Molecular Genetic Approaches to Disease of Neural Development

This study utilized novel genetic techniques in order to find causative gene mutations that underlie diseases of neural development. Our laboratory has collected 175 cases of malformations of cortical development (MCD) from the United States and Europe. Four of these cases are the focus of this manuscript: two familial cases of infantile neuroaxonal dystrophy (INAD), a familial case of hereditary spastic paraparesis (HSP), and a sporadic case of Greig cephalopolysyndactyly (GCPS) and cerebral cavernous malformations (CCMs). The techniques utilized to study the affected patients include microarray-based single nucleotide polymorphism (SNP) genotyping and copy number variation (CNV) analysis, both of which are powerful tools in the hunt for disease-causing gene mutations. In the familial cases of INAD, we report two novel mutations in the PLA2G6 gene, previously shown to cause INAD when mutated. In the familial case of HSP, we demonstrate linkage to the SPG11 locus on chromosome 15q. Finally, in the sporadic case of GCPS and CCM, we published the first report on this novel syndrome along with a genetic analysis that demonstrates a microdeletion on chromosome 7p, resulting in heterozygous loss of both the GLI3 and CCM2 genes. The three studies presented in this manuscript demonstrate the utility of SNP genotyping and CNV analysis in revealing the genetic mutations that underlie diseases of neural development

Does Recombinant Human Bone Morphogenic Protein 2 Affect Perioperative Blood Loss after Lumbar and Thoracic Spinal Fusion?

Study Design Retrospective cohort design. Purpose This study aimed to determine whether recombinant human bone morphogenic protein 2 (rhBMP-2) reduces total perioperative blood loss during lumbar and thoracic fusion. Overview of Literature Previous studies on rhBMP-2 versus iliac crest bone grafting in thoracic and lumbar fusions have yielded mixed results regarding reductions in blood loss and have largely neglected the postoperative period when analyzing total blood loss. Additionally, these studies have been limited by heterogeneity and sample size. Methods We analyzed the blood loss patterns of 617 consecutive adult patients undergoing lumbar and/or thoracic fusions requiring subfascial drain placement at a single institution from January 2009 to December 2016. Patients were divided into BMP and non-BMP cohorts, and a propensity score analysis was conducted to account for the differences between cohorts. Results At a per-level fused basis, the BMP group exhibited a significant reduction in the intraoperative (66.1 mL per-level fused basis; 95% confidence interval [CI], 127.9 to 4.25 mL; p=0.036) and total perioperative blood loss (100.7 mL per-level fused basis; 95% CI, 200.9 to 0.5 mL; p=0.049). However, no significant differences were observed in an analysis when not controlling for the number of levels or when examining the postoperative drain output. Conclusion RhBMP-2 appears to reduce both intraoperative and total blood loss during lumbar and thoracic fusions on a per-level fused basis. This total reduction in blood loss was achieved via intraoperative effects because RhBMP-2 had no significant effect on the postoperative drain output

Incidence and Outcomes of Acute Implant Extrusion Following Anterior Cervical Spine Surgery.

STUDY DESIGN: Multi-institutional retrospective case series of 8887 patients who underwent anterior cervical spine surgery. OBJECTIVE: Anterior decompression from discectomy or corpectomy is not without risk. Surgical morbidity ranges from 9% to 20% and is likely underreported. Little is known of the incidence and effects of rare complications on functional outcomes following anterior spinal surgery. In this retrospective review, we examined implant extrusions (IEs) following anterior cervical fusion. METHODS: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of 21 predefined treatment complications. RESULTS: Following anterior cervical fusion, the incidence of IE ranged from 0.0% to 0.8% across 21 institutions with 11 cases reported. All surgeries involved multiple levels, and 7/11 (64%) involved either multilevel corpectomies or hybrid constructs with at least one adjacent discectomy to a corpectomy. In 7/11 (64%) patients, constructs ended with reconstruction or stabilization at C7. Nine patients required surgery for repair and stabilization following IE. Average length of hospital stay after IE was 5.2 days. Only 2 (18%) had residual deficits after reoperation. CONCLUSIONS: IE is a very rare complication after anterior cervical spine surgery often requiring revision. Constructs requiring multilevel reconstruction, especially at the cervicothoracic junction, have a higher risk for failure, and surgeons should proceed with caution in using an anterior-only approach in these demanding cases. Surgeons can expect most patients to regain function after reoperation

Does Subcutaneous Infiltration of Liposomal Bupivacaine Following Single-Level Transforaminal Lumbar Interbody Fusion Surgery Improve Immediate Postoperative Pain Control?

