Primary Nerve Research Articles

Fractures of the Humeral Shaft with Primary Radial Nerve Palsy: Do Injury Mechanism, Fracture Type, or Treatment Influence Nerve Recovery?

Adult humeral shaft fractures are associated with primary radial nerve palsy in up to 18% of cases. The purpose of this study was to assess the influence of injury mechanism, fracture type, and treatment on nerve recovery in patients with humeral shaft fractures and primary nerve palsy. Data of fifty patients (age—43.5 ± 21.3; female: male—1:1.8) with humeral shaft fractures and concomitant grade I–II primary radial nerve palsy, who underwent either open reduction and internal fixation (ORIF) or intramedullary nailing at an academic level I trauma center between 1994 and 2013, were evaluated. Factors potentially influencing the time to onset of recovery or full nerve recovery (injury mechanism, fracture type, fracture location and treatment) were analyzed in detail. Thirty patients were treated with ORIF and twenty patients with closed unreamed intramedullary nailing of the humeral shaft, respectively. The mean time to onset of recovery was 10.5 ± 3.4 weeks (2–17 weeks). Twenty-six (52%) patients reported significant clinical improvement within the first 12 weeks. Mean time to full recovery was 26.8 ± 8.9 weeks (4–52 weeks). Twenty-five (50%) patients regained full manual strength within the first six months following the injury. Forty-nine (98%) patients regained full manual strength within the first 52 weeks. Trauma mechanism, fracture type, fracture location, and treatment modality did not influence the time to onset of nerve recovery or time to full recovery following humeral shaft fractures with grade I–II primary radial nerve palsy.

Open reduction and internal fixation of humeral midshaft fractures: anterior versus posterior plate fixation

BackgroundFractures of the humeral shaft represent 2–4% of all fractures. Fractures of the humerus have traditionally been approached posteriorly for open reduction and internal fixation. Reports of treating midshaft fractures with an open anterolateral approach and anterior plating are limited. The purpose of this study was to evaluate a series of humeral shaft fractures treated with plate osteosynthesis regarding the effect of the approach and plate location on the healing rate and occurrence of complications.MethodsWe conducted a retrospective chart review of patients aged over 18 years with humeral midshaft fractures treated with anterior or posterior plate fixation. Selection of the approach to the humerus was based on the particular pattern of injury and soft tissue involvement. The minimum follow-up duration was set at six months. The outcomes included the rate of union, primary nerve palsy recovery, secondary nerve damage, infection and revision surgery.ResultsBetween 2006 and 2014, 58 patients (mean age, 59.9; range, 19–97 years) with humeral midshaft fractures were treated with anterior (n = 33) or posterior (n = 25) plate fixation. After a mean follow-up duration of 34 months, 57 of 58 fractures achieved union after index procedure. Twelve fractures were associated with primary radial nerve palsy. Ten of the twelve patients with primary radial palsy recovered completely within six months after the index surgery. In total, one patient developed secondary palsy after anterior plating, and three patients developed secondary palsy after posterior plating. No significant difference in the healing rate (p = 0.4), primary nerve palsy recovery rate (p = 0.6) or prevalence of secondary nerve palsy (p = 0.4) was found between the two clinical groups. No cases of infection after plate fixation were documented.ConclusionsOpen reduction and internal fixation using an anterior approach with plate fixation provides a safe alternative to posterior plating in the treatment of humeral shaft fractures. An anterior approach allows supine positioning of the patient and yields union and complication rates comparable to those of a posterior approach with plate fixation for the treatment of humeral shaft fractures.

Extracapsular dissection in peripheral nerve schwannoma surgery using bright light and fluorescein sodium visualization: case series.

