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1.
Neuromodulation ; 24(6): 1024-1032, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34242440

ABSTRACT

OBJECTIVES: The purpose of the ongoing follow-up of ReActiv8-A clinical trial is to document the longitudinal benefits of episodic stimulation of the dorsal ramus medial branch and consequent contraction of the lumbar multifidus in patients with refractory mechanical chronic low back pain (CLBP). We report the four-year outcomes of this trial. MATERIALS AND METHODS: ReActiv8-A is a prospective, single-arm trial performed at nine sites in the United Kingdom, Belgium, and Australia. Eligible patients had disabling CLBP (low back pain Numeric Rating Scale [NRS] ≥6; Oswestry Disability Index [ODI] ≥25), no indications for spine surgery or spinal cord stimulation, and failed conventional management including at least physical therapy and medications for low back pain. Fourteen days postimplantation, stimulation parameters were programmed to elicit strong, smooth contractions of the multifidus, and participants were given instructions to activate the device for 30-min stimulation-sessions twice daily. Annual follow-up through four years included collection of NRS, ODI, and European Quality of Life Score on Five Dimensions (EQ-5D). Background on mechanisms, trial design, and one-year outcomes were previously described. RESULTS: At baseline (N = 53) (mean ± SD) age was 44 ± 10 years; duration of back pain was 14 ± 11 years, NRS was 6.8 ± 0.8, ODI 44.9 ± 10.1, and EQ-5D 0.434 ± 0.185. Mean improvements from baseline were statistically significant (p < 0.001) and clinically meaningful for all follow-ups. Patients completing year 4 follow-up, reported mean (±standard error of the mean) NRS: 3.2 ± 0.4, ODI: 23.0 ± 3.2, and EQ-5D: 0.721 ± 0.035. Moreover, 73% of participants had a clinically meaningful improvement of ≥2 points on NRS, 76% of ≥10 points on ODI, and 62.5% had a clinically meaningful improvement in both NRS and ODI and 97% were (very) satisfied with treatment. CONCLUSIONS: In participants with disabling intractable CLBP who receive long-term restorative neurostimulation, treatment satisfaction remains high and improvements in pain, disability, and quality-of-life are clinically meaningful and durable through four years.


Subject(s)
Low Back Pain , Adult , Humans , Low Back Pain/therapy , Lumbar Vertebrae , Middle Aged , Pain Measurement , Prospective Studies , Quality of Life , Treatment Outcome
2.
Clin Spine Surg ; 30(2): E90-E98, 2017 03.
Article in English | MEDLINE | ID: mdl-28207620

ABSTRACT

STUDY DESIGN: A prospective single-surgeon nonrandomized clinical study. OBJECTIVE: To evaluate the radiographic and clinical outcomes, by fixation type, in extreme lateral interbody fusion (XLIF) patients and provide an algorithm for determining patients suitable for stand-alone XLIF. SUMMARY OF BACKGROUND DATA: XLIF may be supplemented with pedicle screw fixation, however, since stabilizing structures remain intact, it is suggested that stand-alone XLIF can be used for certain indications. This eliminates the associated morbidity, though subsidence rates may be elevated, potentially minimizing the clinical benefits. MATERIALS AND METHODS: A fixation algorithm was developed after evaluation of patient outcomes from the surgeon's first 30 cases. This algorithm was used prospectively for 40 subsequent patients to determine the requirement for supplemental fixation. Preoperative, postoperative, and 12-month follow-up computed tomography scans were measured for segmental and global lumbar lordosis and posterior disk height. Clinical outcome measures included back and leg pain (visual analogue scale), Oswestry Disability Index (ODI), and SF-36 physical and mental component scores (PCS and MCS). RESULTS: Preoperatively to 12-month follow-up there were increases in segmental lordosis (7.9-9.4 degrees, P=0.0497), lumbar lordosis (48.8-55.2 degrees, P=0.0328), and disk height (3.7-5.5 mm, P=0.0018); there were also improvements in back (58.6%) and leg pain (60.0%), ODI (44.4%), PCS (56.7%), and MCS (16.1%) for stand-alone XLIF. For instrumented XLIF, segmental lordosis (7.6-10.5 degrees, P=0.0120) and disk height (3.5-5.6 mm, P<0.001) increased, while lumbar lordosis decreased (51.1-45.8 degrees, P=0.2560). Back (49.8%) and leg pain (30.8%), ODI (32.3%), PCS (37.4%), and MCS (2.0%) were all improved. Subsidence occurred in 3 (7.5%) stand-alone patients. CONCLUSIONS: The XLIF treatment fixation algorithm provided a clinical pathway to select suitable patients for stand-alone XLIF. These patients achieved positive clinical outcomes, satisfactory fusion rates, with sustained correction of lordosis and restoration of disk height.


