Appropriate dosage, timing, and site of intramuscular injections of brain-derived neurotrophic factor (BDNF) promote motor recovery after facial nerve injury in rats.

INTRODUCTION/AIMS: Daily intramuscular injections of fibroblast growth factor 2 (FGF2) but not of brain-derived neurotrophic factor (BDNF) significantly improve whisking behavior and mono-innervation of the rat levator labii superioris (LLS) muscle 56 days after buccal nerve transection and suture (buccal-buccal anastomosis, BBA). We explored the dose-response of BDNF, FGF2, and insulin growth factor 2 (IGF2) on the same parameters, asking whether higher doses of BDNF would promote recovery. METHODS: After BBA, growth factors were injected (30 µL volume) daily into the LLS muscle over 14, 28, or 56 days. At 56 days, video-based motion analysis of vibrissal whisking was performed and the extent of mono- and poly-reinnervation of the reinnervated neuromuscular junctions (NMJs) of the muscle determined with immunostaining of the nerve with ß-tubulin and histochemical staining of the endplates with Alexa Fluor 488-conjugated α-bungarotoxin. RESULTS: The dose-response curve demonstrated significantly higher whisking amplitudes and corresponding increased mono-innervation of the NMJ in the reinnervated LLS muscle at concentrations of 20-30 µg/mL BDNF administered daily for 14-28 days after BBA surgery. In contrast, high doses of IGF2 and FGF2, or doses of 20 and 40 µg/mL of BDNF administered for 14-56 days had no effect on either whisking behavior or in reducing poly-reinnervation of endplates in the muscle. DISCUSSION: These data suggest that the re-establishment of mono-innervation of whiskerpad muscles and the improved motor function by injections of BDNF into the paralyzed vibrissal musculature after facial nerve injury have translation potential and promote clinical application.

Comparison of five different fluoroscopic methods for identifying the MPFL femoral footprint.

PURPOSE: The success of medial patellofemoral ligament (MPFL) reconstruction is closely linked to the precise positioning of the femoral tunnel. Intraoperative fluoroscopy is commonly utilized to identify the MPFL footprint. This study aimed to ascertain the most accurate fluoroscopic method among the five previously described methods used to determine the MPFL femoral footprint. MATERIALS AND METHODS: Using 44 well-preserved dry femur bones, the MPFL femoral insertion site was demarcated using anatomical bony landmarks, namely the center of the saddle sulcus between the medial epicondyle, adductor tubercle and gastrocnemius tubercle. Fluoroscopic true lateral knee images were acquired and measurements taken, referencing established methods by Schottle et al., Redfern et al., Wijdicks et al., Barnett et al., and Kaipel et al. The distance between anatomic and fluoroscopic MPFL footprints was then measured on digital fluoroscopic images. The accuracy of the locations was compared using a margin of error of 5 and 7 mm. RESULTS: The Schottle method consistently emerged superior, showcasing the smallest mean distance (3.2 ± 1.2 mm) between the anatomic and radiographic MPFL footprints and a high in-point detection rate of 90.9% under 5 mm criteria. While the Redfern method displayed perfect accuracy (100%) within the 7 mm criteria, the Schottle method also performed 97.7% accuracy. CONCLUSIONS: For intraoperative identification of the MPFL footprint using fluoroscopy, the Schottle method is the most consistent and accurate among the assessed methods. Thus, its accuracy in detecting the MPFL footprint makes it recommended for MPFLR to ensure optimal outcomes. LEVEL OF EVIDENCE: Level IV, cadaveric study.

Comparison of Spinal Mobility in Professional Musicians With and Without Pelvic Girdle Pain.