Schwannomas are the most frequent peripheral nerve sheath tumors and are treated by surgical resection when symptomatic. Tumor removal is performed by intraneural dissection and enucleation. In order to safely remove the tumor from the nerve, the use of sodium fluorescein has recently been proposed to distinguish the tumor from the adjacent normal nerve fibers, before incision of the tumor pseudocapsule and during intraneural tumor dissection. We report a consecutive case series of 5 peripheral nerve schwannomas operated in 4 patients, in which we evaluate the usefulness of sodium fluorescein compared to usual visual landmarks, at each step of the surgical procedure. After exposition of the schwannoma, sodium fluorescein helped with the localization of intracapsular en passant nerve fascicles in only one case. Hence, the definition of a safe entry zone for capsular incision relied mainly on nerve monitoring and direct visualization of en passant nerve fascicles under microscope. During intraneural dissection, there was a sharp contrast between the fluorescent tumor and the non-fluorescent adjacent pseudocapsule in most cases but the colorimetric variation between tumor and normal tissue induced by fluorescence did not outperform the natural contrast between the yellow true capsule and the gray-red layers of the pseudocapsule. Based on these results, we consider that the limited additional value of sodium fluorescein in primary peripheral nerve schwannoma surgery does not warrant its use in daily clinical practice. Additional studies are needed to assess its usefulness during the surgery of recurrences and tumors which are intertwined with several fascicles of origin such as neurofibromas.

Contemporary Concepts of Primary Dynamic Facial Nerve Reconstruction in the Oncologic Patient.

Transection of the facial nerve and its branches during extensive ablative procedures in the oncologic patient causes loss of control of facial mimetic muscles with severe functional and aesthetic sequelae. In such patients with advanced tumorous disease, copious comorbidities, and poor prognosis, rehabilitation of the facial nerve has long been considered of secondary priority. However, recent advances in primary facial nerve reconstruction after extensive resection demonstrated encouraging results focusing on rapid and reliable restoration of facial functions. The authors summarize 3 innovative approaches of primary dynamic facial nerve reconstruction by using vascularized nerve grafts, dual innervation concepts, and intra-facial nerve transfers.

Suppression tuning of spontaneous otoacoustic emissions in the barn owl (Tyto alba)

Spontaneous otoacoustic emissions (SOAEs) have been observed in a variety of different vertebrates, including humans and barn owls (Tyto alba). The underlying mechanisms producing the SOAEs and the meaning of their characteristics regarding the frequency selectivity of an individual and species are, however, still under debate. In the present study, we measured SOAE spectra in lightly anesthetized barn owls and suppressed their amplitudes by presenting pure tones at different frequencies and sound levels. Suppression effects were quantified by deriving suppression tuning curves (STCs) with a criterion of 2 dB suppression. SOAEs were found in 100% of ears (n = 14), with an average of 12.7 SOAEs per ear. Across the whole SOAE frequency range of 3.4–10.2 kHz, the distances between neighboring SOAEs were relatively uniform, with a median distance of 430 Hz. The majority (87.6%) of SOAEs were recorded at frequencies that fall within the barn owl’s auditory fovea (5–10 kHz). The STCs were V-shaped and sharply tuned, similar to STCs from humans and other species. Between 5 and 10 kHz, the median Q10dB value of STC was 4.87 and was thus lower than that of owl single-unit neural data. There was no evidence for secondary STC side lobes, as seen in humans. The best thresholds of the STCs varied from 7.0 to 57.5 dB SPL and correlated with SOAE level, such that smaller SOAEs tended to require a higher sound level to be suppressed. While similar, the frequency-threshold curves of auditory-nerve fibers and STCs of SOAEs differ in some respects in their tuning characteristics indicating that SOAE suppression tuning in the barn owl may not directly reflect neural tuning in primary auditory nerve fibers.

2652 Primary Malignant Peripheral Nerve Sheath Tumor of Small Bowel and Colon Presenting With Metastases to Bone, Lung, Liver, Spleen, and Brain