Subject(s)
Lordosis/surgery , Lumbar Vertebrae/surgery , Pedicle Screws , Spinal Fusion/instrumentation , Spinal Fusion/methods , Aged , Aged, 80 and over , Algorithms , Female , Follow-Up Studies , Humans , Lordosis/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Tomography Scanners, X-Ray Computed , Treatment Outcome
3.
Global Spine J ; 6(5): 414-21, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27433424

ABSTRACT

STUDY DESIGN: An international, multicenter cross-sectional image-based study performed in 33 institutions in the Asia Pacific region. OBJECTIVE: The study addressed the role of facet joint angulation and tropism in relation to L4-L5 degenerative spondylolisthesis (DS). METHODS: The study included 349 patients (63% females; mean age: 61.8 years) with single-level DS; 82 had no L4-L5 DS (group A) and 267 had L4-L5 DS (group B). Axial computed tomography and magnetic resonance imaging were utilized to assess facet joint angulations and tropism (i.e., asymmetry between facet joint angulations) between groups. RESULTS: There was a statistically significant difference between group A (left mean: 46.1 degrees; right mean: 48.2 degrees) and group B (left mean: 55.4 degrees; right mean: 57.5 degrees) in relation to bilateral L4-L5 facet joint angulations (p < 0.001). The mean bilateral angulation difference was 7.4 and 9.6 degrees in groups A and B, respectively (p = 0.025). A critical value of 58 degrees or greater significantly increased the likelihood of DS if unilateral (adjusted OR: 2.5; 95% CI: 1.2 to 5.5; p = 0.021) or bilateral facets (adjusted OR: 5.9; 95% CI: 2.7 to 13.2; p < 0.001) were involved. Facet joint tropism was found to be relevant between 16 and 24 degrees angulation difference (adjusted OR: 5.6; 95% CI: 1.2 to 26.1; p = 0.027). CONCLUSIONS: In one of the largest studies assessing facet joint orientation in patients with DS, greater sagittal facet joint angulation was associated with L4-L5 DS, with a critical value of 58 degrees or greater increasing the likelihood of the condition for unilateral and bilateral facet joint involvement. Specific facet joint tropism categories were noted to be associated with DS.

4.
Article in English | MEDLINE | ID: mdl-27252985

ABSTRACT

BACKGROUND: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether tropism is a pre-existing developmental phenomena or secondary to progressive remodeling of the joint structure due to degenerative changes. As such, the following study addressed the occurrence of tropism of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: An international, multi-center cross-sectional study that consisted of 349 patients with single level DS recruited from 33 spine institutes in the Asia Pacific region was performed. Axial MRI/CT from L3-S1 were utilized to assess left and right facet joint sagittal angulation in relation to the coronal plane. The angulation difference between the bilateral facets was obtained. Tropism was noted if there was 8° or greater angulation difference between the facet joints. Tropism was noted at levels of DS and compared to immediate adjacent and distal non-DS levels, if applicable, to the index level. Age, sex-type and body mass index (BMI) were also noted and assessed in relation to tropism. RESULTS: Of the 349 subjects, there were 63.0 % females, the mean age was 61.8 years and the mean BMI was 25.6 kg/m(2). Overall, 9.7, 76.5 and 13.8 % had L3-L4, L4-L5 and L5-S1 DS, respectively. Tropism was present in 47.1, 50.6 and 31.3 % of L3-L4, L4-L5 and L5-S1 of levels with DS, respectively. Tropism involved 33.3 to 50.0 % and 33.3 to 58.8 % of the immediate adjacent and most distal non-DS levels from the DS level, respectively. Patient demographics were not found to be significantly related to tropism at any level (p > 0.05). CONCLUSIONS: To the authors' knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing facet joint tropism. Although levels with DS were noted to have tropism, immediate adjacent and distal levels with no DS also exhibited tropism, and were not related to age and other patient demographics. This study suggests that facet joint tropism or perhaps subsets of facet joint orientation may have a pre-disposed orientation that may be developmental in origin or a combination with secondary changes due to degenerative/slip effects. The presence of tropism should be noted in all imaging assessments, which may have implications in treatment decision-making, prognostication of disease progression, and predictive modeling. Having a deeper understanding of such concepts may further elaborate on the precision phenotyping of the facets and their role in more personalized spine care. Additional prospective and controlled studies are needed to further validate the findings.

