Time to development, clinical and radiographic characteristics, and management of proximal junctional kyphosis following adult thoracolumbar instrumented fusion for spinal deformity.

STUDY DESIGN: A retrospective review. OBJECTIVE: To study time to development, clinical and radiographic characteristics, and management of proximal junctional kyphosis (PJK) following thoracolumbar instrumented fusion for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: PJK continues to be a common mode of failure following ASD surgery. Although literature exists on possible risk factors, data on management remain limited. METHODS: A retrospective review of medical records of 289 consecutive ASD patients who underwent posterior segmental instrumentation incorporating at least 5 segments was conducted. PJK was defined as proximal kyphotic angle >10 degrees. RESULTS: PJK occurred in 32 patients (11%) at a mean follow-up of 34 months (range, 1.3-61.9±19 mo). Sixteen (50%) patients were revised (mean, 1.7 revisions; range, 1-3) at a mean follow-up of 9.6 months (range, 0.7-40 mo); primary indications for revision were pain (n=16), myelopathy (n=6), instability (n=4), and instrumentation protrusion (n=2). Comparison of preindex and postindex surgery radiographic parameters demonstrated significant improvement in mean lumbar lordosis (24 vs. 42 degrees, P<0.001), pelvic incidence-lumbar lordosis mismatch (30 vs. 11 degrees, P<0.001), and pelvic tilt (29 vs. 23 degrees, P<0.011). The mean T5-T12 kyphosis worsened (30 vs. 53 degrees, P<0.001) and the mean global sagittal spinal alignment failed to improve (9.6 vs. 8.0 cm, P=0.76). There was no apparent relationship between the absolute PJK angle and revision surgery (P>0.05). CONCLUSIONS: The patients in this series who developed PJK had substantial preoperative positive sagittal malalignment that remained inadequately corrected following surgery, likely resulting from a combination of inadequate surgical correction and a significant compensatory increase in thoracic kyphosis. In the absence of direct relationship between a greater PJK angle and worse clinical outcome, clinical symptoms and neurological status rather than absolute reliance on radiographic parameters should drive the decision to pursue revision surgery.

The effects of simulated microgravity on intervertebral disc degeneration.

BACKGROUND CONTEXT: Astronauts experience back pain, particularly low back pain, during and after spaceflight. Recent studies have described histologic and biochemical changes in rat intervertebral discs after space travel, but there is still no in vitro model to investigate the effects of microgravity on disc metabolism. PURPOSE: To study the effects of microgravity on disc degeneration and establish an in vitro simulated microgravity study model. STUDY DESIGN: Discs were cultured in static and rotating conditions in bioreactor, and the characteristics of disc degeneration were evaluated. METHODS: The mice discs were cultured in a rotating wall vessel bioreactor where the microgravity condition was simulated. Intervertebral discs were cultured in static and microgravity condition. Histology, biochemistry, and immunohistochemical assays were performed to evaluate the characteristics of the discs in microgravity condition. RESULTS: Intervertebral discs cultured in rotating bioreactors were found to develop changes of disc degeneration manifested by reduced red Safranin-O staining within the annulus fibrosus, downregulated glycosaminoglycan (GAG) content and GAG/hydroxyproline ratio, increased matrix metalloproteinase 3 expression, and upregulated apoptosis. CONCLUSIONS: We conclude that simulated microgravity induces the molecular changes of disc degeneration. The rotating bioreactor model will provide a foundation to investigate the effects of microgravity on disc metabolism.

Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice.

Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. The ApoE knockout (KO) mouse is a well-established model for atheroscelorosis. We hypothesized that ApoE is involved in maintaining disc health and that ApoE KO mice will develop early disc degeneration. Discs of ApoE KO and wild-type (WT) mice were characterized with histological/immunological, biochemical, and real-time RT-PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs, and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulposus (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinase-3, -9, and -13 expressions were increased, which may partially explain the impaired matrix production. We also found collagen I, II, aggrecan, and biglycan mRNA expressions were increased in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in the ApoE KO mice. ApoE may play a critical role in disc integrity and function.

Endoscopic transsphenoidal surgery for cushing disease: techniques, outcomes, and predictors of remission.