INTRODUCTION: Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare diagnosis, with an incidence of 1:100,000 per year and 4–10% of soft tissue sarcoma, contains properties both neural crest cells and mesenchymal cells. Gastrointestinal MPNSTs are rare disease conditions with only 10 cases reported worldwide in the literature. CASE DESCRIPTION/METHODS: A 71-year old Portuguese male, presented with 8-week history of abdominal pain, anorexia with 20Ib weight loss. Vital signs were normal. On physical examination, a firm, tender, fixed abdominal mass in the RLQ was palpated. CT scan of the abdomen showed a 10 cm necrotic mass on the right side of the abdomen with communication to the small bowel was detected with a suggestion of a walled off perforation. Colonoscopy revealed a flattening of the terminal ileum suggesting an extrinsic compression. Biopsy of tumor consisting of mixed spindle and pleomorphic cells with focal rhabdoid features, high grade nuclear features and brisk mitotic activity. A week later, he presented with symptoms of small bowel obstruction, the CT scan at this time showed a 8 cm left sided abdominal mass with communication to the small bowel with dilation of the jejunum suggesting a new partial obstruction in addition. The patient underwent a palliative debulking of the tumor. Multiple large obstructive masses were found in the Ligament of Treitz,significant portion of the small bowel, right colon, left upper quadrant and omentum. For palliation purposes, these masses were resected and anastomosis was performed. Gross examination of the surgical specimens revealed grayish-tan cystic masses filled with brownish tan hemorrhagic material. Histology of the masses were similr to previous mass. On immunohistochemistry, showed patchy weak S100 immunoreactivity and focal BCL-2 and Neuron Specific Enolase stain immunoreactivity. Ki-67 proliferation index was 70%. The pathologic diagnosis of MPNST was established. He developed multiple bone, pulmonary, liver, splenic and hemorrhagic brain metastases. He died under hospice care within six months of his initial presentation. DISCUSSION: MPNST, occurs mostly in association with Neurofibromatosis Type 1 (8–13%). The tumor typically originates from the nerve sheaths of the major nerves in the extremities (40%), trunk/ retroperitoneal (38%) and head and neck region (21%). However, recent case reports have also documented MPNST of the liver, thyroid gland, skin, eighth cranial nerve and rarely the greater omentum without a history of radiation or NF1.

Relationship between Erk1/2 signal pathway and nerve cell apoptosis rats with ischemic stroke

To investigate the relationship between the Erk1/2 signal pathway and neuronal apoptosis in ischemic stroke rats. Male SD(Sprague Dawley) rats (n = 24) were randomly divided into three groups, each containing 8 rats: sham-operated group, MCAO(Midle cerebral artery oclusion) group, and MCAO + U0126 intervention group (U0126 group). In in vitro trial, primary cortical nerve cells were divided into three groups: control group, OGD(Oxygen and glucose deprivation) group, and U0126 intervention group (U0126 group). In vivo protein expression levels of Erk1/2, p-Erk1/2 and Bcl-2 were determined using western blot. The expressions of Bcl-2, Bcl-xl and Bax were assayed using immunohistochemical staining. Nerve cell mortality in cerebral tissue was detected using TUNEL staining. In in vitro trials, cell apoptosis was assayed with flow cytometry and LDH release. The activity of caspase-3 was determined. Nerve cell apoptosis was determined using Hoechst33258 staining method. In in vivo trial, it was found that the protein expression level of p-ERK1/2 in cerebral tissue in the MCAO group was significantly increased, when compared with that of the sham-operated group, while the protein expression level of p-Erk1/2 in the U0126 group was significantly lower than that in the MCAO group. The expression levels of Bcl-2 and Bcl-xl in the MCAO group were significantly lower than the corresponding expression levels in the sham-operated group, while the expressions of Bcl-2 and Bcl-xl in the U0126 group were significantly lower than those in MCAO group. In MCAO group, the expression of Bax was significantly higher than that in the sham-operated group, while Bax expression was higher in U0126 than in MCAO group. There were significantly higher number of dead nerve cells in MCAO group than in the sham-operated group, while nerve cell mortality in U0126 group was significantly lower than in MCAO group. In in vitro trials, flow cytometry revealed significantly higher apoptosis of OGD-treated nerve cells, relative to the control group. Nerve cells exposed to U0126 and treated with ODR (Oxygen-dependent repressor) were significantly decreased in population, when compared with single OGD treatment group. The LDH release level of nerve cells treated OGD was significantly increased, when compared with that of the control group. However, LDH release level of nerve cells treated with OGD after U0126 intervention was significantly decreased, relative to the single OGD treatment group. The dilution of nerve cell nucleus after OGD treatment was significantly increased, when compared with that of the control group. For nerve cells treated with ODR after U0126 intervention, the nuclear dilution was significantly decreased, relative to that of nerve cell nucleus in the single OGD treatment group. The OGD treatment led to significant increase in nerve cell caspase-3 activity, relative the control group. However, the caspase-3 activity of nerve cells treated with ODR after U0126 intervention was significantly decreased, when compared with single OGD treatment group. The activation of Erk1/2 signal pathway during ischemic stroke promotes apoptosis of nerve cells. Based on these findings, it can be reasonably inferred that the ERK1/2 signal pathway may be an important target for treating ischemic stroke.

