John M. Rhee

Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine

Study Design/Setting. Independent, retrospective clinical record review with a concurrent control. Objective. To identify whether rhBMP-2 is associated with an increased incidence of clinically relevant postoperative prevertebral swelling problems in patients undergoing anterior cervical fusions. Summary of Background Data. Bone Morphogenetic Protein-2 (rhBMP-2) is FDA approved as a bone graft substitute in anterior lumbar interbody fusions. rhBMP-2 has also been used “off-label” in anterior cervical fusions. We suspected that rhBMP-2 might increase the incidence of adverse swelling events. Methods. A total of 234 consecutive patients (ages 12–82 years) undergoing anterior cervical fusion with and without rhBMP-2 over a 2-year period at one institution comprised the study population. The incidence of clinically relevant prevertebral swelling was calculated. The populations were compared and statistical significance was determined. Results. A total of 234 patients met the study criteria, 69 of whom underwent anterior cervical spine fusions using rhBMP-2; 27.5% of those patients in the rhBMP-2 group had a clinically significant swelling event versus only 3.6% of patients in the non-rhBMP-2 group. This difference was statistically significant (P < 0.0001) and remained so after controlling for other significant predictors of swelling. Conclusions. Off-label use of rhBMP-2 in the anterior cervical spine is associated with an increased rate of clinically relevant swelling events.

Correlation of Pelvic Incidence With Low- and High-Grade Isthmic Spondylolisthesis

Purpose. The development of isthmic spondylolisthesis is influenced by forces across the lumbosacral region of the spine. Pelvic incidence is a radiographic parameter that has been shown to be an independent parameter that influences both sagittal spinal balance and pelvic orientation. Our hypothesis then is that there is a positive correlation between pelvic incidence and spondylolisthesis. Study Design. A radiographic analysis of cases with spondylolisthesis. Objectives. To try to assess the correlation between pelvic incidence in both low-grade and high-grade spondylolisthesis in both a pediatric and an adult population. Summary of Background Data. The concept of pelvic incidence has been introduced into the literature. Its exact association with spondylolisthesis has not yet been clarified. Methods. Forty patients with spondylolisthesis were identified and divided into two groups: low-grade (Meyerding I–II) and high-grade (Meyerding III and higher). Radiographic parameters measured included lumbar sagittal alignment (T12–S1), sacral inclination, slip angle, and pelvic incidence. The spondylolisthesis was classified according to the Meyerding–Newman classifications and the slip angle. Radiographic measurements were also done in two control groups; there were 20 pediatric and 20 adult controls (mean age 11.8 years and 60.0 years, respectively). Unpaired t test analysis and Pearson correlation analysis were then done. Results. Mean pelvic incidence was 47.4° in the pediatric control group, 57° in the adult control group, 68.5° in the low-grade isthmic spondylolisthesis group, and 79.0° in the high-grade isthmic spondylolisthesis group. Pelvic incidence was found to be significantly higher in the high- and low-grade spondylolisthesis groups compared with both control groups (P = 0.0001). Pelvic incidence was significantly higher in the high-grade isthmic spondylolisthesis group than in the low-grade isthmic spondylolisthesis group (P = 0.007). A significant correlation existed between pelvic incidence and Meyerding–Newman scores (P = 0.03). Conclusions. Pelvic incidence was significantly higher in patients with low- and high-grade isthmic spondylolisthesis as compared with controls and had significant correlation with the Meyerding–Newman grades (P = 0.03).

Reduction of inflammatory reaction of poly(d,l-lactic-co-glycolic Acid) using demineralized bone particles.

