Decompression Alone Versus Interspinous/Interlaminar Device Placement for Degenerative Lumbar Pathologies: Systematic Review and Meta-Analysis.

INTRODUCTION: Interspinous devices (ISDs) and interlaminar devices (ILDs) are marketed as alternatives to conventional surgery for degenerative lumbar conditions; comparisons with decompression alone are limited. The present study reviews the extant literature comparing the cost and effectiveness of ISDs/ILDs with decompression alone. METHODS: Articles comparing decompression alone with ISD/ILD were identified; outcomes of interest included general and disease-specific patient-reported outcomes, perioperative complications, and total treatment costs. Outcomes were analyzed at <6 weeks, 3 months, 6 months, 1 year, 2 years, and last follow-up. Analyses were performed using random effects modeling. RESULTS: Twenty-nine studies were included in the final analysis. ILD/ISD showed greater leg pain improvement at 3 months (mean difference, -1.43; 95% confidence interval, [-1.78, -1.07]; P < 0.001), 6 months (-0.89; [-1.55, -0.24]; P = 0.008), and 12 months (-0.97; [-1.25, -0.68]; P < 0.001), but not 2 years (P = 0.22) or last follow-up (P = 0.09). Back pain improvement was better after ISD/ILD only at 1 year (-0.87; [-1.62, -0.13]; P = 0.02). Short-Form 36 physical component scores or Zurich Claudication Questionnaire (ZCQ) symptom severity scores did not differ between the groups. ZCQ physical function scores improved more after decompression alone at 6 months (0.35; [0.07, 0.63]; P = 0.01) and 12 months (0.23; [0.00, 0.46]; P = 0.05). Oswestry Disability Index and EuroQoL 5 dimensions scores favored ILD/ISD at all time points except 6 months (P = 0.07). Reoperations (odds ratio, 1.75; [1.23, 2.48]; P = 0.002) and total care costs (standardized mean difference, 1.19; [0.62, 1.77]; P < 0.001) were higher in the ILD/ISD group; complications did not differ significantly between the groups (P = 0.41). CONCLUSIONS: Patient-reported outcomes are similar after decompression alone and ILD/ISD; the observed differences do not reach accepted minimum clinically important difference thresholds. ISD/ILDs have higher associated costs and reoperation rates, suggesting current evidence does not support ILD/ISDs as a cost-effective alternative to decompression alone.

Use of global sagittal flexibility to predict proximal junctional kyphosis after spinal deformity surgery.

OBJECTIVE: Sagittal alignment is an important predictor of functional outcomes after surgery for adult spinal deformity (ASD). A rigid spinal column may create a large lever arm that may impact the rate of proximal junctional kyphosis (PJK) after ASD surgery. In this study, the authors sought to determine whether relatively low preoperative global spinal flexibility (i.e., rigid spine) predicts increased incidence of PJK at 1 year after ASD surgery. METHODS: The authors retrospectively reviewed long-segment thoracolumbar fusions with pelvic fixation performed at a single tertiary care center between October 2015 and September 2020 in patients with a minimum of 1-year radiographic and clinical follow-up. Two cohorts were established on the basis of the optimal value for spinal flexibility, as defined by the absolute difference between the preoperative standing and supine C7 sagittal vertical axes, which the authors termed global sagittal flexibility (GSF). Demographic information, radiographs, various associated complications, and patient-reported outcome measures (PROMs) were analyzed. RESULTS: Eighty-five patients met the inclusion criteria. Receiver operating characteristic (ROC) analysis using GSF to predict an increase in the proximal junctional sagittal Cobb angle (PJCA) greater than or equal to 10° at 1-year follow-up provided an area under the curve of 0.64 and identified an optimal GSF threshold value of 3.7 cm. Patients with GSF > 3.7 cm were considered globally flexible (48 patients), and those with GSF ≤ 3.7 cm were classified as rigid (37 patients). Rigid patients were noted to have a significantly higher risk of ΔPJCA ≥ 10° at 1-year follow-up (51.4% vs 29.3%, p = 0.049). No changes in the reoperation rates or PROMs based on GSF were observed in the 1- or 2-year postoperative window. CONCLUSIONS: Based on these retrospective data, preoperative global spinal rigidity portends an independently elevated risk for the development of PJK after ASD surgery. No differences in other complication rates or PROMs data were observed between groups. Data collection was limited to a 2-year postoperative window; therefore, longer follow-up is required to further elucidate the relationship between rigidity and reoperation rates. Based on these retrospective data, flexibility may influence the outcomes of patients with ASD.

Demineralized Bone Matrix and Fibers in Spinal Fusion.

Formation of bony fusion after arthrodesis depends on osteoinduction, osteoconduction, and osteogenesis. Traditionally, the patient's own bone, or autograft, has been used to provide biological material necessary for these steps. However, the amount of autograft obtainable is often inadequate. Modern spine surgery has adopted the use of many autograft extenders or replacements, such as demineralized bone matrix or fibers. The present article covers the history of bone grafting, the production and technical details of demineralized bone matrix, and the evidence supporting its use in spine fusions.

Promotion of higher rates of early fusion using activated titanium versus polyetheretherketone cages in adults undergoing 1- and 2-level transforaminal lumbar interbody fusion procedures: a randomized controlled trial.

OBJECTIVE: There is ongoing debate on the relative benefits and drawbacks of polyetheretherketone (PEEK) versus titanium (Ti) in generating a bone-to-implant surface microenvironment conducive to osseointegration. Micro- and nanoscale internal and topographic cage modifications have recently been posited to facilitate osseointegration and fusion, but human in vivo confirmation remains lacking. The authors of this study sought to directly compare early radiological outcomes in adults undergoing 1- and 2-level transforaminal lumbar interbody fusion (TLIF) procedures using either PEEK or nano-etched Ti interbody cages with an incorporated microlattice structure. METHODS: Patients were enrolled in a single academic center using a single-blind randomized controlled superiority design. Screening was undertaken from a pool of consecutive patients eligible for TLIF to undergo placement in a 1:1 ratio of either lordotic PEEK or activated Ti cages at each level of 1- or 2-level procedures. An a priori power analysis was performed and a preplanned interim analysis was undertaken once 50 of 70 patients were enrolled. Patient study data were collected perioperatively and uploaded to a Research Electronic Data Capture (REDCap) registry. Interbody fusion was assessed based on 6-month postoperative lumbar dual-energy CT (DECT) studies using the method of Brantigan and Steffee, as modified to describe the Fraser definition of locked pseudarthrosis (Brantigan-Steffee-Fraser [BSF] scale). RESULTS: In the final cohort of 50 patients, 40 interbody levels implanted with PEEK cages were compared with 34 interbody levels with activated Ti cages. The trial was stopped early given the results of an interim analysis with respect to the primary outcome. Surgical parameters including number of levels treated, average cage height, and position were not different between groups. For the PEEK and activated Ti groups, 20.6% versus 84.0% demonstrated BSF grade 3 fusion on 6-month postoperative DECT imaging (p < 0.001). Subsidence at 6 months on DECT was identified in 12 (41.4%) of PEEK levels versus 5 (20.8%) of activated Ti levels (p < 0.001). BSF-3 grading was predictive of segmental stability and numeric rating scale (NRS) leg pain improvement at 1 year postoperatively. Oswestry Disability Index and NRS back and leg pain scores all improved similarly in both cohorts at 1 year postoperatively. CONCLUSIONS: Activated Ti interbody cages mediate early fusion at significantly higher rates with lower rates of subsidence as compared with PEEK cages. These findings support the idea that interbody cage microscale properties, including surface topography, may play a primary role in facilitating osseointegration and fusion.

Electronic versus paper patient-reported outcome measure compliance rates: A retrospective analysis.

OBJECTIVE: Patient-reported outcome measures (PROMs) are key tools used to inform clinical research and patient-centered care. Application of data collected from PROMs, however, may be limited by incomplete responses, and little is known regarding the efficacy of varied PROM delivery methods. The objective of this study was to compare PROMs compliance when delivered via paper and electronic formats. METHODS: Elective adult spinal deformity patients were screened for inclusion. Data collected included demographics, type of surgery, PROMs compliance, and discharge care. Descriptive statistics and multivariate analysis (MVA) were performed to compare pre- and postoperative compliance rates. RESULTS: Of the 474 included patients, 177 were administered paper PROMs, while 297 were electronic. Preoperatively, 101 patients (57.1%) had any portion of their paper PROMs available; 179 (60.3%) had any of their electronic PROMs available (p = 0.492). Among all patients, 76 (42.9%) and 170 (57.2%) had all of their completed preop PROMs available (p = 0.003). Among patients with any of their preop PROMs completed, 75.2% with paper and 95.0% with electronic were completed in their entirety (p < 0.001). Similar trends were observed among postoperative PROMs. MVA demonstrated electronic delivery as the only significant correlate with pre- and post-operative PROMs compliance (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: No differences were observed across modalities when considering any available PROMs, yet electronic PROM delivery was associated with higher completion of PROMs. In order to improve the quality of patient-reported data, electronic delivery with alternative methods of quality improvement may be considered to increase PROMs retention rates.

