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Study Design: A retrospective cross-sectional study., Objective: To assess the association between spinal muscle morphology and spinopelvic parameters in lumbar fusion patients, with a special emphasis on lumbar lordosis (LL)., Summary of Background Data: Maintenance of sagittal alignment relies on muscle forces, but the basic association between spinal muscles and spinopelvic parameters is poorly understood., Materials and Methods: Patients operated between 2014 and 2017 who had both lumbar magnetic resonance imaging scan and standing whole-spine radiographs within six months before surgery were included. Muscle measurements were conducted on axial T2-weighted magnetic resonance images at the superior endplate L3-L5 for the psoas and L3-S1 for combined multifidus and erector spinae (paraspinal) muscles. A pixel intensity threshold method was used to calculate the total cross-sectional area (TCSA) and the functional cross-sectional area (FCSA). Spinopelvic parameters were measured on lateral standing whole-spine radiographs and included LL, pelvic incidence (PI), PI-LL mismatch, pelvic tilt, sacral slope, thoracic kyphosis, and sagittal vertical axis. Analyses were stratified by biological sex. Multivariable linear regression analyses with adjustments for age and body mass index (BMI) were performed., Results: A total of 104 patients (62.5% female) were included in the analysis. The patient population was 90.4% White with a median age at surgery of 69 years and a median BMI of 27.8 kg/m 2 . All muscle measurements were significantly smaller in women. PI, pelvic tilt, and thoracic kyphosis were significantly greater in women. PI-LL mismatch was 6.1° (10.6°) in men and 10.2° (13.5°) in women ( P =0.106), and sagittal vertical axis was 45.3 (40.8) mm in men and 35.7 (40.8) mm in women ( P =0.251). After adjusting for age and BMI, paraspinal TCSA at L3-L5, and paraspinal FCSA at L4 showed significant positive associations with LL in women. In men, psoas TCSA at L5 and psoas FCSA at L5 showed significant negative associations with LL, but none of the paraspinal muscle measurements., Conclusion: Our findings indicate that psoas and lumbar spine extensor muscles interact differently on LL among men and women, creating a unique mechanical environment., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal surgery makes prophylactic measures an imperative focus. Therefore, the aim of this review was to evaluate the available research related to the efficacy of different intraoperative irrigation techniques used in spinal surgery for surgical site infection (SSI) prophylaxis., Methods: We performed a comprehensive search using Ovid Medline, EMBASE, Web of Science and the Cochrane library pertaining to this topic. Our meta-analysis was conducted according to PRISMA guidelines. The inclusion criteria consist of spine surgeries with intraoperative use of any wound irrigation technique, comparison groups with a different intraoperative irrigation technique or no irrigation, SSI identified with bacterial cultures or clinically in the postoperative period, reported SSI rates. Data extracted from eligible studies included, but was not limited to, SSI rates, irrigation technique and control technique. Exclusion criteria consist of articles with no human subjects, reviews, meta-analyses and case control studies and no details about SSI identification or rates. Pooled risk ratios were calculated. A meta-analysis was performed with a forest plot to determine risk estimates' heterogeneity with I 2 index, Q-statistic, and p value under a random-effects model. Funnel plot was used to assess publication bias. All databases were last checked on January, 2022. PROBAST tool was used to assess both risk of bias and applicability concerns., Results: After reviewing 1494 titles and abstracts, 18 articles met inclusion criteria. They included three prospective randomized-controlled trials, 13 retrospective cohort studies, two prospective cohort studies. There were 54 (1.8%) cases of SSIs in the povidone-iodine irrigation group (N = 2944) compared to 159 (4.6%) in the control group (N = 3408). Using intraoperative povidone-iodine wound irrigation produced an absolute risk reduction of 2.8%. Overall risk ratio was 0.32 (95% CI 0.20-0.53, p < 0.00001). In a global analysis, study heterogeneity and synthesizing mostly retrospective data were primary limitations., Conclusion: The most evidence exists for povidone-iodine and has Level 2 evidence supporting SSI reduction during spinal surgery. Other antiseptic solutions such as dilute chlorhexidine lack published evidence in this patient population which limits the ability to draw conclusions related to its use in spinal surgery., Level of Evidence: II - Systematic Review with Meta-Analysis., (© 2022. The Author(s).)