BACKGROUND: The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing disease has not been clearly established. OBJECTIVE: To assess efficacy of a pure endoscopic approach for treatment of Cushing disease and determine predictors of remission. METHODS: A prospectively acquired database of 61 patients undergoing ETS was reviewed. Remission was defined as postoperative morning serum cortisol of <5 µg/dL or normal or decreased 24-hour urine-free cortisol level in follow-up. RESULTS: Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by discharge. Tumor size did not predict resolution of hypercortisolemia at discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients (91.8%) were in remission. Fifty patients were followed for at least 12 months (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single ETS. In these patients, there was no significant difference in remission rates between microadenomas (93%), magnetic resonance imaging-negative (70%), and macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were 9 times less likely to achieve follow-up remission (P = .021). In-house cortisol level of <5.7 µg/dL provided the best prediction of follow-up remission (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced postoperative cerebrospinal fluid leak that resolved with further surgery. CONCLUSION: ETS for Cushing disease provides high rates of remission with low rates of complications regardless of size. Although patients with a history of previous surgery are less likely to achieve remission, the majority can still achieve remission following treatment.

Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome.

CONTEXT: Despite the growing application of endoscopic transsphenoidal surgery (ETSS), outcomes for GH adenomas are not clearly defined. OBJECTIVE: We reviewed our experience with ETSS with specific interest in remission rates using the 2010 consensus criteria, predictors of remission, and associated complications. DESIGN AND SETTING: This was a retrospective single institution study. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Sixty acromegalic patients who underwent ETSS were identified. Remission was defined as a normal IGF-I and either a suppressed GH less than 0.4 ng/ml during an oral glucose tolerance test or a random GH less than 1.0 ng/ml. RESULTS: Remission was achieved in all 14 microadenomas and 28 of 46 macroadenomas (61%). Tumor size, age, gender, and history of prior surgery were not predictive on multivariant analysis. In hospital postoperative morning GH levels less than 2.5 ng/ml provided the best prediction of remission (P < 0.001). Preoperative variables predictive of remission included Knosp score (P = 0.017), IGF-I (P = 0.030), and GH (P = 0.042) levels. New endocrinopathy consisted of diabetes insipidus in 5%, adrenal insufficiency in 5.4%, and new hypogonadism in 29% of men and 17% of women. However, 41% of hypogonadal men had normal postoperative testosterone levels and 83% of amenorrheic women regained menses. The most common complaints after surgery were sinonasal (36 of 60, 60%) resolving in all but two. CONCLUSIONS: ETSS for GH adenomas is associated with high rates of remission and a low incidence of new endocrinopathy. Despite the panoramic views offered by the endoscope, invasive tumors continue to have lower rates of remission.

Treatment of intracranial solitary fibrous tumors with gamma knife radiosurgery: report of two cases and review of literature.

BACKGROUND AND IMPORTANCE: Gamma knife radiosurgery (GKRS) as a treatment option has not been described in the management of typical intracranial solitary fibrous tumors. CLINICAL PRESENTATION: After presenting with visual decline, case A underwent a bioccipital craniotomy during which 90% of tumor was thought to have been resected. She unfortunately required re-resection 56 months later for recurrence when she again presented with progressive visual decline, altered mental status, and headaches. A subtotal resection was performed, because there was extensive tumor involvement of the torcula, straight sinus, and bilateral transverse sinuses. She was subsequently referred for GKRS. Although neurologically intact, with the exception of an upper extremity tremor, case B had undergone 7 surgeries for a posterior fossa tumor over the several decades preceding GKRS. The tumors targeted with GKRS were found on serial MRI scans and were thought to be asymptomatic at the time of treatment. At 7 and 14 months after GKRS, case A experienced tumor shrinkage, which remained stable 20 months after treatment. Effective local tumor control was seen in case B with tumor shrinkage at 3, 8, and 13 months after treatment. However, repeat GKRS was required for case B, because an out-of-field recurrence was found 15 months after the initial GKRS. CONCLUSION: Based on this report and available information in the literature, radiosurgery appears to be a reasonable approach for patients with recurrent or residual intracranial solitary fibrous tumors.

Comprehensive analysis of risk factors for seizures after deep brain stimulation surgery. Clinical article.