The Effects of Nicotine- and Cigarette-Related Products on Osteogenesis, Bone Formation, and Bone Mineralization: A Systematic Review.

BACKGROUND: Many clinicians associate nicotine as the causative agent in the negative and deleterious effects of smoking on bone growth and spine fusion. Although nicotine is the primary driver of physiological addiction in smoking, isolated and controlled use of nicotine is one of the most effective adjuncts to quitting smoking. OBJECTIVE: To explore the relationship between nicotine and noncombustion cigarette products on bone growth. METHODS: One thousand five studies were identified, of which 501 studies were excluded, leaving 504 studies available for review. Of note, 52 studies were deemed to be irrelevant. Four hundred fifty-two studies remained for eligibility assessment. Of the remaining 452, 218 failed to assess study outcomes, 169 failed to assess bone biology, 13 assessed 5 patients or fewer, and 12 were deemed to be ineligible of the study criteria. Forty studies remained for inclusion within this systematic review. RESULTS: Of the 40 studies identified for inclusion within the study, 30 studies were classified as "Animal Basic Science," whereas the remaining 10 were categorized as "Human Basic Science." Of the 40 studies, 11 noted decreased cell proliferation and boney growth, whereas 8 showed an increase. Four studies noted an increase in gene expression products, whereas 11 noted a significant decrease. CONCLUSION: The results of this study demonstrate that nicotine has a variety of complex interactions on osteoblast and osteoclastic activities. Nicotine demonstrates dose-dependent effects on osteoblast proliferation, boney growth, and gene expression. Further study is warranted to extrapolate the effects of solitary nicotine on clinical outcomes.

Endoscopic endonasal resection of craniovertebral junction osteomyelitis: illustrative cases.

BACKGROUND: Operative management of craniovertebral junction (CVJ) osteomyelitis has traditionally been extracranial and focused on debriding the infection. In select patients, the endoscopic endonasal approach (EEA) with a focus on additional resection versus debridement may be preferred. The goal of this study is to present the authors' experience with the EEA with gross or subtotal resection for the treatment of osteomyelitis at the CVJ and describe their technique in the context of the literature. OBSERVATIONS: Two patients of the authors' and 6 detailed case reports in the literature were identified with a mean age of 58.9 years. Most patients (n = 5; 62.5%) underwent skull base surgery and debridement (n = 5; 62.5%). Although more common, debridement was inferior to resection in terms of neurological improvement (66.7% vs. 100.0%) postoperatively. The majority (n = 7; 87.5%) of patients underwent occipitocervical fusion. LESSONS: Osteomyelitis is an exceedingly rare lesion of the CVJ. Despite the region's delicate biomechanical stability, resection of infected bone may be superior to debridement alone in terms of clinical outcome. Given how well established the safety of the EEA is to this region, further study of outcomes with resection is warranted.

Baseline parameters and the prediction of treatment failure in patients with intravenous drug use-associated spinal epidural abscesses.

OBJECTIVE: Despite the increasing incidence of spinal epidural abscess (SEA), the baseline parameters potentially predictive of treatment failure remain poorly characterized. In this study, the authors identify the relevant baseline parameters that predict multimodal treatment failure in patients with either intravenous drug use (IVDU)-associated SEA or non-IVDU-associated SEA. METHODS: The authors reviewed the electronic medical records of a large institutional series of consecutive patients with diagnosed SEA between January 2011 and December 2017 to characterize epidemiological trends as well as the complement of baseline measures that are predictive of failure after multimodal treatment in patients with and without concomitant IVDU. The independent impact of clinical and imaging factors in detecting treatment failure was assessed by performing stepwise binary logistic regression analysis. RESULTS: A total of 324 consecutive patients with diagnosed SEA were identified. Overall, 226 patients (69.8%) had SEA related to other causes and 98 (30.2%) had a history of recent IVDU. While non-IVDU SEA admission rates remained constant, year-over-year admissions of patients with IVDU SEA nearly tripled. At baseline, patients with IVDU SEA were distinct in many respects including younger age, greater unemployment and disability, less frequent diabetes mellitus (DM), and more frequent methicillin-resistant Staphylococcus aureus infection. However, differences in length of stay, loss to follow-up, and treatment failure did not reach statistical significance between the groups. The authors constructed independent multivariate logistic regression models for treatment failure based on identified parameters in the two cohorts. For the non-IVDU cohort, the authors identified four variables as independent factors: DM, hepatitis B/C, osteomyelitis, and compression deformity severity. In contrast, for patients with IVDU, the authors identified three variables: albumin, endocarditis, and endplate destruction. Receiver operating characteristic and area under the curve (AUC) analyses were undertaken for the multivariate models predicting the likelihood of treatment failure in the two cohorts (AUC = 0.88 and 0.89, respectively), demonstrating that the derived models could adequately predict the risk of multimodal treatment failure. Treatment failure risk factor point scales were derived for the identified variables separately for both cohorts. CONCLUSIONS: Patients with IVDU SEA represent a unique population with a distinct set of baseline parameters that predict treatment failure. Identification of relevant prognosticating factors will allow for the design of tailored treatment and follow-up regimens.

Radiographic and clinical outcomes in one- and two-level transforaminal lumbar interbody fusions: a comparison of bullet versus banana cages.

OBJECTIVE: The aim of this study was to determine whether cage morphology influences clinical and radiographic outcomes following short-segment transforaminal lumbar interbody fusion (TLIF) procedures. METHODS: The authors retrospectively reviewed one- and two-level TLIFs at a single tertiary care center between August 2012 and November 2019 with a minimum 1-year radiographic and clinical follow-up. Two cohorts were compared based on interbody cage morphology: steerable "banana" cage or straight "bullet" cage. Patient-reported outcome measures (PROMs), radiographs, and complications were analyzed. RESULTS: A total of 135 patients with 177 interbody levels were identified; 45 patients had 52 straight cages and 90 patients had 125 steerable cages. Segmental lordosis increased with steerable cages, while it decreased with straight cages (+3.8 ± 4.6 vs -1.9 ± 4.3, p < 0.001). Conversely, the mean segmental lordosis of adjacent lumbar levels decreased in the former group, while it increased in the latter group (-0.52 ± 1.9 vs +0.52 ± 2.1, p = 0.004). This reciprocal relationship results in global sagittal parameters, including pelvic incidence minus lumbar lordosis and lumbar distribution index, which did not change after surgery with either cage morphology. Multivariate analysis confirmed that steerable cage morphology, anterior cage positioning, and less preoperative index-level segmental lordosis were associated with greater improvement in index-level segmental lordosis. PROMs were improved after surgery with both cage types, and the degree of improvement did not differ between cohorts (p > 0.05). Perioperative and radiographic complications were similar between cohorts (p > 0.05). Overall reoperation rates, as well as reoperation rates for adjacent-segment disease within 2 years of surgery, were not significantly different between cohorts. CONCLUSIONS: Steerable cages are more likely to lie within the anterior disc space, thus increasing index-level segmental lordosis, which is accompanied by a reciprocal change in segmental alignment at the adjacent lumbar levels. The converse relationship occurs for straight cages, with a kyphotic change at the index levels and reciprocal lordosis occurring at adjacent levels.

Resident Night Float or 24-hour Call Hospital Coverage: Impact on Training, Patient Outcome, and Length of Stay.

OBJECTIVE: The impact of neurosurgical resident hospital coverage system, performed via a night float (12-hour shifts overnight) or a 24-hour call, on neurological surgery resident training and patient care is unknown. DESIGN: Retrospective review comparing night float and 24-hour call coverage on trainee surgical experience, elective time, annual program surveys, patient outcomes, and length of stay. SETTING: The Ohio State Wexner Medical Center Neurosurgery residency program, Columbus, Ohio. PARTICIPANTS: The neurosurgical residents from 2016 to 2019. RESULTS: Monthly cases performed by junior residents significantly increased after transitioning to a 24-hour call schedule (18 versus 30, p < 0.001). There were no differences for total cases among program graduates during this time (p = 0.7). Trainee elective time significantly increased after switching to 24-hour call coverage (18 versus 24 months after the transition; p = 0.004). Risk-adjusted mortality and length of stay indices were not different (0.5 versus 0.3, p = 0.1; 0.9 versus 0.9; p = 0.3). Program surveys had minimal change after the transition to 24-hour call. CONCLUSIONS: Transitioning from a night float to a 24-hour call coverage system led to improved junior resident case volume and elective time without detrimental effect on patient-related outcomes.

Negative pressure wound therapy in spinal fusion patients.