Background: Prophylactic anticoagulation is commonly used following operative treatment of spinal fractures to prevent Venous Thromboembolism (VTE) but carries a risk of bleeding complications. The purpose of the study was to compare VTE and bleeding complications for MID (≤72h) versus LATE (>72h) chemoprophylaxis timing after spinal fracture operative intervention., Methods: This is a retrospective review of patients treated for spinal fractures that received anticoagulation chemoprophylaxis between May 2015 and June 2019. Chemoprophylaxis initiation timing (MID vs. LATE) was the primary grouping variable. Patients with traumatic brain injury or evidence of intracranial or intraspinal bleed were excluded. Demographics, injury mechanisms, operative procedures, timing of administration of VTE prophylaxis, Injury Severity Score (ISS) and Spine Abbreviated Injury Scale (AIS), and complications including VTE and bleeding complications were collected. Predictors of VTE were identified using a binary logistic regression., Results: Eighty-eight patients (65M, 23F) met inclusion criteria. The median age was 55 years, and median Injury Severity Score (ISS) was 14. MID had 68 patients and LATE had 20. Nine patients developed VTE (6 LATE, 3 MID, p< 0.01 ) . Three patients developed bleeding complications, and all occurred in the LATE group ( p= 0.01 ) . ISS ( p <0.01) and GCS ( p <0.01) also correlated with an increased VTE rate., Conclusions: Chemoprophylactic anticoagulation at 72 hours in surgically treated spinal fracture patients demonstrates a lower VTE rate without increasing complications. VTE prophylaxis can be initiated at 72 hours following spine fixation to decrease postinjury morbidity and mortality in this high-risk patient population., Competing Interests: None., (© 2022 The Author(s).)

Study Design: Retrospective single-center study., Objective: Investigate the effect of posterior instrumentation on the relationship between lordosis and kyphosis., Methods: Surgically treated patients with a minimum of 6 months of follow-up were analyzed. Asymptomatic volunteers served to show the normal anatomical relationship between thoracic and lumbar curves. Patients were stratified based on postoperative instrumentation: "Thoracic Fusion" = complete fusion of thoracic spine; "Lumbar Fusion" = complete fusion of lumbar spine; and "Complete Fusion" = fusion from sacrum to at least T5. Bivariate correlations and regression analysis were used to evaluate the relationship between change in thoracic kyphosis (ΔTK) and change in spinopelvic mismatch (ΔPI-LL; pelvic incidence-lumbar lordosis) before and after fusion. Analyses were repeated in "Lumbar Fusion" patients with flexible preoperative thoracic spines., Results: For asymptomatic volunteers, the natural anatomical relationship between TK and LL was found to be TK = 41% of LL ( r = 0.425, P < .001). A total of 153 of 167 adult spinal deformity patients were included (62 years old, 26.7 kg/m 2 , 78% female). Mean follow-up was 11.5 ± 6.8 months. "Thoracic Fusion" group showed no alteration in the natural relationship between TK and LL (ΔTK = 39% ΔPI-LL), whereas "Lumbar Fusion" group had a reduction in reciprocal change (ΔTK = 34% ΔPI-LL) although a subanalysis of patients in the "Lumbar Fusion" group with flexible thoracic spines showed a marked compensation in reciprocal change with (ΔTK = 58% ΔPI-LL)., Conclusion: The relationship between ΔTK and ΔPI-LL is dependent on level instrumented. "Thoracic Fusion" drives change in LL while this relationship is affected by TK's natural stiffness in "Lumbar Fusion" patients.

Study Design: Retrospective, cross-sectional., Objective: To evaluate the impact of unoperated adolescent idiopathic scoliosis (AIS) in adulthood on pain, quality of life, and need for operative management., Background: Long-term studies of AIS in adulthood demonstrate most patients function well, though some have increased disability. The Oswestry Disability Index (ODI) and SRS-22r are validated questionnaires for assessing back disability and quality of life. Correlation of these questionnaires to patient outcomes and necessity for surgery have not been fully defined., Methods: Unoperated adults with AIS seen in a tertiary deformity clinic from 2008-2018 were identified. Variables included demographics, comorbidities, family history, curve size/location, pain score, ODI, SRS-22r, and previous treatment. ODI and SRS-22r scores were analyzed across three age groups: 20-39, 40-59, and ≥ 60., Results: 275 eligible patients were identified and 255 (93%) patients had an ODI and/or SRS-22r score. ODI scores (220 patients) had a positive correlation with age, BMI, and curve size (p < .001). SRS-22r (204 patients) pain score was worse in all age-gender-matched domains (p < .05). Of the 255 patients in the study, 10% underwent surgery after presentation. In 118 patients with surgical-size curves (thoracic ≥ 50°; thoracolumbar ≥ 40°), no difference was seen in age or curve size between surgical and non-surgical patients; however, ODI and SRS-22r scores (excluding mental health) were significantly worse in surgical patients (p ≤ .01)., Conclusions: Patients with AIS have SRS-22r scores that are lower than age-gender-matched controls in most domains. ODI had a positive linear correlation with age, body mass index, and curve size. Only 10% of adults with surgical-size curves evaluated for scoliosis elected to undergo surgery. Patients treated surgically reported worse preoperative quality-of-life scores than their non-surgical counterparts. These results can help healthcare providers when counseling patients and families concerning management options., Level of Evidence: III.

