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Competing Interests: I report funding from the National Institute of Aging (R03AG075434), one of the institutes of National Institute of Health, as well as honoraria from Advanced Practice Providers Oncology Summit.

Neurodegenerative diseases (NDDs) encapsulate conditions in which neural cell populations are perpetually degraded and nervous system function destroyed. Generally linked to increased age, the proportion of patients diagnosed with a NDD is growing as human life expectancies rise. Traditional NDD therapies and surgical interventions have been limited. However, recent breakthroughs in understanding disease pathophysiology, improved drug delivery systems, and targeted pharmacologic agents have allowed innovative treatment approaches to treat NDDs. A common denominator for administering these new treatment options is the requirement for neurosurgical skills. In the present narrative review, we highlight exciting and novel preclinical and clinical discoveries being integrated into NDD care. We also discuss the traditional role of neurosurgery in managing these neurodegenerative conditions and emphasize the critical role of neurosurgery in effectuating these newly developed treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Context: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease that can lead to significant functional disability. Improving treatment regimens have extended life expectancy and led to an increase in the number of elective spine surgeries for degenerative conditions in the MS population. Recent literature has reported mixed results regarding the efficacy of elective spine surgery for patients with MS. There is also a paucity of literature comparing postoperative patient reported outcomes (PROs) and reoperation rates between patients with and without MS., Purpose: To determine if patients with MS have worse PROs and higher complication, readmission and reoperation rates after elective spine surgery compared with patients without neurodegenerative conditions when adjusting for baseline covariates through propensity matching., Study Design/setting: Retrospective review of prospectively collected data from the Quality Outcomes Database (QOD), a national, longitudinal, multicenter spine outcomes registry., Patient Sample: For the lumbar cohort, 312 patients with MS and 46,738 patients without MS were included. The cervical myelopathy cohort included 91 patients with MS and 6,426 patients without MS. The cervical radiculopathy cohort consisted of 103 patients with MS and 13,751 patients without MS., Outcome Measures: 1) complication rates, 2) readmission rates, 3) reoperation rates, and 4) PROs at 3- and 12-months including ODI/NDI, NRS back/neck/arm/leg pain, mJOA scores and patient satisfaction ratings., Methods: Data from the QOD was queried for patients with surgeries occurring between 04/2013-01/2019. Three surgical groups were included: 1) Elective lumbar surgery, 2) Elective cervical surgery for myelopathy, 3) Elective cervical surgery for radiculopathy. Patients with any neurodegenerative condition other than MS were excluded. Patients without MS were propensity matched against patients with MS in a 5 to 1 ratio without replacement based on ASA grade, arthrodesis, surgical approach, number of operated levels, age, and baseline ODI/NDI, NRS leg/arm pain, NRS back/neck pain, and EQ-5D. Multivariable regressions with cluster-robust standard errors were used to estimate average effect of how the outcome would change if the MS patient didn't have the disease. The mean difference was used for continuous outcomes and the risk difference was used for binary outcomes., Results: For the lumbar cohort, no differences were found between the 2 groups at 3 or 12 months in any of the outcome measures. For the myelopathy cohort, patients with MS patients had a lower rate of reoperation at 12 months (risk difference=-0.036, p=.007) and worse 3-month mJOA scores (mean difference=-1.044, p=.004) compared with patients without MS. For the radiculopathy cohort, patients with MS had a lower rate of reoperation at 3 months (risk difference=-0.019, p=.018) and 12 months (risk difference=-0.029, p=.007) compared with those without MS., Conclusions: Patients with MS had similar PROs compared with patients without MS when adjusting for baseline covariates through propensity matching, except for 3-month mJOA scores in the myelopathy cohort. Reoperation rates were found to be lower in patients with MS undergoing elective cervical surgery for both myelopathy and radiculopathy. These results suggest that when analyzed independently, a diagnosis of MS does not significantly impact complication, readmission and reoperation rates or PROs, and therefore should not represent a major contraindication to elective spine surgery. Surgical decisions in this patient population should be made based on careful consideration of patient factors including other comorbidities as well as baseline patient functional status., Competing Interests: Declaration of Competing Interest Dr. Jacquelyn Pennings reports a past contract with NeuroPoint Alliance Inc. as well as consulting fees from Steamboat Orthopaedic Spine Institute and 3Spine. Dr. Kristin Archer reports a past contract with NeuroPoint Alliance Inc., past consulting fees from Pacira, current consulting fees from NeuroSpinal Innovation Inc and honorarium from Spine as an editorial board member. Dr. Hui Nian reports a past contract with NeuroPoint Alliance Inc. Dr. Zuckerman reports being an unaffiliated neurotrauma consultant for the National Football League. Dr. Stephens reports educational consulting for Medical Device Business Services and a grant from Stryker Spine [R1160501]. For the remaining authors, none were declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Degenerative diseases alter brain activity and functional connectivity. In this issue of the Neuroscience Letters, Yin and others (2021) [6] present data showing increased activity in lobules VIII and IX of the cerebellar vermis in Parkinson's patients with visuospatial disorders. The study refines the fMRI mapping of the cerebellum, but the functional interpretation of the findings remains complex. The architecture and connectivity of the cerebellum set it apart from the rest of the brain and should be considered when interpreting the functional connectivity data. In degenerative diseases, the cerebellum suffers from the same pathology as the cerebral cortex; hence, it is unlikely that changes in the cerebellum could ameliorate clinical symptoms in degenerative diseases. Clinical, surgical data indicate that the primary function of the cerebellum is motor, not cognition or affective. The cerebellar anatomy buttresses these observations. The cerebellum receives direct motor-related inputs but no direct information from the sensory system. Hence, it likely contributes to the behavioral components of emotions and cognition., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Degenerative cervical myelopathy (DCM) is the most common cause of nontraumatic spinal cord injury in adults worldwide. Surgical decompression is generally effective in improving neurological outcomes and halting progression of myelopathic deterioration. However, a subset of patients experience suboptimal neurological outcomes. Given the emerging evidence that apolipoprotein E4 (ApoE4) allelic status influences neurodegenerative conditions, we examined whether the presence of the ApoE4 allele may account for the clinical heterogeneity of treatment outcomes in patients with DCM. Our results demonstrate that human ApoE4+ DCM patients have a significantly lower extent of improvement after decompression surgery. Functional analysis of our DCM mouse model in targeted-replacement mice expressing human ApoE4 revealed delayed gait recovery, forelimb grip strength, and hind limb mechanical sensitivity after decompression surgery, compared with their ApoE3 counterparts. This was accompanied by an exacerbated proinflammatory response resulting in higher concentrations of TNF-α, IL-6, CCL3, and CXCL9. At the site of injury, there was a significant decrease in gray matter area, an increase in the activation of microglia/macrophages, and increased astrogliosis after decompression surgery in the ApoE4 mice. Our study is the first to our knowledge to investigate the pathophysiological underpinnings of ApoE4 in DCM, which suggests a possible personalized medicine approach for the treatment of DCM in ApoE4 carriers.

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease).

The aim of this study was to capture and understand the immediate recovery journey of patients following lumbar spinal fusion surgery and explore the interacting constructs that shape their journey. A qualitative study using Interpretive Phenomenological Analysis (IPA) approach. A purposive sample of 43 adult patients (≥16 years) undergoing ≤4 level instrumented fusion for back and/or leg pain of degenerative cause, were recruited pre-surgery from 4 UK spinal surgery centres. Patients completed a weekly diary expressed in their own words for the first 4 weeks following surgery to capture their life as lived. Diary content was based on previous research findings and recorded progress, recovery, motivation, symptoms, medications, healthcare appointments, rehabilitation, positive/negative thoughts, and significant moments; comparing to the previous week. To maximise completion and data quality, diaries could be completed in paper form, word document, as online survey or as audio recording. Strategies to enhance diary adherence included a weekly prompt. A framework analysis for individual diaries and then across participants (deductive and inductive components) captured emergent themes. Trustworthiness was enhanced by strategies including reflexivity, attention to negative cases and use of critical co-investigators. Twenty-eight participants (15 female; n = 18 (64.3%) aged 45-64) contributed weekly diaries (12 withdrew post-surgery, 3 did not follow through with surgery). Adherence with diaries was 89.8%. Participants provided diverse and vivid descriptions of recovery experiences. Three distinct recovery trajectories were identified: meaningful recovery (engagement in physical and functional activities to return to functionality/mobility); progressive recovery (small but meaningful improvement in physical ability with increasing confidence); and disruptive recovery (limited purpose for meaningful recovery). Important interacting constructs shaped participants' recovery including their pain experience and self-efficacy. This is the first account of immediate recovery trajectories from patients' perspectives. Recognition of a patient's trajectory may inform patient-centred recovery, follow-up and rehabilitation to improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

Neurodegenerative diseases are caused by a loss of neurons within the peripheral or central nervous system. Inadequate repairability in the central nervous system and failure of treatments are the significant hurdles for several neurological diseases. The regenerative potential of stem cells drew the attention of researchers to cell-based therapy for treating neurodegenerative diseases. The clinical application of stem cells may help to substitute new cells and overcome the inability of the endogenous repairing system to repair the damaged brain. However, the clinical application induced pluripotent stem cells are restricted due to the risk of tumor formation by residual undifferentiated upon transplantation. In this focused review, we briefly discussed different stem cells currently being studied for therapeutic development. Moreover, we present supporting evidence for the utilization of stem cell therapy for the treatment of neurodegenerative diseases. Also, we described the key issues that should be considered to transplantation of stem cells for different neurodegenerative diseases. In our conclusion, stem cell therapy probably would be the only treatment strategy that offers a cure for neurodegenerative disease. Although, further study is required to identify ideal stem cells candidate, dosing and the ideal method of cell transplantation. We suggest that all grafted cells would be transgenically armed with a molecular kill-switch that could be activated by the event of adverse side effects.