BACKGROUND: Prolonged sitting and performance hours in musicians may lead to an increased risk of musculoskeletal pain around the spine and pelvis. This situation may lead to an asymmetry of spinal segments, which in turn may correlate with muscle contractions around the lumbopelvic area and can lead to musculoskeletal pelvic girdle pain. The aim of this study was to investigate the segmental mobility of the vertebral column in two groups of musicians, those with and without pelvic girdle pain. METHODS: This study included 45 musicians who played their instrument for at least 10 years. Musicians were divided into two groups depending on if they had pelvic girdle pain or not. Spinal mobility was evaluated by a hand-held computer-assisted device called the Spinal Mouse system, and pelvic girdle pain assessments were evaluated using orthopedic tests including the active straight leg raise (ASLR), flexion abduction external rotation (FABER), pelvic pain provocation (P4), and long dorsal ligament palpation (LDL). RESULTS: The current study found no significant differences in the thoracic, lumbar, and sacral curves in the trunk flexion tests between musicians with and without pelvic girdle pain (p=0.28, 0.54, and 0.63). However, analysis of spinal mobility revealed that musicians with pelvic pain had significant limitations of spinal flexion mobility, mainly in the thoracolumbar region in the sagittal plane (p=0.02 and 0.01). CONCLUSIONS: This study revealed a significant correlation between pelvic girdle pain and limitations of segmental spinal flexion mainly in the thoracolumbar region of the sagittal plane in musicians. A lack of spinal mobility appears to be prevalent among musicians with pelvic girdle pain.

Variations of cross-sectional meniscal morphology between similar-sized menisci: implications on donor selection for meniscal allograft transplantation.

PURPOSE: This study aimed to investigate the morphological variations in the cross-sectional anatomy of the meniscus between similar-sized matched menisci. MATERIALS AND METHODS: Knee MRI of 329 patients with intact menisci were retrospectively reviewed, and the meniscal length (ML), meniscal width (MW), and cross-sectional dimensions (meniscal height and width) of the anterior, posterior horns, and the corpus were measured. Patients with similar-sized menisci who had less than 1 mm difference in ML and MW were matched. 330 male-to-male medial menisci (MM), 623 male-to-male lateral menisci (LM), 82 female-to-female MM, 233 female-to-female LM, 176 cross-gender MM, and 265 cross-gender LM unique combination of ideally matched pairs (total: 1709) were generated. The disparity in the cross-sectional dimensions, absolute difference, and the paired percent differences was statistically analyzed. RESULTS: The ML and MW in all groups were statistically similar, with a predefined absolute difference of 1 mm both for ML and MW (paired percent difference < 5%). The cross-sectional segmental meniscal dimensions were similar within all groups, but the paired percent differences showed high variations between a mean of 12.1-21.5% and up to 150.9%. The paired percent difference of MM in each segmental dimension was similar among different gender combinations. However, segmental paired percent differences of LM showed statistical differences in anterior horn width (AHW) (p: 0.001) and posterior horn width (PHW) (p: 0.001). In subgroup comparisons, the paired percent difference of AHW was higher in the female-to-female group compared to cross-gender (p: 0.023) and male-to-male groups (p: 0.001). The paired percent difference of PHW was smaller in the male-to-male group compared to female-to-female and cross-gender groups (p: 0.001 for both). CONCLUSIONS: Segmental cross-sectional anatomy showed wide variations despite strict matching in ML and MW. These variations were present in all gender combinations. The meniscal 3D shape is unique, but acceptable limits of similarity need further research. LEVEL OF EVIDENCE: Retrospective study, Level III.

Estimating the adequacy of the free quadriceps tendon autograft length using anthropometric measures in anterior cruciate ligament reconstruction.