Poly(lactide-co-glycolic acid) (PLGA) has been widely applied to tissue engineering as a good biocompatible material because of its biodegradability and nontoxic metabolites, but how the inflammatory reaction of PLGA on the surrounding tissue in vivo is reduced has not been discussed sufficiently. We hypothesized that the cells neighboring the PLGA implant might have an inflammatory response that could be reduced by impregnating demineralized bone particles (DBPs) into the PLGA. We manufactured five different ratios of DBP/PLGA hybrid materials, with each material containing 0, 10, 20, 40, and 80 wt% of DBPs of PLGA. For biocompatibility test, NIH/3T3 mouse fibroblasts were cultured on the DBP/PLGA scaffold for 3 days. The inflammatory potential of PLGA was evaluated using messenger ribonucleic acid expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) on a human acute promyelocytic leukemic cell (HL-60). The in vivo response of DBP/PLGA film was compared with that of PLGA film implanted subcutaneously; the local inflammatory response was observed according to histology. The DBP/PLGA scaffold had no adverse effect on NIH/3T3 initial cell attachment and did not affect cell viability. DBP/PLGA films, especially PLGA films containing 80% DBP, elicited a significantly lower expression of IL-1beta and TNF-alpha from HL-60 cells than PLGA film alone. In vivo, DBP/PLGA film demonstrated a more favorable tissue response profile than PLGA film, with significantly less inflammation and fibrous capsule formation as below only 20% of DBP in PLGA film during implantation. This study shows that application of DBPs reduces the fibrous tissue encapsulation and foreign body giant cell response that commonly occurs at the interface of PLGA.

Nonoperative management of cervical myelopathy: a systematic review

Study Design. Systematic review. Objective. To conduct a systematic review investigating the evidence of (1) efficacy, effectiveness, and safety of nonoperative treatment of patients with cervical myelopathy; (2) whether the severity of myelopathy affects outcomes of nonoperative treatment; and (3) whether specific activities or minor injuries are associated with neurological deterioration in patients with myelopathy or asymptomatic stenosis being treated nonoperatively. Summary of Background Data. Little is known about the appropriate role of nonoperative treatment in the management of cervical myelopathy, which is typically considered a surgical disorder. Methods. A systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 20, 2012. We included all articles that compared nonoperative treatments or observation with surgery for patients with cervical myelopathy or asymptomatic cervical cord compression to determine their effects on clinical outcomes, including myelopathy scales (Japanese Orthopaedic Association, Nurick), general health scores (36-Item Short Form Health Survey), and pain (neck and arm). Nonoperative treatments included physical therapy, medications, injections, orthoses, and traction. We also searched for articles evaluating the effect of specific activities or minor trauma in neurological outcomes. Case reports and studies with less than 10 patients in the exposure group were excluded. Results. Of 54 citations identified from our search, 5 studies reported in 6 articles met inclusion criteria. In 1 randomized controlled study, there was low evidence that nonoperative treatment may yield equivalent or better outcomes than surgery in those with mild myelopathy. For moderate to severe myelopathy, nonoperative treatment had inferior outcomes versus surgery in 2 cohort studies, despite the fact that surgically treated patients were worse at baseline. There was insufficient evidence to determine whether specific activities or minor trauma is a risk factor for neurological deterioration in those with myelopathy or asymptomatic cord compression. Conclusion. There is a paucity of evidence for nonoperative treatment of cervical myelopathy, and further studies are needed to determine its role more definitively. In particular, for the patient with milder degrees of myelopathy, randomized studies comparing nonoperative with surgical treatment would be particularly helpful, as would trials comparing specific types of nonoperative treatments with the natural history of myelopathy. Evidence-Based Clinical Recommendations. Recommendation 1. Because myelopathy is known to be a typically progressive disorder and there is little evidence that nonoperative treatment halts or reverses its progression, we recommend not routinely prescribing nonoperative treatment as the primary modality in patients with moderate to severe myelopathy. Overall Strength of Evidence. Low Strength of Recommendation. Strong Recommendation 2. If there is a role for nonoperative treatment as a primary treatment modality, it may be in the patient with mild myelopathy. However, it is not clear which specific forms of nonoperative treatment provide any benefit compared with the natural history. If nonoperative treatment is selected, we suggest care be taken to observe for neurological deterioration. Overall Strength of Evidence. Low Strength of Recommendation. Weak Recommendation 3. In those with asymptomatic spondylotic cord compression but no clinical myelopathy, the available literature neither supports nor refutes the notion that minor trauma is a risk factor for neurological deterioration. We suggest that patients should be counseled about this uncertainty. Overall Strength of Evidence. Low Strength of Recommendation. Weak Recommendation 4. In those with a clinical diagnosis of cervical spondylotic myelopathy but no ossification of the posterior longitudinal ligament, the available studies did not specifically address the issue of neurological deterioration secondary to minor trauma. However, in those with underlying ossification of the posterior longitudinal ligament, trauma may be more likely to cause worsening of existing myelopathy or even initiate symptoms in those who were previously asymptomatic. We suggest that patients should be counseled about these possibilities. Overall Strength of Evidence. Low Strength of Recommendation. Weak

A comparison of pedicle and lateral mass screw construct stiffnesses at the cervicothoracic junction: a biomechanical study.