OBJECT: The aim of this study was to assess risk factors for postoperative seizures after deep brain stimulation (DBS) lead implantation surgery and the impact of such seizures on length of stay and discharge disposition. METHODS: The authors reviewed a consecutive series of 161 cases involving patients who underwent implantation of 288 electrodes for treatment of movement disorders at a single institution to determine the absolute risk of postoperative seizures, to describe the timing and type of seizures, to identify statistically significant risk factors for seizures, and to determine whether there are possible indications for seizure prophylaxis after DBS lead implantation. The electronic medical records were reviewed to identify demographic details, medical history, operative course, and postoperative outcomes and complications. To evaluate significant associations between potential risk factors and postoperative seizures, both univariate and multivariate analyses were performed. RESULTS: Seven (4.3%) of 161 patients experienced postoperative seizures, all of which were documented to have been generalized tonic-clonic seizures. In 5 (71%) of 7 cases, patients only experienced a single seizure. Similarly, in 5 of 7 cases, patients experienced seizures within 24 hours of surgery. In 6 (86%) of the 7 cases, seizures occurred within 48 hours of surgery. Univariate analysis identified 3 significant associations (or risk factors) for postoperative seizures: abnormal findings on postoperative imaging (hemorrhage, edema, and or ischemia; p < 0.001), age greater than 60 years (p = 0.021), and transventricular electrode trajectories (p = 0.023). The only significant factor identified on multivariate analysis was abnormal findings on postoperative imaging (p < 0.0001, OR 50.4, 95% CI 5.7-444.3). Patients who experienced postoperative seizures had a significantly longer length of stay than those who were seizure free (mean ± SD 5.29 ± 3.77 days vs 2.38 ± 2.38 days; p = 0.002, Student 2-tailed t-test). Likewise, final discharge to home was significantly less likely in patients who experienced seizures after implantation (43%) compared with those patients who did not (92%; p = 0.00194, Fisher exact test). CONCLUSIONS: These results affirm that seizures are an uncommon complication of DBS surgery and generally occur within 48 hours of surgery. The results also indicate that hemorrhage, edema, or ischemia on postoperative images ("abnormal" imaging findings) increases the relative risk of postoperative seizures by 30- to 50-fold, providing statistical credence to the long-held assumption that seizures are associated with intracranial vascular events. Even in the setting of a postimplantation imaging abnormality, long-term anticonvulsant therapy will not likely be required because none of our patients developed chronic epilepsy.

Safety, efficacy, and dosing of recombinant human bone morphogenetic protein-2 for posterior cervical and cervicothoracic instrumented fusion with a minimum 2-year follow-up.

BACKGROUND: Considerable attention has focused on concerns of increased complications with recombinant human bone morphogenetic protein-2 (rhBMP-2) use for anterior cervical fusion, but few reports have assessed its use for posterior cervical fusions. OBJECTIVE: To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior cervical arthrodesis. METHODS: All patients treated by the senior author with posterior cervical or cervicothoracic instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum of 2 years of follow-up were included. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed. RESULTS: Fifty-three patients with a mean age of 55.7 years (range, 2-89 years) and an average follow-up of 40 months (range, 25-80 months) met inclusion criteria. Surgical indications included basilar invagination (n = 6), fracture (n = 6), atlantoaxial instability (n = 16), kyphosis/kyphoscoliosis (n = 22), osteomyelitis (n = 1), spondylolisthesis (n = 1), and cyst (n = 1). Fifteen patients had confirmed rheumatoid disease. The average rhBMP-2 dose was 1.8 mg per level, with a total of 282 levels treated (average, 5.3 levels; SD, 2.8 levels). Among 53 patients, only 2 complications (3.8%) were identified: a superficial wound infection and an adjacent-level degeneration. No cases of dysphagia or neck swelling requiring treatment were identified. At the last follow-up, all patients had achieved fusion. CONCLUSION: Despite many of the patients in the present series having complex pathology and/or rheumatoid arthritis, a 100% fusion rate was achieved. Collectively, these data suggest that use of rhBMP-2 as an adjunct for posterior cervical fusion is safe and effective at an average dose of 1.8 mg per level.

Complications in the surgical treatment of 19,360 cases of pediatric scoliosis: a review of the Scoliosis Research Society Morbidity and Mortality database.

STUDY DESIGN: Retrospective review of a multicenter database. OBJECTIVE: To determine the complication rates associated with surgical treatment of pediatric scoliosis and to assess variables associated with increased complication rates. SUMMARY OF BACKGROUND DATA: Wide variability is reported for complications associated with the operative treatment of pediatric scoliosis. Limited number of patients, surgeons, and diagnoses occur in most reports. The Scoliosis Research Society Morbidity and Mortality (M&M) database aggregates deidentified data, permitting determination of complication rates from large numbers of patients and surgeons. METHODS: Cases of pediatric scoliosis (age ≤18 years), entered into the Scoliosis Research Society M&M database between 2004 and 2007, were analyzed. Age, scoliosis type, type of instrumentation used, and complications were assessed. RESULTS: A total of 19,360 cases fulfilled inclusion criteria. Of these, complications occurred in 1971 (10.2%) cases. Overall complication rates differed significantly among idiopathic, congenital, and neuromuscular cases (P < 0.001). Neuromuscular scoliosis had the highest rate of complications (17.9%), followed by congenital scoliosis (10.6%) and idiopathic scoliosis (6.3%). Rates of neurologic deficit also differed significantly based on the etiology of scoliosis (P < 0.001), with the highest rate among congenital cases (2.0%), followed by neuromuscular types (1.1%) and idiopathic scoliosis (0.8%). Neur-omuscular scoliosis and congenital scoliosis had the highest rates of mortality (0.3% each), followed by idiopathic scoliosis (0.02%). Higher rates of new neurologic deficits were associated with revision procedures (P < 0.001) and with the use of corrective osteotomies (P < 0.001). The rates of new neurologic deficit were significantly higher for procedures using anterior screw-only constructs (2.0%) or wire-only constructs (1.7%), compared with pedicle screw-only constructs (0.7%) (P < 0.001). CONCLUSION: In this review of a large multicenter database of surgically treated pediatric scoliosis, neuromuscular scoliosis had the highest morbidity, but relatively high complication rates occurred in all groups. These data may be useful for preoperative counseling and surgical decision-making in the treatment of pediatric scoliosis.