5.
Global Spine J ; 6(1): 35-45, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26835200

ABSTRACT

Study Design A multinational, multiethnic, cross-sectional image-based study was performed in 33 institutions, representing 10 countries, which were part of the AOSpine Asia Pacific Research Collaboration Consortium. Objective Lumbar facet joint orientation has been reported to be associated with the development of degenerative spondylolisthesis (DS). The role of ethnicity regarding facet joint orientation remains uncertain. As such, the following study was performed across a wide-ranging population base to assess the role of ethnicity in facet joint orientation in patients with DS in the Asia Pacific region. Methods Lateral standing X-rays and axial magnetic resonance imaging scans were obtained for patients with lumbar DS. The DS parameters and facet joint angulations were assessed from L3-S1. Sex, age, body mass index (BMI), and ethnicity were also noted. Results The study included 371 patients with known ethnic origin (mean age: 62.0 years; 64% males, 36% females). The mean BMI was 25.6 kg/m(2). The level of DS was most prevalent at L4-L5 (74.7%). There were 28.8% Indian, 28.6% Japanese, 18.1% Chinese, 8.6% Korean, 6.5% Thai, 4.9% Caucasian, 2.7% Filipino, and 1.9% Malay patients. Variations in facet joint angulations were noted from L3 to S1 and between patients with and without DS (p < 0.05). No differences were noted with regards to sex and overall BMI to facet joint angulations (p > 0.05); however, increasing age was found to increase the degree of angulation throughout the lumbar spine (p < 0.05). Accounting for age and the presence or absence of DS at each level, no statistically significant differences between ethnicity and degree of facet joint angulations from L3-L5 were noted (p > 0.05). Ethnic variations were noted in non-DS L5-S1 facet joint angulations, predominantly between Caucasian, Chinese, and Indian ethnicities (p < 0.05). Conclusions This study is the first to suggest that ethnicity may not play a role in facet joint orientation in the majority of cases of DS in the Asia-Pacific region. Findings from this study may facilitate future comparative studies in other multiethnic populations. An understanding of ethnic variability may assist in identifying those patients at risk of postsurgical development or progression of DS. This study also serves as a model for large-scale multicenter studies across different ethnic groups and cultural boundaries in Asia.

6.
Neurosci Lett ; 602: 126-32, 2015 Aug 18.
Article in English | MEDLINE | ID: mdl-26141613

ABSTRACT

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Oligopeptides/administration & dosage , Animals , Carbocyanines/administration & dosage , Carbocyanines/chemistry , Drug Carriers , Encephalomyelitis, Autoimmune, Experimental/metabolism , Female , Fibrin/chemistry , Fibrin/metabolism , Fluorescent Dyes/administration & dosage , Fluorescent Dyes/chemistry , Hydrophobic and Hydrophilic Interactions , Lactones/chemistry , Laminin/chemistry , Membrane Glycoproteins/metabolism , Multiple Sclerosis/drug therapy , Multiple Sclerosis/metabolism , Nanoparticles , Oligopeptides/chemistry , Polyethylene Glycols/chemistry , Rats , Rats, Inbred F344 , Spinal Cord/drug effects , Spinal Cord/metabolism , Up-Regulation
7.
Asian Spine J ; 9(3): 327-37, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26097647

ABSTRACT

STUDY DESIGN: Radiologic imaging measurement study. PURPOSE: To assess the accuracy of detecting lateral mass and facet joint injuries of the subaxial cervical spine on plain radiographs using computed tomography (CT) scan images as a reference standard; and the integrity of morphological landmarks of the lateral mass and facet joints of the subaxial cervical spine. OVERVIEW OF LITERATURE: Injuries of lateral mass and facet joints potentially lead to an unstable subaxial cervical spine and concomitant neurological sequelae. However, no study has evaluated the accuracy of detecting specific facet joint injuries. METHODS: Eight spinal surgeons scored four sets of the same, randomly re-ordered, 30 cases with and without facet joint injuries of the subaxial cervical spine. Two surveys included conventional plain radiographs series (test) and another two surveys included CT scan images (reference). Facet joint injury characteristics were assessed for accuracy and reliability. Raw agreement, Fleiss kappa, Cohen's kappa and intraclass correlation coefficient statistics were used for reliability analysis. Majority rules were used for accuracy analysis. RESULTS: Of the 21 facet joint injuries discerned on CT scan images, 10 were detected in both plain radiograph surveys (sensitivity, 0.48; 95% confidence interval [CI], 0.26-0.70). There were no false positive facet joint injuries in either of the first two X-ray surveys (specificity, 1.0; 95% CI, 0.63-1.0). Five of the 11 cases with missed injuries had an injury below the lowest visible articulating level on radiographs. CT scan images resulted in superior inter- and intra-rater agreement values for assessing morphologic injury characteristics of facet joint injuries. CONCLUSIONS: Plain radiographs are not accurate, nor reliable for the assessment of facet joint injuries of the subaxial cervical spine. CT scans offer reliable diagnostic information required for the detection and treatment planning of facet joint injuries.

