Evidence-based Spine-care Journal[JOURNAL]
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186 papers
Avarice, evidence, and the media.
Jens C
Evid Based Spine Care J · 2011 May · PMID 23637675 · Full text
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Spinal cord compression secondary to intrathecal catheter-induced granuloma: a report of four cases.
Arnold PM, Harsh V, Oliphant SM
Evid Based Spine Care J · 2011 Feb · PMID 22956937 · Full text
OBJECTIVE: The management of nonmalignant pain by morphine pump implantation has become an effective and increasingly frequent strategy of care. We report a rare complication of intrathecal granuloma formation adjacent t...
OBJECTIVE: The management of nonmalignant pain by morphine pump implantation has become an effective and increasingly frequent strategy of care. We report a rare complication of intrathecal granuloma formation adjacent to the intrathecal catheter tip resulting in spinal cord compression in four patients undergoing intrathecal treatment for chronic pain. METHODS: Four patients presented with chronic back pain and lower extremity pain and weakness and were treated with morphine pump implantation (Fig 1). Each patient developed a mass at the level of the intrathecal catheter tip resulting in increased back pain and diminished neurological function. Following clinical examination and x-ray workup, the patients underwent surgical resection of the mass and removal of the intrathecal catheter. One patient received conservative saline therapy first, and another patient had granuloma resection first and removal of the intrathecal catheter at a later date. Pathological analysis showed granulation tissue with extensive necrosis and chronic inflammation, with negative culture results. No evidence of neoplasm was found. RESULTS: Patients showed varying degrees of improvement following removal of the intrathecal mass. Two patients had moderate pain reduction following resection of the granuloma; a third had minimal pain improvement; and a fourth had significant pain improvement but continued lower extremity weakness. CONCLUSIONS: The formation of granulomas caused by intrathecal catheter implantation is a rare but serious complication. Imaging studies including magnetic resonance imaging with contrast and computed tomography with myelogram should be used to follow up a neurological examination consistent with spinal cord compression. Timely surgical intervention may result in marked improvement of symptoms.
Efficacy of interspinous device versus surgical decompression in the treatment of lumbar spinal stenosis: a modified network analysis.
Chou D, Lau D, Hermsmeyer J … +1 more , Norvell D
Evid Based Spine Care J · 2011 Feb · PMID 22956936 · Full text
STUDY DESIGN: Systematic review using a modified network analysis. OBJECTIVES: To compare the effectiveness and morbidity of interspinous-device placement versus surgical decompression for the treatment of lumbar spinal...
STUDY DESIGN: Systematic review using a modified network analysis. OBJECTIVES: To compare the effectiveness and morbidity of interspinous-device placement versus surgical decompression for the treatment of lumbar spinal stenosis. SUMMARY: Traditionally, the most effective treatment for degenerative lumbar spinal stenosis is through surgical decompression. Recently, interspinous devices have been used in lieu of standard laminectomy. METHODS: A review of the English-language literature was undertaken for articles published between 1970 and March 2010. Electronic databases and reference lists of key articles were searched to identify studies comparing surgical decompression with interspinous-device placement for the treatment of lumbar spinal stenosis. First, studies making the direct comparison (cohort or randomized trials) were searched. Second, randomized controlled trials (RCTs) comparing each treatment to conservative management were searched to allow for an indirect comparison through a modified network analysis approach. Comparison studies involving simultaneous decompression with placement of an interspinous device were not included. Studies that did not have a comparison group were not included since a treatment effect could not be calculated. Two independent reviewers assessed the strength of evidence using the GRADE criteria assessing quality, quantity, and consistency of results. The strengths of evidence for indirect comparisons were downgraded. Disagreements were resolved by consensus. RESULTS: We identified five studies meeting our inclusion criteria. No RCTs or cohort studies were identified that made the direct comparison of interspinous-device placement with surgical decompression. For the indirect comparison, three RCTs compared surgical decompression to conservative management and two RCTs compared interspinous-device placement to conservative management. There was low evidence supporting greater treatment effects for interspinous-device placement compared to decompression for disability and pain outcomes at 12 months. There was low evidence demonstrating little to no difference in treatment effects between the groups for walking distance and complication rates. CONCLUSION: The indirect treatment effect for disability and pain favors the interspinous device compared to decompression. The low evidence suggests that any further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimate. No significant treatment effect differences were observed for postoperative walking distance improvement or complication rates; however, findings should be considered with caution because of indirect comparisons and short follow-up periods.
Spinal cord injury and quality of life: a systematic review of outcome measures.
Wilson JR, Hashimoto RE, Dettori JR … +1 more , Fehlings MG
Evid Based Spine Care J · 2011 Feb · PMID 22956935 · Full text
STUDY DESIGN: Systematic review. STUDY RATIONALE: According to current estimates, there are more than 1 million people living with a spinal cord injury (SCI) in the United States alone. Given the potentially devastating...
STUDY DESIGN: Systematic review. STUDY RATIONALE: According to current estimates, there are more than 1 million people living with a spinal cord injury (SCI) in the United States alone. Given the potentially devastating impact of SCI on health-related quality of life (QoL), we sought to gain an improved understanding of QoL outcomes in SCI. OBJECTIVE: To identify and describe common QoL outcomes measures in patients with SCI. METHODS: A systematic review of the English-language literature was undertaken for articles published from 1998 through December 2010. Electronic databases and reference lists of key articles were searched to identify measures or indices used to evaluate QoL outcomes in patients with SCI. The titles and abstracts of the SCI peer-reviewed literature were searched to determine which of these outcome measures were most commonly used to evaluate QoL in patients with SCI. RESULTS: We identified 27 outcome measures used to evaluate QoL in patients with SCI. In SCI literature, the six most commonly used objective outcome measures were the Short-form 36 (SF-36); Craig Handicap Assessment and Reporting Technique (CHART); Short-form 12 (SF-12); Sickness Impact Profile (SIP68); Reintegration to Normal Living Index (RNL); and Community Integration Questionnaire (CIQ). The six subjective measures that were most frequently used were the Satisfaction with Life Scale (SWLS); Quality of Life Index (QLI); Life Satisfaction Questionnaire (LISAT-9/-1); World Health Organization Quality of Life-BREF scale (WHOQOL-BREF); Perceived Quality of Life (PQOL); and global QoL. All six objective measures have been validated in an SCI population, and four of the six subjective measures have been similarly validated. Three of each of the objective and subjective measures have been reliability tested in a population with SCI. CONCLUSION: In addition to neurological and functional changes after SCI, QoL outcomes should be routinely assessed. Choice of appropriate QoL measure should be influenced by the study objectives and design, as well as the psychometric properties of the particular measure within the context of SCI.
Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc.
Gebhard H, James AR, Bowles RD … +5 more , Dyke JP, Saleh T, Doty SP, Bonassar LJ, Härtl R
Evid Based Spine Care J · 2011 Feb · PMID 22956934 · Full text
STUDY DESIGN: Prospective randomized animal study. OBJECTIVE: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. METHODS: The caudal 3/4 inter...
STUDY DESIGN: Prospective randomized animal study. OBJECTIVE: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. METHODS: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. RESULTS: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. CONCLUSIONS: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc.
Vertebral compression model and comparison of augmentation agents.
Hill C, Wingerter S, Parsell D … +1 more , McGuire R
Evid Based Spine Care J · 2011 Feb · PMID 22956933 · Full text
STUDY DESIGN: Biomechanical study. OBJECTIVES: To evaluate the compression strengths of various bone fillers used in treating vertebral compression fractures using a third-generation sawbone model and to evaluate the via...
STUDY DESIGN: Biomechanical study. OBJECTIVES: To evaluate the compression strengths of various bone fillers used in treating vertebral compression fractures using a third-generation sawbone model and to evaluate the viability of this novel model as an alternative to actual human or animal vertebrae for biomechanical testing of vertebral-filling materials. METHODS: Cavities were created in the osteoporotic vertebral body sawbone models and filled with PMMA, SRS, MIIGX3 HiVisc, and BoneSource fillers. These were cured according to manufacturers' recommendations and then tested to failure in the compression model. Elastic modulus was calculated and compared with the control group which was not augmented. RESULTS: The mean modulus of elasticity for the control group vertebrae was 92.44 ± 19.28 MPa. The mean modulus of elasticity was highest in the polymethylmethacrylate (PMMA) group (195.47 ± 2.33 MPa) and lowest in the MIIG group (25.79 ± 4.77 MPa). The results for the SRS-tricalcium phosphate group (79.14 ± 20.20 MPa) were closest to the control group, followed by the BoneSource group (57.49 ± 8.35 MPa). Statistical analysis, for comparison of individual group means, identified significant differences between the control group and all other groups (P < .05), with the exception of the SRS-tricalcium phosphate group (P = .65, versus control). The modulus of elasticity for the PMMA group was significantly higher than all other groups (P < .001). CONCLUSION: The third-generation osteoporotic sawbones model simulates in vitro physiological specimen function. It was effective for comparing which osteoconductive agents may provide adequate strength while minimizing potential adjacent level fracture. Increased stiffness was seen with PMMA compared with the unaugmented control as well as with calcium phosphate or calcium sulfate cements suggesting that these may reduce adjacent segment fractures.
Long-term outcome of surgical correction of congenital kyphosis in patients with myelomeningocele (MMC) with segmental spino-pelvic fixation.
Schroeder JE, Barzilay Y, Hasharoni A … +1 more , Kaplan L
Evid Based Spine Care J · 2011 Feb · PMID 22956932 · Full text
STUDY DESIGN: A retrospective case series of patients with myelomeningocele (MMC) who underwent kyphectomy and posterior segmental fixation using Luque rods and 16-gauge wires. OBJECTIVE: To assess outcomes after posteri...
STUDY DESIGN: A retrospective case series of patients with myelomeningocele (MMC) who underwent kyphectomy and posterior segmental fixation using Luque rods and 16-gauge wires. OBJECTIVE: To assess outcomes after posterior kyphectomy and segmental fixation for kyphosis in patients with MMC. METHODS: Thirteen consecutive patients who underwent posterior kyphectomy for transforaminal fixation contiguous to "everted lamina." Fusion rates, time to fusion, change in Cobb angle, complications, and improvement in activities of daily living using the Katz score were measured. RESULTS: Average age at time of surgery was 9.2 (range, 4.5-17) years. Average time to follow-up was 120 (range, 20-310) months. Solid fusion was achieved in 9 patients (69%) with a mean time to fusion of 12 months. The mean postoperative kyphotic curve was 22° with an average correction of 90°. Five patients (38%) experienced a postoperative complication. The mean improvement in activities of daily living score was 1.6 points and all patients achieved independent sitting balance. CONCLUSION: Segmental spino-pelvic fixation is a solid alternative mode of fixation in patients with MMC with congenital kyphosis. Patient selection, proper perioperative multidisciplinary assessment, and surgeons' expertise are significant in the success of this complex surgery.METHODS evaluation and class of evidence (CoE)STUDY DESIGN: Prospective cohort Retrospective cohort Case control Case series•METHODS Patients at similar point in course of treatment• Follow-up ≥ 85%• Similarity of treatment protocols for patient groups• Patients followed-up long enough for outcomes to occur Control for extraneous risk factorsOverall class of evidenceIVThe definiton of the different classes of evidence is available on page 63.
Evidence-based medicine (EBM): origins and modern application to spine care.
Skelly AC, Chapman J
Evid Based Spine Care J · 2011 Feb · PMID 22956931 · Full text
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Loss to follow-up.
Dettori JR
Evid Based Spine Care J · 2011 Feb · PMID 22956930 · Full text
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Rating an academic journal-indexing and impact factor.
Chapman J
Evid Based Spine Care J · 2011 Feb · PMID 22956929 · Full text
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Brachial plexus injury mimicking a spinal-cord injury.
Macyszyn LJ, Gonzalez-Giraldo E, Aversano M … +3 more , Heuer GG, Zager EL, Schuster JM
Evid Based Spine Care J · 2010 Dec · PMID 22956928 · Full text
OBJECTIVE: High-energy impact to the head, neck, and shoulder can result in cervical spine as well as brachial plexus injuries. Because cervical spine injuries are more common, this tends to be the initial focus for man...
OBJECTIVE: High-energy impact to the head, neck, and shoulder can result in cervical spine as well as brachial plexus injuries. Because cervical spine injuries are more common, this tends to be the initial focus for management. We present a case in which the initial magnetic resonance imaging (MRI) was somewhat misleading and a detailed neurological exam lead to the correct diagnosis. CLINICAL PRESENTATION: A 19-year-old man presented to the hospital following a shoulder injury during football practice. The patient immediately complained of significant pain in his neck, shoulder, and right arm and the inability to move his right arm. He was stabilized in the field for a presumed cervical-spine injury and transported to the emergency department. INTERVENTION: Initial radiographic assessment (C-spine CT, right shoulder x-ray) showed no bony abnormality. MRI of the cervical-spine showed T2 signal change and cord swelling thought to be consistent with a cord contusion. With adequate pain control, a detailed neurological examination was possible and was consistent with an upper brachial plexus avulsion injury that was confirmed by CT myelogram. The patient failed to make significant neurological recovery and he underwent spinal accessory nerve grafting to the suprascapular nerve to restore shoulder abduction and external rotation, while the phrenic nerve was grafted to the musculocutaneous nerve to restore elbow flexion. CONCLUSION: Cervical spinal-cord injuries and brachial plexus injuries can occur by the same high energy mechanisms and can occur simultaneously. As in this case, MRI findings can be misleading and a detailed physical examination is the key to diagnosis. However, this can be difficult in polytrauma patients with upper extremity injuries, head injuries or concomitant spinal-cord injury. Finally, prompt diagnosis and early surgical renerveration have been associated with better long-term recovery with certain types of injury.
Anterior cervical discectomy and fusion for the management of axial neck pain in the absence of radiculopathy or myelopathy.
Riew KD, Ecker E, Dettori JR
Evid Based Spine Care J · 2010 Dec · PMID 22956927 · Full text
STUDY DESIGN: Systematic reviewStudy rationale: Anterior cervical discectomy and fusion (ACDF) is a proven, effective treatment for relieving neck pain due to degenerative conditions of the cervical spine. Since most pa...
STUDY DESIGN: Systematic reviewStudy rationale: Anterior cervical discectomy and fusion (ACDF) is a proven, effective treatment for relieving neck pain due to degenerative conditions of the cervical spine. Since most patients also present with radiculopathy or myelopathy, little is known as to the effectiveness of ACDF to relieve pain and improve function in patients without radicular or myelopathic symptoms. OBJECTIVE: To examine the clinical outcome in patients undergoing (ACDF) for axial neck pain without radicular or myelopathic symptoms. METHODS: A systematic review was undertaken for articles published up to March 2010. Electronic databases and reference lists of key articles were searched to identify studies evaluating ACDF for the treatment of axial neck pain only. Radiculopathy and myelopathy, patients who suffered severe trauma, or with tumor/metastatic disease or infection were excluded. Two independent reviewers assessed the strength of evidence using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. RESULTS: No comparative studies were identified. Three case series met our inclusion criteria and were evaluated. All studies showed a mean improvement of pain of at least 50% approximately 4-years following surgery. Functional outcomes improved between 32% and 52% from baseline. Most patients reported satisfaction with surgery, 56% in one study and 79% in another. Complications varied among studies ranging from 1% to 10% and included pseudoarthrosis (9%), nonunion and revision (3%) and screw removal (1%). CONCLUSION: There is low evidence suggesting that patients with axial neck pain without radicular or myelopathic symptoms may receive some improvement in pain and function following ACDF. However, whether this benefit is greater than nontreatment or other treatments cannot be determined with the present literature.
Chronic sacroiliac joint pain: fusion versus denervation as treatment options.