Objective: Osteoporosis is a metabolic bone disease that increases the risk for fragility fractures. Screening and diagnosis can be achieved by measuring bone mineral density (BMD) using quantitative CT tomography (QCT) in the lumbar spine. QCT-derived BMD measurements can be used to diagnose osteopenia or osteoporosis based on American College of Radiology (ACR) thresholds. Many reports exist regarding the disease prevalence in asymptomatic and disease-specific populations; however, osteoporosis/osteopenia prevalence rates in lumbar spine fusion patients without fracture have not been reported. The purpose of this study was to define osteoporosis and osteopenia prevalence in lumbar fusion patients using QCT., Methods: A retrospective review of prospective data was performed. All patients undergoing lumbar fusion surgery who had preoperative fine-cut CT scans were eligible. QCT-derived BMD measurements were performed at L1 and L2. The L1-2 average BMD was used to classify patients as having normal findings, osteopenia, or osteoporosis based on ACR criteria. Disease prevalence was calculated. Subgroup analyses based on age, sex, ethnicity, and history of abnormal BMD were performed. Differences between categorical groups were calculated with Fisher's exact test., Results: Overall, 296 consecutive patients (55.4% female) were studied. The mean age was 63 years (range 21-89 years). There were 248 (83.8%) patients with ages ≥ 50 years. No previous clinical history of abnormal BMD was seen in 212 (71.6%) patients. Osteopenia was present in 129 (43.6%) patients and osteoporosis in 44 (14.9%). There were no prevalence differences between sex or race. Patients ≥ 50 years of age had a significantly higher frequency of osteopenia/osteoporosis than those who were < 50 years of age., Conclusions: In 296 consecutive patients undergoing lumbar fusion surgery, the prevalence of osteoporosis was 14.9% and that for osteopenia was 43.6% diagnosed by QCT. This is the first report of osteoporosis disease prevalence in lumbar fusion patients without vertebral fragility fractures diagnosed by QCT.

Objective: There have been some reports on the association between spinal balance parameters and regional bone mineral density (BMD), but the results are controversial. The purpose of this study is to evaluate the relationship between spinopelvic parameters and regional volumetric BMDs (vBMDs) measured by quantitative computed tomography (QCT) in the lumbosacral region of patients undergoing lumbar fusion surgery., Methods: The data of consecutive patients undergoing posterior lumbar spinal fusion with preoperative computed tomography was reviewed. QCT measurements were conducted in L1-S1 vertebral trabecular bone. The associations between spinopelvic sagittal parameters and vBMDs were evaluated. Multivariate analyses adjusted with age, gender, race, and body mass index were conducted with vBMD as the response variable., Results: A total of 144 patients were included in the final analyses. Mean age (± standard deviation) was 65.4 ± 11.8 years. Mean vBMD in L1 (± standard deviation) was 118.3 ± 37.4 mg/cm 3 . After adjusting by cofactors, lumbar lordosis was negatively associated with vBMDs in all levels from L1 to L5 (% regression coefficients and adjusted R 2 values: L1, -0.438, 0.268; L2, -0.556, 0.296; L3, -0.608, 0.362; L4, -0.554, 0.228; L5, -0.424, 0.194), but not in S1. Sacral slope was negatively associated with vBMD only at L4 (% coefficient, -0.588; R 2 , 0.208). Other parameters were not significantly associated with vBMDs at any levels., Conclusions: Higher lumbar lordosis was associated with lower vBMDs in all lumbar spine levels. Our results suggest that BMD is affected not only by metabolic factors but also by the mechanical environment. Further longitudinal studies are needed to elucidate this effect of vBMD on clinical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Study Design: Prospective cohort study., Objective: To examine preoperative urinary cross-linked n-telopeptide (uNTx) and assess for association with fusion rates in patients undergoing single and multi-level anterior cervical decompression and fusion (ACDF)., Summary of Background Data: Although high rates of fusion have been reported for ACDF, the risk of pseudarthrosis remains substantial. An established marker of bone turnover, uNTx may prove useful as a predictor of fusion., Methods: Patients undergoing primary ACDF with allograft/plating technique from 2015 to 2017 by a single surgeon were consecutively enrolled and preoperative uNTx was collected. Patients undergoing revision, with creatinine >1.2, and with improperly-collected uNTx were