Post-operative wound complications are some of the most common acute complications following spine surgery. These surgical site infections (SSI) contribute to increased healthcare related costs. Negative pressure wound therapy (NPWT) has long been used for treatment of soft tissue injury or defects. NPWT may reduce the incident of SSI following spinal fusion procedures; however, its potential applications need further clarification. Thus, we conducted a retrospective analysis of two cohorts to compare NPWT to traditional sterile dressings following spinal fusions in regards to post-operative outcomes. Following institutional review board approval, 42 patients who had a NPWT were matched by type of surgery to 42 patients who had traditional dressings. A retrospective chart-review was completed. Outcome measures, particularly SSI and need for reoperation, were analyzed using one-way ANOVA for both univariate and multivariate analysis. When controlled for sex and body-mass index, the use of a NPWT was independently correlated with decreased SSI (P = .035). Superficial dehiscence, seroma, need for additional outpatient care, and need for operative revision were all found to occur at higher rates in the traditional dressing cohort. Closed incisional negative pressure wound therapy provides a cost-effective method of decreasing surgical site infection for posterior elective spine surgeries.

Risk factors associated with reoperation in posterior cervical fusions: A large-scale retrospective analysis.

OBJECTIVES: To identify risk factors for reoperation in patients who have undergone posterior cervical fusion (PCF). PATIENTS AND METHODS: A retrospective cohort analysis was performed of patients undergoing PCF during a 12-year period at a single institution. Demographic and surgical characteristics were collected from electronic medical records. This study addressed reoperations, from all causes, of PCF. Different strategies, including the addition of anterior fusion, were also compared. RESULTS: Of the 370 patients meeting inclusion criteria there were 44 patients (11.9 %) that required a revision and of those 5 required a second revision. The most common reasons for revision were adjacent segment disease and infection, 13 (3.5 %) and 11 patients (3.0 %), respectively. There was not a higher revision rate (for any cause) for patients who had a subaxial fusion and compared with those that included C2 or those that failed to cross the cervicothoracic junction. Of patients who required reoperation, there was a statistically significant higher fraction of smokers (p =  0.023). CONCLUSION: The risks and benefits of posterior cervical instrumentation and fusion should be thoroughly discussed with patients. This report implicates smoking as a risk factor for all-cause reoperation in patients who have had this PCF and provides surgeons with additional data regarding this complication. When possible, preoperative optimization should include smoking cessation therapy.

Impact of the Inclusion of C2 in Posterior Cervical Fusions for Cervical Myelopathy on Sagittal Cervical Alignment.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the impact of including C2 in posterior fusions on radiographic parameters of cervical alignment in cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Despite the use of posterior instrumentation and arthrodesis after cervical laminectomy, loss of lordosis and the development of kyphosis are prevalent. Inadequate cervical lordosis and other measures of sagittal cervical alignment have been shown to correlate with disability, general health scores, and severity of myelopathy. The role of C2 in the posterior tension band, which maintains sagittal alignment, differs from the subaxial spine, as it is the insertion point for erector spinae muscles that play a critical role in maintaining posture. PATIENTS AND METHODS: This study compares the radiographic outcomes of sagittal balance between 2 cohorts of patients who underwent posterior cervical decompression and fusion for cervical myelopathy over a 12-year period at a single institution. Demographic and surgical characteristics were collected using the electronic medical record of patients undergoing posterior cervical fusions (PCF) which included the axis [axial fusion (AF)] and those that were subaxial fusions (SAF). Radiographic measurements included preopertaive and postoperative C2-C7 lordosis (CL), C2-C7 sagittal vertical axis (SVA), and T1 slope (T1S). RESULTS: After review of the electronic medical records, 229 patients were identified as having PCF and decompression for treatment of myelopathy. One hundred sixty-seven patients had AF, whereas 62 had SAF. PCF resulted in loss of CL in both cohorts. Although there was no statistical difference in postoperative CL, there was a significant increase in SVA (P<0.001) and T1S (P<0.001) with AF. CONCLUSIONS: PCF often result in loss of lordosis. When compared with SAF, inclusion of C2 into the fusion construct may result in worsened sagittal balance, increasing the SVA and T1S.

Efficacy of Intravenous Tranexamic Acid in Reducing Perioperative Blood Loss and Blood Product Transfusion Requirements in Patients Undergoing Multilevel Thoracic and Lumbar Spinal Surgeries: A Retrospective Study.