Ashman B, Norvell DC, Hermsmeyer JT
Evid Based Spine Care J · 2010 Dec · PMID 22956926 · Full text
STUDY DESIGN: Systematic reviewObjective: To compare the safety and effectiveness of fusion versus denervation for chronic sacroiliac joint pain after failed conservative management. SUMMARY OF BACKGROUND: METHODS of c...
STUDY DESIGN: Systematic reviewObjective: To compare the safety and effectiveness of fusion versus denervation for chronic sacroiliac joint pain after failed conservative management. SUMMARY OF BACKGROUND: METHODS of confirming the sacroiliac joint as a pain source have been extensively studied and reported in the literature. After confirmation of the origin of the pain by positive local anesthetic blocks, chronic sacroiliac joint pain is usually managed with a combination of medication, physical therapies, and injections. We have chosen to compare two alternative treatments for sacroiliac pain that was refractory to conservative therapies. METHODS: A systematic review of the English-language literature was undertaken for articles published between 1970 and June 2010. Electronic databases and reference lists of key articles were searched to identify studies evaluating fusion or denervation for chronic sacroiliac joint pain after failed conservative management. Studies involving only conservative treatment or traumatic onset of injury were excluded. Two independent reviewers assessed the level of evidence quality using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. RESULTS: We identified eleven articles (six fusion, five denervation) meeting our inclusion criteria. The majority of patients report satisfaction after both treatments. Both treatments reported mean improvements in pain and functional outcome. Rates of complications were higher among fusion studies (13.7%) compared to denervation studies (7.3%). Only fusion studies reported infections (5.3%). No infections were reported among denervation patients. The evidence for all findings were very low to low; therefore, the relative efficacy or safety of one treatment over another cannot be established. CONCLUSIONS: Sacroiliac joint fusion or denervation can reduce pain for many patients. Whether a true arthrodesis of the joint is achieved by percutaneous techniques is open to question and whether denervation of the joint gives durable pain relief is not clear. Further comparative studies of these two techniques may provide the answers.
Open door expansive laminoplasty and postoperative axial symptoms: a comparative study between two different procedures.
Sun Y, Zhang F, Wang S … +4 more , Zhang L, Pan S, Yu M, Qiu S
Evid Based Spine Care J · 2010 Dec · PMID 22956925 · Full text
STUDY DESIGN: Retrospective cohortObjective: To determine if there are differences in important clinical outcomes between patients treated with a "preservation of the unilateral posterior muscular-ligament complex (PMLC...
STUDY DESIGN: Retrospective cohortObjective: To determine if there are differences in important clinical outcomes between patients treated with a "preservation of the unilateral posterior muscular-ligament complex (PMLC) procedure" and a "hinge side anchoring procedure (HSAP)" for the treatment of cervical spondylotic myelopathy (CSM). METHODS: Nine hundred and forty-six patients underwent the above procedures for treatment of CSM between January 2006 and December 2009. Five hundred and fifty-two (58%) subjects met study criteria and 136 were analyzed (76% unavailable for follow-up). One group (70 patients) received a "preservation of unilateral PMLC procedure" and another group (66 patients) received an HSAP. The rate and severity of postoperative axial symptoms were assessed, and the changes of cervical-spine curvature and postoperative decompression were measured. RESULTS: The mean time to follow-up in the preservation of unilateral PMLC group was 6.9 months (range, 6-8 months) and the HSAP group was 6.4 months (6-8 months). The overall rate of any axial symptoms (AS) among all subjects was 35%. No AS was reported in 45.7% of the preservation of unilateral PMLC group and 23.8% of the HSAP group (P = .008). Severe AS was reported in 4.3% and 11.1% of patients per group, respectively (P = .14). Cervical spinal lordosis was improved in the unilateral PMLC group and decreased in the HSAP group. The risk of losing lordosis was more than two times higher in the HSAP group compared with the unilateral PMLC group (70% and 34%, respectively; P < .001). CONCLUSION: Differences were observed between the two groups; however, a high loss to follow-up rate weakens the findings. Cervical expansive laminoplasty with preservation of unilateral PMLC may have the advantage of a lower rate of postoperative AS and maintenance of cervical spinal lordosis compared with the HSAP group.
