Faculty Bibliography

OBJECTIVE:Little is known about socioeconomic differences in postoperative outcomes after neurosurgery. We assessed the relation between insurance status and postoperative complication risk, neurosurgical intensive care unit stay, and hospital stay after neurosurgery. METHODS:We collected data on 918 consecutive craniotomy or spine-related neurosurgical cases in patients at least 18 years of age at the University of Michigan Hospitals after April 2006. Bivariate χ(2) tests and analysis of variance were used to assess bivariate relations, and multivariable logistic regression models and analysis of covariance were used to adjust for potential confounders. RESULTS:A total of 11.2% of privately insured patients, 23.6% of Medicare patients, 25.8% of Medicaid patients, and 27.3% of uninsured patients suffered complications within 30 days of surgery (P < 0.001). In adjusted models, odds of postoperative complications among Medicare (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.3-3.3), Medicaid (OR = 3.1, 95% CI 1.5-6.1), and uninsured patients (OR = 3.6. 95% CI 1.3-10.3) were higher than among privately insured patients. By analysis of covariance, only Medicaid patients had significantly longer intensive care unit (P = 0.040) and hospital stays (P = 0.028) than privately insured patients. CONCLUSIONS:Our findings suggest important socioeconomic disparities in outcomes after neurosurgical intervention. Access to postoperative outpatient care may mediate our findings.

STUDY DESIGN/METHODS: Comparative effectiveness review. STUDY RATIONALE/OBJECTIVE: Spinal fusion is believed to accelerate the degeneration of the vertebral segment above or below the fusion site, a condition called adjacent segment disease (ASD). The premise of dynamic stabilization is that motion preservation allows for less loading on the discs and facet joints at the adjacent, non-fused segments. In theory, this should decrease the rate of ASD. However, clinical evidence of this theoretical decrease in ASD is still lacking. We performed a systematic review to evaluate the evidence in the literature comparing dynamic stabilization with fusion. CLINICAL QUESTION/OBJECTIVE: In patients 18 years or older with degenerative disease of the cervical or lumbar spine, does dynamic stabilization lead to better outcomes and fewer complications, including ASD, than fusion in the short-term and the long-term? METHODS: A systematic search and review of the literature was undertaken to identify studies published through March 7, 2011. PubMed, Cochrane, and National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Two individuals independently reviewed articles based on inclusion and exclusion criteria which were set a priori. Each article was evaluated using a predefined quality-rating scheme. RESULTS: No significant differences were identified between fusion and dynamic stabilization with regard to VAS, ODI, complications, and reoperations. There are no long-term data available to show whether dynamic stabilization decreases the rate of ASD. CONCLUSIONS: There are no clinical data from comparative studies supporting the use of dynamic stabilization devices over standard fusion techniques.

Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, down-regulated Id-1 gene expression in aggressive human breast cancer cells in culture. Using cell proliferation and invasion assays, cell flow cytometry to examine cell cycle and the formation of reactive oxygen species, and Western analysis, we determined pathways leading to the down-regulation of Id-1 expression by CBD and consequently to the inhibition of the proliferative and invasive phenotype of human breast cancer cells. Then, using the mouse 4T1 mammary tumor cell line and the ranksum test, two different syngeneic models of tumor metastasis to the lungs were chosen to determine whether treatment with CBD would reduce metastasis in vivo. We show that CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression.

Before the advent of minimally invasive spine surgery (MIS), open transforaminal lumbar interbody fusion (TLIF) was performed to treat spondylosis, spondylolisthesis, and spondylolysis. Minimally invasive TLIF has recently become more popular based upon the premise that a smaller, less traumatic incision should afford better recovery and outcomes. However, the learning curve associated with this technique must be considered. To analyze the perioperative factors associated with the learning curve in patients who underwent MIS TLIF versus open TLIF, we identified 22 patients who underwent TLIF from 2005 to 2008 within levels L4-S1 by the senior author (D.C.). Patients were subdivided into two groups according to whether they underwent: (i) MIS TLIF (10 patients, the first MIS TLIF procedures performed by D.C.); or (ii) open TLIF (12 patients). Preoperative, perioperative and postoperative factors were evaluated. Patients who underwent MIS TLIF had a statistically significant lower intraoperative transfusion rate, and rate of required postoperative surgical drains; and shorter periods of required drainage, and time to ambulation. However, the MIS TLIF group tended to have a higher rate of complications, which might have been associated with the learning curve. Both groups had a minimum of 1-year follow-up.

