✓ Recent advances in the laboratory have improved the current understanding of neurobiological mechanisms underlying the initiating events and pathological progression observed in amyotrophic lateral sclerosis (ALS). Whereas initial studies have revealed the late-stage intracellular cascades contributing to neuronal dysfunction and cell death, more recently collected data have begun to elucidate the presence and importance of a “non–cell autonomous” component indicating that affected glial cell subtypes may serve distinct and required roles. Pharmacological interventions for ALS have largely been disappointing likely in part because they have failed to address either the proximate events contributing to neuronal dysfunction and death or the deleterious contributions of non-neuronal cells within the local microenvironment. Alternatively, cell-based therapeutics offer the potential of a multifaceted approach oriented toward the dual ends of protecting remaining viable neurons and attempting to restore neuronal function lost as a manifestation of disease progression. The authors review the evolving knowledge of disease initiation and progression, with specific emphasis on the role of affected glia as crucial contributors to the observed ALS phenotype. This basis is used to underscore the potential roles of cell-based therapeutics as modifiers of the ALS-specific microenvironment.
Jonathan Riley, Walter Sweeney and Nicholas Boulis
Jonathan Riley, Alejandro Spiotta and Nicholas Boulis
✓Discovery that the Schwann cell is the primary cell type responsible for both the neurofibroma as well as the schwannoma has proven to represent a crucial milestone in understanding the pathogenesis of peripheral nerve tumor development. This information and related findings have served as a nidus for research aimed at more fully characterizing this family of conditions. Recent discoveries in the laboratory have clarified an understanding of the molecular mechanisms underlying the pathogenesis of benign peripheral nerve tumors. Similarly, the mechanisms whereby idiopathic and syndromic (NF1- and NF2-associated) nerve sheath tumors progress to malignancy are being elucidated. This detailed understanding of the molecular pathogenesis of peripheral nerve tumors provides the information necessary to create a new generation of therapies tailored specifically to the prevention, cessation, or reversal of pathological conditions at the fundamental level of dysfunction. The authors review the data that have helped to elucidate the molecular pathogenesis of this category of conditions, explore the current progress toward exploitation of these findings, and discuss potential therapeutic avenues for future research.
Sameer H. Halani, Griffin R. Baum, Jonathan P. Riley, Gustavo Pradilla, Daniel Refai, Gerald E. Rodts Jr and Faiz U. Ahmad
Esophageal perforation is a rare but well-known complication of anterior cervical spine surgery. The authors performed a systematic review of the literature to evaluate symptomatology, direct causes, repair methods, and associated complications of esophageal injury.
A PubMed search that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines included relevant clinical studies and case reports (articles written in the English language that included humans as subjects) that reported patients who underwent anterior spinal surgery and sustained some form of esophageal perforation. Available data on clinical presentation, the surgical procedure performed, outcome measures, and other individual variables were abstracted from 1980 through 2015.
The PubMed search yielded 65 articles with 153 patients (mean age 44.7 years; range 14–85 years) who underwent anterior spinal surgery and sustained esophageal perforation, either during surgery or in a delayed fashion. The most common indications for initial anterior cervical spine surgery in these cases were vertebral fracture/dislocation (n = 77), spondylotic myelopathy (n = 15), and nucleus pulposus herniation (n = 10). The most commonly involved spinal levels were C5–6 (n = 51) and C6–7 (n = 39). The most common presenting symptoms included dysphagia (n =63), fever (n = 24), neck swelling (n = 23), and wound leakage (n = 18). The etiology of esophageal perforation included hardware failure (n = 31), hardware erosion (n = 23), and intraoperative injury (n = 14). The imaging modalities used to identify the esophageal perforations included modified contrast dye swallow studies, CT, endoscopy, plain radiography, and MRI. Esophageal repair was most commonly achieved using a modified muscle flap, as well as with primary closure. Outcomes measured in the literature were often defined by the time to oral intake following esophageal repair. Complications included pneumonia (n = 6), mediastinitis (n = 4), osteomyelitis (n = 3), sepsis (n = 3), acute respiratory distress syndrome (n = 2), and recurrent laryngeal nerve damage (n = 1). The mortality rate of esophageal perforation in the analysis was 3.92% (6 of 153 reported patients).
Esophageal perforation after anterior cervical spine surgery is a rare complication. This systematic review demonstrates that these perforations can be stratified into 3 categories based on the timing of symptomatic onset: intraoperative, early postoperative (within 30 days of anterior spinal surgery), and delayed. The most common source of esophageal injury is hardware erosion or migration, each of which may vary in their time to symptomatic manifestation.
Max S. Riley, Keith H. Bridwell, Lawrence G. Lenke, Jonathan Dalton and Michael P. Kelly
Significant health-related quality of life (HRQOL) benefits have been observed for patients undergoing primary and revision adult spinal deformity (ASD) surgery. The purpose of this study was to report changes in HRQOL measures in a consecutive series of patients undergoing complex spinal reconstructive surgery, using Scoli-RISK-1 (SR-1) inclusion criteria.
This was a single-center, retrospective cohort study. The SR-1 inclusion criteria were used to define patients with complex ASD treated between June 1, 2009, and June 1, 2011. Standard preoperative and perioperative data were collected, including the Scoliosis Research Society (SRS)–22r instrument. The HRQOL changes were evaluated at a minimum 2-year follow-up. Standardized forms were used to collect surgery-related complications data for all patients. Complications were defined as minor, transient major, or permanent major. Patients who achieved a minimum 2-year follow-up were included in the analysis.