Reliability of classification systems for subaxial cervical injuries.
Stone AT, Bransford RJ, Lee MJ … +4 more , Vilela MD, Bellabarba C, Anderson PA, Agel J
Evid Based Spine Care J · 2010 Dec · PMID 22956924 · Full text
STUDY DESIGN: Interobserver and intraobserver reliabilityObjective: To measure and compare the interobserver and intraobserver reliability of the cervical spine injury severity score (CSISS), the subaxial injury classif...
STUDY DESIGN: Interobserver and intraobserver reliabilityObjective: To measure and compare the interobserver and intraobserver reliability of the cervical spine injury severity score (CSISS), the subaxial injury classification (SLIC) and severity scale, and the Allen-Ferguson system in patients with subaxial cervical spine injuries presenting to the emergency department. METHODS: Five examiners independently reviewed c-spine x-rays (CT/MRI) of 50 consecutive patients with subaxial cervical-spine injuries. They classified each case using CSISS, SLIC, and the Allen-Ferguson system. Examiners also documented if they believed the case required surgical management. At least 6 weeks later, the above steps were repeated for ten randomly chosen cases. RESULTS: The interobserver and intraobserver reliability for the total CSISS and total SLIC score are excellent. There is poor interobserver reliability and excellent intraobserver reliability when a total kappa score is calculated using all 21 groups for the Allen-Ferguson system. With respect to surgical management decisions, the interobserver agreement is moderate and the intraobserver agreement is excellent. CONCLUSIONS: There is no universally accepted classification scheme for subaxial cervical-spine injuries. A useful classification system must have excellent reliability to consistently and accurately describe injury patterns between different observers and allow for comparison across systems or cohorts. Both the CSISS and the SLIC and severity scale are promising classification systems with excellent interobserver and intraobserver reliability. Future studies will need to determine if their quantitative scores correlate with management and clinical outcomes.
Outcome of major spinal deformity surgery in high-risk patients: comparison between two departments.
Murans G, Gustavsson B, Saraste H
Evid Based Spine Care J · 2010 Dec · PMID 22956923 · Full text
STUDY DESIGN: Retrospective cohort studyObjective: To describe the outcome and resource use in major spine surgery on high-risk patients, and analyze possible differences between two surgical departments. METHODS: Data...
STUDY DESIGN: Retrospective cohort studyObjective: To describe the outcome and resource use in major spine surgery on high-risk patients, and analyze possible differences between two surgical departments. METHODS: Data from the deformity register and medical records of 136 patients, median age 12-years, with neuromuscular and congenital spinal deformities with and without intraspinal pathology, surgically treated by one surgeon from 1997 through 2004 at two departments. H1 with a pediatric multidisciplinary team, and H2 with focus on adult spine. Variables at baseline: age, gender, diagnosis, curve size, and type of surgical procedure. Result variables included clinical and radiographic outcome, surgery time, length of intensive care and hospital stay, relative blood loss, and occurrence of complications during 2 or more years follow-up. RESULTS: There was no perioperative or postoperative mortality, no spinal-cord damage, no neurological or ambulatory function deterioration. The overall complication rate was 36%, and the overall major complication rate was 15.4%. The mean loss of correction was 2° during the follow-up. There were statistically significant differences between the H1 and H2 departments. At H1, deformity correction was better and surgery time shorter. Infections were more frequent at H2 (P = .04; 6/65 at H1; 16/71 at H2), tendency (P = .06) of more department-related complications was higher at H2. CONCLUSIONS: Major spine surgery in high-risk patients can be performed safely and with good outcoms. Impact of organization and workplace culture on the outcome might be important and worth further study.
The random allocation process: two things you need to know.
Dettori J
Evid Based Spine Care J · 2010 Dec · PMID 22956922 · Full text
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The 'burden of evidence'.
Evid Based Spine Care J · 2010 Dec · PMID 22956921 · Full text
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Letters to the editor.
