Treatment of Depression in Huntington's Disease: A Systematic Review.

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.

Distal femoral osteotomy and patellar tendon advancement for the treatment of crouch gait in patients with bilateral spastic cerebral palsy.

BACKGROUND: Crouch gait, or flexed knee gait, represents a common gait pattern in patients with spastic bilateral cerebral palsy (CP). Distal femoral extension and/or shortening osteotomy (DFEO/DFSO) and patellar tendon advancement (PTA) can be considered as viable options when knee flexion contractures are involved. Better outcomes have been reported after a combination of both, independently of the presence of knee extensor lag. In this study, we evaluated the clinical and kinematic outcomes of these procedures. PATIENTS AND METHODS: We reviewed a cohort of 52 limbs (28 patients) who were treated for crouch gait by DFEO/DFSO alone (group 1, n = 15) or DFEO/DFSO + PTA (group 2, n = 37) as a part of single event multilevel surgery (SEMLS). The mean age at surgery was 14 years, and the mean follow-up time was 18 months. The physical examination data and three-dimensional standardized gait analysis were collected and analyzed before the surgery and postoperatively. RESULTS: Overall knee range of motion improved in all limbs. The knee flexion decreased significantly in both groups at initial, mid, and terminal stance. Hip flexion significantly decreased in mid-stance for limbs in group 2. Both clinical and gait parameters were most improved in limbs who underwent DFEO/DFSO + PTA. Increased pelvic tilt was observed in both groups after surgery. CONCLUSION: Although DFEO/DFSO alone was successful in correcting knee flexion contractures, PTA has helped to improve knee extensor lag and knee extension during gait. LEVEL OF EVIDENCE: Therapeutic level IV.

Obsessive-compulsive and perseverative behaviors in Huntington's disease.

Obsessive-compulsive and perseverative behaviors (OCBs/PBs) are characteristic features of Huntington's Disease (HD). Although a few recent research have attempted to discriminate between OCBs and PBs, most of the available evidence on OCBs does not consistently make this distinction. In this article, we aimed to explore the current inconsistencies in assessing and reporting OCBs/PBs and map the body of existing evidence. Up to half of the patients with motor manifest HD can experience OCBs. Separate reporting of PBs in HD patients has been uncommon among the studies and was frequently reported as a part of obsessive-compulsive symptoms. The structural limitation of the currently used rating scales and the overlaps in neuropathology and definition of OCBs and PBs are among the main reasons for the mixed reporting of OCBs/PBs. Perseverative thinking or behavior as a separate item is found in a few assessment tools, such as the Problem Behaviors Assessment - Short form (PBA-s). Even when the item exists, it is commonly reported as a composite score in combination with the obsessive-compulsive item. In addition to the significant psychological burden in individuals with HD, PBs are associated with somatic effects (e.g., cardiovascular symptoms) and high-risk behaviors (e.g., suicide). Recognition and monitoring of PBs in HD can aid in early detection of concerning symptoms and differentiating overlapping illnesses.

Incidence of traumatic spinal cord injury worldwide: A systematic review, data integration, and update.

Objectives: This review was designed to update our earlier systematic review which evaluated both published and unpublished evidence on the incidence of traumatic spinal cord injury (TSCI) worldwide. Methods: We used various search methods including strategic searching, reference checking, searching for grey literature, contacting registries, authors, and organizations requesting unpublished data, browsing related websites, and hand searching key journals. The quality of included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tools. Records published between April 2013 and May 2020 were added to the original systematic review. Results: Overall, 58 resources including 45 papers, 10 SCI registry reports, 1 book, and 2 theses were retrieved. We found TSCI incidence data for eight new countries, which overall shapes our knowledge of TSCI incidence for 49 countries. The incidence of TSCI ranges from 3.3 to 195.4 cases per million (cpm) based on subnational studies and from 5.1 to 150.48 cpm based on national studies. Most of the studies were low quality, lacked consistent case selection due to unclear definition of TSCI and unclear ascertainment methods. Conclusions: There is an increasing number of publications in the literature focusing on the epidemiologic data of TSCI. The absence of a standard form of reporting TSCI hinders the comparability of data across different data sources. Use of various definitions for TSCI may lead to heterogeneity in reports. Use of sensitivity analyses based on reasonable classification criteria can aid in offering a uniform set of case identification and ascertainment criteria for TSCI.