Eighty-four patients meeting SR-1 criteria were identified. Baseline demographic and surgical data were available for 74/84 (88%) patients. Forty-seven of 74 (64%) patients met the additional HRQOL criteria with a minimum 2-year follow-up (mean follow-up 3.4 years, range 2–6.5 years). Twenty-one percent of patients underwent posterior fusion only, 40% of patients had a posterior column osteotomy, and 38% had a 3-column osteotomy. Seventy-five percent of patients underwent a revision procedure. Significant improvements were observed in all SRS-22r domains: Pain: +0.8 (p < 0.001); Self-Image: +1.4 (p < 0.001); Function: +0.46 (p < 0.001); Satisfaction: +1.6 (p < 0.001); and Mental Health: +0.28 (p = 0.04). With the exception of Mental Health, more than 50% of patients achieved a minimum clinically important difference (MCID) in SRS-22r domain scores (Mental Health: 20/47, 42.6%). A total of 65 complications occurred in 31 patients. This includes 29.8% (14/47) of patients who suffered a major complication and 17% (8/47) who suffered a postoperative neurological deficit, most commonly at the root level (10.6%, 5/47). Of the 8 patients who suffered a neurological deficit, 1 (13%) was able to achieve MCID in the SRS Function domain.
The majority of patients experienced clinically relevant improvement in SRS-22r HRQOL scores after complex ASD surgery. The greatest improvements were seen in the SRS Pain and SRS Self-Image domains. Although 30% of patients suffered a major or permanent complication, benefits from surgery were still attained. Patients sustaining a neurological deficit or major complication were unlikely to achieve HRQOL improvements meeting or exceeding MCID for the SRS Function domain.
Joshua J. Chern, Markus Bookland, Javier Tejedor-Sojo, Jonathan Riley, Mohammadali M. Shoja, R. Shane Tubbs and Andrew Reisner
The rate of readmission after CSF shunt surgery is significant and has caught the attention of purchasers of health care. However, a detailed description of clinical scenarios that lead to readmissions and reoperations after index shunt surgery is lacking in the medical literature.
This study included 1755 shunt revision and insertion surgeries that were performed at a single institution between May 1, 2009, and April 30, 2013. Demographic, socioeconomic, and clinical characteristics were prospectively collected in the administrative, business, and operating room databases. Clinical events within the 30 days following discharge were reviewed and analyzed. Two events of interest, Emergency Department (ED) utilization and reoperation, were further analyzed for risk factor associations by using multivariate logistic regression.
There were 290 readmissions within 30 days of discharge (16.5%). Admission sources included ED (n = 216), hospital transfers (n = 23), and others. Of the 290 readmissions, 184 were associated with an operation, but only 165 of these were performed by the neurosurgical service. These included surgeries for shunt occlusion and externalization (n = 150), wound revision (n = 7), and other neurosurgical procedures that were not shunt related (n = 8). The remaining readmissions (n = 106) were not associated with an operation, and only 59 patients were admitted for issues related to the index shunt surgery.
When return to the ED was the dependent variable in a multivariate regression model, patients who returned to the ED were more likely to be from the Atlanta metropolitan area and to be either uninsured or insured with public assistance. When reoperation was the dependent variable, patients whose surgery started after 3 p.m. were more likely to undergo subsequent CSF shunt revision surgery on readmission.
Of the readmissions within 30 days of shunt surgery, 74.5% were related to the index shunt surgery. Whether and to what extent these readmissions are preventable continues to be controversial. Further study is needed to identify modifiable risk factors that may eventually improve patient care.
Jennifer Muller, Mahdi Alizadeh, Feroze B. Mohamed, Jonathan Riley, John J. Pearce, Benjamin Trieu, Tsao-Wei Liang, Victor Romo, Ashwini Sharan and Chengyuan Wu
Deep brain stimulation (DBS) is an effective procedure in improving motor symptoms for patients with advanced Parkinson’s disease (PD) through the use of high-frequency stimulation. Although one of the most commonly used target sites for DBS, sensorimotor regions of the globus pallidus interna (GPi) have yet to be thoroughly described with advanced neuroimaging analysis in vivo for human subjects. Furthermore, many imaging studies to date have been performed in a research setting and bring into question the feasibility of their applications in a clinical setting, such as for surgical planning. This study compares two different tractography methods applied to clinically feasible acquisition sequences in identifying sensorimotor regions of the GPi and the subthalamic nucleus (STN) in patients with advanced PD selected to undergo DBS.
Seven patients with refractory PD selected for DBS were examined by MRI. Diffusion images were acquired with an average acquisition time of 15 minutes. Probabilistic and deterministic tractography methods were applied to each diffusion-weighted data set using FSL and MRtrix, respectively. Fiber assignment was performed using combined sensorimotor areas as initiation seeds and the STN and GPi, separately, as inclusion masks. Corticospinal tracts were excluded by setting the cerebral peduncles as exclusion masks. Variability between proposed techniques was shown using center of gravity (CoG) coordinates.
Deterministic and probabilistic corticopallidal and corticosubthalamic pathways were successfully reconstructed for all subjects across all target sites (bilaterally). Both techniques displayed large connections between the sensorimotor cortex with the posterolateral aspect of the ipsilateral GPi and the posterosuperolateral aspect of the ipsilateral STN. The average variability was 2.67 mm, with the probabilistic method identifying the CoG consistently more posterior and more lateral than the deterministic method.
Successful delineation of the sensorimotor regions in both the GPi and STN is achievable within a clinically reasonable timeframe. The techniques described in this paper may enhance presurgical planning with increased accuracy and improvement of patient outcomes in patients undergoing DBS. The variability found between tracking techniques warrants the use of the probabilistic tractography method over the deterministic method for presurgical planning. Probabilistic tractography was found to have an advantage over deterministic tractography in its sensitivity, in accurately describing previously described tracts, and in its ability to detect a larger number of fibers.