Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol ...(vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.
Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold ...mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (
= 27), radial (
= 8), and peroneal (
= 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.
Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.
Objective
To describe our technical and preliminary clinical experience with ultrasound-guided diagnostic deep peroneal nerve (DPN) blocks for patients considering deep peroneal neurectomy.
Materials ...and methods
Retrospective analysis of ultrasound-guided diagnostic DPN blocks performed in the anterior lower leg in patients pursuing deep peroneal neurectomy for foot pain not directly attributable to the DPN. Patient age, sex, foot laterality, diagnosis, nerve block complications, location of the DPN with respect to vascular landmarks in the lower leg, pain relief from nerve block, and pain relief from neurectomy (if performed) were recorded.
Results
Twenty-six DPN blocks were performed for 25 feet, of which a majority had pain attributable to midfoot osteoarthritis (22/25). Variable DPN locations with respect to vascular landmarks in the lower leg were observed, including lateral to the anterior tibial artery (12/25), anterior to the artery (5/25), medial to the artery (3/25), lateral to the lateral paired vein (4/25), and 1-cm lateral to the artery (1/25). After DPN blocks, patients reported pain relief in 22/25 feet. Of the eleven patients who proceeded to have a deep peroneal neurectomy, ten reported improved foot pain.
Conclusion
Diagnostic deep peroneal nerve blocks for patients considering deep peroneal neurectomy for denervation therapy should be performed in the anterior lower leg where the anterior tibial vessels serve as anatomic landmarks. Those who perform DPN blocks with ultrasound guidance should be aware of variable DPN position with respect to the vascular landmarks.
Deep fibular nerve is one of the two terminal branches of the common fibular nerve. The deep fibular nerve can be damaged in procedures related the anterior compartment of the leg such as the ...application of an external fixator to the leg and operations using intramedullary nailing after tibial fracture. Therefore, it is important to know the anatomy and variations of the deep fibular nerve. An anatomical variation concerning the deep fibular nerve was detected in the right lower extremity of the 65-year-old cadaver we dissected. In this case, it was observed that the deep fibular nerve split into two nerve arms in the distal half of the leg and reunited after continuing 9cm apart to form a loop. This loop formation may increase the iatrogenic damage of the deep fibular nerve as a result of surgery and percutaneous interventions to the anterior leg compartment. We described in this case report a hitherto unobserved finding of the branching pattern of the deep fibular nerve. We think that this unique anatomical variation seen in the right lower extremity of the case of academic interest and will also help orthopedicians in anterior leg compartment surgery.
•RetroDISCO optically clears whole mouse spinal cord while retaining fluorescent signal.•The technique is tracer dependent and detects expected differences after repair.•RetroDISCO is inexpensive, ...simple, robust and uses confocal microscopy.
Quantification of the number of axons reinnervating a target organ is often used to assess regeneration after peripheral nerve repair, but because of axonal branching, this method can overestimate the number of motor neurons regenerating across an injury. Current methods to count the number of regenerated motor neurons include retrograde labeling followed by cryosectioning and counting labeled motor neuron cell bodies, however, the process of sectioning introduces error from potential double counting of cells in adjacent sections.
We describe a method, retroDISCO, that optically clears whole mouse spinal cord without loss of fluorescent signal to allow imaging of retrograde labeled motor neurons using confocal microscopy.
Complete optical clearing of spinal cords takes four hours and confocal microscopy can obtain z-stacks of labeled motor neuron pools within 3–5min. The technique is able to detect anticipated differences in motor neuron number after cross-suture and conduit repair compared to intact mice and is highly repeatable.
RetroDISCO is inexpensive, simple, robust and uses commonly available microscopy techniques to determine the number of motor neurons extending axons across an injury site, avoiding the need for labor-intensive cryosectioning and potential double counting of motor neuron cell bodies in adjacent sections.
RetroDISCO allows rapid quantification of the degree of reinnervation without the confounding produced by axonal sprouting.
The loss of the fat pad surrounding the fibular head after rapid and excessive weight loss after bariatric surgery can lead to foot drop symptoms due to peroneal nerve entrapment (PNE). Conservative ...and surgical approaches have been described for the treatment of this condition, but there is some controversy over the effectiveness of the treatment modalities.
We aimed to investigate the causes and frequency of foot drop due to PNE after bariatric surgery and to investigate the effects of peroneal nerve decompression (PND) as a surgical treatment for PNE.
Single center, university surgical department.
We retrospectively evaluated a series of 2607 patients in terms of neurologic complications after bariatric surgery. Patients' age, sex, co-morbid diseases, vitamin and electrolyte levels, body mass index and postoperative excess weight loss, affected limb, duration of symptoms, and muscle strength scores (according to the Medical Research Council scale) were recorded.