Reliability and Validity of the AOSpine Thoracolumbar Injury Classification System: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The AOSpine thoracolumbar injury classification system (ATLICS) is a relatively simple yet comprehensive classification of spine injuries introduced in 2013. This systematic review summarizes the evidence on measurement properties of this new classification, particularly the reliability and validity of the main morphologic injury types with and without inclusion of the subtypes. METHODS: A literature search was performed using PubMed and Embase in September 2016. A revised version of the COSMIN checklist was used for evaluation of the quality of studies. Two independent reviewers performed all steps of the review. RESULTS: Nine articles were included in the final review, all of which evaluated the reliability of the ATLICS and had a fair methodological quality. The reliability of the modifiers was unknown. Overall, the quality of evidence for reliability of the morphologic and neurologic classification sections was low. However, there was moderate evidence for poor interobserver reliability of the morphologic classification when all subtypes were included, and moderate evidence for good intraobserver reliability with exclusion of subtypes. The reliability of the morphologic classification was independent of the observer's experience and cultural background. CONCLUSIONS: ATLICS represents the most current system for evaluation of thoracolumbar injuries. Based on this review, further studies with robust methodological quality are needed to evaluate the measurement properties of ATLICS. Shortcomings of the reliability studies are discussed.

Axonal degeneration and demyelination following traumatic spinal cord injury: A systematic review and meta-analysis.

The pathophysiology of spinal cord injury (SCI) related processes of axonal degeneration and demyelination are poorly understood. The present systematic review and meta-analysis were performed such to establish quantitative results of animal studies regarding the role of injury severity, SCI models and level of injury on the pathophysiology of axon and myelin sheath degeneration. 39 related articles were included in the analysis. The compiled data showed that the total number of axons, number of myelinated axons, myelin sheath thickness, axonal conduction velocity, and internode length steadily decreased as time elapsed from the injury (Pfor trend<0.0001). The rate of axonal retrograde degeneration was affected by SCI model and severity of the injury. Axonal degeneration was higher in injuries of the thoracic region. The SCI model and the site of the injury also affected axonal retrograde degeneration. The number of myelinated axons in the caudal region of the injury was significantly higher than the lesion site and the rostral region. The findings of the present meta-analysis show that the pathophysiology of axons and myelin sheath differ in various phases of SCI and are affected by multiple factors related to the injury.

Biofunctionalized peptide-based hydrogel as an injectable scaffold for BDNF delivery can improve regeneration after spinal cord injury.

BACKGROUND: The complex pathophysiological events occurring after traumatic spinal cord injuries (TSCI) make this devastating trauma still incurable. Peptide amphiphile (PA) hydrogels are nanobiomaterials displaying desirable properties for application in regenerative medicine because they are absorbable, injectable, allowing biofunctionalization, controlling release of trophic factors and mimic extracellular matrix (ECM). In this study, we explored the potentiality of the IKVAV-functionalized PA hydrogel to provide a permissive environment for cell migration and growth as well as sustained release of BDNF at the lesion after severe compression injury model. METHODS: The IKVAV-functionalized PA was synthesized by automated solid-phase approach and its secondary structure was evaluated by Circular dichroism (CD) spectroscopy. The potential of IKVAV-functionalized PA to self-assemble into nanofibers and hydrogel formation were assessed using transmission electron microscopy (TEM). Release profiles of BDNF from hydrogel and the bioactivity of the released BDNF from hydrogel were determined using ELISA and DRG bioassay, respectively. Severe spinal cord injury was induced using clip compression at T7-T8 vertebral segment. Twenty four hours post-injury the animals were treated by either IKVAV PA hydrogel, BDNF-loaded IKVAV PA hydrogel, BDNF solution or saline. Two and six weeks later, animals were sacrificed and the lesion site was evaluated based on GFAP, CD68 and ß III tubulin immunoreactivity. Also, locomotor recovery was assessed during 6 weeks using Basso, Beattie, Bresnahan (BBB) scoring test. RESULTS: The IKVAV PA arranged into nanofibrous structure and provided a sustained release of BDNF over 21 days while preserved the bioactivity of BDNF. Also, BDNF loading influenced the hydrogel nanostructure resulting in aligned orientation of nanofibers. Injection of BDNF-loaded IKVAV PA hydrogel resulted in a considerable axon preservation and astrogliosis reduction at 6 weeks post-injury without showing any inflammatory reaction. However, the BBB score was not statistically different between different treatment groups. CONCLUSION: Although the locomotor functional recovery was not observed in this study, the axon preservation and minimal inflammation in animals treated with BDNF-incorporated hydrogel indicate the potentiality of the designed intervention for further evaluations in the path of developing efficient therapies for severe spinal cord injury.

