Cervical spine surgery for tandem spinal stenosis: The impact on low back pain

Objective Tandem spinal stenosis (TSS) can present similarly to cervical myelopathy, but often has a worse prognosis. Few studies have investigated outcomes and compared treatment approaches for patients with TSS. We sought to determine the impact of cervical spine surgery on cervical and lumbar spine symptoms in patients with symptomatic tandem spinal stenosis. Patients Methods 84 patients with TSS were identified over 5 years. 48 underwent cervical spine surgery alone, 20 underwent both cervical and lumbar spine surgery, and 16 received conservative treatment alone (conservative cohort). Quality of life (QOL) measures included the Visual Analogue Scale (VAS) for arm, neck, and back pain, and EuroQOL-5 Dimensions (EQ-5D). QOL data were acquired at baseline (pre-operative) and 1 year postoperatively via an institutional prospectively collected database. Results Both surgical cohorts showed significant (p < 0.01) pre- to postoperative improvement for VAS neck and arm scores at 1-year post-op and significantly (p < 0.01) greater improvements than the conservative cohort. In addition, the cohort undergoing cervical spine surgery alone experienced significant improvement in the EQ-5D score whereas those undergoing both cervical and lumbar spine surgery did not. Conclusions Cervical spine surgery with or without follow-up lumbar spine surgery significantly improves neck pain in patients with TSS. In contrast, cervical spine surgery in these patients does not improve lumbar symptoms. Lumbar surgery also did not improve low back pain or quality of life. Future prospective studies are necessary to examine the impact of lumbar decompression alone on cervical spine symptoms in patients with TSS

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

Quality of life changes after lumbar decompression in patients with tandem spinal stenosis

Objective Tandem spinal stenosis (TSS) is a degenerative spinal condition characterized by spinal canal narrowing at 2 or more distinct spinal levels. It is an aging-related condition that is likely to increase as the population ages, but which remains poorly described in the literature. Here we sought to determine the impact of primary lumbar decompression on quality-of-life (QOL) outcomes in patients with symptomatic TSS. Patients and methods We retrospectively reviewed 803 patients with clinical and radiographic evidence of TSS treated between 2008 and 2014 with a minimum 2-year follow-up. The records of patients with clinical and radiographic evidence of concurrent cervical and lumbar stenosis were reviewed. Prospectively gathered QOL data, including the Pain Disability Questionnaire (PDQ), Patient Health Questionnaire-9 (PHQ-9), EuroQOL-5 Dimensions (EQ-5D), and Visual Analogue Scale (VAS) for low back pain, were assessed at the 6-month, 1-year, and 2-year follow-ups. Results Of 803 identified patients (mean age 66.2 years; 46.9% male), 19.6% underwent lumbar decompression only, 14.1% underwent cervical + lumbar decompression, and 66.4% underwent conservative management only. Baseline VAS scores were similar across all groups, but patients undergoing conservative management had better baseline QOL scores on all other measures. Both surgical cohorts experienced significant improvements in the VAS, PDQ, and EQ-5D at all time points; patients in the cervical + lumbar cohort also had significant improvement in the PHQ-9. Conservatively managed patients showed no significant improvement in QOL scores at any follow-up interval. Conclusion Lumbar decompression with or without cervical decompression improves low back pain and QOL outcomes in patients with TSS. The decision to prioritize lumbar decompression is therefore unlikely to adversely affect long-term quality-of-life improvements

Incidental durotomy: predictive risk model and external validation of natural language process identification algorithm

OBJECTIVE Incidental durotomy is a common complication of elective lumbar spine surgery seen in up to 11% of cases. Prior studies have suggested patient age and body habitus along with a history of prior surgery as being associated with an increased risk of dural tear. To date, no calculator has been developed for quantifying risk. Here, the authors' aim was to identify independent predictors of incidental durotomy, present a novel predictive calculator, and externally validate a novel method to identify incidental durotomies using natural language processing (NLP).METHODS The authors retrospectively reviewed all patients who underwent elective lumbar spine procedures at a tertiary academic hospital for degenerative pathologies between July 2016 and November 2018. Data were collected regarding surgical details, patient demographic information, and patient medical comorbidities. The primary outcome was incidental durotomy, which was identified both through manual extraction and the NLP algorithm. Multivariable logistic regression was used to identify independent predictors of incidental durotomy. Bootstrapping was then employed to estimate optimism in the model, which was corrected for; this model was converted to a calculator and deployed online.RESULTS Of the 1279 elective lumbar surgery patients included in this study, incidental durotomy occurred in 108 (8.4%). Risk factors for incidental durotomy on multivariable logistic regression were increased surgical duration, older age, revision versus index surgery, and case starts after 4 PM. This model had an area under curve (AUC) of 0.73 in predicting incidental durotomies. The previously established NLP method was used to identify cases of incidental durotomy, of which it demonstrated excellent discrimination (AUC 0.97).CONCLUSIONS Using multivariable analysis, the authors found that increased surgical duration, older patient age, cases started after 4 PM, and a history of prior spine surgery are all independent positive predictors of incidental durotomy in patients undergoing elective lumbar surgery. Additionally, the authors put forth the first version of a clinical calculator for durotomy risk that could be used prospectively by spine surgeons when counseling patients about their surgical risk. Lastly, the authors presented an external validation of an NLP algorithm used to identify incidental durotomies through the review of free-text operative notes. The authors believe that these tools can aid clinicians and researchers in their efforts to prevent this costly complication in spine surgery

Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation

AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization