as exploring such nerve injuries (PNB-related) in living patients or volunteers may be impractical or unethical. Understanding the pathophysiology of various types of nerve injury is vital to dealing with them further. Processes like degeneration, regeneration, remyelination, and reinnervation can influence the findings of electrophysiological studies. Events occurring in such a process and their impact during the assessment determine the prognosis and the need for further interventions. This educational review describes various types of PNB-related nerve injuries and their associated pathophysiology.

UNASSIGNED: Peripheral nerve injuries are common neurologic injuries that are challenging to treat with current therapies. Electrical stimulation has been shown to accelerate reinnervation and enhance functional recovery. This study aims to review the literature on clinical application of electrical stimulation for peripheral nerve injury.
UNASSIGNED: PubMed and Embase were sourced from 1995 to August 2022. Selection was based on predetermined inclusion/exclusion criteria. Eight hundred and thirty-five articles were screened with seven being included in this review.
UNASSIGNED: Two hundred and twenty-nine patients with peripheral nerve injuries were represented. Six of the studies were randomized controlled trials. A variety of nerve injuries were represented with all being in the upper extremity and supraclavicular region. Electrical stimulation protocols and evaluation varied. Electrodes were implanted in four studies with one also implanting the stimulator. Length of stimulation per session was either 20 mins or 1 h. Median stimulation frequency was 20 Hz. Stimulation intensity varied from 3 to 30V; pulse width ranged from 0.1 to 1.007 ms. Three protocols were conducted immediately after surgery. Patients were followed for an average of 13.5 months and were evaluated using electrophysiology and combinations of motor, sensory, and functional criteria.
UNASSIGNED: Patients who received electrical stimulation consistently demonstrated better recovery compared to their respective controls. Electrical stimulation for peripheral nerve injury is a novel treatment that has not been well-studied in humans. Our review illustrates the potential benefit in implementing this approach into everyday practice. Future research should aim to optimize protocol for clinical use.

Introduction: There are three main potential mechanisms of recovery after nerve lesion: (1) resolution of conduction block, (2) collateral reinnervation, and (3) nerve regeneration. Their relative contributions in recovery after focal neuropathies are not well established. Methods: In a group of previously reported prospective cohort of patients with ulnar neuropathy at the elbow (UNE), I performed a post-hoc analysis of their clinical and electrodiagnostic findings. I compared amplitudes of the compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) on ulnar nerve stimulation, as well as qualitative concentric needle electromyography (EMG) findings in the abductor digiti minimi muscle on the initial and follow-up examinations several years later. Results: Altogether, 111 UNE patients (114 arms) were studied. During median follow-up period of 880 days (range: 385-1545 days), CMAP amplitude increased (p = 0.02), and conduction block in the elbow segment recovered (from median 17% to 7%; p < 0.001). By contrast, SNAP amplitude did not change (p = 0.89). On needle EMG, spontaneous denervation activity diminished (p < 0.001), motor unit potential (MUP) amplitude increased (p < 0.001), and MUP recruitment remained unchanged (p = 0.43). Conclusions: Findings of the present study indicate that nerve function in chronic focal compression/entrapment neuropathies seems to improve mainly due to the resolution of the conduction block and collateral reinnervation. Contribution of nerve regeneration seems to be minor; the majority of axons lost in chronic focal neuropathies probably never recover. Further studies using quantitative methods are needed to validate present findings.

Recent studies of in vivo muscle function in guinea fowl revealed that distal leg muscles rapidly modulate force and work to stabilize running in uneven terrain. Previous studies focused on running only, and it remains unclear how muscular mechanisms for stability differ between walking and running. Here, we investigated in vivo function of the lateral gastrocnemius (LG) during walking over obstacles. We compared muscle function in birds with intact (iLG) versus self-reinnervated LG (rLG). Self-reinnervation results in proprioceptive feedback deficit due to loss of monosynaptic stretch reflex. We tested the hypothesis that proprioceptive deficit results in decreased modulation of EMG activity in response to obstacle contact, and a delayed obstacle recovery compared with that for iLG. We found that total myoelectric intensity (Etot) of iLG increased by 68% in obstacle strides (S 0) compared with level terrain, suggesting a substantial reflex-mediated response. In contrast, Etot of rLG increased by 31% in S 0 strides compared with level walking, but also increased by 43% in the first post-obstacle (S +1) stride. In iLG, muscle force and work differed significantly from level walking only in the S 0 stride, indicating a single-stride recovery. In rLG, force increased in S 0, S +1 and S +2 compared with level walking, indicating three-stride obstacle recovery. Interestingly, rLG showed little variation in work output and shortening velocity in obstacle terrain, indicating a shift towards near-isometric strut-like function. Reinnervated birds also adopted a more crouched posture across level and obstacle terrains compared with intact birds. These findings suggest gait-specific control mechanisms in walking and running.

