On-Site Laser Photobiomodulation Treatment of Crushed Muscle Due to Prolonged Pressure in Rats.

BACKGROUND AND OBJECTIVES: Crush injuries and prolonged pressure on muscles lead to bruises and sprains and, in most of the cases, cause distraction of the muscle and release of particles into the blood stream, causing renal and systemic complications in severe cases. Laser photobiomodulation treatment (i.e., laser phototherapy) is a method suggested to decrease the pressure damage in the first 24-48 hours after muscle injury, allowing a faster and more complete physical rehabilitation. We studied the efficacy of non-invasive laser photobiomodulation treatment as an on-site treatment for crush-injured gastrocnemius muscles, developing a moderate muscle crush injury model and aiming at decreasing damage extent while regaining physical competence faster. STUDY DESIGN/MATERIALS AND METHODS: Muscle crush injury was performed on 30 female Wistar rats using direct pressure for 10 minutes on the gastrocnemius muscle in both left and right hindlimbs. Immediately after the injury, only the left hindlimb were irradiated for 16 minutes (with 780 nm laser with a power of 250 mW, the energy at the target was 240 J, and the fluence was 1019 J/cm2 ) for 1, 3, or 7 consecutive days, and sacrificed accordingly. During the follow-up period, 1, 3, or 7 days, both gastrocnemius muscles (of the treated and untreated hindlimbs) were evaluated for electrophysiology and functionality. RESULTS: The laser photobiomodulation treatment showed a significant electrophysiological and functional recovery of the gastrocnemius muscle during the first 3 days after injury, in comparison with the untreated hindlimb. CONCLUSIONS: These preliminary results are promising, showing a significant effect of the laser photobiomodulation treatment during the first 3 days after the induction of the muscle crush injury, which is the most critical period in the clinical aspect. These findings suggest a therapeutic approach, which may help restore the muscle after crush injury.

Dynamic mapping using an electrified ultrasonic aspirator in lipomyelomeningocele and spinal cord detethering surgery-a feasibility study.

BACKGROUND: Intraoperative neurophysiologic monitoring (IONM) is an established technique and adjunct of brain and spinal lesion resection surgery. In spina bifida syndrome surgery, mapping of the surgical wound is a common and accepted method in determining the position and functionality of nerve roots of the cauda equina (CE), especially when the anatomy is not straightforward and roots are splayed across or entangled within the lesion. Here, we describe a novel technique of continuous CE mapping using an electrified cavitron ultrasonic aspirator (eCUSA) in children with lipomyelomeningocele (LMMC) lesions. METHODS: We assessed a method of dynamic CE mapping using an eCUSA as a stimulation probe. Twenty children (0.5-18 years) were included in this study, diagnosed with occult spina bifida LMMC in which the eCUSA stimulator was applied. IONM data and 2-weeks post-operative data were collected. RESULTS: LMMC lesions were located in the lumbar, sacral, and lumbosacral spine. eCUSA stimulation at 0.3-3.0 mA intensities elicited positive lower extremity muscle responses in 12 of the 20 patients included in the study. These responses allowed the surgeon real-time identification of the nerve roots tangent at the LMMC-cauda equina structure and intensive removal of the fat tissue in the area non-responding to the eCUSA stimulation. CONCLUSION: Continuous eCUSA-based stimulation of the cauda equina during LMMC resection is a feasible mapping technique with potential added value improving safety of untethering. Future studies evaluating extension of untethering, as well as the rates of retethering and long-term neurological and urological outcomes, are warranted.

Modified Hyaluronic Acid-Laminin-Hydrogel as Luminal Filler for Clinically Approved Hollow Nerve Guides in a Rat Critical Defect Size Model.

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model.

Muscle Response to Complete Peripheral Nerve Injury: Changes of Acetylcholine Receptor and Creatine Kinase Activity over Time.

Background This study was designed to assess the changes of acetylcholine receptor (AChR) and creatine kinase (CK) levels, which are important biochemical markers for muscle viability in cases of long-term muscle denervation. Scientists and peripheral nerve surgeons may find these data important regarding maximal range of muscle viability applicable for timing of effective peripheral nerve reconstructive surgery. Methods The study was conducted on 48 rats (96 gastrocnemius muscles), whose right legs were denervated by removing a 10-mm segment of sciatic nerve, while their left legs remained intact. Under general anesthesia, the rats were euthanized at seven points in time, on days 7, 14, 21, 30, 60, 120, and 210. In both legs, AChR was quantified by 125I-α-bungarotoxin, whereas CK activity was measured using a spectrophotometric method. Results CK levels in the denervated limb reached a minimal level of 34% on day 30 in comparison to the intact limb and remained at this level up to 210 days after operation. AChR levels in the denervated limb reached a minimal level of 38% on day 120 in comparison to the intact limb and remained at this level up to 210 days after operation. Conclusion The present study shows that AChR and CK levels in rat denervated muscles remain constant at about third of its intact condition for a period of at least a third of rat's lifetime postinjury.