Innate immune response to bacterial urinary tract infection sensitises high-threshold bladder afferents and recruits silent nociceptors.

The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, through projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) bacteria are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function are yet to be explored. Here, we isolated supernatants from the bladders of female mice acutely infected with UPEC (strain CFT073), or those sham-treated with phosphate buffered saline. Supernatants were then applied into the bladder lumen of healthy donor mice, and multiunit bladder afferent nerve responses to distension measured ex-vivo. Supernatant constituents from UPEC or sham-treated mice were analysed using a mouse cytokine multiplex assay. Supernatants from UPEC-infected mice significantly enhanced bladder afferent firing to distension in the absence of changes in muscle compliance. Further evaluation revealed that UPEC supernatants exclusively sensitised high-threshold bladder mechanoreceptors to graded bladder distension and also recruited a population of "silent nociceptors" to become mechanosensitive, thereby amplifying bladder afferent responses to physiological stimuli. UPEC supernatants contained significantly elevated concentrations of a range of cytokines released from innate immune cells, including but not limited to TNF-α, IL-1β, IL-6, IL-17, IFN-gamma, and MCP-1. These data provide novel mechanistic insight into how UPEC-mediated UTI induces bladder hypersensitivity and the symptoms of frequency, urgency, and pelvic pain.

MiR-463-3p inhibits tibial nerve regeneration via post-transcriptional suppression of SPRR1A

Background miRNAs have been involved in neural development, degeneration, and regeneration. MiR-463-3p is expressed in reproductive and nervous systems. In this study, the role of miR-463-3p in tibial nerve injury and regeneration was explored. Materials and methods A model of tibial nerve injury was established with the crush method, and the levels of miR-463-3p were detected at days 0, 3, 7, 12, 18 and 24 post-injury. Then, primary tibial nerve cells were isolated from newborn mice, and miR-463-3p was respectively overexpressed and knocked down in cultured cells. Behaviors of tibial nerve cells were detected. Furthermore, bioinformatics technology was used to investigate the underlying mechanism. Results The expression miR-463-3p was robustly increased in the injured tibial nerve in vivo and in tibial nerve cells treated with oxygen-glucose deprivation. The data on gain- and loss-of-function demonstrated that miR-463-3p negatively regulated including neurite length, percentage of cells with neurites, and cell branching in tibial nerve cells. Small proline-rich repeat protein 1 A (SPRR1A), an identified nerve regeneration associated genes, was identified as a target gene of miR-463-3p. Conclusion Inhibition of miR-463-3p could increase SPRR1A expression in the tibial nerve tissue and improve regeneration of the tibial nerve post-injury in vivo.

Upper Extremity Axon Counts and Clinical Implications for Motor Nerve Transfer.

Nerve transfers are planned based on the following parameters: location, number of branches, and axon count matching of the donor and recipient nerves. The authors have previously defined the former two in upper limb muscles. In the literature, axon counts are obtained from various sources, using different methods of histomorphometry. This study describes the axon counts of the same primary motor nerve branches from the authors' previous study using a uniform method of manual histomorphometry and completes the authors' blueprint of upper limb neuromuscular anatomy for reconstructive surgery. The distal ends of the primary nerve branches of 23 upper limb muscles were harvested from 10 fresh frozen cadaveric upper limbs. Manual quantitative histomorphometry was performed by two independent investigators, and the average was reported. The primary nerve branches of the arm muscles had higher average axon counts (range, 882 to 1835) compared with those of the forearm muscles (range, 267 to 883). In the forearm, wrist flexor (range, 659 to 746) and extensor (range, 543 to 745) nerve branches had axons counts that were similar to those of potential donors (e.g., supinator, n = 602; pronator teres, n = 625; flexor digitorum superficialis, n = 883; and flexor digitorum profundus, n = 832). Apart from describing the axon counts of the upper limb, the authors have found that the forearm axon counts are very comparable. This insight, when combined with information on the location and number of primary nerve branches, will empower surgeons to tailor bespoke nerve transfers for every clinical situation.

Clinical presentation and long-term outcome of primary spinal intradural malignant peripheral nerve sheath tumors

ObjectivePrimary spinal intradural malignant peripheral nerve sheath tumors (MPNSTs) are exceedingly rare, and there is limited published information regarding these lesions. The purpose of this study was to analyze the clinical course, treatment, and outcome of primary spinal intradural MPNSTs. Patients and MethodsA retrospective study was performed on 8 patients with primary spinal intradural MPNSTs who were surgically treated and pathologically confirmed in our institution between 2007 and 2018. ResultsThere were 3 females and 5 males, with a median age of 46.5 years (range, 21–68 years). Limb weakness was the most common clinical symptom (5/8, 62.5%). The radiological diagnosis was meningioma or schwannoma in most patients (7/8, 87.5%). Malignancies were graded high in 5 cases (62.5%) and low in 3 cases (37.5%). Gross total resection (GTR) was performed in 5 cases, while subtotal resection (STR) was achieved in 3 cases. The mean follow-up period was 48.9 months (range, 10–160 months). During follow-up, local recurrence occurred in 6/8 cases (75.0%) and distant metastasis occurred in 2/8 cases (25.0%). The median survival time (MST) of these 8 patients was 21.0 months. The overall 1-year, 2-year, and 5-year survival rates were 87.5% (7/8), 50.0% (4/8), and 25.0% (2/8), respectively. ConclusionsPrimary spinal intradural MPNST is a challenging clinical entity given its high local relapse rate. Primary spinal intradural MPNSTs radiologically present themselves heterogeneous and thus difficult to distinguish from schwannomas or meningiomas. Surgical resection, especially GTR, is the preferential treatment for primary spinal intradural MPNSTs.

Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy

We analysed the long-term outcomes of patients with primary optic nerve sheath meningioma (ONSM) treated with stereotactic radiotherapy (SRT). 26 patients with primary ONSM were treated with SRT between 2004 and 2013 at a single institution. SRT was delivered with image guidance to a median dose of 50.4 Gy in 28 fractions. 4 patients had prior surgical debulking. At a median radiological follow-up of 68 months, the MRI based tumour control was 100%. Visual acuity improved in 10 (38.4%), remained stable in 10 (38.4%) and was reduced in 6 (23.1%) patients following treatment. Stable or improved vision post-treatment was seen in 92.3% of patients with good pre-treatment vision (best corrected visual acuity 6/18 or better), compared to only 61.5% of patients with poor pre-treatment vision (best corrected visual acuity 6/24 or worse). Overall, the treatment was well tolerated with no Grade 2 or greater acute toxicity. Minimal other ophthalmic complications were seen with only one patient developing late onset Grade 3 radiation retinopathy.

Prognostic factors in the surgical treatment of intracanalicular primary optic nerve sheath meningiomas.