Schoones JW
Evid Based Spine Care J · 2010 Aug · PMID 23641214 · Full text
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Evaluation of the sodium-glutamate blocker riluzole in a preclinical model of ervical spinal cord injury.
Wu Y, Satkundrarajah K, Teng Y … +2 more , Chow DS, Fehlings MG
Evid Based Spine Care J · 2010 Aug · PMID 23637674 · Full text
STUDY TYPE: Basic research Introduction: Because sodium and glutamate play integrated roles in the pathology of spinal cord injury (SCI), there is intense interest in the potential role of the sodium-glutamate blocker...
STUDY TYPE: Basic research Introduction: Because sodium and glutamate play integrated roles in the pathology of spinal cord injury (SCI), there is intense interest in the potential role of the sodium-glutamate blocker riluzole as a neuroprotective agent for spinal cord injury. A phase I safety clinical trial of riluzole is about to commence in the USA and Canada. OBJECTIVE: The key challenges in translating riluzole to the clinic relate to uncertainty regarding the time window for post-injury administration of riluzole and the optimal dose. Hence, the current study was undertaken to study these issues in a preclinical model of cervical SCI in rodents. METHODS: Adult female rats received moderate cervical spinal cord clip compression injury (35 g × 1 min at C7-T1) and were randomly assigned to one of the following three groups (n = 12/group): a) 8 mg/kg of riluzole intraperitoneally at 1 hour (P1 group) ; b) 3 hours (P3 group) after injury or c) a control group (vehicle). The P1 and P3 groups then received 6 mg/kg of riluzole intraperitoneally every 12 hours for 7 days. A smaller group of rats (n = 10) received a higher dose (8 mg/kg IP Q12 h for 7 days) of riluzole following the initial dosing. Functional recovery was tested by open field locomotion (BBB score, BBB subscore) and grid walk. Sensory function (tactile allodynia) was assessed by quantitative von Frey filament testing. Somatosensory evoked potentials (SSEP) were performed to quantitatively assess central axonal conduction. Western blotting for neurofilament 200 (NF200) was used to assess axonal integrity. Quantitative image analysis of lesion histology (HE/LFB stained sections) was undertaken to assess tissue sparing at the injury site. High performance liquid chromatography (HPLC) was used to test pharmacokinetics of riluzole. ANOVA followed by the Tukey's post-hoc testing was used to compare the results. RESULTS: A total of 92.3% of injured rats that received repeated dose of 6 mg/kg riluzole survived during the term of 6 weeks, showing tolerance to this dosage. In contrast, higher doses of riluzole (8mg/kg IP q12h post-injury) were associated with significant respiratory depression and high mortality (7/10 rats). Riluzole treatment (P1 group) decreased the functional deficit significantly (P < 0.05) at 6 weeks after injury by showing 11.4 in BBB, 3.8 in BBB subscore and 2.8 in grid walk test, compared with 10.25 in BBB, 1.1 in BBB subscore, and 8.0 in grid walk test of control group (Figure 1). Quantitative analysis of SSEPs confirmed the neuroprotective effects of riluzole (P1 group) by showing significantly larger amplitude (control = 20.67 µV, P1 = 42.67 µV and P3 = 37.00 µV, Figure 2) and reduced response latency (control = 4.05 ms and P1 = 3.9 ms). Western blotting of NF200 indicated greater axonal preservation with riluzole treatment (P1 group) at 1 week after injury. The P3 group showed trends to improved neurobehavioral recovery and axonal preservation that did not attain significance. HPLC showed riluzole penetrated into the spinal cord as fast as 15 minutes, accumulated in the spinal cord at a concentration six times higher than in plasma, and two times higher than in brain. The drug stayed in spinal cord with a high concentration before the next injection. Figure 1 Riluzole treatment improved functional recovery. The most robust effects were seen when the drug was injected at one hour after SCIFigure 2 Riluzole treatment increased amplitude of somatosensory evoked potentials Conclusions: The sodium-glutamate blocker riluzole confers neurobehavioral and anatomical neuroprotection when administered one hour after moderately severe cervical contusive/compressive injury.
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