Comparison of results between chitosan hollow tube and autologous nerve graft in reconstruction of peripheral nerve defect: An experimental study.

OBJECT: This study evaluated a chitosan tube for regeneration of the injured peripheral nerve in a rodent transected sciatic nerve model in comparison to autologous nerve graft repair. METHODS: Chitosan hollow tube was used to bridge a 10-mm gap between the proximal and distal ends in 11 rats. In the control group, an end-to-end coaptation of 10-mm long autologous nerve graft was performed in 10 rats for nerve reconstruction. RESULTS: SFI showed an insignificant advantage to the autologous group both at 30 days (P = 0.177) and at 90 days post procedure (P = 0.486). Somato-sensory evoked potentials (SSEP) and compound muscle action potentials (CMAP) tests showed similar results between chitosan tube (group 1) and autologous (group 2) groups with no statistically significant differences. Both groups presented the same pattern of recovery with 45% in group 1 and 44% in group 2 (P = 0.96) showing SSEP activity at 30 days. At 90 days most rats showed SSEP activity (91% vs.80% respectively, P = 0.46). The CMAP also demonstrated no statistically significant differences in latency (1.39 ms in group 1 vs. 1.63 ms in group 2; P = 0.48) and amplitude (6.28 mv vs. 6.43 mv respectively; P = 0.8). Ultrasonography demonstrated tissue growth inside the chitosan tube. Gastrocnemius muscle weight showed no statistically significant difference. Histomorphometry of the distal sciatic nerve, 90 days post reconstructive procedure, showed similar number of myelinated fibers and size parameters in both groups (P ≥ 0.05). CONCLUSIONS: Chitosan hollow tube used for peripheral nerve reconstruction of rat sciatic nerve showed similar results in comparison to autologous nerve grafting. © 2015 Wiley Periodicals, Inc. Microsurgery 36:664-671, 2016.

Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot.

OBJECTIVES: Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury. METHODS: This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years). RESULTS: Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p < 0.05). Presence of foreign particles in shrapnel injured patients has a negative impact on the surgical outcome in terms of rate of pain improvement (28 % compared to 67 % in patients with and without foreign particles, respectively). Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later. CONCLUSIONS: This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient's functional activity and quality of life.

Nerve Reconstruction Using ActiGraft Blood Clot in Rabbit Acute Peripheral Injury Model: Preliminary Study.

This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results.

Peroneal and tibial intraneural ganglion cysts in children.

BACKGROUND/AIMS: Intraneural ganglion cyst is a rare and underrecognized clinical entity in the pediatric population, which may cause pain as well as motor and sensory neurological deficits. This study presents 4 pediatric patients harboring ganglion cysts involving the peroneal and tibial nerves. METHODS: Data encompassing pre- and postoperative analyses of 4 pediatric patients with intraneural ganglion cyst was evaluated. RESULTS: Out of these 4 patients, 3 had an intraneural ganglion cyst involving the peroneal nerve, and 1 patient had his tibial nerve involved. Two patients were operated for recurrent ganglion cysts with severe postoperative neurological deficits, after preceding operations in other institutions. The other 2 patients had no history of previous surgery, and they had their initial surgical treatment in our institute for primarily diagnosed ganglion cysts. With a mean follow-up of 24 months, all patients experienced pain relief. Significant improvement of motor deficits was achieved in 3 patients. No recurrences were encountered during the 24-month follow-up. CONCLUSION: Intraneural ganglion cysts in children can be treated with excellent outcome in experienced and dedicated centers, which specialize in peripheral nerve microsurgery.