Morbidity and mortality in the surgical treatment of 10,242 adults with spondylolisthesis.

OBJECT: This is a retrospective review of 10,242 adults with degenerative spondylolisthesis (DS) and isthmic spondylolisthesis (IS) from the morbidity and mortality (M&M) index of the Scoliosis Research Society (SRS). This database was reviewed to assess complication incidence, and to identify factors that were associated with increased complication rates. METHODS: The SRS M&M database was queried to identify cases of DS and IS treated between 2004 and 2007. Complications were identified and analyzed based on age, surgical approach, spondylolisthesis type/grade, and history of previous surgery. Age was stratified into 2 categories: > 65 years and ≤ 65 years. Surgical approach was stratified into the following categories: decompression without fusion, anterior, anterior/posterior, posterior without instrumentation, posterior with instrumentation, and interbody fusion. Spondylolisthesis grades were divided into low-grade (Meyerding I and II) versus high-grade (Meyerding III, IV, and V) groups. Both univariate and multivariate analyses were performed. RESULTS: In the 10,242 cases of DS and IS reported, there were 945 complications (9.2%) in 813 patients (7.9%). The most common complications were dural tears, wound infections, implant complications, and neurological complications (range 0.7%-2.1%). The mortality rate was 0.1%. Diagnosis of DS had a significantly higher complication rate (8.5%) when compared with IS (6.6%; p = 0.002). High-grade spondylolisthesis correlated strongly with a higher complication rate (22.9% vs 8.3%, p < 0.0001). Age > 65 years was associated with a significantly higher complication rate (p = 0.02). History of previous surgery and surgical approach were not significantly associated with higher complication rates. On multivariate analysis, only the grade of spondylolisthesis (low vs high) was in the final best-fit model of factors associated with the occurrence of complications (p < 0.0001). CONCLUSIONS: The rate of total complications for treatment of DS and IS in this series was 9.2%. The total percentage of patients with complications was 7.9%. On univariate analysis, the complication rate was significantly higher in patients with high-grade spondylolisthesis, a diagnosis of DS, and in older patients. Surgical approach and history of previous surgery were not significantly correlated with increased complication rates. On multivariate analysis, only the grade of spondylolisthesis was significantly associated with the occurrence of complications.

Gamma knife radiosurgery of meningiomas involving the foramen magnum.

BACKGROUND: Foramen magnum meningiomas represent a challenging clinical entity. Although resection is performed for those with a mass effect, complete resection is not always feasible. For some patients, stereotactic radiosurgery may be used as the primary treatment modality. We evaluatedthe long-term outcome of Gamma Knife radiosurgery (GKRS) for the treatment of patientswith a foramen magnum meningioma. MATERIALS AND METHODS: Between 1991 and 2005, 222 patients with a meningioma in the posterior fossa were treated with GKRS at the University of Virginia. Of these patients, 5 had meningiomas involving the foramen magnum. At the time of GKRS, the median age of the patients was 60 years (range, 51-78). Three patients were treated with radiosurgery following an initial resection and 2 were treated with upfront radiosurgery. The patients were assessed clinically and radiologically at routine intervals following GKRS. RESULTS: The median tumor volume was 6.8 cc (range 1.9-17 cc). The GKRS tumor received a marginal dose of 12 Gy (range 10-15), and the median number of isocenters was 5 (range 3-19). The mean follow-up was 6 years (range 4-13). One lesion increased in size following GKRS requiring a second treatment, resulting in size stabilization. At the time of the last follow-up, all meningiomas had either demonstrated no growth (n = 4) or reduction in size (n = 1). No patients experienced post-radiotherapy complications. CONCLUSIONS: GKRS affords a high rate of tumor control and preservation of neurologic function for patients with foramen magnum meningiomas. Further study of its role in the neurosurgical management of such patients seems warranted.