Study Design. Biomechanical comparison of five different posterior cervicothoracic junction (C7–T1) fixation constructs in a cadaveric model. Objectives. To determine whether augmenting C7 lateral mass screws with spinous process wires or additional fixation in the C6 lateral mass can create constructs of similar normalized stiffness to that of C7 pedicle screws. Summary of Background Data. Cervical pedicle screws are known to provide excellent fixation but are potentially dangerous and technically demanding to insert. Lateral mass screws are safer and easier to insert but have less pullout strength and must often be short at C7. Methods. Twelve cadaveric cervicothoracic specimens (C5–T2) were randomly assigned to one of three experiments: Experiment A (Part 1 and Part 2), Experiment B, and Experiment C (Part 1 and Part 2) (n = 4 each for each experiment). First, the intact specimens were biomechanically tested according to a seven-part loading protocol. The specimens were then destabilized, and then restabilized with the following constructs in conjunction with bilateral T1 pedicle screws and biomechanically tested again using the same seven-part biomechanical protocol as was applied to the intact specimens. Experiment A: Part 1: lateral mass screw fixation at C7 (C7LM); then Part 2: retested after augmentation with triple wiring (C7LM+W). Experiment B: pedicle screw fixation at C7 (C7PS). Experiment C: Part 1: C6 and C7 lateral mass screws (C6C7LM); then Part 2: retested after augmentation with triple wiring (C6C7LM+W). Thus, five different constructs were biomechanically compared in these three experiments. Results. None of the lateral mass constructs demonstrated a significant increase in normalized stiffness when augmented with wiring in any mode of testing. In axial compression, the C7PS construct showed significantly higher (P < 0.001) normalized stiffness than any of the other four constructs. In extension, there were no significant differences among any of the five constructs. Inflexion, right/left lateral bending and right/left axial torsion, the C7PS construct again showed significantly higher normalized stiffness (P < 0.05) than lateral mass fixation at C7 alone. However, in these five modes of testing, the addition of a secondary point of lateral mass fixation at C6 (C6C7LM) produced a construct with a normalized stiffness similar to that of C7PS with no significant difference (P > 0.05). Conclusion. C7 pedicle screw fixation provides the construct with the highest normalized stiffness for stabilizing the cervicothoracic junction. If C7 pedicle fixation is not possible, then performing two-level lateral mass fixation at C6 and C7 will achieve a construct with similar normalized stiffness except in axial compression. The addition of triple wiring to the spinous processes does not significantly increase lateral mass construct normalized stiffness.

Radiculopathy and the herniated lumbar disc. Controversies regarding pathophysiology and management.

Lumbar disc herniations remain among the most common diagnoses encountered in clinical spine practice. The incidence of symptomatic lumbar disc herniations in the American population has been estimated to be 1% to 2%1, for which approximately 200,000 lumbar discectomies are performed annually2. Yet despite the frequency with which lumbar disc herniation occurs, there is substantial controversy regarding its pathophysiology and treatment. For example, from the standpoint of basic science, mounting evidence suggests that biochemical factors—in addition to the mechanical effects of the disc material on the nerve root—underlie the development of symptomatic radiculopathy, but those factors remain to be clearly elucidated. On the clinical end of the spectrum, large (five-to-fifteen-fold) variations3 in the rates of lumbar surgery in geographically adjacent areas suggest radical heterogeneity in the application of surgical criteria to this diagnosis. In this lecture, we examine the available basic science regarding the anatomy and pathophysiology of lumbar disc herniations as well as the clinical evidence supporting nonoperative compared with surgical management of this common, yet surprisingly poorly understood, orthopaedic disorder. Structurally, the lumbar disc has three components: the anulus fibrosus, which forms the circumferential rim of the disc; the nucleus pulposus, which composes its central core; and the cartilaginous end plates on the adjacent vertebral bodies. The anulus has a multilayer lamellar architecture made of collagen fibers. Within each layer, the collagen is oriented at approximately 30° to the horizontal. Each successive layer is oriented at 30° to the horizontal in the opposite direction, leading to a “crisscross” type pattern. This composition allows the anulus, and in particular the outer anulus, which has the highest tensile modulus, to resist torsional, axial, and tensile loads. The nucleus pulposus provides resistance to axial compression and is the principal determinant of disc height because of its …