OBJECTIVE: This prospective study aimed to predict the adequacy of free quadriceps tendon (QT) autograft length using simple anthropometric measures. MATERIALS AND METHODS: One hundred and eighty-four consecutive patients who underwent knee high-resolution MRI were enrolled in this study. The QT and native anterior cruciate ligament (ACL) length were measured using the oblique sagittal section. The adequate free QT length was calculated using the native ACL length and 30 mm for femoral and tibial tunnels in each patient. A QT shorter than the calculated length was considered inadequate. Age, sex, height, weight, body mass index, thigh circumference, and activity score were used to predict the adequacy of QT length with regression analysis. RESULTS: There were 92 men and 92 women with a mean age of 34.1 ± 8.0 years (range 18-45). The mean QT and ACL lengths were 69.0 ± 8.8 mm (range 48.1-90.3 mm) and 35.6 ± 2.5 mm (range 29.2-42.6 mm), respectively. The QT and the ACL lengths were longer in men (p < 0.001 for both). Twenty-three men and 39 women (total: 62, 33.7%) had inadequate QT length for a free QT autograft, and 6 patients (3 males, 3 females, 3.3%) had inadequate QT length with the bone block technique. There was a weak positive correlation between QT length and height (p < 0.001), weight (p < 0.001), and activity score (p = 0.007). Height was the only independent variable that predicted the QT length adequacy (r2 = 0.051, p = 0.009) but ROC analysis showed that height did not have an ability to detect a subject with an inadequate QT length (AUC: 0.384, 95% CI 0.300-0.468). CONCLUSIONS: Free QT autografts may be inadequate in one-third of the patients, while a QT autograft with a bone block is almost always sufficient. Inadequate free QT autograft is more common in women. Although QT length correlated with height, it cannot be used as an accurate diagnostic tool to identify patients with an inadequate QT autograft. Preoperative measurement of the ACL and QT lengths by MRI might be beneficial to decide whether QT is usable, especially when harvesting without a bone block. LEVEL OF EVIDENCE: Level II, diagnostic, prospective cohort study.

A rare cause of foot pain in an adolescent due to os paracuneiforme: a case report and review of the literature.

Os paracuneiforme is an extremely rare accessory ossicle located at the medial aspect of the medial cuneiform bone. Although foot pain secondary to accessory ossicles is well known, symptomatic os paracuneiforme that requires surgical excision is rarely reported in the current literature. Herein, a 12-year-old boy with symptomatic os paracuneiforme is presented, and its clinical and imaging findings as well as the treatment are discussed.

Neutralizing BDNF and FGF2 injection into denervated skeletal muscle improve recovery after nerve repair.

BACKGROUND: After facial nerve injury and surgical repair in rats, recovery of vibrissal whisking is associated with a high proportion of mono-innervated neuro-muscular junctions (NMJs). Our earlier work with Sprague Dawley (SD)/Royal College of Surgeons (RCS) rats, which are blind and spontaneously restore NMJ-monoinnervation and whisking, showed correlations between functional recovery and increase of fibroblast growth factor-2 (FGF2) and brain-derived neurotrophic factor (BDNF) in denervated vibrissal muscles. METHODS: We used normally sighted rats (Wistar), in which NMJ-polyinnervation is highly correlated with poor whisking recovery, and injected the vibrissal muscle levator labii superioris (LLS) with combinations of BDNF, anti-BDNF, and FGF2 at different postoperative periods after facial nerve injury. RESULTS: Rats receiving anti-BDNF+FGF2 showed low NMJ-polyinnervation and best recovery of whisking amplitude. CONCLUSIONS: Restoration of target reinnervation after peripheral nerve injury requires a complex mixture of trophic factors with a specific time course of availability for each of them.

Assessment of axonal sprouting and motor performance after hypoglossal-facial end-to-side nerve repair: experimental study in rats.

Hypoglossal-facial nerve anastomosis (HFA) aims to reanimate denervated mimic muscles with hypoglossal axons when the transected facial nerve is not accessible. The aim of this study was to evaluate the recovery of HFA using a "Y" tube in two variants: (1) the proximal stump of the hypoglossal nerve was entubulated to the "Y" tube (classic "Y" tube HFA) and (2) the "Y" tube was sutured to an epineurial window of a slightly damaged hypoglossal nerve (end-to-side "Y" tube HFA). A total of 48 adult female rats were divided into four groups: intact controls (group 1), sham operated (group 2), classic "Y" tube HFA (group 3) and end-to-side "Y" tube HFA (group 4). The abdominal aorta with both common iliac arteries of isogeneic male rats served as the Y-tube conduit. Animals from group 4 recovered better than those from group 3: the degree of collateral axonal branching (3 ± 1%) was significantly lower than that determined in group 3 (13 ± 1%). The mean deviation of the tongue from the midline was significantly smaller in group 4 (6 ± 4°) than that measured in animals from group 3 (41 ± 6°). In the determination of vibrissal motor function in group 3 and group 4, a decrease in amplitude was found to be - 66% and - 92%, respectively. No differences in the reinnervation pattern of the target muscles were detected. As a result, these surgical models were not determined to be able to improve vibrissal movements. It was concluded that performance of end-to-side "Y" tube HFA diminishes collateral axonal branching at the lesion site, which in turn, promotes better recovery of tongue- and vibrissal-motor performance.