8.
J Neurol Surg A Cent Eur Neurosurg ; 76(4): 303-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25915498

ABSTRACT

BACKGROUND AND STUDY AIMS: The learning curve associated with the adoption of minimally invasive surgery techniques has limited its adoption by many traditionally open surgeons. The use of dynamic electromyography (EMG) to guide the placement of percutaneous pedicle screws (PS) can lessen the learning curve by providing real-time feedback on neural proximity relative to the screw. This study aimed to investigate the safety and accuracy of a single surgeon's experience transitioning from open pedicle screws (OS) to PS using intraoperative fluoroscopy and dynamic EMG. MATERIALS AND METHODS: Forty consecutive patients were treated with EMG and fluoroscopy-guided PS placement by a single surgeon and followed through a prospective registry. This was cross-referenced with a cohort of 53 consecutive patients treated with OS in 2011. Computed tomography was used to check the screw position 1 day after surgery. A misplaced pedicle screw was defined as a breach of the pedicle wall. The accuracy of PS placement in association with dynamic EMG was compared with that of OS. RESULTS: A total of 204 PS were inserted in the study cohort with 97.5% accuracy. Five (2.5%) were misplaced (three medial and two lateral). All three medial screws displayed a caution message (yellow: 8mA) on insertion. No screw caused visceral or neurologic complications postoperatively, and none required revision. In the OS cohort, 254 screws were placed with 94.9% accuracy, 13 (5.1%) were misplaced (8 medial, 3 lateral, and 2 superior), and 3 (1.2%) required revision. CONCLUSIONS: Dynamic EMG combined with intraoperative fluoroscopy and advanced instrumentation provides a safe, real-time, and accurate method for PS placement.


Subject(s)
Electromyography/methods , Neurosurgical Procedures/methods , Pedicle Screws , Spine/surgery , Cohort Studies , External Fixators , Fluoroscopy , Humans , Learning Curve , Medical Errors , Minimally Invasive Surgical Procedures , Pedicle Screws/adverse effects , Prospective Studies , Surgeons , Surgery, Computer-Assisted
9.
Global Spine J ; 5(1): 23-30, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25648168

ABSTRACT

Study Design Surgeon survey. Objective To evaluate the reliability of bone single-photon emission computed tomography (SPECT) versus bone SPECT images co-registered with computed tomography (bone SPECT-CT) by analyzing interobserver agreement for identification of the anatomical location of technetium(99m)-labeled oxidronate uptake in the lumbar disk and/or facet joint. Methods Seven spine surgeons interpreted 20 bone scans: 10 conventional black-and-white tomograms (bone SPECT) and 10 color-graded bone SPECT-CT scans. Each surgeon was asked to identify the location of any diagnostically relevant uptake in the disk and/or facet joint between L1 and S1. Reliability was evaluated using the free-marginal kappa statistic, and the level of agreement was assessed using the Landis and Koch interpretation. Results Conventional bone SPECT scans and bone SPECT-CT scans were reliable for the identification of diagnostically relevant uptake, with bone SPECT-CT having higher reliability (kappa = 0.72) than bone SPECT alone (0.59). Bone SPECT and bone SPECT-CT were also reliable in identifying disk pathology, with kappa values of 0.72 and 0.81, respectively. However, bone SPECT-CT was more reliable (0.81) than bone SPECT (0.60) when identifying facet disease. Conclusions For the identification of disk pathology, it is reasonable to use either conventional bone SPECT or bone SPECT-CT; however, bone SPECT-CT is more reliable for facet joint pathology.