Study DesignRetrospective case-control study using prospectively collected data.PurposeEvaluate the impact of liposomal bupivacaine (LB) on postoperative pain management and narcotic use following standardized single-level low lumbar transforaminal lumbar interbody fusion (TLIF).Overview of LiteraturePoor pain control after surgery has been linked with decreased pain satisfaction and increased economic burden. Unfortunately, opioids have many limitations and side effects despite being the primary treatment of postoperative pain. LB may be a form of pre-emptive analgesia used to reduce the use of postoperative narcotics as evidence in other studies evaluating its use in single-level microdiskectomies.MethodsThe infiltration of LB subcutaneously during wound closure was performed by a single surgeon beginning in July 2014 for all single-level lumbar TLIF spinal surgeries at Landstuhl Regional Medical Center. This cohort was compared against a control cohort of patients who underwent the same surgery by the same surgeon in the preceding 6 months. Statistical analysis was performed on relevant variables including: morphine equivalents of narcotic medication used (primary outcome), length of hospitalization, Visual Analog Scale pain scores, and total time spent on a patient-controlled analgesia (PCA) pump.ResultsA total of 30 patients were included in this study; 16 were in the intervention cohort and 14 were in the control cohort. The morphine equivalents of intravenous narcotic use postoperatively were significantly less in the LB cohort from day of surgery to postoperative day 3. Although the differences lost their statistical significance, the trend remained for total (oral and intravenous) narcotic consumption to be lower in the LB group. The patients who received the study intervention required an acute pain service consult less frequently (62.5% in LB cohort vs. 78.6% in control cohort). The amount of time spent on a PCA pump in the LB group was 31 hours versus 47 hours in the control group (p=0.1506).ConclusionsLocal infiltration of LB postoperatively to the subcutaneous tissues during closure following TLIF significantly decreased the amount of intravenous narcotic medication required by patients. Well-powered prospective studies are still needed to determine optimal dosing and confirm benefits of LB on total narcotic consumption and other measures of pain control following major spinal surgery

Epidemiology and Outcomes of Vertebral Artery Injury in 16 582 Cervical Spine Surgery Patients: An AOSpine North America Multicenter Study.

STUDY DESIGN: A multicenter retrospective case series was compiled involving 21 medical institutions. Inclusion criteria included patients who underwent cervical spine surgery between 2005 and 2011 and who sustained a vertebral artery injury (VAI). OBJECTIVE: To report the frequency, risk factors, outcomes, and management goals of VAI in patients who have undergone cervical spine surgery. METHODS: Patients were evaluated on the basis of condition-specific functional status using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36). RESULTS: VAIs were identified in a total of 14 of 16 582 patients screened (8.4 per 10 000). The mean age of patients with VAI was 59 years (±10) with a female predominance (78.6%). Patient diagnoses included myelopathy, radiculopathy, cervical instability, and metastatic disease. VAI was associated with substantial blood loss (770 mL), although only 3 cases required transfusion. Of the 14 cases, 7 occurred with an anterior-only approach, 3 cases with posterior-only approach, and 4 during circumferential approach. Fifty percent of cases of VAI with available preoperative imaging revealed anomalous vessel anatomy during postoperative review. Average length of hospital stay was 10 days (±8). Notably, 13 of the 14 (92.86%) cases resolved without residual deficits. Compared to preoperative baseline NDI, Nurick, mJOA, and SF-36 scores for these patients, there were no observed changes after surgery (P = .20-.94). CONCLUSIONS: Vertebral artery injuries are potentially catastrophic complications that can be sustained from anterior or posterior cervical spine approaches. The data from this study suggest that with proper steps to ensure hemostasis, patients recover function at a high rate and do not exhibit residual deficits

The Role of Alginate Hydrogels as a Potential Treatment Modality for Spinal Cord Injury: A Comprehensive Review of the Literature

Objective To comprehensively characterize the utilization of alginate hydrogels as an alternative treatment modality for spinal cord injury (SCI). Methods An extensive review of the published literature on studies using alginate hydrogels to treat SCI was performed. The review of the literature was performed using electronic databases such as PubMed, EMBASE, and OVID MEDLINE electronic databases. The keywords used were “alginate,” “spinal cord injury,” “biomaterial,” and “hydrogel.” Results In the literature, we identified a total of 555 rat models that were treated with alginate scaffolds for regenerative biomarkers. Alginate hydrogels were found to be efficient and promising substrates for tissue engineering, drug delivery, neural regeneration, and cellbased therapies for SCI repair. With its ability to act as a pro-regenerative and antidegenerative agent, the alginate hydrogel has the potential to improve clinical outcomes. Conclusion The emerging developments of alginate hydrogels as treatment modalities may support current and future tissue regenerative strategies for SCI

Epidural Hematoma Following Cervical Spine Surgery.

STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. METHODS: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. CONCLUSION: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Duration of indwelling drain following instrumented posterolateral fusion of the lumbar spine does not predict surgical site infection requiring reoperation

The objective of this study was to determine the incidence and predictors of reoperation for surgical site infections (SSI) among patients whose lumbar, closed wound suction drains were removed in the inpatient setting prior to hospital discharge (pre-discharge cohort) versus after inpatient discharge during the first follow up visit (post-discharge cohort). All patients who were admitted for first-time, posterolateral decompression and fusion for degenerative lumbar spine disease were retrospectively reviewed at a single institution. In order to eliminate biases, neither the pre-discharge nor post-discharge cohorts experienced any intra-/postoperative sentinel events other than the primary outcome measure: reoperation for SSI. Of 209 patients in the pre-discharge (n=130) and post-discharge (n=79) cohorts, 15 patients required reoperation for SSI. Although time to drain discontinuation was significantly longer in the post-discharge (8.28days) than the pre-discharge (4.65days) cohorts (p\u3c0.001), the incidences of reoperation for SSI did not significantly differ (6.33 vs 7.69%, respectively, p=0.711). In a multivariable regression, only smoking (OR=5.75, p=0.007) and depression (OR=4.11, p=0.040) predicted reoperation for SSI. Neither time to drain removal nor setting of drain removal was a predictor of reoperation for SSI. Although time to drain discontinuation was expectedly longer in the post-discharge versus pre-discharge cohorts, the incidences of reoperation for SSI did not significantly differ. Neither time to drain removal nor setting of drain removal predicted reoperation for SSI. These results suggest that patients may be safely discharged from the hospital with the surgical drain in place