Early and continued manual stimulation is required for long-term recovery after facial nerve injury.

INTRODUCTION: We previously have shown that manual stimulation (MS) of vibrissal muscles for 2 months after facial nerve injury in rats improves whisking and reduces motor end plate polyinnervation. Here, we seek to determine whether discontinuing or delaying MS after facial-facial anastomosis (FFA) leads to similar results. METHODS: Rats were subjected to FFA and received MS for (1) 4 months (early and continued), (2) the first but not the last 2 months (discontinued), or (3) the last 2 months (delayed). Intact animals and those not receiving MS (no MS) were also examined. RESULTS: Early and continued MS restored whisking amplitude to 43°, a value significantly higher compared with the discontinued, delayed, and no MS groups (32°, 24°, and 10°, respectively). Motor end plate polyinnervation occurred in all experimental groups but was significantly higher in the delayed group. DISCUSSION: Early and continued MS results in better recovery than when it is either discontinued or delayed. Muscle Nerve 57: 100-106, 2018.

Constantin von Monakow (1853-1930) and his legacy to science.

Constantin von Monakow was a Russian-born Swiss neurologist. Monakow was an outstanding scientist of his time. He will be remembered by his important contributions to our knowledge on the organization, location, and direction of tracts of the nervous system.

Sir Herbert Seddon (1903-1977) and his classification scheme for peripheral nerve injury.

Sir Herbert Seddon was a visionary neuroscientist and surgeon. Internationally, he is best known for his classification of the peripheral nerve injury, now known as Seddon's classification. The authors reviewed his life with a special emphasis on his legacy to neuroscience.

Charles Harrison Frazier (1870-1936) and his legacy to neurosurgery.

Charles Harrison Frazier (1870-1936) was a visionary neurosurgeon of his time. He devoted himself almost exclusively to neurosurgery based on his training in Germany on neurology, surgery, and surgical pathology and his accomplishments as a military physician during war years. The authors reviewed his life with a special emphasis on his legacy to neurosurgery.

Manual stimulation of the whisker pad after hypoglossal-facial anastomosis (HFA) using a Y-tube conduit does not improve recovery of whisking function.

Facial nerve injury is a common clinical trauma involving long-term functional deficits with facial asymmetry leading to associated psychological issues and social hardship. We have recently shown that repair by hypoglossal-facial or facial-facial nerve surgical end-to-end anastomosis and suture [hypoglossal-facial anastomosis (HFA) or facial-facial anastomosis (FFA)] results in collateral axonal branching, polyinnervation of neuromuscular junctions (NMJs) and poor function. We have also shown that another HFA repair procedure using an isogenic Y-tube (HFA + Y-tube) and involving a 10-mm gap reduces collateral axonal branching, but fails to reduce polyinnervation. Furthermore, we have previously demonstrated that manual stimulation (MS) of facial muscles after FFA or HFA reduces polyinnervation of NMJs and improves functional recovery. Here, we examined whether HFA + Y-tube and MS of the vibrissal muscles reduce polyinnervation and restore function. Isogenic Y-tubes were created using abdominal aortas. The proximal hypoglossal nerve was inserted into the long arm and sutured to its wall. The distal zygomatic and buccal facial nerve branches were inserted into the two short arms and likewise sutured to their walls. Manual stimulation involved gentle stroking of the vibrissal muscles by hand mimicking normal whisker movement. We evaluated vibrissal motor performance using video-based motion analysis, degree of collateral axonal branching using double retrograde labeling and the quality of NMJ reinnervation in target musculature using immunohistochemistry. MS after HFA + Y-tube reduced neither collateral branching, nor NMJ polyinnervation. Accordingly, it did not improve recovery of function. We conclude that application of MS after hypoglossal-facial nerve repair using an isogenic Y-tube is contraindicated: it does not lead to functional recovery but, rather, worsens it.