10.
Eur Spine J ; 24 Suppl 3: 339-45, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25681117

ABSTRACT

PURPOSE: The lateral approach for anterior interbody fusion allows placement of a large footprint intervertebral spacer to indirectly decompress the neural elements through disc height restoration and resultant soft tissue changes. However, it is not well understood under what circumstances indirect decompression in lateral approach surgery is sufficient. This report aimed to evaluate clinical scenarios where indirect decompression was and was not sufficient in symptom resolution when using lateral interbody fusion. METHODS: A prospective study was undertaken of 122 consecutive patients treated with lateral interbody fusion without direct decompression. Pre- and postoperative symptomatology was assessed to evaluate the extent of neural decompression following implantation with a lateral polyetheretherketone spacer. Failure to improve or resolve preoperative radicular pain was considered a failure of indirect decompression and indicated these patients for additional posterior decompressive surgery. RESULTS: Unplanned second stage decompression was required in 11 patients. Of these patients, 7/11 early in this series had pathology that was underappreciated including spondylolisthesis from high grade facet arthropathy with instability (3), bony lateral recess stenosis (3) and both spondylolisthesis/stenosis (1). Three patients had iatrogenic leg pain through cage misplacement. There was one failure of indirect decompression that could not be explained through retrospective analysis of the patient's record. CONCLUSION: Indirect decompression clearly has a role in minimizing the amount of surgery that is required. However, it is important to consider the circumstances where this technique may be effective and preoperative considerations that may improve patient selection.


Subject(s)
Decompression, Surgical/methods , Lumbar Vertebrae/surgery , Spinal Fusion/instrumentation , Spinal Stenosis/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Joint Instability/surgery , Male , Middle Aged , Prospective Studies , Prostheses and Implants , Spinal Fusion/methods , Spondylolisthesis/complications , Spondylolisthesis/surgery , Zygapophyseal Joint/surgery
11.
Spine (Phila Pa 1976) ; 39(22): E1303-10, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25099325

ABSTRACT

STUDY DESIGN: Retrospective analysis of prospectively collected, nonrandomized radiographical data. OBJECTIVE: To examine the relationship between the presence of preoperative metabolically active facet arthropathy (FA) and the amount of indirect foraminal decompression gained after extreme lateral interbody fusion (XLIF). SUMMARY OF BACKGROUND DATA: Although evidence of significant radiographical indirect decompression after XLIF has been shown, the relationship between the extent of indirect decompression and the presence of potentially attenuating, FA is yet to be studied. METHODS: A prospective database of consecutive patients undergoing XLIF was retrospectively analyzed. Posterior disc height, foraminal height, and cross-sectional foraminal area were measured on computed tomographic scans obtained preoperatively and 2 days postoperatively. The selected radiographical parameters were examined with respect to the presence of FA based on preoperative computed tomographic and bone scans. RESULTS: Fifty-two consecutive patients underwent 79 levels of XLIF without direct decompression. Average age was 66.4 years and 34 (65.4%) were females. Surgery resulted in significant increases in posterior disc height 3.0 to 5.7 mm (89.0% increase), P<0.0001; foraminal height 1.4 to 1.7 cm (38.0% increase), P<0.0001; and foraminal area 1.1 to 1.4 cm (45.1% increase), P<0.0001. These increases were independent of the presence of metabolically active arthropathy. CONCLUSION: Significant indirect neural decompression is possible in XLIF, regardless of the presence of metabolically active FA. LEVEL OF EVIDENCE: 3.


Subject(s)
Joint Diseases/surgery , Lumbar Vertebrae/surgery , Radiculopathy/surgery , Spinal Fusion/methods , Aged , Aged, 80 and over , Decompression, Surgical , Female , Humans , Intervertebral Disc/diagnostic imaging , Joint Diseases/diagnostic imaging , Male , Middle Aged , Pain Measurement , Radiculopathy/etiology , Radiography , Retrospective Studies , Tomography, Emission-Computed, Single-Photon , Zygapophyseal Joint/diagnostic imaging
12.
Tissue Eng Part B Rev ; 20(6): 697-712, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24906469

ABSTRACT

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.