BACKGROUND:Anterior approaches for thoracolumbar corpectomies can have significant morbidity. Spine surgeons have historically performed their own anterior approaches, but recently access surgeons are being used more frequently. OBJECTIVE:To evaluate the morbidity rates of approaches performed by an access surgeon and by an approach-trained spinal neurosurgeon. METHODS:From 2004 to 2008, 46 patients undergoing anterior thoracolumbar corpectomies (levels T2-L5) by the senior author (D.C.) were identified and subdivided into 2 groups based on whether an access surgeon was involved. Nine patients were excluded, leaving 37 patients in the final analysis. Blood loss, operative times, length of hospital stay, complications, and neurological outcomes were evaluated. RESULTS:Eighteen patients had anterior spinal access by an approach-trained spinal neurosurgeon, and 19 patients underwent the approach by an access surgeon. Surgeries performed by the spinal neurosurgeon alone were comparable to those performed by an access surgeon with respect to operative time, days spent in the hospital, blood loss, complication rates, and improvement in neurological function. CONCLUSION/CONCLUSIONS:There appears to be no increased morbidity of anterior approaches performed by an approach-trained spinal neurosurgeon compared with approaches performed by an access surgeon in terms of operative time, complication rate, and improvement in neurological function.

BACKGROUND CONTEXT/BACKGROUND:Intracranial hypotension typically occurs spontaneously. Acquired or secondary intracranial hypotension is less common but has been reported after spinal procedures, such as lumbar puncture. Cranial nerve (CN) III palsy is a rare sequela of intracranial hypotension. There are currently no established or standard interventions to treat intracranial hypotension. PURPOSE/OBJECTIVE:To describe a case of delayed CN III palsy resulting from intracranial hypotension because of a spinal cerebrospinal fluid (CSF) leak occurring during resection of a paraspinous tumor. STUDY DESIGN/METHODS:Case report. METHODS:A 41-year-old woman underwent resection of a large thoracic schwannoma complicated by dural tear. Postoperatively, the patient was neurologically normal. She subsequently became acutely unresponsive and required reintubation. She awakened with intermittent headaches and was noted to have a right ptosis, which progressed to a complete right CN III palsy. RESULTS:Initial head computed tomography showed evidence of a small, right-sided subdural hematoma. Magnetic resonance imaging (MRI) of the brain showed diffuse leptomeningeal enhancement and crowding of the foramen magnum consistent with intracranial hypotension. The patient's symptoms were treated successfully with flat bed rest. She fully recovered by time of discharge and at 6-month follow-up was neurologically normal. CONCLUSIONS:Spinal surgery complicated by CSF leak is a potential cause of intracranial hypotension. Although most commonly associated with positional headaches, intracranial hypotension can cause uncommon symptoms, including acute mental status changes and CN deficits. Symptoms highly suspicious for intracranial hypotension accompanied by MRI of the brain are important for establishing a diagnosis of intracranial hypotension. Conservative treatment should be considered before attempting invasive intervention. As in the case presented, simple bed rest was a successful treatment option.

STUDY DESIGN/METHODS:Systematic review using a modified network analysis. OBJECTIVES/OBJECTIVE:To compare the effectiveness and morbidity of interspinous-device placement versus surgical decompression for the treatment of lumbar spinal stenosis. SUMMARY/CONCLUSIONS: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/CONCLUSIONS: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.

Before the advent of minimally invasive surgery for microdiscectomy, an open microdiscectomy had been the standard surgical intervention. Minimally invasive techniques have recently become more popular based upon the premise that smaller, less traumatic incisions should afford better recovery times and outcomes. From 2005 to 2008 we analyzed the outcomes of 25 patients who received an open microdiscectomy compared to 20 patients who received a minimally invasive microdiscectomy by the senior author (DC) in the lumbar region for disc herniation. A retrospective analysis was performed by carefully reviewing medical records for perioperative and immediate postoperative outcomes, and clinical follow-up was obtained either in the clinic or by telephone. There were no statistically significant differences between the minimally invasive and open groups in terms of operative time, length of stay, neurological outcome, complication rate, or change in pain score (pain improvement).

OBJECT/OBJECTIVE:Whereas standard anterior approaches for thoracolumbar corpectomies have commonly been used, the transpedicular technique is increasingly used to perform corpectomies from a posterior approach. The authors conducted a study to analyze whether there was a difference in outcomes by comparing transpedicular corpectomies to standard anterior thoracolumbar corpectomies. METHODS:The senior author performed thoracolumbar corpectomies in 80 patients between 2004 and 2008. The authors reviewed medical records and follow-up data, consisting of clinic visits, radiographs, or telephone interviews. Neurological outcome, complications, operative times, revision surgery rates, and estimated blood loss (EBL) were evaluated. RESULTS:Thirty-four patients underwent transpedicular corpectomies, and 46 patients underwent anterior thoracolumbar approaches. Single-level transpedicular corpectomies appear to be comparable to anterior-only corpectomies in terms of EBL, operative time, and complication rates. There was a higher complication rate, increased EBL, and longer operative time with anterior-posterior corpectomies compared with transpedicular corpectomies. Patients undergoing transpedicular corpectomies had a greater recovery of neurological function than those in whom anterior-approach corpectomies were performed. CONCLUSIONS:The transpedicular corpectomy appears to have a comparable morbidity rate to anterior-only corpectomies, but its morbidity rate is lower than that of anterior-posterior corpectomies.

The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors, can modulate the actions of Delta(9)-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Delta(9)-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of Delta(9)-THC in the treatment of glioblastoma in cancer patients.