Temporal and spatial distribution of the aquaporin 1 in spinal cord and dorsal root ganglia after traumatic injuries of the sciatic nerve.

PURPOSE: The aquaporin family comprises a large family of integral membrane proteins that enable the movement of water and other small, neutral solutes across plasma membranes. Although function and mechanism of aquaporins in central nervous system injury have been reported, the pathophysiologic role of aquaporin 1 (AQP1) in peripheral nerve has not been extensively documented. In the present study, we aimed to study the temporal and spatial distribution of AQP1 in spinal cord and dorsal root ganglia after sciatic nerve injury. METHODS: Forty-eight adult female mice were randomly divided into four groups (intact controls, sham operated, cut injury, and crush injury). Animals receiving cut or crush injuries were sacrificed at the 2nd, 24th, and 48th postoperative hours. Spinal cord samples at the level of lumbosacral intumescences and corresponding dorsal root ganglia on the experimental and contralateral side were dissected free and proceeded to AQP1 immunohistochemistry. RESULTS: Our quantitative estimations revealed that a sharp increase in AQP1 immunoreactivity at the 24th postoperative hour was observed. This sharp increase was no more evident at 48 h after sciatic nerve injury. Identical peak was observed after both cut and crush injuries. CONCLUSIONS: We demonstrated that there was a temporal relationship with an increased expression of AQP1 following injury sustained to the sciatic nerve that was significantly observed in dorsal root ganglia and spinal cord. Those expressions were also subsided over time.

Investigation into a new denervation model of the sciatic nerve zones in rats: Selective motor or sensorial denervation.

OBJECTIVE: This study aimed to introduce a reliable and useful model of selective sensorial or motor denervations of the sciatic nerve in rats with clinical and laboratory outcomes. METHODS: The surgical technique was determined via detailed cadaveric dissections of rat sciatic nerve roots and cross-sectional histoanatomy. Forty animals were divided into the sham, sensorial denervation (SD), motor denervation (MD), and combined denervation (CD) groups and evaluated clinically via the pinch test and observation. Electrophysiological tests, retrograde neuronal labeling, and histologic and radiographic studies were performed. The weights of the muscles innervated by the sciatic nerve were measured. RESULTS: The nerve root topography at the L4 level was consistent. Hemilaminectomy satisfactorily exposed all the roots contributing to the sciatic nerve and selectively denervated its sensorial and motor zones. Sensorial denervation caused foot deformities and wound problems, which were more severe in SD than in MD and CD. Nerve histomorphometry, electrophysiological tests, retrograde neuronal labeling studies, and measurements of the muscle weights also verified the denervations. CONCLUSION: This study has shown the feasibility of selective (sensory or motor) sciatic nerve denervation through a single-level hemilaminectomy. The surgical technique is reliable and has a confounding effect on gait. Sensorial denervation had more severe foot problems than motor and combined denervation in rats.

Comparison of the beneficial effect of melatonin on recovery after cut and crush sciatic nerve injury: a combined study using functional, electrophysiological, biochemical, and electron microscopic analyses.