Thoracic Outlet Syndrome Part II: Consensus on the Management of Neurogenic Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: In the first part of this report, the European Association of Neurosurgical Societies' section of peripheral nerve surgery presented a systematic literature review and consensus statements on anatomy, classification, and diagnosis of thoracic outlet syndrome (TOS) along with a subclassification system of neurogenic TOS (nTOS). Because of the lack of level 1 evidence, especially regarding the management of nTOS, we now add a consensus statement on nTOS treatment among experienced neurosurgeons. OBJECTIVE: To document consensus and controversy on nTOS management, with emphasis on timing and types of surgical and nonsurgical nTOS treatment, and to support patient counseling and clinical decision-making within the neurosurgical community. METHODS: The literature available on PubMed/MEDLINE was systematically searched on February 13, 2021, and yielded 2853 results. Screening and classification of abstracts was performed. In an online meeting that was held on December 16, 2021, 14 recommendations on nTOS management were developed and refined in a group process according to the Delphi consensus method. RESULTS: Five RCTs reported on management strategies in nTOS. Three prospective observational studies present outcomes after therapeutic interventions. Fourteen statements on nonsurgical nTOS treatment, timing, and type of surgical therapy were developed. Within our expert group, the agreement rate was high with a mean of 97.8% (± 0.04) for each statement, ranging between 86.7% and 100%. CONCLUSION: Our work may help to improve clinical decision-making among the neurosurgical community and may guide nonspecialized or inexperienced neurosurgeons with initial patient management before patient referral to a specialized center.

Reviving matrix for nerve reconstruction in rat model of acute and chronic complete spinal cord injury.

This study aimed to investigate the innovative antigliotic guiding regenerative gel (AGRG) as reviving matrix for reconnection of spinal cord defect in rat models of complete acute and chronic spinal cord injury (SCI). In acute SCI, a 2 mm segment of the spinal cord (SC) was removed at Th7-Th8. Then AGRG was injected to the gap or left untreated. In chronic SCI, a 1 mm segment of the spinal cord (SC) was removed at Th7-Th8. One month later, the injured area was cleaned from connective and scar tissue, creating a gap of 2-3 mm. Then, AGRG was injected to the gap or left untreated. Functional, electrophysiological, histological and immunohistochemical assessments were performed. In acute SCI, at week 24, 75% of AGRG group showed a somatosensory evoked potential (SEP) signal. Appearance of myelin basic protein (MBP) was observed in the injured area in the AGRG group (p < 0.1), compared to the untreated group. In chronic SCI, 24 weeks after 2nd surgery, appearance of MBP, indicating presence of myelinated axons, was observed in AGRG group, compared to the untreated group (p < 0.01). These preliminary results suggest that AGRG can serve as a vital bridging station inducing regeneration of injured SC in acute and chronic cases of paraplegia.

A Rabbit Model for Peripheral Nerve Reconstruction Studies Avoiding Automutilation Behavior.

Background The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods In 20 adult female New Zealand White rabbits, instead of transecting the complete sciatic nerve, we unilaterally transected the tibial portion and preserved the peroneal portion. Thereby loss of sensation in the dorsal aspect of the paw was avoided. The tibial portion was repaired in a reversed autograft approach in a length of 2.6 cm. In an alternative repair approach, a gap of 2.6 cm in length was repaired with a chitosan-based nerve guide. Results During the 6-month follow-up period, there were no incidents of autotomy. Nerve regeneration of the tibial portion of the sciatic nerve was evaluated histologically and morphometrically. A clear difference between the distal segments of the healthy contralateral and the repaired tibial portion of the sciatic nerve was detectable, validating the model. Conclusion By transecting the isolated tibial portion of the rabbit sciatic nerve and leaving the peroneal portion intact, it was possible to eliminate automutilation behavior.

Thoracic Outlet Syndrome Part I: Systematic Review of the Literature and Consensus on Anatomy, Diagnosis, and Classification of Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: Although numerous articles have been published not only on the classification of thoracic outlet syndrome (TOS) but also on diagnostic standards, timing, and type of surgical intervention, there still remains some controversy because of the lack of level 1 evidence. So far, attempts to generate uniform reporting standards have not yielded conclusive results. OBJECTIVE: To systematically review the body of evidence and reach a consensus among neurosurgeons experienced in TOS regarding anatomy, diagnosis, and classification. METHODS: A systematic literature search on PubMed/MEDLINE was performed on February 13, 2021, yielding 2853 results. Abstracts were screened and classified. Recommendations were developed in a meeting held online on February 10, 2021, and refined according to the Delphi consensus method. RESULTS: Six randomized controlled trials (on surgical, conservative, and injection therapies), 4 "guideline" articles (on imaging and reporting standards), 5 observational studies (on diagnostics, hierarchic designs of physiotherapy vs surgery, and quality of life outcomes), and 6 meta-analyses were identified. The European Association of Neurosurgical Societies' section of peripheral nerve surgery established 18 statements regarding anatomy, diagnosis, and classification of TOS with agreement levels of 98.4 % (±3.0). CONCLUSION: Because of the lack of level 1 evidence, consensus statements on anatomy, diagnosis, and classification of TOS from experts of the section of peripheral nerve surgery of the European Association of Neurosurgical Societies were developed with the Delphi method. Further work on reporting standards, prospective data collections, therapy, and long-term outcome is necessary.

Reviving Matrix for Nerve Reconstruction in Rabbit Model of Chronic Peripheral Nerve Injury With Massive Loss Defect.

Background and Aims: The aim of this study was to investigate the innovative guiding regenerative gel (GRG) and antigliotic GRG (AGRG) fillings for nerve conduits, prepared with Food and Drug Administration (FDA)-approved agents and expected to provide an alternative to autologous nerve graft and to enable reconnection of massive nerve gaps in a rabbit model of chronic peripheral nerve injury with massive loss defect that simulates the human condition of chronic injury with a large gap. Methods: The components and dosimetry for GRG and AGRG formulations were investigated in vitro on nerve cell culture and in vivo on 10-mm reconstructed sciatic nerves of 72 rats using different concentrations of agents and completed on a rabbit model of delayed (chronic) complete peripheral nerve injury with a 25-mm gap. Forty rabbits underwent delayed (9 weeks after complete injury of the tibial portion of the sciatic nerve) nerve tube reconstruction of a gap that is 25 mm long. GRG and AGRG groups were compared with autologous and empty tube reconstructed groups. Rats and rabbits underwent electrophysiological and histochemical assessments (19 weeks for rats and 40 weeks for rabbits). Results: Application of AGRG showed a significant increase of about 78% in neurite length per cell and was shown to have the most promising effect on neuronal outgrowth, with total number of neurites increasing by 4-fold. The electrophysiological follow-up showed that AGRG treatment is most promising for the reconstruction of the tibial portion of the sciatic nerve with a critical gap of 25 mm. The beneficial effect of AGRG was found when compared with the autologous nerve graft reconstruction. Thirty-one weeks post the second surgery (delayed reconstruction), histochemical observation showed significant regeneration after using AGRG neurogel, compared with the empty tube, and succeeded in significantly regenerating the nerve, as well as the autologous nerve graft, which was almost similar to a healthy nerve. Conclusion: We demonstrate that in the model of delayed peripheral nerve repair with massive loss defect, the application of AGRG led to a stronger nerve recovery and can be an alternative to autologous nerve graft.

In Vivo and In Vitro Evaluation of a Novel Hyaluronic Acid-Laminin Hydrogel as Luminal Filler and Carrier System for Genetically Engineered Schwann Cells in Critical Gap Length Tubular Peripheral Nerve Graft in Rats.

In the current study we investigated the suitability of a novel hyaluronic acid-laminin hydrogel (HAL) as luminal filler and carrier system for co-transplanted cells within a composite chitosan-based nerve graft (CNG) in a rat critical nerve defect model. The HAL was meant to improve the performance of our artificial nerve guides by giving additional structural and molecular support to regrowing axons. We filled hollow CNGs or two-chambered nerve guides with an inserted longitudinal chitosan film (CNG[F]s), with cell-free HAL or cell-free HA or additionally suspended either naïve Schwann cells (SCs) or fibroblast growth factor 2-overexpressing Schwann cells (FGF2-SCs) within the gels. We subjected female Lewis rats to immediate 15 mm sciatic nerve gap reconstruction and comprehensively compared axonal and functional regeneration parameters with the gold standard autologous nerve graft (ANG) repair. Motor recovery was surveyed by means of electrodiagnostic measurements at 60, 90, and 120 days post-reconstruction. Upon explantation after 120 days, lower limb target muscles were harvested for calculation of muscle-weight ratios. Semi-thin cross-sections of nerve segments distal to the grafts were evaluated histomorphometrically. After 120 days of recovery, only ANG treatment led to full motor recovery. Surprisingly, regeneration outcomes revealed no regeneration-supportive effect of HAL alone and even an impairment of peripheral nerve regeneration when combined with SCs and FGF2-SCs. Furthermore, complementary in vitro studies, conducted to elucidate the reason for this unexpected negative result, revealed that SCs and FGF2-SCs suspended within the hydrogel relatively downregulated gene expression of regeneration-supporting neurotrophic factors. In conclusion, cell-free HAL in its current formulation did not qualify for optimizing regeneration outcome through CNG[F]s. In addition, we demonstrate that our HAL, when used as a carrier system for co-transplanted SCs, changed their gene expression profile and deteriorated the pro-regenerative milieu within the nerve guides.

Increase of neuronal sprouting and migration using 780 nm laser phototherapy as procedure for cell therapy.

BACKGROUND AND OBJECTIVES: The present study focuses on the effect of 780 nm laser irradiation on the growth of embryonic rat brain cultures embedded in NVR-Gel (cross-linked hyaluronic acid with adhesive molecule laminin and several growth factors). Dissociated neuronal cells were first grown in suspension attached to cylindrical microcarriers (MCs). The formed floating cell-MC aggregates were subsequently transferred into stationary cultures in gel and then laser treated. The response of neuronal growth following laser irradiation was investigated. MATERIALS AND METHODS: Whole brains were dissected from 16 days Sprague-Dawley rat embryos. Cells were mechanically dissociated, using narrow pipettes, and seeded on positively charged cylindrical MCs. After 4-14 days in suspension, the formed floating cell-MC aggregates were seeded as stationary cultures in NVR-Gel. Single cell-MC aggregates were either irradiated with near-infrared 780 nm laser beam for 1, 4, or 7 minutes, or cultured without irradiation. Laser powers were 10, 30, 50, 110, 160, 200, and 250 mW. RESULTS: 780 nm laser irradiation accelerated fiber sprouting and neuronal cell migration from the aggregates. Furthermore, unlike control cultures, the irradiated cultures (mainly after 1 minute irradiation of 50 mW) were already established after a short time of cultivation. They contained a much higher number of large size neurons (P<0.01), which formed dense branched interconnected networks of thick neuronal fibers. CONCLUSIONS: 780 nm laser phototherapy of embryonic rat brain cultures embedded in hyaluronic acid-laminin gel and attached to positively charged cylindrical MCs, stimulated migration and fiber sprouting of neuronal cells aggregates, developed large size neurons with dense branched interconnected network of neuronal fibers and, therefore, can be considered as potential procedure for cell therapy of neuronal injury or disease.

Phototherapy in peripheral nerve regeneration: From basic science to clinical study.

OBJECT: This review summarizes the continuous study of low-power laser radiation treatment of a severely injured peripheral nerve. Laser phototherapy was applied as a supportive factor for accelerating and enhancing axonal growth and regeneration after injury or a reconstructive peripheral nerve procedure. In nerve cell cultures, laser phototherapy was used to stimulate activation of nerve cells. METHODS: Low-power laser radiation was used for treatment of peripheral nerve injury using a rat sciatic nerve model after crush injury, neurorrhaphy, or neurotube reconstruction. Nerve cell growth and axonal sprouting were investigated using laser phototherapy on embryonic rat brain cultures. The outcome in animal studies facilitated a clinical double-blind, placebo-controlled, randomized study that measured the effectiveness of 780-nm laser phototherapy on patients suffering from incomplete peripheral nerve injuries for 6 months to several years. RESULTS: Animal studies showed that laser phototherapy has an immediate protective effect, maintains functional activity of the injured nerve, decreases scar tissue formation at the injury site, decreases degeneration in corresponding motor neurons of the spinal cord, and significantly increases axonal growth and myelinization. In cell cultures, laser irradiation accelerates migration, nerve cell growth, and fiber sprouting. A pilot clinical double-blind, placebocontrolled, randomized study showed that in patients with incomplete long-term peripheral nerve injury, 780-nm laser radiation can progressively improve peripheral nerve function, which leads to significant functional recovery. CONCLUSIONS: Using 780-nm laser phototherapy accelerates and enhances axonal growth and regeneration after injury or a reconstructive peripheral nerve procedure. Laser activation of nerve cells, their growth, and axonal sprouting can be considered as potential treatment of neuronal injury. Animal and clinical studies show the promoting action of phototherapy on peripheral nerve regeneration, making it possible to suggest that the time for broader clinical trials has arrived.

Experimental repair of tracheal defects using a new biodegradable membrane.