Introduction: Acute perioperative blood loss is a common and potentially major complication of multilevel spinal surgery, usually worsened by the number of levels fused and of osteotomies performed. Pharmacological approaches to blood conservation during spinal surgery include the use of intravenous tranexamic acid (TXA), an anti-fibrinolytic that has been widely used to reduce blood loss in cardiac and orthopedic surgery. The primary objective of this study was to assess the efficacy of intraoperative TXA in reducing estimated blood loss (EBL) and red blood cell (RBC) transfusion requirements in patients undergoing multilevel spinal fusion. Materials and Methods: This a single-center, retrospective study of subjects who underwent multilevel (≥7) spinal fusion surgery who received (TXA group) or did not receive (control group) IV TXA at The Ohio State University Wexner Medical Center between January 1st, 2016 and November 30th, 2018. Patient demographics, EBL, TXA doses, blood product requirements and postoperative complications were recorded. Results: A total of 76 adult subjects were included, of whom 34 received TXA during surgery (TXA group). The mean fusion length was 12 levels. The mean total loading, maintenance surgery and total dose of IV TXA was 1.5, 2.1 mg per kilo (mg/kg) per hour and 33.8 mg/kg, respectively. The mean EBL in the control was higher than the TXA group, 3,594.1 [2,689.7, 4,298.5] vs. 2,184.2 [1,290.2, 3,078.3] ml. Among all subjects, the mean number of intraoperative RBC and FFP units transfused was significantly higher in the control than in the TXA group. The total mean number of RBC and FFP units transfused in the control group was 8.1 [6.6, 9.7] and 7.7 [6.1, 9.4] compared with 5.1 [3.4, 6.8] and 4.6 [2.8, 6.4], respectively. There were no statistically significant differences in postoperative blood product transfusion rates between both groups. Additionally, there were no significant differences in the incidence of 30-days postoperative complications between both groups. Conclusion: Our results suggest that the prophylactic use of TXA may reduce intraoperative EBL and RBC unit transfusion requirements in patients undergoing multilevel spinal fusion procedures ≥7 levels.

Drug repositioning in epilepsy reveals novel antiseizure candidates.

Objective: Epilepsy treatment falls short in ~30% of cases. A better understanding of epilepsy pathophysiology can guide rational drug development in this difficult to treat condition. We tested a low-cost, drug-repositioning strategy to identify candidate epilepsy drugs that are already FDA-approved and might be immediately tested in epilepsy patients who require new therapies. Methods: Biopsies of spiking and nonspiking hippocampal brain tissue from six patients with unilateral mesial temporal lobe epilepsy were analyzed by RNA-Seq. These profiles were correlated with transcriptomes from cell lines treated with FDA-approved drugs, identifying compounds which were tested for therapeutic efficacy in a zebrafish seizure assay. Results: In spiking versus nonspiking biopsies, RNA-Seq identified 689 differentially expressed genes, 148 of which were previously cited in articles mentioning seizures or epilepsy. Differentially expressed genes were highly enriched for protein-protein interactions and formed three clusters with associated GO-terms including myelination, protein ubiquitination, and neuronal migration. Among the 184 compounds, a zebrafish seizure model tested the therapeutic efficacy of doxycycline, metformin, nifedipine, and pyrantel tartrate, with metformin, nifedipine, and pyrantel tartrate all showing efficacy. Interpretation: This proof-of-principle analysis suggests our powerful, rapid, cost-effective approach can likely be applied to other hard-to-treat diseases.

Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals.

Differential DNA methylation in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to postmortem samples. The use of surrogate tissues has become common in identifying methylation changes associated with psychiatric disease. In this study, we determined the extent to which peripheral tissues can be used as surrogates for DNA methylation in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 patients with medically intractable epilepsy undergoing brain resection were collected (age range 5-61 years). Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n = 12) and HumanMethylationEPIC BeadChip arrays (n = 21). For the EPIC methylation data averaged for each CpG across subjects, the saliva-brain correlation (r = 0.90) was higher than that for blood-brain (r = 0.86) and buccal-brain (r = 0.85) comparisons. However, within individual CpGs, blood had the highest proportion of CpGs correlated to brain at nominally significant levels (20.8%), as compared to buccal tissue (17.4%) and saliva (15.1%). For each CpG and each gene, levels of brain-peripheral tissue correlation varied widely. This indicates that to determine the most useful surrogate tissue for representing brain DNA methylation, the patterns specific to the genomic region of interest must be considered. To assist in that objective, we have developed a website, IMAGE-CpG, that allows researchers to interrogate DNA methylation levels and degree of cross-tissue correlation in user-defined locations across the genome.