The fate of neurons after traumatic spinal cord injury in rats: A systematic review.

OBJECTIVES: To reach an evidence-based knowledge in the context of the temporal-spatial pattern of neuronal death and find appropriate time of intervention in order to preserve spared neurons and promote regeneration after traumatic spinal cord injury (TSCI). MATERIALS AND METHODS: The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched (24 October, 2015) with no temporal or linguistic restrictions. Hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies evaluating time-dependent neuronal death following acute mechanical trauma to the spinal cord were included. We separately evaluated the fate of various populations of neurons including propriospinal neurons, ventral motor neurons, Clarke's column neurons, and supraspinal neurons. RESULTS: We found 11,557 non-duplicated studies. Screening through the titles and abstracts led to 549 articles, 49 of which met the inclusion criteria. Both necrotic and apoptotic neuronal deaths occur after TSCI, though necrosis is the prominent mechanism. There are differences in the responses of intrinsic neurons of the spinal cord to the TSCI. Also, the extent of neuronal death in the supraspinal neurons depends on the anatomical location of their axons. CONCLUSION: In order to develop new therapies, selection of the injury model and time of intervention has a crucial role in the efficacy of therapy. In addition, examining the safety and efficacy of an intervention by reliable methods not confounded by the injury-related changes would promote translation of therapies to the clinical application.

Corticosteroid Administration to Prevent Complications of Anterior Cervical Spine Fusion: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: Anterior cervical approach is associated with complications such as dysphagia and airway compromise. In this study, we aimed to systematically review the literature on the efficacy and safety of corticosteroid administration as a preventive measure of such complications in anterior cervical spine surgery with fusion. METHODS: Following a systematic literature search of MEDLINE, Embase, and Cochrane databases in July 2016, all comparative human studies that evaluated the effect of steroids for prevention of complications in anterior cervical spine surgery with fusion were included, irrespective of number of levels and language. Risk of bias was assessed using MINORS (Methodological Index for Non-Randomized Studies) checklist and Cochrane Back and Neck group recommendations, for nonrandomized and randomized studies, respectively. RESULTS: Our search yielded 556 articles, of which 9 studies (7 randomized controlled trials and 2 non-randomized controlled trials) were included in the final review. Dysphagia was the most commonly evaluated complication, and in most studies, its severity or incidence was significantly lower in the steroid group. Although prevertebral soft tissue swelling was less commonly assessed, the results were generally in favor of steroid use. The evidence for airway compromise and length of hospitalization was inconclusive. Steroid-related complications were rare, and in both studies that evaluated the fusion rate, it was comparable between steroid and control groups in long-term follow-up. CONCLUSIONS: Current literature supports the use of steroids for prevention of complications in anterior cervical spine surgery with fusion. However, evidence is limited by substantial risk of bias and small number of studies reporting key outcomes.

Evidence-based prevention and treatment of osteoporosis after spinal cord injury: a systematic review.