Although meningiomas frequently involve the optic nerve, primary optic nerve sheath meningiomas (ONSMs) are rare, accounting for only 1% of all meningiomas. Given the high risk of vision loss with these tumors, surgical intervention is seldom considered, and radiation or observation is commonly applied. Here, the authors describe the visual outcomes for a series of patients who were treated with surgery aiming at maximal tumor resection and highlight their prognostic factors. The authors retrospectively analyzed the data for 8 patients with intracanalicular ONSMs who had been surgically treated by the senior author (O.A.) between 1998 and 2016. Meningiomas extending into the optic canal from the intracranial cavity (i.e., clinoid, sphenoid wing, tuberculum sellae, diaphragma sellae) were excluded. Diagnosis was based on ophthalmological, radiological, and intraoperative findings, which were confirmed by the typical histological findings. Preoperative, postoperative, and follow-up visual assessments were performed by neuro-ophthalmologists in all cases. The patients included 7 females and 1 male. The mean age at diagnosis was 45.1 years (range 25.0-70.0 years). Mean duration of follow-up was 38.9 months (range 3.0-88.0 months). All patients reported visual complaints, and all had objective evidence of optic nerve dysfunction. Their evaluation included visual field, visual acuity, funduscopy, and retinal fiber thickness. Total resection was obtained in 4 cases. Comparing preoperative and postoperative visual function revealed that 4 patients had improvement at the last follow-up, 1 patient had stable vision, and 3 patients had decreased function but none had total vision loss. All patients with good preoperative visual acuity maintained this status following surgical treatment. There was no surgical mortality or infection. Operative complications included binocular diplopia in 4 patients, which remitted spontaneously. Surgery can play a beneficial role in the primary treatment of ONSM, especially lesions located in the posterior third of the nerve. Total removal can be achieved with vision preservation or improvement, without major surgical complications, especially at early stages of the disease. Patients with good preoperative vision and CSF flow in the optic sheath have better chances of a favorable outcome than those with poor vision.

Photoreceptors in a mouse model of Leigh syndrome are capable of normal light-evoked signaling

Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation's severity. Primary optic nerve atrophy resulting from death of retinal ganglion cells is the most prominent ocular manifestation of mitochondrial disease. However, dysfunction of other retinal cell types has also been described, sometimes leading to a loss of photoreceptors and retinal pigment epithelium that manifests clinically as pigmentary retinopathy. A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy. It has also been reported that ndufs4-/- mice display diminished light responses at the level of photoreceptors or bipolar cells. By conducting electroretinography (ERG) recordings in live ndufs4-/- mice, we now demonstrate that this defect occurs at the level of retinal photoreceptors. We found that this deficit does not arise from retinal developmental anomalies, photoreceptor degeneration, or impaired regeneration of visual pigment. Strikingly, the impairment of ndufs4-/- photoreceptor function was not observed in ex vivo ERG recordings from isolated retinas, indicating that photoreceptors with complex I deficiency are intrinsically capable of normal signaling. The difference in electrophysiological phenotypes in vivo and ex vivo suggests that the energy deprivation associated with severe mitochondrial impairment in the outer retina renders ndufs4-/- photoreceptors unable to maintain the homeostatic conditions required to operate at their normal capacity.

Differential Gene Expression in Nerves Repaired Under Low and High Tension

PURPOSE: Tension has been shown to be detrimental to nerve regrowth and reinnervation after primary nerve repair, likely via local ischemia and aberrant wound healing. We hypothesize that an improved understanding of the mechanisms underlying pathologic nerve healing may provide insight into potential targets for optimizing outcomes after nerve repair. The purpose of this study was to use RNA sequencing to identify differentially expressed genes in nerves repaired under minimal and significant tension. METHODS: Sciatic nerve transection was performed in male Lewis rats. The nerve was repaired via either a minimal-tension, interrupted epineural repair with 9-0 Nylon sutures, or a repair under tension for which a 9-mm segment of nerve was excised before interrupted epineural repair. The contralateral nerve served as each subject’s matched control. Nerve specimens were harvested at 14 weeks postoperatively. Following RNA extraction, sequencing was performed using Illumina HiSeq 2500. Reads were mapped back to the genome, and differentially expressed genes were identified using EBSeq. All analyses were conducted using R (R Development Core Team, 2012), a publicly available platform. RESULTS: Nerve repair was performed in 17 subjects (n = 8 minimal tension, n = 9 tension). Accounting for outliers, and using the hypothesis that all 3 groups (control, minimal tension, and tension) were different, 37 differentially expressed genes were identified. Many of the identified genes code for transcription factors and/or are involved in cell-signaling pathways. Col10a1, Crebzf, Prr34, Rsl1, and Setd4 were all found to be differentially upregulated in the tension group. Tfrc, a transferrin receptor upregulated in immunodeficiency syndromes, was downregulated in the tension group. For some genes, such as Bl6 and Naf1, expression in the tension group was more similar to that in the uninjured group. Heat maps allowed for qualitative visual comparison among uninjured control, minimal tension, and tension groups. CONCLUSIONS: To our knowledge, this is the first study to compare molecular signatures of nerves repaired using minimal and significant tension. Further study of these up- and downregulated genes could help identify targets for optimizing nerve healing and regeneration. Similar methodologies using RNA-Seq could be applied to studying neuroma in continuity and other nerve pathology that often requires intervention.