PURPOSE: Following tissue injury, melatonin is known to reduce detrimental effects of free radicals by stimulating antioxidant enzymes and also to inhibit posttraumatic polymorphonuclear infiltration. Beneficial effects after peripheral nerve injury have been suggested, but not studied in detail. Therefore, we aimed to elucidate the effects of melatonin on the recovery of the lesioned rat sciatic nerve by means of combined analysis. METHODS: A total number of 90 rats were randomly distributed into six groups: control (group 1), sham-operated (group 2), sciatic nerve cut (group 3), sciatic nerve cut + melatonin treatment (group 4), sciatic nerve crush (group 5), and sciatic nerve crush + melatonin treatment (group 6). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 6 weeks. Recovery of function was analyzed by assessment of the sciatic functional index based on walking track analysis, somatosensory evoked potentials, biochemical quantification of malondialdehyde, antioxidant enzymes levels, and ultrastructural analysis. RESULTS: Our data showed the beneficial effect of melatonin on sciatic nerve recovery. Rats treated with melatonin demonstrated better structural preservation of the myelin sheaths compared to the nontreated group. The biochemical analysis confirmed the beneficial effects of melatonin displaying lower lipid peroxidation and higher superoxide dismutase, catalase, and glutathione peroxidase activities in sciatic nerve samples in comparison to nontreated groups. CONCLUSIONS: The beneficial effects of melatonin administration on the recovery of the cut and crush injured sciatic nerve may be attributed to its antioxidant properties. Based on these investigations, we think that our data would be helpful for clinicians who deal with peripheral nerve injuries.

Vitamin D3 Promotes Structural and Functional Recovery After Vincristine-Induced Peripheral Neuropathy in Rats: An Experimental Study.

Background Vincristine-induced peripheral neuropathy (VIPN) is a distal axonopathy characterized by the loss of distal myelinated axons. This study aimed to assess the potential neuroregenerative roles of vitamin D3 using functional and electron microscopic analyses in a rat model of VIPN. Methodology A total of 40 female Wistar rats were randomly divided into four main groups: Group 1 (control, n = 10), Group 2 (vincristine, n = 10), Group 3 (vincristine + vitamin D3, n = 10), and Group 4 (vincristine + vehicle, n = 10). Vincristine was administered intraperitoneally at a dose of 0.15 mg/kg, for two weeks, to induce peripheral neuropathy. Following successful induction, vitamin D3 (500 IU/kg/day) and vehicle treatments were applied weekly over four weeks. Structural (electron microscopic analysis) and functional analysis (von Frey test, pinch test, and electrophysiological analysis) were performed to assess functional recovery after peripheral nerve impairment. Results Withdrawal responses to mechanical allodynia and pinch tests were significantly higher in the vitamin D3-treated group (P < 0.05). The electrophysiological analysis also supported these results. Electron microscopic evaluation revealed that the remyelinated nerve fibers in the vitamin D3-treated group (Group 3) had thick myelin sheaths and normal axonal morphology. Conclusions Our study demonstrated that vitamin D3 could promote functional and structural recovery in a rat model of VIPN. Further studies should be conducted to elucidate the underlying mechanisms by which vitamin D3 exerts its regenerative effects in VIPN, using alternative administration protocols.

Effects of platelet-rich fibrin and dexamethasone on nerve regeneration after acute facial-nerve injury.

BACKGROUND: Acute facial-nerve injury. OBJECTIVE: To investigate the effects of platelet-rich fibrin (PRF) and dexamethasone on nerve regeneration. MATERIALS AND METHODS: Thirty-six rats were randomly divided into six groups. Facial-nerve injury was created using a full-thickness incision in all groups except Group E. Next, primary anastomosis, PRF application, topical dexamethasone application, primary anastomosis with topical PRF and dexamethasone application, and no facial-nerve repair were performed in Groups A, B, C, D, and F, respectively. Clinical, functional, and structural improvements were evaluated at eight weeks. RESULTS: The mean eye-closure movement score in Group B was significantly higher than that in Group F (p < .001). The mean whisker-movement score in Group B was significantly higher than that in Group F (p = .001). The mean amplitude of whisker movement in Group F was significantly lower than those in Groups A, B, C, and E, and the mean amplitude in Group D was significantly lower than that in Group E (p < .001). Furthermore, an improvement in nerve ultrastructure was observed in Group B. CONCLUSION: PRF application has a positive effect on nerve recovery after anastomosis. SIGNIFICANCE: Contribute to the literature to improve nerve regeneration.