Subject(s)
Biocompatible Materials/pharmacology , Blood Coagulation/drug effects , Bone Regeneration/drug effects , Prostheses and Implants , Hemostasis , Humans , Platelet-Rich Plasma/metabolism
13.
J Neurotrauma ; 31(21): 1807-13, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-24836764

ABSTRACT

Inflammation of the spinal cord after traumatic spinal cord injury (SCI) leads to destruction of healthy tissue. This "secondary degeneration" is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study, we showed that combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor, significantly reduced secondary degeneration after hemisection injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30 days, compared to control animals, and further reduced the cavity at 90 days in treated animals, whereas in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behavior after spinal contusion injury, a more relevant pre-clinical model of SCI. The growth factors were delivered for the first 7 days to the injury site by osmotic minipump. Locomotor behavior was monitored at 1-28 days after injury using the Basso, Beattie and Bresnahan (BBB) score and at 30 days using automated gait analysis. Treated animals had BBB scores of 18; control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.


Subject(s)
Motor Activity/drug effects , Platelet-Derived Growth Factor/therapeutic use , Recovery of Function/drug effects , Spinal Cord Injuries/drug therapy , Vascular Endothelial Growth Factor A/therapeutic use , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Contusions/drug therapy , Contusions/pathology , Contusions/physiopathology , Female , Motor Activity/physiology , Platelet-Derived Growth Factor/pharmacology , Rats , Rats, Wistar , Recovery of Function/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Vascular Endothelial Growth Factor A/pharmacology
14.
J Mater Chem B ; 2(20): 3009-3021, 2014 May 28.
Article in English | MEDLINE | ID: mdl-32261676

ABSTRACT

Most research virtually ignores the important role of a blood clot in supporting bone healing. In this study, we investigated the effects of surface functional groups carboxyl and alkyl on whole blood coagulation, complement activation and blood clot formation. We synthesised and tested a series of materials with different ratios of carboxyl (-COOH) and alkyl (-CH3, -CH2CH3 and -(CH2)3CH3) groups. We found that surfaces with -COOH/-(CH2)3CH3 induced a faster coagulation activation than those with -COOH/-CH3 and -CH2CH3, regardless of the -COOH ratios. An increase in -COOH ratios on -COOH/-CH3 and -CH2CH3 surfaces decreased the rate of coagulation activation. The pattern of complement activation was entirely similar to that of surface-induced coagulation. All material coated surfaces resulted in clots with thicker fibrin in a denser network at the clot/material interface and a significantly slower initial fibrinolysis when compared to uncoated glass surfaces. The amounts of platelet-derived growth factor-AB (PDGF-AB) and transforming growth factor-ß (TGF-ß1) released from an intact clot were higher than a lysed clot. The release of PDGF-AB was found to be correlated with the fibrin density. This study demonstrated that surface chemistry can significantly influence the activation of blood coagulation and complement system, resultant clot structure, susceptibility to fibrinolysis as well as release of growth factors, which are important factors determining the bone healing process.

15.
J Hand Surg Am ; 37(7): 1467-74, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22652177

ABSTRACT

Dupuytren contracture of the proximal interphalangeal (PIP) joint can be reversed by an extension torque transmitted from an external device, the Digit Widget, by skeletal pins to the middle phalanx. This extension torque, generated by the same elastic bands dentists use to align teeth, gradually restores length to soft tissues palmar to the PIP joint's axis of rotation. Simultaneously, tissues dorsal to the joint's axis will shorten toward normal length as the PIP progressively straightens. Although the contractile nodules and bands of Dupuytren disease may be excised either before or after reversal of the joint's contracture, a 2-staged approach is preferred: (1) reverse the PIP flexion contracture, and (2) excise the diseased tissue from the straightened finger. We believe this 2-staged approach yields better results. In addition, it is technically easier to avoid injury to nerves and arteries while excising the nodules and bands, when one operates through palmar skin of more nearly normal length.


Subject(s)
Dupuytren Contracture/physiopathology , Dupuytren Contracture/therapy , External Fixators , Finger Joint/physiopathology , Traction/instrumentation , Equipment Design , Humans , Torque
16.
J Neurotrauma ; 29(5): 957-70, 2012 Mar 20.
Article in English | MEDLINE | ID: mdl-21568693