MINI: In this study we analyze rates of readmission, and the timing and reasons for readmission after one to two level anterior cervical decompression and fusion. Among 18,833 patients who underwent anterior cervical decompression and fusion, 3% were readmitted to the hospital within 30 days. 39.5% of readmissions were for reasons related to surgical site., Study Design: Retrospective review of a national database., Objective: In this study we analyze rates of readmission, and the timing and reasons for readmission after one to two level anterior cervical decompression and fusion (ACDF)., Summary of Background Data: The safety profile of ACDF has been previously described with readmission rates typically between 2% and 4%. However no studies have investigated the primary diagnoses driving readmission, and whether these diagnoses are related to the surgical site., Methods: Demographics, comorbidities, and procedural characteristics were collected for all patients undergoing one or two-level ACDF for degenerative indications identified by Current Procedural Terminology (CPT) coding in the National Surgical Quality Improvement Program (NSQIP) database. The incidence of 30-day complications and readmissions was calculated, and the reasons for readmission as well as the timing of readmission were reviewed. Multivariate logistic regression analyses were performed to identify risk factors associated with complications or readmissions within 30 days of surgery., Results: Eighteen thousand eight hundred thirty three patients underwent ACDF (15,464 single-level and 3369 two-level, mean age 53.7 yrs, standard deviation [SD]: 11.6; 50% male). Postoperative complication rate of was 4.3% in two-level fusions and 3.5% in single-level fusion (P = 0.027). Five hundred sixty nine unplanned readmissions were identified (3.0%), of which 39.5% were related to the surgical site and 49.7% were unrelated to the surgical site (10.5% unknown cause of readmission). The most frequent reason for 30-day readmission was pneumonia (9.3%, mean time to readmission of 11.3 d) followed by dysphagia (7.4%, 6.3 d), and acute postoperative pain (7.2%, 11.4 d)., Conclusion: In this nationwide analysis of 18,833 ACDF cases, 3.0% of patients were readmitted within 30 days, of which at least 49.7% were for reasons unrelated to the surgical site., Level of Evidence: 3.

A 20-year-old man with a rare neurodegenerative disease developed hypermetabolic symptoms with dyskinesia after a third ventriculostomy for hydrocephalus. The initial presentation was concerning for an acute dystonic reaction after metoclopramide was administered for nausea. He concurrently developed hypermetabolic symptoms, including hyperthermia, tachycardia, and a lactic acidosis. The diagnosis was broadened to include neuroleptic malignant syndrome, serotonin syndrome, and malignant hyperthermia. Although perhaps less intellectually satisfying but more true to clinical reality, we did not isolate a single diagnosis but treated effectively all 3 with dantrolene sodium and benzodiazepine.

MINI: Postsurgical foot complaints occurred frequently in 853 degenerative lumbar surgeries (prevalence, 20.6%; n = 176). Risk factor analysis showed that the incidence of postsurgical foot complaint was significantly higher in patients with preoperative foot symptoms (adjusted odds ratio, 5.532) and in those with preoperative sensory deficits on the leg (adjusted odds ratio, 1.904)., Study Design: Retrospective., Objective: To investigate the prevalence and risk factors of postsurgical foot complaints (PFCs) following spinal surgery by using a modified pain drawing (PD) instrument., Summary of Background Data: Although many patients report nonspecific foot symptoms with various clinical presentation, there is not a well defined diagnostic criterion. PDs are essential for measuring spinal surgery outcomes. We created a modified patient-physician communication-based PD instrument to overcome the limitations of the previous system., Methods: We included 853 consecutive patients who underwent decompression with or without fusion. PFCs were defined as sensory foot symptoms, including ambiguous sensations that were not clearly due to spinal pathology. Patients who complained of postoperative foot symptoms at more than two consecutive visits were assigned to the PFC group. The remaining patients were assigned to the asymptomatic group. We collected medical records using our PD instrument and compared variables between the two groups., Results: In total, 176 (20.6%) of the 853 patients had PFCs. The duration of preoperative leg pain was significantly longer in the PFC group than in the asymptomatic group (2.8 vs. 2.2 years; P = 0.048). The proportions of preoperative foot symptoms (82.9% vs. 43.3%) and sensory deficits on the leg (48.6% vs. 27%) were significantly greater in the PFC group than in the asymptomatic group (P < 0.001). Multivariable logistic regression analysis revealed two independent risk factors: the presence of preoperative foot symptoms (adjusted odds ratio, 5.532) and preoperative sensory deficits on the leg (adjusted odds ratio, 1.904)., Conclusion: PFCs occurred frequently after degenerative lumbar spinal surgery (prevalence, 20.6%). Based on our data using PD instrument, it can help reduce the incidence of PFCs if patients are informed and educated that preoperatively existing foot symptom and sensory deficits on the leg are significant risk factors for PFC development., Level of Evidence: 4.

Study Design: Retrospective analysis., Objective: To investigate the prevalence of osteoporosis (OP) in patients undergoing lumbar fusion for lumbar degenerative diseases (LDD)., Summary of Background Data: OP is related to many complications after lumbar fusion for patients with LDD. There are sparse data on the prevalence of OP among this specific population. Moreover, LDD can falsely elevate the bone mineral density measured by dual energy x-ray absorptiometry (DXA), leading to unreliable diagnostic results. Computed tomography (CT) Hounsfield unit (HU) values can help identify osteoporotic patients undetected by DXA., Methods: A total of 479 patients aged≥50 years undergoing lumbar fusion for LDD were reviewed. The diagnosis of OP using DXA was based on World Health Organization criterion. The criterion for OP diagnosed on CT scan was the L1-HU value≤110., Results: The prevalence of OP diagnosed on lumbar DXA, hip DXA, and both was 32.4%, 19.6%, 39.7%, respectively. The females had higher prevalence of OP diagnosed on DXA (spine and hip) than males (48.9% vs. 27.1%, P < 0.001). In females but not males, the prevalence of OP significantly increased with age (females, 50-59: 28.0%, 60-69: 58.1%, ≥70: 78.8%, P < 0.001). Patients having primary diagnosis of degenerative lumbar scoliosis had the higher prevalence of OP than the rest patients (56.5% vs. 36.8%, P = 0.002). Among the 324 patients diagnosed with non-OP by lumbar DXA, the prevalence of OP diagnosed on CT scan was 25.9%, it increased with age and was also highest in patients with degenerative lumbar scoliosis., Conclusion: OP was quite common among patients aged≥50 years undergoing lumbar fusion for LDD, especially for females aged≥60 years or patients having degenerative lumbar scoliosis. Older patients or patients having degenerative lumbar scoliosis are more likely to have unreliable lumbar T-scores. Measurements of HU values can help identify more osteoporotic patients in this population., Level of Evidence: 3.

Objective: To investigate the treatment of iatrogenic cerebrospinal fluid (CSF) leak that develops after degenerative lumbar spinal surgery with a subfascial drainage and clipping (SDC) technique., Methods: This study retrospectively reviewed the medical records of 46 patients who developed iatrogenic CSF leak after surgery for lumbar degenerative spine disease from 2007 to 2019. Twenty-five patients were treated with the SDC procedure (SDC group), whereas 21 were not (control group). Outcomes were compared between the two groups., Results: CSF leakage ceased within 6-9 days (average 7.4+/-1) after the procedure in the SDC group. In the control group, CSF leakage was controlled with conservative measures in 14 patients, and in 7 patients, lumbar external drainage was performed. Among these 7, the CSF leak was controlled by lumbar external drainage in 3, and 4 required reoperation to repair the dural defect. No infection occurred in either group. Length of hospital stay was also shorter in SDC group (8.4+/-1 vs 10.0+/-1.3 days, p less than 0.001)., Conclusion: The SDC technique is effective for the treatment of iatrogenic CSF leak that develops after degenerative lumbar spinal surgery.