Extramedullary hematopoiesis within the clivus: an unusual cause of lower cranial nerve palsy.

We report one year follow up of a case of extramedullary hematopoiesis within the clivus. The imaging findings, brief clinical course, and endoscopic transphenoidal approach are described. A 29-year-old female with thalassemia developed worsening cranial nerve signs. After imaging studies discovered a large clival mass, she underwent endoscopic transphenoidal biopsy of the lesion. Neural compression from exuberant erythrogenesis within tissue normally quiescent of red blood cell production was found to be the etiology of her neural deficit. Treatment for this condition is generally non-operative unless significant neural compression is present. Radiotherapy and anti-neoplastic agents have been used with success.

Use of recombinant human bone morphogenetic protein-2 as an adjunct for instrumented posterior arthrodesis in the occipital cervical region: An analysis of safety, efficacy, and dosing.

BACKGROUND: There have been few reports on the use of recombinant human bone morphogenetic protein (rhBMP)-2 in posterior spine. However, no study has investigated the dosing, safety, and efficacy of its use in the posterior atlantoaxial, and/or craniovertebral junction. Recent case report of the cytokine-mediated inflammatory reaction, following off label use of rhBMP-2 as an adjunct for cervical fusion, particularly in complex cases, has increased concern about complications associated with the product. OBJECTIVE: To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior atlantoaxial and/or craniovertebral junction arthrodesis. MATERIALS AND METHODS: We included all patients treated by the senior author that included posterior atlantoaxial and/or craniovertebral junction instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum two year follow-up. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed. RESULTS: Twenty three patients with a mean age of 60.9 years (range 4 - 89 years) and an average follow-up of 45 months (range 27 to 84 months) met inclusion criteria. The indications for surgery included, atlantoaxial instability (n = 16), basilar invagination (n = 6), and kyphoscoliosis (n = 1). The specific pathologic diagnosis included type 2 dens fracture (n = 7), complex C1 and C2 ring fracture (n = 2), chordoma (n = 2), degenerative/osteoporosis (n = 3), rheumatoid disease (n = 8), and pseudogout (n = 1). The average rhBMP-2 dose was 2.38 mg/level, with a total of 76 levels treated (average 3.3 levels, SD= 1.4 levels). There were no complications. During the most recent follow-up, all patients had achieved fusion. CONCLUSIONS: In a series of patients with complex pathology and/or rheumatoid arthritis, 100% fusion rate was achieved with adjunct use of rhBMP-2, with a safe and effective average rhBMP-2 dose of 2.38 mg per level.

The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha.

In this study we addressed the role of sphingolipid metabolism in the inflammatory response. In a L929 fibroblast model, tumor necrosis factor-alpha (TNF) induced prostaglandin E2 (PGE2) production by 4 h and cyclooxygenase-2 (COX-2) induction as early as 2 h. This TNF-induced PGE2 production was inhibited by NS398, a COX-2 selective inhibitor. GC-MS analysis revealed that only COX-2-generated prostanoids were produced in response to TNF, thus providing further evidence of COX-2 selectivity. As sphingolipids have been implicated in mediating several actions of TNF, their role in COX-2 induction and PGE2 production was evaluated. Sphingosine-1-phosphate (S1P) induced both COX-2 and PGE2 in a dose-responsive manner with an apparent ED50 of 100-300 nM. The related sphingolipid sphingosine also induced PGE2, though with much less efficacy. TNF induced a 3.5-fold increase in sphingosine-1-phosphate levels at 10 min that rapidly returned to baseline by 40 min. Small interfering RNAs (siRNAs) directed against mouse SK1 decreased (typically by 80%) SK1 protein and inhibited TNF-induced SK activity. Treatment of cells with RNAi to SK1 but not SK2 almost completely abolished the ability of TNF to induce COX-2 or generate PGE2. By contrast, cells treated with RNAi to S1P lyase or S1P phosphatase enhanced COX-2 induction leading to enhanced generation of PGE2. Treatment with SK1 RNAi also abolished the effects of exogenous sphingosine and ceramide on PGE2, revealing that the action of sphingosine and ceramide are due to intracellular metabolism into S1P. Collectively, these results provide novel evidence that SK1 and S1P are necessary for TNF to induce COX-2 and PGE2 production. Based on these findings, this study indicates that SK1 and S1P could be implicated in pathological inflammatory disorders and cancer.