ABSTRACT

Trauma to the spinal cord creates an initial physical injury damaging neurons, glia, and blood vessels, which then induces a prolonged inflammatory response, leading to secondary degeneration of spinal cord tissue, and further loss of neurons and glia surrounding the initial site of injury. Angiogenesis is a critical step in tissue repair, but in the injured spinal cord angiogenesis fails; blood vessels formed initially later regress. Stabilizing the angiogenic response is therefore a potential target to improve recovery after spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) can initiate angiogenesis, but cannot sustain blood vessel maturation. Platelet-derived growth factor (PDGF) can promote blood vessel stability and maturation. We therefore investigated a combined application of VEGF and PDGF as treatment for traumatic spinal cord injury, with the aim to reduce secondary degeneration by promotion of angiogenesis. Immediately after hemisection of the spinal cord in the rat we delivered VEGF and PDGF and to the injury site. One and 3 months later the size of the lesion was significantly smaller in the treated group compared to controls, and there was significantly reduced gliosis surrounding the lesion. There was no significant effect of the treatment on blood vessel density, although there was a significant reduction in the numbers of macrophages/microglia surrounding the lesion, and a shift in the distribution of morphological and immunological phenotypes of these inflammatory cells. VEGF and PDGF delivered singly exacerbated secondary degeneration, increasing the size of the lesion cavity. These results demonstrate a novel therapeutic intervention for SCI, and reveal an unanticipated synergy for these growth factors whereby they modulated inflammatory processes and created a microenvironment conducive to axon preservation/sprouting.


Subject(s)
Nerve Degeneration/prevention & control , Platelet-Derived Growth Factor/pharmacology , Spinal Cord Injuries/pathology , Vascular Endothelial Growth Factor A/pharmacology , Animals , Fluorescent Antibody Technique , Male , Nerve Degeneration/etiology , Rats , Rats, Wistar
17.
Evid Based Spine Care J ; 3(4): 21-5, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23531776

ABSTRACT

STUDY DESIGN: Retrospective cohort study. Clinical question or objective: Is there a benefit to additional transforaminal lumbar interbody fusion (TLIF) if a solid posterolateral (PL) fusion can be achieved with routine bone morphogenetic protein (BMP) use in low-grade spondylolisthesis? METHODS: We performed a retrospective review of patients who had undergone surgery for grade I or II lumbar spondylolisthesis stratified into two groups. Group 1 had 46 patients who underwent TLIF along with PL instrumented fusion. Group 2 had 40 patients who underwent PL instrumented fusion alone. In both groups, adequate posterior decompression with pedicle screw instrumentation was performed and rhBMP-7 was used. All patients were evaluated clinically using the Oswestry Disability Index (ODI) and by independent radiological examination at 3 and 12 months. RESULTS: At a minimum follow-up of 12 months, there was no statistically significant difference in the rate of fusion. In addition, there were no differences in the proportion of patients who had a minimal clinically significant difference in their ODI. There was a similar rate of complications between each cohort. CONCLUSIONS: The use of BMP was associated with a high rate of PL lumbar fusion. In the presence of a PL fusion, there appears to be little clinical benefit to additional anterior TLIF in degenerative spondylolisthesis. [Table: see text].

18.
J Biomed Mater Res B Appl Biomater ; 100(3): 660-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22121034

ABSTRACT

Vertebral cement augmentation is reported to be a safe and effective technique for providing stabilization and pain relief. However, adjacent intervertebral discs may be at risk of accelerated degeneration as a result of aggravated nutritional constraints. Therefore, we investigated the effects of injecting polymethylmethacrylate (PMMA) into three adjacent lumbar vertebrae on intervertebral disc and vertebral bone tissue in 12 skeletally mature sheep. After 6 and 12 months of augmentation, the sheep were euthanized and their spines were processes for histological evaluation. Semiquantitative histomorphological analysis of discs and endplates was conducted using published criteria. Histomorphological changes in the augmented bone were assessed qualitatively. Approximately 80% of the length of the endplates was in contact with PMMA. However, there was no significant difference between the histopathological score of the discs adjacent to augmented vertebrae and the score of the control discs. Bone tissue reaction to PMMA was characterized by a thin fibrous tissue layer and occasional foreign-body reactions. New bone formation was present in all augmented vertebrae. Concerns about aggravation of disc degeneration as a result of vertebral cement augmentation seem to be unsubstantiated. Furthermore, adverse effects of PMMA cement on bone biology do not seem to be a relevant issue.