A total of 14 (.5%) patients had foot drop symptoms due to PNE. Of these patients, 9 underwent PND. The mean excess weight loss of PND patients at postoperative months 6 and 12 were 68.8 ± 13.5 and 100.9 ± 10.8, respectively. Foot drop symptoms became evident 5 to 11 months after bariatric surgery, affecting only a unilateral lower extremity in all patients. In laboratory analysis, there were no signs of nutritional and vitamin deficiency or insufficiency in any of the PND cases. Muscular strength was Medical Research Council grade 0 in all patients. The median duration of symptoms was 9 days, and the median complete recovery time was 40 days after PND. Patients who had a duration of symptoms for a maximum of 12 days were completely healed 30 days after PND.
PND should be the first-choice treatment procedure for acute foot drop due to PNE after bariatric surgery.
Adipose lesions of nerve are rare tumors that can cause nerve symptoms from either intrinsic or extrinsic compression.
The authors present a case of a patient with a 10-year history of progressive, ...persistent leg pain and dorsal foot paresthesias/dysesthesias. Imaging revealed several nondistinct nodules of indeterminate significance along the course of the superficial peroneal nerve (SPN). Surgery demonstrated six distinct extraneural lipomas studded on a 10-cm segment of the main SPN and one of its muscular branches in the midleg. The lesions were adherent to the SPN, without an easy dissection plane; therefore, a neurectomy was performed. Histology revealed the nerve was associated with multiple extraneural lipomas with focal evidence of prior trauma. At 4 months postoperatively, the patient's pain had resolved completely, and she was able to resume normal physical activities.
The current classification of adipose lesions of nerve includes intraneural and extraneural lipomas and lipomatosis of nerve (fibrolipomatous hamartoma). The unique features of the present case include the discrete and segmental nature of the extraneural lipomas adherent to the nerve. Its etiology is unknown, and the histology would be suggestive of either a traumatic or a degenerative process.
Introduction/Aims
Isolated injuries to the lateral cutaneous nerve of the calf (LCNC) branch of the common peroneal nerve can cause obscure chronic posterolateral knee and upper calf pain and sensory ...symptoms. Routine examination and electrodiagnostic testing do not detect them because the LCNC has no motor distribution and it is not interrogated by the typical peroneal nerve conduction study. There are only about 10 prior cases, thus scant physician awareness, so most LCNC injuries remain misdiagnosed or undiagnosed, hindering care.
Methods
We extracted pertinent records from seven patients with unexplained posterolateral knee/calf pain, six labeled as complex regional pain syndrome, to investigate for mononeuropathies. Patients were asked to outline their skin area with abnormal responses to pin self‐examination independently. Three underwent an LCNC‐specific electrodiagnostic study, and two had skin‐biopsy epidermal innervation measured. Cadaver dissection of the posterior knee nerves helped identify potential entrapment sites.
Results
Initiating events included knee surgery (three), bracing (one), extensive kneeling (one), and other knee trauma. All pin‐outlines included the published LCNC neurotome. One oftwo LCNC‐specific electrodiagnostic studies revealed unilaterally absent potentials. Longitudinal, controlled skin biopsies documented profound LCNC‐neurotome denervation then re‐innervation contemporaneous with symptom recovery. Cadaver dissection identified the LCNC traversing through the dense fascia of the proximolateral gastrocnemius muscle insertion.
Discussion
Isolated LCNC mononeuropathy can cause unexplained posterolateral knee/calf pain syndromes. This series characterizes presentations and supports patient pin‐mappings as a sensitive, globally available, low‐cost diagnostic aid. Improved recognition may facilitate more rapid, accurate diagnosis and, thus, optimize management and improve outcomes.
The cadherin Celsr3 regulates the directional growth and targeting of axons in the CNS, but whether it acts in collaboration with or in parallel to other guidance cues is unknown. Furthermore, the ...function of Celsr3 in the peripheral nervous system is still largely unexplored. Here we show that Celsr3 mediates pathfinding of motor axons innervating the hindlimb. In mice, Celsr3-deficient axons of the peroneal nerve segregate from those of the tibial nerve but fail to extend dorsally, and they stall near the branch point. Mutant axons respond to repulsive ephrinA-EphA forward signaling and glial cell-derived neurotrophic factor (GDNF). However, they are insensitive to attractive EphA-ephrinA reverse signaling. In transfected cells, Celsr3 immunoprecipitates with ephrinA2, ephrinA5, Ret, GDNF family receptor α1 (GFRα1) and Frizzled3 (Fzd3). The function of Celsr3 is Fzd3 dependent but Vangl2 independent. Our results provide evidence that the Celsr3-Fzd3 pathway interacts with EphA-ephrinA reverse signaling to guide motor axons in the hindlimb.