Time-Dependent Inhibitory Effects of Indomethacin on Spinal Fusion

Background: The use of nonsteroidal anti-inflammatory drugs following spine arthrodesis is discouraged because of the negative effects on bone-healing. We are not aware of any data regarding when nonsteroidal anti-inflammatory drugs may be safely resumed postoperatively. We hypothesized that these drugs have a time-dependent deleterious effect on fusion, with the greatest inhibition during the early phases of fusion.Methods: Seventy New Zealand White rabbits underwent posterior intertransverse process arthrodesis at L5-L6 with use of iliac autograft. Rabbits randomly received indomethacin (10 mg/kg orally) starting at two weeks after surgery (twenty-four animals), indomethacin starting at four weeks postoperatively (twenty-three), or saline starting at two weeks postoperatively (twenty-three) (the control group). The animals were killed at six weeks, and the spines were denuded of soft tissues and palpated for L5-L6 motion. Fusion was defined as the complete absence of motion.Results: Sixty-five percent (fifteen) of the twenty-three spines in the control group and 48% (eleven) of the twenty-three in the four-week group fused. However, only 21% (five) of the twenty-four spines in the two-week group fused. The difference between the two-week and control groups was significant (p < 0.002), as was the difference between the two and four-week groups (p = 0.05). The difference between the four-week and control groups was not significant (p = 0.2).Conclusions: The earlier that indomethacin was resumed postoperatively, the greater was its negative effect on fusion. Indomethacin appears to play a significant inhibitory role in the early phase of healing. Initiating indomethacin treatment in the latter phase of healing does not appear to significantly affect fusion rates, although there was a nonsignificant trend toward inhibition. To our knowledge, this is the first investigation of the time-dependent nature of indomethacins effect on bone-healing.Clinical Relevance: Our data suggest that caution be used when initiating nonsteroidal anti-inflammatory drugs after spinal arthrodesis, particularly in the early phase of healing.

Correction of Thoracic Adolescent Idiopathic Scoliosis With Segmental Hooks, Rods, and Wisconsin Wires Posteriorly: It’s Bad and Obsolete, Correct?

Study Design. Forty-four consecutive thoracic idiopathic adolescent curves surgically treated between 1995 and 1999 at one institution were analyzed. All were thoracic curves; there were no lumbar curves, double major curves, or triple major curves. Objectives. To study the clinical and radiographic results for these 44 patients. Summary of Background Data. There is currently ongoing discussion regarding the “best treatment” for right thoracic idiopathic scoliosis. Methods. Patients were administered preoperative and postoperative Scoliosis Research Society questionnaires. Radiographs were studied for coronal correction, sagittal correction, junctional deformities two segments above/two segments below, fusion status, loss of correction status, complications, and imbalance of curves above and below. Radiographic analysis was by two independent observers. All patients were treated with bilateral 5.5-mm CD Horizon (M-10) instrumentation. Corrective forces were translational and in situ contouring. An average of 10 hooks and 4 Wisconsin wires were used for an average of 14 fixation points per 11 segments. Follow-up was minimum 2 years to maximum 5 years, with an average of 3-year, 10-month follow-up. Results. All were out of bed on postoperative day 1; none was braced after surgery. The average preoperative thoracic curve was 56°; the average ultimate postoperative curve was 31° (P = 0.0001). In the sagittal plane T5–T12 averaged 22° preoperation and 20° postoperation. For the complete study group (n = 44), the Cobb measurement (P = 0.001) and apical vertebral translation of the lumbar curve (P = 0.001) below improved. For the false double major curve (n = 11) patterns, the unfused lumbar curve averaged preoperation 46° and postoperation 27° (P = 0.0001). There were no neurologic deficits, no wound infections, and no respiratory complications. In regards to the Scoliosis Research Society questionnaires, significant (P < 0.05) changes preoperative to ultimate postoperative were found for questions 3, 5, 11, and 14. Conclusion. “Satisfactory” results were obtained in 44 patients treated with this technique. The complication rate was low and the fusion rate was high. Posterior treatment as described above produces reasonable and dependable results.