excluded. Demographics, laboratory values, and fusion status were assessed at 6 months, 1 year, and 2 years postoperatively., Results: Of the 97 patients enrolled, 69 met inclusion criteria. Of included cases, 41%, 33%, 18%, and 8% underwent 1-, 2-, 3-, and 4-level ACDF, respectively. Overall, fusion rates were 37.3%, 70.9%, and 95.3% at 6 months, 1 year, and 2 years, respectively. uNTx was higher in the fusion group (31.1 vs. 22.2, P = 0.001) at 6 months and 1 year (30.0 vs. 21.0, P = 0.006), with no difference at 2 years. No differences were identified in the proportion of smokers, immunomodulatory agents, corpectomies, or fusion levels between groups. Multivariate regression analysis demonstrated that uNTx is an independent predictor of fusion (odds ratio, OR, 1.124, P = 0.003). Both groups experienced improvements in NDI and VAS neck pain at 6 months with no significant differences noted between groups. Of 16 patients with pseudarthrosis at 1 year, 2 underwent posterior cervical fusion for symptoms., Conclusion: Preoperative uNTx was greater in patients with successful ACDF fusion compared with patients with pseudarthrosis at 6 months and 1 year. A negative correlation was found between preoperative uNTx and motion on dynamic imaging. These results suggest that uNTx could serve to identify patients at risk for pseudarthrosis after ACDF., Level of Evidence: 3.

Background: Transforaminal lumbar interbody fusion (TLIF) is a well-accepted surgical technique for the treatment of degenerative spinal conditions and spinal deformity. The TLIF procedure can be performed open or using minimally invasive techniques. While several studies have found that minimally invasive TLIF (MI-TLIF) has advantages over open TLIF procedures with less blood loss, postoperative pain and hospital length of stay, opponents of the minimally invasive technique cite the lack of restoration of lumbar lordosis as a major drawback. With the increasing awareness of restoring sagittal alignment parameters in degenerative and deformity procedures, surgeons should understand the capabilities of different procedures to achieve surgical goals. To our knowledge, few studies have specifically studied the radiographic restoration of lumbar lordosis after MI-TLIF procedures. The purpose of this study was to perform a systematic review of the literature describing the sagittal lumbar radiographic parameter changes after MI-TLIF., Methods: Following PRISMA guidelines, systematic review was performed. With the assistance of a medical librarian, a highly-sensitive search strategy formulated on 1/19/2018 utilized the following search terms: "minimally invasive procedures," "transforaminal lumbar interbody fusion," "lumbar interbody fusion," "diagnostic imaging," "radiographs," "radiography," "x-rays," "lordosis," "lumbar vertebrae," "treatment," "outcome," and "lumbosacral" using Boolean operators 'AND' and 'OR'. Three databases were searched (PubMed/Medline, Embase, and Cochrane Library). An online system (www.covidence.org) was used to standardize article review. All studies were independently analyzed by two investigators and discrepancies mitigated by a third reviewer. Study selection for each cycle was Yes/No/Maybe. Cycles were: (1) (Title/Abstract); (2) (Full Text); (3) (Extraction). Inclusion criteria were: (1) All study designs, (2) MI-TLIF procedures, (3) Reporting total lumbar lordosis (LL) and/or segmental lordosis (SL) pre- and postoperatively. Exclusion criteria were: (1) non MI-TLIF procedures (ALIF, XLIF, LLIF, conventional TLIF, OLIF), (2) No reported LL or SL., Results: The search yielded 4,036 results with 836 duplicates leaving 3,200 studies for review. Cycle 1 eliminated 3,153 studies as irrelevant, thus, 47 were eligible for full-text review. Cycle 2 excluded 31 studies for No English full text (9), Oral/Poster (8), Wrong intervention/outcome (10), Duplicate listing (2), Full text not available (1), Literature review (1) resulting in 16 included studies. Study designs were: Randomized-controlled trial (3), Case series (6) and Retrospective (7). Mean # of subjects were 32.0 (range 8-95). Weighted-mean LL was 39.6°±9.2 (range 28-57) and postoperative LL was 45.0°±7.4 (range 36-67) with a LL post-pre difference of 5.2°±5.9 (range -7 to 15). Weighted-mean preoperative SL was 12.7°±4.3 (range 5-21) and postoperative SL was 15.0°±4.5 (range 5-22) with a SL post-pre difference of 2.1°±1.7 (range 0-8)., Conclusions: The current literature on MI-TLIF and restoration of LL/SL is limited to 16 published studies, 44% of which are retrospective. The published evidence supporting LL and SL restoration with MI-TLIF is sparse with variable results. This systematic