OBJECTIVE: This systematic review aims to provide an overview of the current evidence-base for paediatric surgical reinnervation in unilateral and bilateral vocal fold palsies in clinical practice. We aim to assess patient demographics, surgical technique and pre- and post-operative outcome measures.
METHODS: A systematic literature review was performed and reported according to international PRISMA recommendations. A comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for relevant publications for all available dates with appropriate MESH search criteria was performed. Articles were categorised by four authors independently. A pooled summative analysis was carried out to allow review of demographic and outcome data.
RESULTS: Our systematic PRISMA approach resulted in 19 papers being selected for inclusion and analysis with 179 patients undergoing reinnervation (153 unilateral, 26 bilateral). The youngest patient was 1.9 years. Iatrogenic injury to recurrent laryngeal nerve most common aetiology (65.4% and 19.2% of unilateral and bilateral vocal fold palsies, respectively). Patent ductus arteriosus ligation was the single most common procedure resulting in unilateral vocal fold palsies (43.1% of cases). Statistically significant improvements in subjective and objective outcomes for both voice and swallowing were seen. Meta-analysis was able to be performed on the particularly evident improvements in GRBAS score and Maximum Phonation Time (MPT). GRBAS scores improved by 3.64 (p < 0.01, 95% CI 2.65 to 4.63). MPT showed a statistically significant improvement of 5.26 s (p < 0.05, 95% CI 4.28 to 6.24). No major complications were reported.
CONCLUSIONS: The current published evidence on one-hundred and seventy-nine paediatric surgical reinnervation procedures demonstrates its role as a safe and effective treatment for both unilateral and bilateral vocal fold palsies. Anatomically it has been shown to improve vocal fold tone, bulk and position. Both post-operative voice and swallowing outcomes show improvement as well as associated quality of life measures.

Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration via their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury. BDNF knockdown (KD) MSCs were created using an anti-BDNF shRNA lentivirus vector. A scrambled sequence was used as a transduction control (scrambled). Cells were cultured for 24 h before media was concentrated 50x to create concentrated conditioned media (CCM) containing MSC secretome. CCM of unmanipulated MSCs was screened for high BDNF expression (high BDNF CCM). Concentrated control media (CM) was created by concentrating media not conditioned by cells. Female Sprague-Dawley rats underwent bilateral pudendal nerve crush and vaginal distension (Injury) or sham injury. One hour and 1 week after injury, sham injured rats received CM, and injured rats received CM, high BDNF CCM, KD CCM, or scrambled CCM (300 μl intraperitoneally). Three weeks after injury, rats underwent leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings. The urethra and pudendal nerve were harvested for anatomical assessment. ANOVA followed by the Student-Newman-Keuls test determined significant differences between groups (p < 0.05). BDNF KD CCM had significantly decreased BDNF concentration compared to scrambled CCM, while the concentration in high BDNF CCM was significantly increased. LPP was significantly decreased in CM and KD CCM treated animals compared to sham injury, but not with scrambled or high BDNF CCM. PNSBP firing rate showed a significant decrease with CM treatment compared to sham injury. Neuromuscular junctions in the urethral sphincter in KD CCM, scrambled CCM, and high BDNF CCM were healthier than CM treated rats. While anatomical and nerve function tests demonstrate regeneration of the pudendal nerve with any CCM treatment, LPP results suggest it takes longer to recover continence with reduced BDNF in CCM. BDNF in MSC CCM is an important factor for the acceleration of recovery from a dual nerve and muscle injury.