Plate-only open door laminoplasty maintains stable spinal canal expansion with high rates of hinge union and no plate failures.

Study Design. Prospective clinical series. Objective. To evaluate the ability of plate-only laminoplasty to achieve stable laminar arch reconstruction and to determine the rate and time course with which bony healing occurs in such constructs. Summary of Background Data. Reconstruction of a stable laminar arch with sufficient room for the decompressed spinal cord is a desired goal when performing cervical laminoplasty for myelopathy. Traditional forms of laminoplasty fixation, such as sutures, bone struts, and ceramic spacers, may be associated with complications including loss of fixation, dislodgement with neurologic compromise, and premature laminoplasty closure. Plates, in contrast, provide more rigid fixation. Plate-only laminoplasty is gaining popularity as a method of laminoplasty fixation, but there is little data on its effectiveness. Methods. Fifty-four patients who underwent open door laminoplasty for cervical myelopathy and had available postoperative computed tomography (CT) scans formed the basis of this study. In all cases, a 4-mm round burr was used to create the hinge at the junction of the lateral mass and lamina by completely removing the dorsal cortex and thinning the ventral cortex until a greenstick deformation of the hinge could be produced. Laminoplasty plates were used as the sole method of fixation. No supplemental bone graft struts were used on the plated side, and the hinge side was not bone grafted. Axial CT scans obtained at 3, 6, and 12 months postoperatively were assessed for plate complications and bony healing of the hinge. Results. No plate failures, dislodgements, or premature closures occurred in any of the levels at any time postoperatively. Computed tomography scan review demonstrated that 55% of levels were healed at 3 months, 77% at 6 months, and 93% at 12 months. At each timepoint, C6 and C7 had the highest hinge healing rates. Laminar screw backout was seen in 5/217 (2.3%) of levels, but was not associated with plate dislodgement, laminoplasty closure, or neurologic consequences, and did not occur in any case in which 2 laminar screws had been placed. Conclusion. Plate-only laminoplasty provided stable reconstruction of an expanded laminar arch with no failures, dislodgements, adverse neurologic consequences, or premature closures in 217 levels. Ninety-three percent of hinges demonstrated radiographic union at 12 months, and even those that did not heal by CT scan criteria maintained patent expansion of the spinal canal without adverse neurologic consequences. Supplemental bone graft does not appear necessary when plated laminoplasty is performed.

Prevalence of Physical Signs in Cervical Myelopathy : A Prospective, Controlled Study

Study Design. Prospective case-control study. Objective. To determine the prevalence and utility of commonly tested myelopathic signs in surgically treated patients with cervical myelopathy (CM). Summary of Background Data. Although physical signs are sought in making the diagnosis of CM, their importance remains unclear, as patients with CM may have normal examinations while those without CM can demonstrate “myelopathic” signs. Methods. Patients presenting with cervical complaints and advanced imaging were evaluated over a 6-month interval in a single surgical practice. The CM group consisted of those with (1) a history of myelopathic symptoms and (2) correlative spinal cord compression on imaging, who then (3) underwent surgery and (4) improved Nurick score by ≥1 grade after surgery. The controls consisted of patients with neck/radicular complaints but no myelopathic symptoms and no cord compression on imaging. Myelopathic signs included hyperreflexia or provocative signs (Hoffman inverted brachioradialis reflex, clonus, Babinski). Results. There were 39 CM patients and 37 controls. Myelopathic signs were more prevalent in the CM group (79% vs. 57%; P = 0.05), with significantly higher rates of all provocative signs but not hyperreflexia. Overall, myelopathic signs were not highly sensitive in diagnosing the presence of CM, as 21% of CM patients failed to demonstrate any myelopathic signs. There was no correlation between the presence of myelopathic signs and diabetes or preoperative Nurick score. However, those with cord signal changes were significantly more likely to demonstrate myelopathic signs. Conclusion. Although myelopathic signs are significantly more common in CM patients, they may be negative in approximately one-fifth and can not be relied on to make the diagnosis. In patients who lack myelopathic signs but otherwise seem myelopathic with no alternative explanations, symptoms combined with correlative imaging studies must be used to base treatment decisions, as the absence of signs does not preclude the diagnosis of myelopathy nor its successful surgical treatment.