Modeling the daily rhythm of human pain processing in the dorsal horn.

Experimental studies show that human pain sensitivity varies across the 24-hour day, with the lowest sensitivity usually occurring during the afternoon. Patients suffering from neuropathic pain, or nerve damage, experience an inversion in the daily modulation of pain sensitivity, with the highest sensitivity usually occurring during the early afternoon. Processing of painful stimulation occurs in the dorsal horn (DH), an area of the spinal cord that receives input from peripheral tissues via several types of primary afferent nerve fibers. The DH circuit is composed of different populations of neurons, including excitatory and inhibitory interneurons, and projection neurons, which constitute the majority of the output from the DH to the brain. In this work, we develop a mathematical model of the dorsal horn neural circuit to investigate mechanisms for the daily modulation of pain sensitivity. The model describes average firing rates of excitatory and inhibitory interneuron populations and projection neurons, whose activity is directly correlated with experienced pain. Response in afferent fibers to peripheral stimulation is simulated by a Poisson process generating nerve fiber spike trains at variable firing rates. Model parameters for fiber response to stimulation and the excitability properties of neuronal populations are constrained by experimental results found in the literature, leading to qualitative agreement between modeled responses to pain and experimental observations. We validate our model by reproducing the wind-up of pain response to repeated stimulation. We apply the model to investigate daily modulatory effects on pain inhibition, in which response to painful stimuli is reduced by subsequent non-painful stimuli. Finally, we use the model to propose a mechanism for the observed inversion of the daily rhythmicity of pain sensation under neuropathic pain conditions. Underlying mechanisms for the shift in rhythmicity have not been identified experimentally, but our model results predict that experimentally-observed dysregulation of inhibition within the DH neural circuit may be responsible. The model provides an accessible, biophysical framework that will be valuable for experimental and clinical investigations of diverse physiological processes modulating pain processing in humans.

Reconstruction of the spinal accessory nerve with selective fascicular nerve transfer of the upper trunk.

Spinal accessory nerve palsy is frequently caused by iatrogenic damage during neck surgery in the posterior triangle of the neck. Due to late presentation, treatment regularly necessitates nerve grafts, which often results in a poor outcome of trapezius function due to long regeneration distances. Here, the authors report a distal nerve transfer using fascicles of the upper trunk related to axillary nerve function for reinnervation of the trapezius muscle. Five cases are presented in which accessory nerve lesions were reconstructed using selective fascicular nerve transfers from the upper trunk of the brachial plexus. Outcomes were assessed at 20 ± 6 months (mean ± SD) after surgery, and active range of motion and pain levels using the visual analog scale were documented. All 5 patients regained good to excellent trapezius function (3 patients had grade M5, 2 patients had grade M4). The mean active range of motion in shoulder abduction improved from 55° ± 18° before to 151° ± 37° after nerve reconstruction. In all patients, unrestricted shoulder arm movement was restored with loss of scapular winging when abducting the arm. Average pain levels decreased from 6.8 to 0.8 on the visual analog scale and subsided in 4 of 5 patients. Restoration of spinal accessory nerve function with selective fascicle transfers related to axillary nerve function from the upper trunk of the brachial plexus is a good and intuitive option for patients who do not qualify for primary nerve repair or present with a spontaneous idiopathic palsy. This concept circumvents the problem of long regeneration distances with direct nerve repair and has the advantage of cognitive synergy to the target function of shoulder movement.

Primary intraosseous hybrid epithelioid schwannoma/perineurioma in the proximal tibia: a case report of benign hybrid neoplasm with local hypercellularity

BackgroundAs a new entity included in the 4th edition of the WHO classification of tumours of soft tissue and bone in 2013, hybrid peripheral nerve sheath tumours are benign composite neoplasms that demonstrate features of more than one type of nerve sheath tumour, with a wide age distribution and a predilection for superficial location. Those involving deep sites are relatively rare. To the best of our knowledge, only one case of primary intraosseous hybrid peripheral nerve sheath tumours has been documented. In this article, we report another case of hybrid peripheral nerve sheath tumours occurring in bone with different clinical, radiological and pathological features from those in the previously reported cases.Case presentationA 28-year-old female presented with a painful nodule in the right tibia. Radiological examination revealed an oval eccentric osteolytic lesion in the proximal tibia. Histologically, the circumscribed but unencapsulated lesion demonstrated biphasic cellular differentiation. Bland, small epithelioid cells arranged in clusters in the myxoid or collagenous stroma and inconspicuous spindle cells scattered in the hypercellular areas were suggested to originate from Schwann cells according to the detection of S100. Both the elongated spindle cells with thin, wavy nuclei and the spindle cells in fascicular or storiform pattern in hypercellular areas showed a positive immunoreaction for epithelial membrane antigen, indicating perineurial differentiation. Based on histological and immunochemical examinations, the patient was diagnosed with hybrid epithelioid schwannoma/perineurioma. The lesion was resected and has not recurred for 8 months since resection.ConclusionThe present case is the second primary intraosseous hybrid peripheral nerve sheath tumour to be reported. This is also the first reported intraosseous tumour composed of epithelioid schwannoma and perineurioma with hypercellularity, indicating diverse involvement sites and a wide range of histological features among hybrid peripheral nerve sheath tumours. Awareness of such diversity is critical for accurate diagnoses. The morphological overlap with other spindle and epithelioid cell neoplasms, especially pure peripheral nerve sheath tumours, requires that immunochemical and molecular examinations be used as objective tools to provide the necessary information for a differential diagnosis.

Long-term quality of voice is usually acceptable after initial hoarseness caused by a thyroidectomy or a parathyroidectomy

Vocal cord (VC) palsy following a thyroidectomy or parathyroidectomy can result in significant morbidity for the patient. We aimed to investigate the incidence of VC palsy in a tertiary referral Institution, track the management of these cases and record the long-term outcomes and VC recovery rates. Retrospective review of all thyroidectomy/parathyroidectomy operations performed over 11 years. Patients with an unequivocal hoarse voice postoperatively were included. We analysed the patient's clinical characteristics and voice outcomes, operative, pathology and laryngoscopy reports during their follow-up. Ten patients fitted the inclusion criteria and were analysed. Median age at date of operation was 47.5 years (range, 16-81 years) and the M:F ratio was 1:2.3 (M:3, F:7). The median FU was 62.5 months (range, 12-144 months). The median hospital stay was 1.5 days (range, 1-87 days). There were 7 recurrent laryngeal nerve (RLN) injuries by manipulation, 1 case of RLN resection, 1 inadvertent division (with primary nerve repair) and 1 RLN was shaved off the thyroid. Long-term voice outcomes for the 7 patients with an RLN manipulation injury were: 3/7 patients had normal voice, 3/7 had moderate hoarseness and 1/7 had long-term hoarseness. The long-term voice outcome of the patient with RLN shaving off the thyroid gland was excellent while the 2 remaining patients (RLN resection and inadvertent division) needed 12 and 18 months respectively to achieve a normal quality of voice. Four out of the 10 patients had permanent VC palsy in the long-term and their voice outcomes varied: 1 patient had a normal voice, 2 patients had moderate hoarseness and 1 patient had persistent hoarseness. Only 1/10 patients did not show any voice improvement after 12 months. In the vast majority of cases post-operative hoarseness due to RLN palsy improves in the long-term, albeit voice may not return completely to normal.

Primary malignant peripheral nerve sheath tumour of the pericardium.

Primary malignant peripheral nerve sheath tumour of the pericardium.