PURPOSE: Spinal cord injury (SCI) results in accelerated bone mineral density (BMD) loss and disorganization of trabecular bone architecture. The mechanisms underlying post-SCI osteoporosis are complex and different from other types of osteoporosis. Findings of studies investigating efficacy of pharmacological or rehabilitative interventions in SCI-related osteoporosis are controversial. The aim of this study was to review the literature pertaining to prevention and evidence-based treatments of SCI-related osteoporosis. METHODS: In this systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to identify papers from 1946 to December 31, 2015. The search strategy involved the following keywords: spinal cord injury, osteoporosis, and bone loss. RESULTS: Finally, 56 studies were included according to the inclusion criteria. Only 16 randomized controlled trials (involving 368 patients) were found. We found following evidences for effectiveness of bisphosphonates in prevention of BMD loss in acute SCI: very low-quality evidence for clodronate and etidronate, low-quality evidence for alendronate, and moderate-quality evidence for zoledronic acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic SCI cases, we found low-quality evidence for effectiveness of vitamin D3 analogs combined with 1-alpha vitamin D2. However, low-quality inconsistent evidence exists for alendronate. For non-pharmacologic interventions, very low-quality evidence exists for effectiveness of standing with or without treadmill walking in acute SCI. Other low-quality evidences indicated that electrical stimulation, tilt-table standing, and ultrasound provide no significant effects. Very low-quality evidence did not show any benefit for low-intensity (3 days per week) cycling with functional electrical stimulator in chronic SCI. CONCLUSIONS: No recommendations can be made from this review, regarding overall low quality of evidence as a result of high risk of bias, low sample size in most of the studies, and notable heterogeneity in type of intervention, outcome measurement, and duration of treatment. Therefore, future high-quality RCT studies with higher sample sizes and more homogeneity are strongly recommended to provide high-quality evidence and make applicable recommendations for prevention and treatment of SCI-related bone loss.

Clinical Application of Ceramics in Anterior Cervical Discectomy and Fusion: A Review and Update.

STUDY DESIGN: Narrative review. OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is a reliable procedure, commonly used for cervical degenerative disc disease. For interbody fusions, autograft was the gold standard for decades; however, limited availability and donor site morbidities have led to a constant search for new materials. Clinically, it has been shown that calcium phosphate ceramics, including hydroxyapatite (HA) and tricalcium phosphate (TCP), are effective as osteoconductive materials and bone grafts. In this review, we present the current findings regarding the use of ceramics in ACDF. METHODS: A review of the relevant literature examining the clinical use of ceramics in anterior cervical discectomy and fusion procedures was conducted using PubMed, OVID and Cochrane. RESULT: HA, coralline HA, sandwiched HA, TCP, and biphasic calcium phosphate ceramics were used in combination with osteoinductive materials such as bone marrow aspirate and various cages composed of poly-ether-ether-ketone (PEEK), fiber carbon, and titanium. Stand-alone ceramic spacers have been associated with fracture and cracks. Metallic cages such as titanium endure the risk of subsidence and migration. PEEK cages in combination with ceramics were shown to be a suitable substitute for autograft. CONCLUSION: None of the discussed options has demonstrated clear superiority over others, although direct comparisons are often difficult due to discrepancies in data collection and study methodologies. Future randomized clinical trials are warranted before definitive conclusions can be drawn.

Comparison of Pediatric and General Orthopedic Surgeons' Approaches in Management of Developmental Dysplasia of the Hip and Flexible Flatfoot: the Road to Clinical Consensus.

Developmental dysplasia of the hip (DDH) and flatfoot are common pediatric orthopedic disorders, being referred to and managed by both general and pediatric orthopedic surgeons, through various modalities. Our study aimed to evaluate their consensus and perspective disagreements in terms of diagnostic and therapeutic approaches of the mentioned deformities. Forty participants in two groups of general orthopedic surgeons (GOS) (n=20) and pediatric orthopedic surgeons (POS) (n=20), were asked to answer an 8-item questionnaire on DDH and flexible flatfoot. The questions were provided with two- or multiple choices and a single choice was accepted for each one. Chi-square and Fisher's exact tests was performed to compare the responses. For a neonate with limited hip abduction, hip ultrasonography was the agreed-upon approach in both groups (100% POS vs 71% GOS), and for its interpretation 79% of POS relied on their own whereas 73% of GOS relied on radiologist's report (P=0.002). In failure of a 3-week application of the Pavlik harness, ending it and closed reduction (57% POS vs. 41% GOS) followed by surgery quality assessment with CT scan (64% POS vs. 47% GOS) and without the necessity for avascular necrosis evaluation (79% POS vs. 73% GOS) were the choice measures. In case of closed reduction failure, open reduction via medial approach was the favorite next step in both groups (62% POS and 80% GOS). For the patient with flexible flat foot, reassurance was the choice plan of 79% of pediatric orthopedists. Our findings demonstrated significant disagreements among the orthopedic surgeons. This proposes insufficiency of high-level evidence.