Subject(s)
Bone Cements/chemistry , Intervertebral Disc , Lumbar Vertebrae , Materials Testing , Polymethyl Methacrylate/chemistry , Animals , Female , Foreign-Body Reaction/metabolism , Foreign-Body Reaction/pathology , Sheep , Time Factors
19.
Spine (Phila Pa 1976) ; 37(9): 763-8, 2012 Apr 20.
Article in English | MEDLINE | ID: mdl-21897345

ABSTRACT

STUDY DESIGN: A sheep study designed to compare the accuracy of static radiographs, dynamic radiographs, and computed tomographic (CT) scans for the assessment of thoracolumbar facet joint fusion as determined by micro-CT scanning. OBJECTIVE: To determine the accuracy and reliability of conventional imaging techniques in identifying the status of thoracolumbar (T13-L1) facet joint fusion in a sheep model. SUMMARY OF BACKGROUND DATA: Plain radiographs are commonly used to determine the integrity of surgical arthrodesis of the thoracolumbar spine. Many previous studies of fusion success have relied solely on postoperative assessment of plain radiographs, a technique lacking sensitivity for pseudarthrosis. CT may be a more reliable technique, but is less well characterized. METHODS: Eleven adult sheep were randomized to either attempted arthrodesis using autogenous bone graft and internal fixation (n = 3) or intentional pseudarthrosis (IP) using oxidized cellulose and internal fixation (n = 8). After 6 months, facet joint fusion was assessed by independent observers, using (1) plain static radiography alone, (2) additional dynamic radiographs, and (3) additional reconstructed spiral CT imaging. These assessments were correlated with high-resolution micro-CT imaging to predict the utility of the conventional imaging techniques in the estimation of fusion success. RESULTS: The capacity of plain radiography alone to correctly predict fusion or pseudarthrosis was 43% and was not improved using plain radiography and dynamic radiography with also a 43% accuracy. Adding assessment by reformatted CT imaging to the plain radiography techniques increased the capacity to predict fusion outcome to 86% correctly. The sensitivity, specificity, and accuracy of static radiography were 0.33, 0.55, and 0.43, respectively, those of dynamic radiography were 0.46, 0.40, and 0.43, respectively, and those of radiography plus CT were 0.88, 0.85, and 0.86, respectively. CONCLUSION: CT-based evaluation correlated most closely with high-resolution micro-CT imaging. Neither plain static nor dynamic radiographs were able to predict fusion outcome accurately.


Subject(s)
Arthrography/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Tomography, X-Ray Computed , Zygapophyseal Joint/surgery , Animals , Bone Transplantation , Female , Fracture Healing , Internal Fixators , Models, Animal , Pseudarthrosis/diagnostic imaging , Pseudarthrosis/etiology , Reproducibility of Results , Sensitivity and Specificity , Sheep , Spinal Fusion/adverse effects , Spinal Fusion/instrumentation , Spinal Fusion/methods , Tomography, Spiral Computed , X-Ray Microtomography
20.
Spine (Phila Pa 1976) ; 36(15): E1038-41, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21289559

ABSTRACT

STUDY DESIGN: A case report with review of the literature on the cause of computed tomographic (CT) artifacts and recommendations for identification of such artifacts. OBJECTIVE: To describe the presentation of a patient with a CT scan suggesting a cervical facet dislocation that ultimately proved to be artifactual. SUMMARY OF BACKGROUND DATA: CT scanning is routinely used in the detection of cervical spine injuries. This technique has a reported sensitivity of 98%, although specificity has proved more difficult to estimate. CT artifacts such as the case reported here is a significant cause of a decrease in specificity for this technique. METHODS: A 30-year-old woman with a history of a cervical fracture developed severe neck pain without neurologic deficit after trauma to the back of her neck. CT scans were obtained and reviewed at a local secondary level hospital. A cervical fracture dislocation was diagnosed and cervical spinal injury protocols were initiated and the patient transferred to authors', tertiary level institution for surgical management. A repeat CT scan showed her cervical spine to be in normal alignment. RESULTS: A movement artifact in the patient's original CT scans was misinterpreted as a unilateral facet fracture subluxation at C5-C6. There are two clues that in hindsight indicate that this finding was artifactual; an ill-defined tracheal margin in contrast with the sharply defined margin above and below the level of the artifact and a double bone margin seen on axial sections at the level of the artifact. CONCLUSION: Motion artifacts are an important cause in the reduction in specificity of CT scans and can be easily missed. It is important to be aware of the indicators of motion artifacts to reduce the risk of unnecessary treatments.


Subject(s)
Cervical Vertebrae/injuries , Joint Dislocations/diagnosis , Spinal Injuries/diagnosis , Tomography, X-Ray Computed/standards , Adult , Artifacts , Diagnostic Errors , Female , Humans , Joint Dislocations/diagnostic imaging , Neck Pain/diagnosis , Neck Pain/diagnostic imaging , Spinal Injuries/diagnostic imaging , Tomography, X-Ray Computed/methods
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