Background: Multiple studies have established the safety and efficacy of surgical intervention for degenerative cervical myelopathy (DCM). Although the main goal of surgery is symptom stabilization, a subset of patients achieves remarkable improvements., Objective: To identify predictors of return to normal neurological function after surgery for moderate or severe DCM., Methods: This is an analysis of 2 prospective multicenter studies (the AOSpine CSM-North America and CSM-International studies) conducted between 2005 and 2011. For patients with complete preoperative magnetic resonance imaging (MRI) and 2-yr follow-up, characteristics were compared between those who achieved a modified Japanese Orthopaedic Association (mJOA) score of 18 at 2 yr (no signs of myelopathy) vs controls. Only patients with baseline mJOA ≤ 14 (moderate and severe myelopathy) were included to minimize ceiling effects., Results: A total of 51 patients (20.3%) out of 251 with moderate or severe baseline myelopathy achieved an mJOA score of 18 at 2 yr. On stepwise multiple logistic regression analysis, T1-weighted (T1W1)-hypointensity (odds ratio [OR] 0.10; 95% confidence interval [CI], 0.01-0.79; P = .03) and longer walking time on the 30-m walking test (OR 0.95; 95% CI, 0.92-0.99; P = .03) were independent predictors of outcome, with an area under the curve of 0.71 for the model., Conclusion: In this study, T1W-hypointensity on MRI and longer walking time were found to predict a less likelihood of achieving return to normal neurological function after surgery for moderate or severe DCM. These findings may provide useful information for patient counseling and perioperative expectations., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: Degenerative lumbar spine disorders are common among musculoskeletal disorders. When disabling pain and radiculopathy persists after adequate course of rehabilitation and imaging confirms compressive pathology, surgical decompression is indicated. Prehabilitation aiming to augment functional capacity pre-surgery may improve physical function and activity levels pre and post-surgery. This study aims to evaluate the effect and dose-response of pre-surgery physiotherapy on quadriceps femoris strength and walking ability in patients with degenerative lumbar spine disorders compared to waiting-list controls and their association with postoperative physical activity level., Method: In this single blinded, 2-arm randomised controlled trial, 197 patients were consecutively recruited. Inclusion criteria were: MRI confirmed diagnosis and scheduled for surgery due to disc herniation, lumbar spinal stenosis, degenerative disc disease or spondylolisthesis, ages 25-80 years. Patients were randomised to 9 weeks of pre-surgery physiotherapy or to waiting-list. Patient reported physical activity level, walking ability according to Oswestry Disability Index item 4, walking distance according to the SWESPINE national register and physical outcome measures including the timed ten-meter walk test, maximum voluntary isometric quadriceps femoris muscle strength, patient-rated were collected at baseline and follow-up. Parametric or non-parametric within and between group comparisons as well as multivariate regression was performed., Results: Patients who received pre-surgery physiotherapy significantly improved in all variables from baseline to follow-up (p < 0.001 - p < 0.05) and in comparison to waiting-list controls (p < 0.001 - p < 0.028). Patients adhering to ≥12 treatment sessions significantly improved in all variables (p < 0.001 - p < 0.032) and those receiving 0-11 treatment session in only normal walking speed (p0.035) but there were no significant differences when comparing dosages. Physical outcome measures after pre-surgery physiotherapy together significantly explain 27.5% of the variation in physical activity level 1 year after surgery with pre-surgery physical activity level having a significant multivariate association., Conclusion: Pre-surgery physiotherapy increased walking ability and lower extremity strength in patients with degenerative lumbar spine disorders compared to waiting-list controls. A clear treatment dose-response response relationship was not found. These results implicate that pre-surgery physiotherapy can influence functional capacity before surgical treatment and has moderate associations with maintained postoperative physical activity levels mostly explained by physical activity level pre-surgery., Trial Registration: NCT02454400 . Trial registration date: August 31st 2015, retrospectively registered.

Background: Conventional posterior open lumbar surgery is associated with considerable trauma to the paraspinal muscles. Severe damage to the paraspinal muscles could cause low back pain (LBP), resulting in poor functional outcomes. Thus, several studies have proposed numerous surgical techniques that can minimize damage to the paraspinal muscles, particularly unilateral laminotomy for bilateral decompression. The purpose of this study is to compare the degree of postoperative LBP, functional outcome, and quality of life of patients between bilateral decompression via unilateral laminotomy (BDUL; group U) and conventional laminectomy (CL; group C)., Methods: Of 87 patients who underwent diagnostic and decompression surgery, 50 patients who met the inclusion and exclusion criteria and were followed up for > 2 years were enrolled. The patients were asked to record their visual analog scale pain score after 6, 12, and 24 months postoperatively. BDUL was used for group U, whereas CL was used for group C. The patients were randomly divided based on one of the two techniques, and they were followed up for over 2 years. Functional outcomes were assessed by the Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), and SF-36., Results: Operation time was significantly shorter in group U than in group C (p = 0.003). At 6, 12, and 24 months, there was no significant difference between the two groups in terms of spine-related pain (all p > 0.05). Functional outcomes using ODI and RMDQ and quality of life using SF-36 were not significantly different between the groups (all p > 0.05)., Conclusions: Regarding single-level decompression for degenerative lumbar spinal stenosis, group U had the advantages of shorter operation time than group C, but not in terms of back pain, functional outcome, and quality of life.

Introduction : The importance of excessive cerebral tumor necrosis factor (TNF) concentrations as one of the central tenets of the pathogenesis of the neurodegenerative diseases is now widely known, but variably accepted. Areas covered : Here we update the field by including material that is freely available on the large databases, particularly PubMed. We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,6 1 -dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. Expert opinion : Remarkably, considering the ample literature that links SB623 cells, maraviroc, MCC950 and irisin to TNF, these publications do not mention this cytokine, and therefore not their implicit involvement with controlling its cerebral levels. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity.

Objectives: Degenerative cervical myelopathy (DCM) presents insidiously, making initial diagnosis challenging. Surgery has been shown to prevent further disability but existing spinal cord damage may be permanent. Delays in surgery lead to increased disability and reduced postoperative improvements. Therefore, rapid surgical assessment is key to improving patient outcomes. Unfortunately, diagnosis of DCM in primary care is often delayed. This study aimed to characterise patients with DCM route to diagnosis and surgical assessment as well as to plot disease progression over time., Design: Retrospective, observational cohort study., Setting: Single, tertiary centre using additional clinical records from primary and secondary care centres., Participants: One year of cervical MRI scans conducted at a tertiary neurosciences centre (n=1123) were screened for cervical cord compression, a corresponding clinical diagnosis of myelopathy and sufficient clinical documentation to plot a route to diagnosis (n=43)., Primary Outcome Measures: Time to diagnosis from symptom onset, route to diagnosis and disease progression were the primary outcome measures in this study. Disease severity was approximated using a prospectively validated method for inferring modified Japanese Orthopaedic Association (i-mJOA) functional scoring from clinical documentation., Results: Patients received a referral to secondary care 6.4±7.7 months after symptom onset. Cervical MRI scanning and neurosurgical review occurred 12.5±13.0 and 15.8±13.5 months after symptom onset, respectively. i-mJOA was 16.0±1.7 at primary care assessment and 14.8±2.5 at surgical assessment. 61.0% of patients were offered operations. For those who received surgery, time between onset and surgery was 22.1±13.2 months., Conclusions: Route to surgical assessment was heterogeneous and lengthy. Some patients deteriorated during this period. This study highlights the need for a streamlined pathway by which patients with cervical cord compression can receive timely assessment and treatment by a specialist. This would improve outcomes for patients using existing treatments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objective: To compare the clinical accuracy and perioperative outcomes for pedicle screw placement in transforaminal lumbar interbody fusion (TLIF) between the robot-assisted (RA) technique and fluoroscopy-guided (FG) technique., Methods: Seventy-seven patients scheduled to undergo RA (n = 43) and FG (n = 44) TLIF surgery were included. Patient demographics, radiographic accuracy, and perioperative outcomes were recorded and compared. The accuracy of pedicle screw placement was according to the Gertzbein and Robbins scale and facet joint violation. Perioperative outcomes mainly included operative time, radiation exposure, and revisions., Results: Of the 176 screws in the RA group, 164 screws were grade A, and 9, 2, and 1 screws were grades B, C, and D, respectively. Of the 204 screws in the FG group, 175 screws were grade A, with 16 screws scored as grade B, 8 screws scored as grade C, 3 screws scored as grade D, and 2 screws scored as grade E. The rate of perfect screw position (grade A) was higher in the RA group than in the FG group (93.2% vs. 85.8%, respectively; P = 0.020). In the FG group, 191 screws (93.6%) were clinically acceptable (groups A and B), whereas more acceptable screw positions were achieved in the RA group (98.3%; P = 0.024). Fewer screws in the RA group violated the proximal facet joint (5 vs. 24 screws, respectively; P = 0.001). The radiation dose was lower in the RA group (25.9 ± 14.2 vs. 70.5 ± 27.3 μSv, respectively; P < 0.001). Two screws in the FG group required a revision, but no revision was required in the RA group., Conclusions: RA pedicle screw placement is an accurate and safe procedure in TLIF for lumbar degenerative disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To examine the subsidence rate in patients undergoing extreme lateral interbody fusion (XLIF) using data from a 2-year retrospective study to assess the effect of supplemental fixation on the stand-alone procedure., Methods: Demographic and perioperative data for all patients who underwent XLIF for degenerative lumbar disorders between June 2012 and January 2016 were collected and divided into 4 groups: the stand-alone (SA), lateral fixation, unilateral pedicle screw, and bilateral pedicle screw (BPS) groups. The disk height (DH), lumbar lordotic (LL) angle, and segmental lordotic (SL) angle were measured preoperatively and 3 days, 3 months, 1 year, and 2 years postoperatively. Clinical outcomes were evaluated using Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores. Fusion was defined according to computed tomography scan., Results: There were 126 vertebrae in 107 patients treated. SL angle, LL angle, and DH significantly increased postoperatively in all groups. Although the preoperative and 2-year postoperative DHs in the SA group were similar, the other measures showed significant differences from baseline at each follow-up visit. No significant effects on SL angle or DH were found in any of the groups. A significant difference in the LL angle was found in the BPS group compared with the other groups. At the last follow-up, high-grade subsidence was found in 26.89% of all cases, the fusion rate was 85.71%, and the VAS and JOA scores were significantly improved in all groups., Conclusions: Supplemental fixation did not significantly influence cage subsidence or SL angle. Only BPS fixation significantly improved the LL angle. The 2-year fusion rate was satisfactory., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A high rate of instrumentation failure is frequently seen in osteoporotic spines, especially at the sacral segment because of the great shear stress. Several techniques of sacral pedicle screw placement, such as bicortical and tricortical fixation, have been developed; however, the problems of loosening and pulling out of the screws are still a concern. Recently, the polymethylmethacrylate (PMMA)-augmented pedicle screws have been shown to strengthen the purchase in osteoporotic spine, but there are few reports on the effect of S1 pedicle screw with PMMA augmentation., Methods: Seventy-five patients receiving cement-augmented pedicle screws at lumbosacral vertebra were enrolled and divided into 3 groups by different patterns of S1 pedicle screw placement: S1 pedicle screw with PMMA augmentation (group A, 25 patients), S1 bicortical pedicle screw fixation (group B, 25 patients), and S1 tricortical pedicle screw fixation (group C, 25 patients). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were assessed preoperatively and at the last follow-up. Besides, the complications, loosening rate, and fusion rate were recorded., Results: The VAS and ODI scores at the last follow-up were significantly improved in the 3 groups compared with preoperative results. Better pain relief and functional improvement at the last follow-up was seen in group A compared with the other 2 groups; however, no significant difference was detected between groups B and C. Although the lowest screws loosening rates and the highest fusion rate were found in group A, no significant difference among these 3 groups. Furthermore, longer fusion segments and larger postoperative pelvic incidence-lumbar lordosis (PL-LL) were found as risks related to S1 screw loosening without cement augmentation., Conclusions: The S1 pedicle screws with PMMA augmentation achieved better stability with less screw loosening in the osteoporotic spine with lumbosacral degenerative diseases compared with bicortical/tricortical fixation at S1. This procedure is especially recommended for patients with long segment fixation and large postoperative PI-LL, but there is also a risk of bone cement leakage and a learning curve., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Degenerative Cervical Myelopathy [DCM] often presents with non-specific symptoms and signs. It progresses insidiously and leads to permanent neurological dysfunction. Decompressive surgery can halt disease progression, however significant delays in diagnosis result in increased disability and limit recovery. The nature of early DCM symptoms is unknown, moreover it has been suggested incomplete examination contributes to missed diagnosis. This study examines how DCM is currently assessed, if assessment differs between stages of healthcare, and whether this influences patient management., Study Design: Retrospective cohort study., Methods: Cervical MRI scans (N = 1123) at a tertiary neurosciences center, over a single year, were screened for patients with DCM (N = 43). Signs, symptoms, and disease severity of DCM were extracted from patient records. Patients were considered at 3 phases of clinical assessment: primary care, secondary care, and surgical assessment., Results: Upper limb paraesthesia and urinary dysfunction were consistently the most and least prevalent symptoms respectively. Differences between assessing clinicians were present in the reporting of: limb pain (p<0.005), objective limb weakness (p = 0.01), hyperreflexia (p<0.005), Hoffmann reflex (p<0.005), extensor plantar reflex (p = 0.007), and lower limb spasticity (p<0.005). Pathological reflexes were least frequently assessed by primary care doctors., Conclusion: DCM assessment varies significantly between assessors. Reporting of key features of DCM is especially low in primary care. Incomplete assessment may hinder early diagnosis and referral to spinal surgery., Competing Interests: The authors have declared that no competing interests exist.

Background: Superficial siderosis of the central nervous system is a rare neurologic disorder characterized by the superficial deposition of hemosiderin in the subpial layer resulting in iron-related progressive neurodegeneration., Case Description: In this report, we present a case of superficial siderosis of the central nervous system secondary to an intradural thoracic disk herniation causing a cerebrospinal fluid (CSF) leak., Conclusions: The patient was successfully treated with T6-T8 transpedicular partial corpectomy, as well as diskectomy with decompression followed by watertight closure of the CSF leak. Intraoperative watertight closure of the CSF leak was achieved., (Copyright © 2018. Published by Elsevier Inc.)

Study Design: This was a single-institute retrospective study., Objective: To evaluate postoperative complications in dialysis-dependent patients undergoing elective cervical and lumbar decompression surgery., Summary of Background Data: Spinal surgery in dialysis-dependent patients is very challenging due to the high risk of serious postoperative complications and mortality associated with their fragile general condition. However, the outcome of decompression surgery alone has not been evaluated in such patients., Methods: An electronic medical record review showed that 338 and 615 patients had undergone cervical and lumbar spine posterior decompression, respectively. Among them, 48 and 42, respectively were dialysis-dependent patients. Postoperative complications were compared between dialysis-dependent and non-dialysis-dependent patients., Results: Among patients who underwent cervical decompression, the rate of perioperative blood transfusion in dialysis-dependent patients (14.6%) was significantly higher than that in non-dialysis-dependent patients (0.7%). No severe complications or mortality occurred in association with cervical decompression. The incidence of postoperative complications in dialysis-dependent patients (6.3%) was not significantly different from that in non-dialysis-dependent patients (4.1%). Among patients who underwent lumbar decompression, the rate of perioperative transfusion in dialysis-dependent patients (11.9%) was also significantly higher than that in non-dialysis-dependent patients (0.7%). With respect to severe complications among patients who underwent lumbar decompression, cerebral hemorrhage occurred in one dialysis-dependent patient, and no mortality occurred. The incidence of postoperative complications in dialysis-dependent patients (9.2%) was not significantly different from that in non-dialysis-dependent patients (6.8%)., Conclusion: Among patients who underwent posterior decompression alone for cervical or lumbar lesions, the rate of perioperative blood transfusion was significantly higher in dialysis-dependent than in non-dialysis-dependent patients. However, the postoperative rates of severe complications and mortality were not significantly different between the two groups. Therefore, decompression surgery alone is considered a rational surgical method with less invasiveness for dialysis-dependent patients with a fragile general condition., Level of Evidence: 3.

Background: Direct lateral (DLIF) and transforaminal (TLIF) lumbar interbody fusions have been shown to produce satisfactory clinical outcomes with significant reduction in pain and functional disability. Despite their increasing use in complex spinal deformity surgeries, there is a paucity of data comparing outcome measures, which this study addresses., Methods: This is a retrospective, comparative study of patients who underwent minimally invasive, 1-level TLIF or DLIF between 2013 and 2015. Only patients 18 years and older were included. Preoperative and demographic variables were collected, and clinical outcome measures were compared between cohorts., Results: In total, 46 patients were included (DLIF: 17 patients; TLIF: 29 patients). Preoperatively, there was no difference in visual analog scale pain score or Oswestry Disability Index. Overall, there was a significant improvement in the postoperative visual analog scale score and Oswestry Disability Index in the separate cohorts, without significant difference when compared. The duration of postoperative narcotic use was similar in both cohorts (DLIF: 4.8 ± 4.7 months vs. TLIF: 5.2 ± 5.1 months, P = 0.82). Significantly more patients in DLIF cohort were cleared for work after surgery. Patients who underwent MIS TLIF had a significantly longer time to return to work (7.1 ± 4.8 months) compared with patients undergoing DLIF (2.3 ± 1.3, P = 0.006). There was a greater incidence of reoperation in the TLIF cohort., Conclusions: Both MIS TLIF and DLIF provide long-term improvement in pain andfunctional outcomes, with an overall reduction in postoperative narcotic requirement. However, there was a significantly longer time to return to work and a greater incidence of reoperation in the TLIF cohort compared with the patients who underwent DLIF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Many collective phenomena in Nature emerge from the -partial- synchronisation of the units comprising a system. In the case of the brain, this self-organised process allows groups of neurons to fire in highly intricate partially synchronised patterns and eventually lead to high level cognitive outputs and control over the human body. However, when the synchronisation patterns are altered and hypersynchronisation occurs, undesirable effects can occur. This is particularly striking and well documented in the case of epileptic seizures and tremors in neurodegenerative diseases such as Parkinson's disease. In this paper, we propose an innovative, minimally invasive, control method that can effectively desynchronise misfiring brain regions and thus mitigate and even eliminate the symptoms of the diseases. The control strategy, grounded in the Hamiltonian control theory, is applied to ensembles of neurons modelled via the Kuramoto or the Stuart-Landau models and allows for heterogeneous coupling among the interacting unities. The theory has been complemented with dedicated numerical simulations performed using the small-world Newman-Watts network and the random Erdős-Rényi network. Finally the method has been compared with the gold-standard Proportional-Differential Feedback control technique. Our method is shown to achieve equivalent levels of desynchronisation using lesser control strength and/or fewer controllers, being thus minimally invasive., Competing Interests: The authors have declared that no competing interests exist.

Study Design: Multicenter, retrospective, institutional-review-board -approved study at 18 institutions in the United States with 24 treating investigators., Objective: This study was designed to retrospectively assess the prevalence of spinopelvic malalignment in patients who underwent one- or two-level lumbar fusions for degenerative (nondeformity) indications and to assess the incidence of malalignment after fusion surgery as well as the rate of alignment preservation and/or correction in this population., Summary of Background Data: Spinopelvic malalignment after lumbar fusion has been associated with lower postoperative health-related quality of life and elevated risk of adjacent segment failure. The prevalence of spinopelvic malalignment in short-segment degenerative lumbar fusion procedures from a large sample of patients is heretofore unreported and may lead to an under-appreciation of these factors in surgical planning and ultimate preservation or correction of alignment., Methods: Lateral preoperative and postoperative lumbar radiographs were retrospectively acquired from 578 one- or two-level lumbar fusion patients and newly measured for lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt. Patients were categorized at preop and postop time points as aligned if PI-LL < 10° or malaligned if PI-LL≥10°. Patients were grouped into categories based on their alignment progression from pre- to postoperative, with preserved (aligned to aligned), restored (malaligned to aligned), not corrected (malaligned to malaligned), and worsened (aligned to malaligned) designations., Results: Preoperatively, 173 (30%) patients exhibited malalignment. Postoperatively, 161 (28%) of patients were malaligned. Alignment was preserved in 63%, restored in 9%, not corrected in 21%, and worsened in 7% of patients., Conclusion: This is the first multicenter study to evaluate the preoperative prevalence and postoperative incidence of spinopelvic malalignment in a large series of short-segment degenerative lumbar fusions, finding over 25% of patients out of alignment at both time points, suggesting that alignment preservation/restoration considerations should be incorporated into the decision-making of even degenerative lumbar spinal fusions., Level of Evidence: 3.

Objective: To compare outcomes between K-rod dynamic stabilization system (KDSS) and posterior lumbar intervertebral fusion (PLIF) for lumbar degenerative disease., Methods: This study retrospectively reviewed 98 patients who underwent lumbar surgery from March 2012 to June 2014, including 48 in the KDSS group and 50 in the PLIF group. All patients were followed up for at least 2 years. Duration of operation, blood loss, hospital stay, complications, and patient satisfaction were recorded and analyzed. Clinical outcomes were evaluated by visual analog scale and Oswestry Disability Index. Radiographic results including disk height index, foraminal height, and range of motion (ROM) were compared between groups., Results: Compared with PLIF group, KDSS group had shorter duration of operation and less blood loss (P < 0.001). There were no differences in hospital stay, complications, and patient satisfaction. Both groups demonstrated significant improvement in visual analog scale back and leg pain and Oswestry Disability Index. No significant difference was found between groups at any time point (P > 0.05). Postoperative disk height index and foraminal height increased significantly compared with preoperatively (P < 0.05). Although disk height index and foraminal height in KDSS group were smaller than PLIF group values, there were no significant differences between groups. ROM of total lumbar and implanted segment was decreased compared with preoperative ROM in both groups (P < 0.05), but the 2 values were higher in KDSS group (P < 0.05)., Conclusions: Both KDSS and PLIF can improve clinical and radiographic outcomes for early-stage lumbar degenerative disease. Compared with PLIF, KDSS has better operative time, less blood loss, and better preservation of ROM, but prospective, randomized, controlled trials with larger sample size and longer follow-up are required., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Acute bilateral isolated foot drop due to lumbar disk prolapse with canal stenosis is rare with only 3 cases reported in literature. Our patient was managed using the percutaneous full endoscopic technique. This is mainly to highlight the ease of access and patient outcome with preoperative and postoperative images to support our minimally invasive treatment for this rare condition., Case Description: A 46-year-old male presented with sudden-onset severe back pain with bilateral foot drop. Clinical examination showed a bilateral L5 radiculopathy with normal perianal sensation. Investigations excluded other causes of bilateral foot drop. A magnetic resonance imaging scan showed disk herniation at the right L4-L5 (inferior migrated) and L5-S1 level (paracentral and extraforaminal) with spinal canal stenosis at the L2-L3 and L5-S1 levels due to ligamentum flavum hypertrophy. The patient underwent percutaneous endoscopic stenosis lumbar decompression at the L2-L3 and L5-S1 level. At the right L4-L5, L5-S1 level, transforaminal endoscopic diskectomy was done using the conventional percutaneous approach. The inferior migrated disk of the L4-L5 level was removed using a left L5-S1 contralateral approach. The patient recovered with favorable outcome and added benefits of minimally invasive surgery., Conclusion: Lumbar disk prolapse with canal stenosis should be considered in patients presenting with bilateral isolated foot drop. To our best knowledge, this is the first report of percutaneous endoscopic treatment to address multiple-lumbar-level pathology for this rare condition of acute bilateral isolated foot drop., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The transnasal approach to lesions involving the craniovertebral junction represents a technical challenge because of limited inferior exposure. The endoscopic transseptal approach (EtsA) with posterior nasal spine (PNS) removal is described. This technique can create a wide exposure of the craniovertebral junction, thereby increasing the caudal exposure., Methods: On patients undergoing anterior craniovertebral junction decompression, we calculated the degree of exposure on the sagittal plan through a paraseptal route, an EtsA without and with PNS removal. The horizontal exposure and working area with the latter approach were also evaluated., Results: Five patients underwent the transnasal procedure. The age of patients ranged from 34-71 years. All patients harbored basilar impression. The mean postoperative Nurick grade (1, 8) was improved versus the average preoperative grade (3). The average follow-up duration was 16 months. All patients underwent occipitocervical fixation. The mean vertical distances, from the clinoid recess to the inferior most limit with the paraseptal approach, EtsA without and with PNS removal were 38.52, 44.12, and 51.16 mm, respectively. The difference between our approach and a standard paraseptal route was statistically significant (P = 0.041; P< 0.05). The mean horizontal distances were 31.68 mm (mononostril entry) and 35.37 mm (binostril entry). The mean working area was 1795.53 mm 2 ., Conclusions: Endoscopic endonasal approaches to the craniovertebral junction are increasing, but the downward extension on the anterior cervical spine represents a limit. Therefore, many surgeons prefer transoral or transcervical approaches. The EtsA with PNS removal allows for a more caudal exposure than the standard paraseptal approach, with reduced nasal trauma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the clinical and radiological differences among three advanced guided technologies in adult degenerative scoliosis. A total of 1012 pedicle screws were inserted in 83 patients using a spine robot (group A), 886 screws were implanted in 75 patients using a drill guide template (group B), and 1276 screws were inserted in 109 patients using CT-based navigation (group C). Screw positions were evaluated using postoperative CT scans according to the Gertzbein and Robbins classification. Other relevant data were also collected. Perfect pedicle screw insertion (Grade A) accuracy in groups A, B, and C was 91.3%, 81.3%, and 84.1%, respectively. Clinically acceptable accuracy of screw implantation (Grades A + B) respectively was 96.0%, 90.6%, and 93.0%. Statistical analysis showed the perfect and clinically acceptable accuracy in group A was significant different compared with groups B and C. Group A exhibited the lowest intra-op radiation dose and group B showed the shortest surgical time compared with the other two groups. Robotic-assisted technology demonstrated significantly higher accuracy than the drill guide template or CT-based navigation systems for difficult screw implantations in adult degenerative scoliosis and reduced the intra-op radiation dose, although it failed to reduce surgery time.

Progressive neurodegeneration of the optic nerve and the loss of retinal ganglion cells is a hallmark of glaucoma, the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) being the most frequent form of glaucoma in the Western world. While some genetic mutations have been identified for some glaucomas, those associated with POAG are limited and for most POAG patients, the etiology is still unclear. Unfortunately, treatment of this neurodegenerative disease and other retinal degenerative diseases is lacking. For POAG, most of the treatments focus on reducing aqueous humor formation, enhancing uveoscleral or conventional outflow, or lowering intraocular pressure through surgical means. These efforts, in some cases, do not always lead to a prevention of vision loss and therefore other strategies are needed to reduce or reverse the progressive neurodegeneration. In this review, we will highlight some of the ocular pharmacological approaches that are being tested to reduce neurodegeneration and provide some form of neuroprotection.

Neural stem cells (NSCs) are multipotent self-renewing cells that could be used in cellular-based therapy for a wide variety of neurodegenerative diseases including Alzheimer's diseases (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Being multipotent in nature, they are practically capable of giving rise to major cell types of the nervous tissue including neurons, astrocytes, and oligodendrocytes. This is in marked contrast to neural progenitor cells which are committed to a specific lineage fate. In previous studies, we have demonstrated the ability of NSCs isolated from human olfactory bulb (OB) to survive, proliferate, differentiate, and restore cognitive and motor deficits associated with AD, and PD rat models, respectively. The use of carbon nanotubes (CNTs) to enhance the survivability and differentiation potential of NSCs following their in vivo engraftment have been recently suggested. Here, in order to assess the ability of CNTs to enhance the therapeutic potential of human OBNSCs for restoring cognitive deficits and neurodegenerative lesions, we co-engrafted CNTs and human OBNSCs in TMT-neurodegeneration rat model. The present study revealed that engrafted human OBNSCS-CNTs restored cognitive deficits, and neurodegenerative changes associated with TMT-induced rat neurodegeneration model. Moreover, the CNTs seemed to provide a support for engrafted OBNSCs, with increasing their tendency to differentiate into neurons rather than into glia cells. The present study indicate the marked ability of CNTs to enhance the therapeutic potential of human OBNSCs which qualify this novel therapeutic paradigm as a promising candidate for cell-based therapy of different neurodegenerative diseases., (© 2017 Wiley Periodicals, Inc.)

Incidental durotomy (ID) is a common intraoperative complication of spine surgery. It can lead to persistent cerebrospinal fluid leakage, which may cause serious complications, including severe headache, pseudomeningocele formation, nerve root entrapment, and intracranial hemorrhage. As a result, it contributes to higher healthcare costs and poor patient outcomes. The purpose of this study was to clarify the independent risk factors that can cause ID during posterior open spine surgery for degenerative diseases in adults. We conducted a prospective multicenter study of adult patients who underwent posterior open spine surgery for degenerative diseases at 10 participating hospitals from July 2010 to June 2013. A total of 4,652 consecutive patients were enrolled. We evaluated potential risk factors, including age, sex, body mass index, American Society of Anesthesiologists physical status classification, the presence of diabetes mellitus, the use of hemodialysis, smoking status, steroid intake, location of the surgery, type of operative procedure, and past surgical history in the operated area. A multivariate logistic regression analysis was performed to identify the risk factors associated with ID. The incidence of ID was 8.2% (380/4,652). Corrective vertebral osteotomy and revision surgery were identified as independent risk factors for ID, while cervical surgery and discectomy were identified as factors that independently protected against ID during posterior open spine surgery for degenerative diseases in adults. Therefore, we identified 2 independent risk factors for and 2 protective factors against ID. These results may contribute to making surgeons aware of the risk factors for ID and can be used to counsel patients on the risks and complications associated with open spine surgery.

Background: Over the past decades, supported by preliminary anatomic and clinical studies exploring its feasibility and safety, experience has increased of the use of the endoscopic endonasal approach (EEA) to ventral diseases at the craniocervical junction (CCJ)., Methods: A multicenter study was carried out over a 4-year period of 14 patients managed by EEA odontoidectomy for CCJ diseases causing irreducible atlantoaxial dislocation. The surgical setup included an IGS system based on computed tomography and magnetic resonance images fusion, and 0° and 30° angled endoscopes with dedicated endoscopic tools., Results: Nine men and 5 women, with a mean age of 60.7 years, were included. The mean follow-up was 28.5 months; 9 patients had basilar impression, whereas 5 had a degenerative pannus. The quality of anterior decompression was excellent in all cases; nonetheless, a posterior stabilization was deemed necessary in 13 patients, and no external orthosis was used during the postoperative course. No tracheostomy or gastrostomy was required after surgery; no deaths, no new neurologic deficits/complications, and no postoperative cerebrospinal fluid leak were recorded. At follow-up, the neurologic status assessed with Frankel grade did not deteriorate in any of the patients but improved in 13 of them; and no new listhesis was shown on neuroradiologic follow-up., Conclusions: The results show that EEA provides a direct surgical corridor to the CCJ, allowing an adequate decompression as with the more invasive transoral route. Morbidity is less than with a transoral approach, resulting in higher patient comfort and faster recovery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

OBJECTIVE Minimally invasive spine surgery can minimize damage to normal anatomical structures. Recently, fully endoscopic spine surgeries have been attempted for lumbar fusion surgery. In this study, the authors performed a percutaneous unilateral biportal endoscopic (UBE) technique as a minimally invasive surgery for lumbar fusion. The purpose of this study is to present the UBE technique of fully endoscopic lumbar interbody fusion (LIF) and to analyze the clinical results. METHODS Patients who were to undergo single-level fusion surgery from L3-4 to L5-S1 were enrolled. Two channels (endoscopic portal and working portal) were used for endoscopic lumbar fusion surgery. All patients underwent follow-up for more than 12 months. Demographic characteristics, diagnosis, operative time, and estimated blood loss were evaluated. MRI was performed on postoperative Day 2. Clinical evaluations (visual analog scale [VAS] for the leg and Oswestry Disability Index [ODI] scores) were performed preoperatively and during the follow-up period. RESULTS A total of 69 patients (24 men and 45 women) were enrolled in this study. The mean follow-up period was 13.5 months. Postoperative MRI revealed optimal direct neural decompression after fully endoscopic fusion surgery. VAS and ODI scores significantly improved after the surgery. There was no postoperative neurological deterioration. CONCLUSIONS Fully endoscopic LIF using the UBE technique may represent an alternative minimally invasive LIF surgery for the treatment of degenerative lumbar disease. Long-term follow-up and larger clinical studies are needed to validate the clinical and radiological results of this surgery.

OBJECTIVE Lumbar spondylolisthesis is a degenerative condition that can be surgically treated with either open or minimally invasive decompression and instrumented fusion. Minimally invasive surgery (MIS) approaches may shorten recovery, reduce blood loss, and minimize soft-tissue damage with resultant reduced postoperative pain and disability. METHODS The authors queried the national, multicenter Quality Outcomes Database (QOD) registry for patients undergoing posterior lumbar fusion between July 2014 and December 2015 for Grade I degenerative spondylolisthesis. The authors recorded baseline and 12-month patient-reported outcomes (PROs), including Oswestry Disability Index (ODI), EQ-5D, numeric rating scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society satisfaction questionnaire). Multivariable regression models were fitted for hospital length of stay (LOS), 12-month PROs, and 90-day return to work, after adjusting for an array of preoperative and surgical variables. RESULTS A total of 345 patients (open surgery, n = 254; MIS, n = 91) from 11 participating sites were identified in the QOD. The follow-up rate at 12 months was 84% (83.5% [open surgery]; 85% [MIS]). Overall, baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts. Two hundred fifty seven patients underwent 1-level fusion (open surgery, n = 181; MIS, n = 76), and 88 patients underwent 2-level fusion (open surgery, n = 73; MIS, n = 15). Patients in both groups reported significant improvement in all primary outcomes (all p < 0.001). MIS was associated with a significantly lower mean intraoperative estimated blood loss and slightly longer operative times in both 1- and 2-level fusion subgroups. Although the LOS was shorter for MIS 1-level cases, this was not significantly different. No difference was detected with regard to the 12-month PROs between the 1-level MIS versus the 1-level open surgical groups. However, change in functional outcome scores for patients undergoing 2-level fusion was notably larger in the MIS cohort for ODI (-27 vs -16, p = 0.1), EQ-5D (0.27 vs 0.15, p = 0.08), and NRS-BP (-3.5 vs -2.7, p = 0.41); statistical significance was shown only for changes in NRS-LP scores (-4.9 vs -2.8, p = 0.02). On risk-adjusted analysis for 1-level fusion, open versus minimally invasive approach was not significant for 12-month PROs, LOS, and 90-day return to work. CONCLUSIONS Significant improvement was found in terms of all functional outcomes in patients undergoing open or MIS fusion for lumbar spondylolisthesis. No difference was detected between the 2 techniques for 1-level fusion in terms of patient-reported outcomes, LOS, and 90-day return to work. However, patients undergoing 2-level MIS fusion reported significantly better improvement in NRS-LP at 12 months than patients undergoing 2-level open surgery. Longer follow-up is needed to provide further insight into the comparative effectiveness of the 2 procedures.

Objective: The fusion rate in spinal surgery may vary in relation to the technique, and it remains unknown which surgical technique provides the best fusion rate and surgical outcome. We aimed to compare radiologic and surgical results between 3 surgical techniques used for lumbar interbody fusion., Methods: Participants included 77 patients diagnosed with degenerative spinal stenosis including spondylolytic spondylolisthesis. Patients were divided into 3 groups according to surgical technique: anterior lumbar interbody fusion (ALIF, n = 26), transforaminal lumbar interbody fusion (TLIF, n = 21), and posterior lumbar interbody fusion (PLIF, n = 30). Various radiologic parameters were measured, including fusion rates., Results: Significant changes after surgery were observed in the ALIF group for the percentage of vertebral body slippage, anterior disk height, posterior disk height, and segmental range of movement (ROM). The fusion rate on computed tomography (CT) scan at the final follow-up was 69.2% in the ALIF group, 72.7% in the TLIF group, and 64.3% in the PLIF group. The cage subsidence rate 2 years after surgery was 15.4% in the ALIF group, 38.1% in the TLIF group, and 10% in the PLIF group., Conclusions: ALIF was associated with better restoration of segmental lordosis. The fusion rate on CT scan and with segmental ROM did not differ between the 3 groups. TLIF was associated with a better postoperative visual analog scale. PLIF showed the lowest cage subsidence rate. Therefore, it is difficult to know which surgical technique is better among the 3 groups because each surgical method has its own advantages., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure., Objective: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications., Methods: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models., Results: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality., Conclusion: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153)., (Copyright © 2017 by the Congress of Neurological Surgeons)

Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission. Subpopulations of the derived neurons were electrically excitable, showing tetrodotoxin-sensitive action potentials in patch-clamp experiments. Coculture of the derived neurons with rat Schwann cells under myelinating conditions resulted in upregulated levels of neuronal neuregulin 1 type III in conjunction with the phosphorylated receptors ErbB2 and ErbB3, consistent with amenability of the neuritic network to myelination. As surrogates of embryonic dorsal root ganglia neurons, the derived sensory neurons provided contact-dependent cues to commit bone marrow-derived Schwann cell-like cells to the Schwann cell fate. Our rapid and efficient induction protocol promises not only controlled differentiation of human iPSCs into sensory neurons, but also utility in the translation to a protocol whereby human bone marrow-derived Schwann cells become available for autologous transplantation and remyelination therapy. Stem Cells Translational Medicine 2017;6:369-381., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Study Design: Analysis of a combined prospective dataset., Objective: To evaluate the impact of preoperative body mass index (BMI) on surgical outcomes in degenerative cervical myelopathy (DCM)., Summary of Background Data: Although elevated BMI has been shown to have a deleterious impact on outcomes after lumbar spine surgery, limited evidence is available regarding its impact in DCM., Methods: Analyses were completed using a combined North American/International prospective surgical DCM dataset from 26 participating centers. Outcome measures included Neck Disability Index (NDI), modified Japanese Orthopedic Association (mJOA) score, and Short Form- 36 (SF-36) scores at 1 year postoperatively. Bivariate and multivariable statistics were used to model the relationship between preoperative BMI, as both a continuous and categorical variable with these outcomes., Results: Of 757 patients, mean BMI was 27.3 (±5.7) with 17 patients (3.5%) underweight, 271 patients (35.8%) normal weight, 275 patients (36.3%) overweight, and 194 patients (25.7%) obese. Controlling for preoperative mJOA, NDI, smoking status, age, and sex, elevated BMI was associated with increased neck disability at 1 year (P < 0.01). On average, NDI scores were 4.5 points higher (95% confidence interval, CI: 1.6-7.6) for overweight patients and 5.7 points higher (95% CI: 2.6-8.9) for obese patients compared with individuals of normal weight. Obese patients had 0.5 times odds (odds ratio, OR = 0.5, 95% CI: 0.3-0.8, P < 0.01) of showing improvement equal to the minimal clinically important difference of NDI compared with their normal weight counterparts. Although there were strong trends towards reduced SF-36 mental component scores and physical component scores with elevated BMI, no association was found between BMI and 1-year mJOA., Conclusion: Increased BMI, particularly obesity, was associated with increased postoperative disability. This represents a potentially modifiable risk factor which clinicians can target to optimize postoperative outcomes., Level of Evidence: 2.

Study Design: A retrospective study., Objective: The purpose of this study was to determine the incidence and risk factors of adjacent segment disease (ASD) after transforaminal inter-body fusion (TLIF) for degenerative lumbar disease., Summary of Background Data: ASD is a major complication after spinal fusion. Many reports have been published concerning the risk factors for ASD after TLIF. A number of quantitative relationships to spino-pelvic parameters have been established. A retrospective cohort study was carried out to investigate spino-pelvic alignment in patients with ASD after TLIF., Methods: This study evaluated 263 subjects (150 subjects undergoing floating fusion (FF group), and 113 patients undergoing lumbosacral fusion (LF group)) who underwent TLIF from 2009 to 2012. The mean follow-up period was 37.6 months. Several parameters were measured using pre- and postoperative full-length free-standing radiographs, including lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), and PI-LL. Multivariate logistic regression analysis was performed to evaluate these parameters as potential risk factors of early onset radiographic ASD., Results: Radiographic ASD was found in 65 cases (43.3%) in the FF group, and 49 cases (43.3%) in the LF group. LL improved by 7.5° and 3.9° in each group respectively after TLIF. However, PT worsened by 6.4° in the LF group. When comparing with ASD positive cases and ASD negative cases, a significant difference in preoperative PT was observed in both FF (P = 0.001) and LF groups (P = 0.0001). Logistic regression analysis and receiver operating characteristic analysis revealed that preoperative PT of more than 22.5° was a significant risk factor of the incidence of ASD after TLIF (P = 0.02; odds ratio: 5.1, 95% CI: 1.62-9.03)., Conclusion: Patients with preoperative sagittal imbalance have a statistically significant increased risk of ASD. The risk of ASD incidence was 5.1 times greater in subjects with preoperative PT of more than 22.5°.

Few studies have compared the clinical and radiological outcomes between Coflex interspinous stabilization and posterior lumbar interbody fusion (PLIF) for degenerative lumbar disease. We compared the at least 5-year clinical and radiological outcomes of Coflex stabilization and PLIF for lumbar degenerative disease. Eighty-seven consecutive patients with lumbar degenerative disease were retrospectively reviewed. Forty-two patients underwent decompression and Coflex interspinous stabilization (Coflex group), 45 patients underwent decompression and PLIF (PLIF group). Clinical and radiological outcomes were evaluated. Coflex subjects experienced less blood loss, shorter hospital stays and shorter operative time than PLIF (all p<0.001). Both groups demonstrated significant improvement in Oswestry Disability Index and visual analogue scale back and leg pain at each follow-up time point. The Coflex group had significantly better clinical outcomes during early follow-up. At final follow-up, the superior and inferior adjacent segments motion had no significant change in the Coflex group, while the superior adjacent segment motion increased significantly in the PLIF group. At final follow-up, the operative level motion was significantly decreased in both groups, but was greater in the Coflex group. The reoperation rate for adjacent segment disease was higher in the PLIF group, but this did not achieve statistical significance (11.1% vs. 4.8%, p=0.277). Both groups provided sustainable improved clinical outcomes for lumbar degenerative disease through at least 5-year follow-up. The Coflex group had significantly better early efficacy than the PLIF group. Coflex interspinous implantation after decompression is safe and effective for lumbar degenerative disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In general, older patients with degenerative cervical myelopathy (DCM) are felt to have lower recovery potential following surgery due to increased degenerative pathology, comorbidities, reduced physiological reserves and age-related changes to the spinal cord. This study aims to determine whether age truly is an independent predictor of surgical outcome and to provide evidence to guide practice and decision-making., Methods: A total of 479 patients with DCM were prospectively enrolled in the CSM-International study at 16 centres. Our sample was divided into a younger group (<65 years) and an elderly (≥65 years) group. A mixed model analytic approach was used to evaluate differences in the modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36) and Neck Disability Index (NDI) scores between groups. We first created an unadjusted model between age and surgical outcome and then developed two adjusted models that accounted for variations in (1) baseline characteristics and (2) both baseline and surgical factors., Results: Of the 479 patients, 360 (75.16%) were <65 years and 119 (24.84%) were ≥65 years. Elderly patients had a worse preoperative health status (p<0.0001) and were functionally more severe (p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery, whereas the preferred approach in the elderly group was posterior (58.62%, p<0.0001). Elderly patients had a greater number of decompressed levels than younger patients (p<0.0001). At 24 months after surgery, younger patients achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score (p<0.0001) than elderly patients. After adjustments for patient and surgical characteristics, these differences in postoperative outcome scores decreased but remained significant., Conclusions: Older age is an independent predictor of functional status in patients with DCM. However, patients over 65 with DCM still achieve functionally significant improvement after surgical decompression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background Context: A posterior decompression with an instrumented fusion is one of the most common surgical procedures performed for treating symptomatic spinal stenosis associated with degenerative spondylolisthesis (DS). However, some patients may benefit from a decompression alone, avoiding complications related to instrumentation and fusion., Objective: To identify the characteristics of patients with symptomatic DS who may be successfully treated with an isolated decompression., Study Design: A systematic literature review of studies including patients who underwent decompression without instrumentation for treatment of DS., Methods: A systematic review of the Medline database was performed. Retrospective and prospective studies of patients with DS who underwent a decompression were included, as well as studies comparing decompression with instrumented decompression. All the articles were classified according to their level of evidence., Results: Thirteen studies met all inclusion and exclusion criteria. We identified several characteristics that may be associated with a less favorable outcome after a decompression alone: a facet angle >50 degrees, a disk space of >6.5 mm, presence of low back pain rather than lower extremity symptoms, presence of hypermobility in the listhetic level on dynamic radiographs (>1.25 to 2 mm), and resection of the posterior elements. The majority of the studies comparing decompression alone to decompression and instrumented fusion included in our review suggested similar clinical outcomes with both procedures; however, with long-term follow-up, fusion may provide better outcomes. Decompression with a noninstrumented fusion is also a good alternative to improve symptoms in selected patients, potentially decreasing the risk of reoperation compared with an instrumented fusion., Conclusions: Satisfactory clinical outcome can be achieved with an isolated decompression in selected patients, avoiding the additional risks and costs of instrumentation and spinal fusion. Noninstrumented fusion is also an interesting alternative to instrumented fusion for well-selected patients to decrease complications related to instrumentation.

OBJECTIVE The minimum clinically important difference (MCID) is defined as the minimum change in a measurement that a patient would identify as beneficial. Before undergoing surgery, patients are likely to inquire about the ultimate goals of the operation and of their chances of experiencing meaningful improvements. The objective of this study was to define significant predictors of achieving an MCID on the modified Japanese Orthopaedic Association (mJOA) scale at 2 years following surgery for the treatment of degenerative cervical myelopathy (DCM). METHODS Seven hundred fifty-seven patients were prospectively enrolled in either the AOSpine North America or International study at 26 global sites. Fourteen patients had a perfect preoperative mJOA score of 18 and were excluded from this analysis (n = 743). Data were collected for each participating subject, including demographic information, symptomatology, medical history, causative pathology, and functional impairment. Univariate log-binominal regression analyses were conducted to evaluate the association between preoperative clinical factors and achieving an MCID on the mJOA scale. Modified Poisson regression using robust error variances was used to create the final multivariate model and compute the relative risk for each predictor. RESULTS The sample consisted of 463 men (62.31%) and 280 women (37.69%), with an average age of 56.48 ± 11.85 years. At 2 years following surgery, patients exhibited a mean change in functional status of 2.71 ± 2.89 points on the mJOA scale. Of the 687 patients with available follow-up data, 481 (70.01%) exhibited meaningful gains on the mJOA scale, whereas 206 (29.98%) failed to achieve an MCID. Based on univariate analysis, significant predictors of achieving the MCID on the mJOA scale were younger age; female sex; shorter duration of symptoms; nonsmoking status; a lower comorbidity score and absence of cardiovascular disease; and absence of upgoing plantar responses, lower-limb spasticity, and broad-based unstable gait. The final model included age (relative risk [RR] 0.924, p < 0.0001), smoking status (RR 0.837, p = 0.0043), broad-based unstable gait (RR 0.869, p = 0.0036), and duration of symptoms (RR 0.943, p = 0.0003). CONCLUSIONS In this large multinational prospective cohort, 70% of patients treated surgically for DCM exhibited a meaningful functional gain on the mJOA scale. The key predictors of achieving an MCID on the mJOA scale were younger age, shorter duration of symptoms, nonsmoking status, and lack of significant gait impairment.

Background and Aim: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are one of the sources of adult stem cells being explored for potential use in repairing neurodegenerative disorders. In this study, it was aimed to investigate the useful effects of BM-MSCs therapy on the streptozotocin-induced neurodegeneration in rats., Materials and Methods: Adult female Wistar rats were bilaterally injected intra-cerebroventricularly with streptozotocin (3 mg/kg) for neurodegeneration. Water maze tests were used to monitor spatial learning and memory. One or two intravenous injections of BM-MSCs were administrated to rat via the tail veins. At the end of the study, all rats were sacrificed for histological evaluation and immunohistochemistry., Results: Streptozotocin group demonstrated a significant increase in escape latency in comparison with both control groups (Sham and Saline), whereas rats treated with BM-MSCs exhibited a decrease in escape latency in comparison with streptozotocin group. The percentage of time spent in the target quadrant and the mean number of platform crossings did not change in all the groups. BM-MSCs administration improved spatial learning but not memory. However, improvement in neuronal cells in hippocampal CA1 region was only observed in the rats treated with BM-MSCs twice as opposed to the rats treated with BM-MSCs once or with saline., Conclusions: In this study, mesenchymal stem cells therapy failed to improve the streptozotocin-induced neurodegeneration like Alzheimer's disease in rats.

Study Design: A retrospective kinematic magnetic resonance imaging (kMRI) study., Objective: To evaluate the utility of kMRI in determining the relationship between cervical sagittal balance and TI alignment., Summary of Background Data: Thoracic inlet parameters play an important role in cervical spine sagittal balance. However, most of the literature is based on lower resolution cervical X-rays or CT scans in the supine position., Methods: Cervical spine kMRI of 83 patients with degenerative cervical spine conditions (20-68 yr of age) was analyzed for: (1) cervical spine parameters: C2-C7 angle, C2-C7 sagittal vertical axis (SVA), cranial tilt, and cervical tilt; and (2) T1 parameters: thoracic inlet angle (TIA), T1 slope, and neck tilt (NT). Multiple logistic regression analysis and Pearson correlation coefficients were performed., Results: The mean TIA, T1 slope, and NT were 78.0, 33.2, and 44.8°, respectively. The mean C2-7 angle, SVA of C2-C7, cervical tilt, and cranial tilt were -15.4°, 22.0 mm, 18.1°, and 15.1°, respectively. The ratio of cervical:cranial tilt was maintained as 55:45%. A significant correlation was found between the C2-C7 angle and T1 slope (r = 0.731), TIA and C2-C7 angle (r = 0.406), cervical tilt with C2-C7 angle (r = 0.671), T1 slope with TIA (r = 0.429), TIA with neck tilt (r = 0.733), TIA with cervical tilt (r = 0.377), SVA C2-C7 with cervical tilt (r = -0.480), SVA C2-C7 with cranial tilt (r = 0.912), and C2-7 SVA with the ratio of cranial tilt to cervical tilt (r = 0.694)., Conclusion: An individual with a large T1 slope required large cervical lordosis to preserve physiologic sagittal balance of the cervical spine. Cranial tilt was the cervical parameter most strongly correlated with SVA C2-C7, and thus may be a good parameter to assess decompensation of cervical sagittal balance., Level of Evidence: 3.