Bone Morphogenetic Proteins in Anterior Cervical Fusion: A Systematic Review and Meta-Analysis.

OBJECTIVE: Bone morphogenetic proteins (BMPs) have been commonly used as a graft substitute in spinal fusion. Although the U.S. Food and Drug Administration issued a warning on life-threatening complications of recombinant human BMPs (rhBMPs) in cervical spine fusion in 2008, their off-label use has been continued. This investigation aimed to review the evidence for the use of rhBMP-2 and rhBMP-7 in anterior cervical spine fusions. METHODS: A comprehensive search was performed through Ovid (MEDLINE), PubMed, and Embase. The risk of bias assessment was according to the recommended criteria by the Cochrane Back and Neck group and MINORS (Methodological Index for Non-Randomized Studies). A wide array of radiographic and clinical outcomes including the adverse events were collated. RESULTS: Eighteen articles (1 randomized and 17 nonrandomized) were eligible for inclusion. The fusion rate was higher with use of rhBMP in most studies and our meta-analysis of the pooled data from 4782 patients confirmed this finding (odds ratio, 5.45; P < 0.00001). Altogether, the rhBMP and control groups were comparable in patient-reported outcomes. However, most studies tended to show a significantly higher incidence of overall complication rate, dysphagia/dysphonia, cervical swelling, readmission, wound complications, neurologic complications, and ossification. CONCLUSIONS: Application of rhBMPs in cervical spine fusion yields a significantly higher fusion rate with similar patient-reported outcomes, yet increased risk of life-threatening complications. Thus, we do not recommend the use of rhBMP in anterior cervical fusions.

Epidemiology of Joint Dislocations and Ligamentous/Tendinous Injuries among 2,700 Patients: Five-year Trend of a Tertiary Center in Iran.

BACKGROUND: The epidemiology of traumatic dislocations and ligamentous/tendinous injuries is poorly understood. In this study, we aimed to evaluate the prevalence and distribution of various dislocations and ligamentous/tendinous injuries in a tertiary orthopedic hospital in Iran. METHODS: Musculoskeletal injuries in an academic tertiary health care center in Tehran February 2005 to October 2010 were recorded. The demographic details of patients with pure dislocations and ligamentous/tendinous injuries were extracted and the type and site of injuries were classified according to their specific age/gender groups. RESULTS: Among 18,890 admitted patients, 628 (3.3%) were diagnosed with dislocations and 2.081 (11%) with ligamentous/tendinous injuries. The total male/female ratio was 4.2:1 in patients with dislocations and 1.7:1 in patients with ligamentous/tendinous injuries. Shoulder was the most prevalent site of dislocation (50.6%), followed by fingers (10.1%), toes (7.6%), hip (7.3%), and elbow (6.5%). Ankle was the most common site of ligamentous/tendinous injury (53.5%), followed by midfoot (12.3%), knee (8.3%), hand (7%), and shoulder (5%). The mean ages of the patients in dislocations and ligamentous/tendinous injuries were 35.0±18.2 and 31.3± 15.1, respectively. There was no seasonal variation. CONCLUSION: Shoulder dislocation and ankle ligamentous injury are the most frequent injuries especially in younger population and have different distribution patterns in specific age and sex groups. Epidemiologic studies can help develop and evaluate the injury prevention strategies, resource allocation, and training priorities.

Demineralized bone matrix in anterior cervical discectomy and fusion: a systematic review.

PURPOSE: Anterior cervical discectomy and fusion (ACDF) is one of the most widely used procedures in cervical spine. Demineralized bone matrix (DBM) is one of the fusion options that has been used in treatment of the bone defects for years. The purpose of this review is to provide an evidence-based analysis on the current evidence for effectiveness of DBM in ACDF. METHODS: A systematic search of the literature was conducted using MEDLINE, Scopus, and CENTRAL. The risk of bias was evaluated with the criteria recommended by the Cochrane Back and Neck group and the Methodological Index for Non-Randomized Studies (MINORS). The patient-reported outcome measures included the visual analog scale (VAS), Odom's criteria, Japanese Orthopaedic Association (JOA), and Neck Disability Index (NDI). Secondary outcome measures were fusion rate, non-union, subsidence, collapse, displacement, spinal alignment, and re-operation. RESULTS: Twelve studies met the eligibility criteria, of which three were randomized and nine were non-randomized. Patient-reported outcomes were non-inferior for DBM compared with the autograft and other bone substitute materials. The DBM had a fusion rate comparable with other graft materials, particularly in long term (88.8-100%, after 18 months follow-up). The majority of studies reported no collapse, subsidence or displacement with DBM. The revision surgery was mainly due to the symptomatic non-union in 4.1-8.3% of the DBM cases. Preservation of the angle of cervical lordosis was acceptable with DBM fusion. CONCLUSIONS: Most of the studies reported non-inferior results for DBM compared with autograft and other graft substitute materials in terms of patient-reported outcomes, fusion rate, and safety. However, the quantity and quality of evidence is very limited.

A Time Course Study of Different Methods of Extraneural Scar Induction in a Rat Model.

Background Extraneural scar formation is a challenging problem in nerve repair. Rodent models of scar induction, with their high regenerative capacity, suffer from lack of comparable similarities with human cases. In this study, we attempted to find a reliable and reproducible method of extraneural scarring with a significant impact on the peripheral nerve function. Methods A total of 60 rats were divided into three scar induction groups: abrasion (with a small piece of compressed steel wool), mincing (with extracorporeal mincing of adductor muscle and a 5-mm wide strip of the anterior border of the biceps femoris), and electrocoagulation (with a bipolar coagulator). Extraneural scarring was evaluated macroscopically and histologically during 8 weeks. The tibial functional index was used for behavioral analysis. Results Among three different physical methods of scar induction that were applied, electrocoagulation had the most functional impairment (p < 0.001, two-way analysis of variance); whereas mincing produced the most adhesive and intensive scar, morphologically (p < 0.001). Conclusion We conclude that: (1) the impact of the extraneural scar on the nerve is morphologically and functionally different, based on the method of scarring; (2) to achieve a scar model comparable to the human situation, a method in which the involved nerve is functionally impaired, is preferred over the ones that merely produce a bulky scar.

Two-Stage Nerve Graft in Severe Scar: A Time-Course Study in a Rat Model.

BACKGROUND: Peripheral nerve repair outcomes are suboptimal in the presence of severe soft tissue injury and excessive scarring paralleling the process in tendon reconstruction of the hand. Inspired by the advantages of the two-stage technique in tendon grafting and with encouraging preliminary results, we aimed to investigate the two-stage nerve grafting technique as an alternative method of secondary nerve repair. METHODS: Thirty female rats (~200 g) were randomly distributed into two groups (n=15). A 15 mm gap was created in the sciatic nerve of the animals and an excessive extraneural scar was induced using the "mincing" method. In this method, a thin strip of muscle was removed, minced in a petri dish and returned to the peripheral nerve. In the two-stage nerve graft group, a silicone tube was interposed in the first stage. After 4 weeks, in the second stage, the silicone tube was removed and a median nerve autograft was interposed through the newly formed vascularized sheath. In the conventional graft group, two nerve ends were protected with silicone caps in the first stage. After 4 weeks the caps were removed and the median graft was interposed. Behavioral assessments were performed at week 15 after surgery with the withdrawal reflex latency (WRL) and extensor postural thrust (EPT) and at the 3, 6 and 15-week time points with the TOA (toe out angle). Masson Trichrome staining method was used for histological assessments at week 15. RESULTS: According to the EPT and WRL, the two-stage nerve graft showed significant improvement (P=0.020 and P=0.017 respectively). The TOA showed no significant difference between the two groups. The total vascular index was significantly higher in the two-stage nerve graft group (P<0.001). CONCLUSIONS: Two-stage nerve graft using a silicone tube enhances vascularity of the graft and improves functional recovery.