BACKGROUND: The increasing number of newborns requiring intubation and artificial ventilation in the sophisticated premature and intensive care units of recent years has been followed by a concomitant increase in the number of children who develop tracheal stenosis as a sequela of prolonged intubation, with a consequent increasing need for tracheal surgical repair. This study was designed to evaluate the ability of a new tissue-engineered biodegradable membrane to tightly seal significant tracheal defects. MATERIALS AND METHODS: A surgically induced tracheal defect of 10 x 5 mm was repaired in rabbits using the NVR-7 membrane--a cross-linked copolymer derived from a dextran sulphate gelatin construct. The unique features of this new membrane are biocompatibility, biodegradability, elasticity, and suturability, as well as a smooth sterilization process. The animals were sacrificed and the tracheas examined at 2, 3, 4, and 8 weeks postsurgery. RESULTS: Seven (7) of 8 rabbits undergoing tracheal surgery survived, with a tight air seal and an almost normal airway. Macroscopic and microscopic studies of the removed specimens showed variable degrees of immunogenic reaction toward the membrane. In the long term (2-3 months), a complete regeneration of all the tracheal layers occurred, simulating the original structure and orderly arrangement of a normal trachea. CONCLUSIONS: The surgical correction using the above membrane enabled the operated animals to overcome any respiratory distress, adequately correcting the induced tracheal defect. From this experimental study, we conclude that the new NVR-7 membrane appears to be a promising therapeutic adjunct in the treatment of patients with tracheal defects.

Laser phototherapy (780 nm), a new modality in treatment of long-term incomplete peripheral nerve injury: a randomized double-blind placebo-controlled study.

OBJECTIVE: The authors conducted this pilot study to prospectively investigate the effectiveness of low-power laser irradiation (780 nm) in the treatment of patients suffering from incomplete peripheral nerve and brachial plexus injuries for 6 months up to several years. BACKGROUND DATA: Injury of a major nerve trunk frequently results in considerable disability associated with loss of sensory and motor functions. Spontaneous recovery of long-term severe incomplete peripheral nerve injury is often unsatisfactory. METHODS: A randomized, double-blind, placebo-controlled trial was performed on 18 patients who were randomly assigned placebo (non-active light: diffused LED lamp) or low-power laser irradiation (wavelength, 780 nm; power, 250 mW). Twenty-one consecutive daily sessions of laser or placebo irradiation were applied transcutaneously for 3 h to the injured peripheral nerve (energy density, 450 J/mm(2)) and for 2 h to the corresponding segments of the spinal cord (energy density, 300 J/mm(2)). Clinical and electrophysiological assessments were done at baseline, at the end of the 21 days of treatment, and 3 and 6 months thereafter. RESULTS: The laser-irradiated and placebo groups were in clinically similar conditions at baseline. The analysis of motor function during the 6-month follow-up period compared to baseline showed statistically significant improvement (p = 0.0001) in the laser-treated group compared to the placebo group. No statistically significant difference was found in sensory function. Electrophysiological analysis also showed statistically significant improvement in recruitment of voluntary muscle activity in the laser-irradiated group (p = 0.006), compared to the placebo group. CONCLUSION: This pilot study suggests that in patients with long-term peripheral nerve injury noninvasive 780-nm laser phototherapy can progressively improve nerve function, which leads to significant functional recovery.

Efficacy of 780-nm laser phototherapy on peripheral nerve regeneration after neurotube reconstruction procedure (double-blind randomized study).

OBJECTIVE: This pilot double-blind randomized study evaluated the efficacy of 780-nm laser phototherapy on the acceleration of axonal growth and regeneration after peripheral nerve reconstruction by polyglycolic acid (PGA) neurotube. BACKGROUND DATA: The use of a guiding tube for the reconstruction of segmental loss of injured peripheral nerve has some advantages over the regular nerve grafting procedure. Experimental studies have shown that laser phototherapy is effective in influencing nerve regeneration. METHODS: The right sciatic nerve was transected, and a 0.5-cm nerve segment was removed in 20 rats. A neurotube was placed between the proximal and the distal parts of the nerve for reconnection of nerve defect. Ten of 20 rats received post-operative, transcutaneous, 200-mW, 780-nm laser irradiation for 14 consecutive days to the corresponding segments of the spinal cord (15 min) and to the reconstructed nerve (15 min). RESULTS: At 3 months after surgery, positive somato-sensory evoked responses were found in 70% of the irradiated rats (p = 0.015), compared to 30% of the non-irradiated rats. The Sciatic Functional Index in the irradiated group was higher than in the non-irradiated group (p < 0.05). Morphologically, the nerves were completely reconnected in both groups, but the laser-treated group showed an increased total number of myelinated axons. CONCLUSION: The results of this study suggest that postoperative 780-nm laser phototherapy enhances the regenerative process of the peripheral nerve after reconnection of the nerve defect using a PGA neurotube.