review demonstrates the need for future high-level studies to fully elucidate the capabilities of MI-TLIF procedures for restoring lumbar and segmental lordosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Intervertebral disc herniation (IDH) can cause back pain and/or radiculopathy and accounts for a significant portion of patients having spinal surgery in the USA. One of the most impactful and well-executed randomized trials to study diagnosis, treatments, and outcomes in patients with three commonly treated spinal conditions was the Spine Patient Outcomes Research Trial (SPORT). This study and the subsequent data analyses have resulted in numerous publications related to IDH. The purpose of this review is to summarize SPORT publications with IDH results to better understand what we have learned from this important landmark trial., Methods: Publications utilizing SPORT data that reported findings related to IDH patients were identified from Medline, PubMed, and PubMed Central. The primary findings pertaining to IDH were summarized., Results: There were 25 studies identified reporting findings related to IDH from the SPORT data published between 2004 and 2017. Publications in the following areas were summarized: epidemiology and baseline patient characteristics (1), treatment preferences and expectations (2), radiological and MRI (3), primary study objectives at two years (2), four years (1) and eight years (1), subgroup analyses (13), cost-effectiveness (1), and reherniation (1)., Conclusions: This report reviewed the current state of SPORT publications related to IDH to identify and summarize what we have learned about diagnosis, patient characteristics, treatments, outcomes, and cost-effectiveness in patients with lumbar disc herniations. Many important findings are now published from this robust trial's data. Clinicians should incorporate these results into their clinical decision-making and during counseling patients presenting with lumbar disc herniations.

Background Context: Quantitative computed tomography (QCT) of the lumbar spine is used as an alternative to dual-energy X-ray absorptiometry in assessing bone mineral density (BMD). The average BMD of L1-L2 is the standard reportable metric used for diagnostic purposes according to current recommendations. The density of L1 and L2 has also been proposed as a reference value for the remaining lumbosacral vertebrae and is commonly used as a surrogate marker for overall bone health. Since regional BMD differences within the spine have been proposed, it is unclear if the L1-L2 average correlates with the remainder of the lumbosacral spine., Purpose: The aim of this study was to determine possible BMD variations throughout the lumbosacral spine in patients undergoing lumbar fusion and to assess the correlation between the clinically used L1-L2 average and the remaining lumbosacral vertebral levels., Study Design/setting: This is a retrospective case series., Patient Sample: Patients undergoing posterior lumbar spinal fusion from 2014 to 2017 at a single, academic institution with available preoperative CT imaging were included in this study., Outcome Measures: The outcome measure was BMD measured by QCT., Methods: Standard QCT measurements at the L1 and L2 vertebra and additional experimental measurements of L3, L4, L5, and S1 were performed. Subjects with missing preoperative lumbar spine CT imaging were excluded. The correlations between the L1-L2 average and the other vertebral bodies of the lumbosacral spine (L3, L4, L5, S1) were evaluated., Results: In total, 296 consecutive patients (55.4% female, mean age of 63.1 years) with available preoperative CT were included. The vertebral BMD values showed a gradual decrease from L1 to L3 and increase from L4 to S1 (L1=118.8 mg/cm 3 , L2=116.6 mg/cm 3 , L3=112.5 mg/cm 3 , L4=122.4 mg/cm 3 , L5=135.3 mg/cm 3 , S1=157.4 mg/cm 3 ). There was strong correlation between the L1-L2 average and the average of the other lumbosacral vertebrae (L3-S1) with a Pearson's correlation coefficient (r=0.85). We also analyzed the correlation between the L1-L2 average and each individual lumbosacral vertebra. Similar relationships were observed (r value, 0.67-0.87), with the strongest correlation between the L1-L2 average and L3 (r=0.87)., Conclusions: Our data demonstrate regional BMD differences throughout the lumbosacral spine. Nevertheless, there is high correlation between the clinically used L1-L2 average and the BMD values in the other lumbosacral vertebrae. We, therefore, conclude the standard clinically used L1-L2 BMD average is a useful bone quantity measure of the entire lumbosacral spine in patients undergoing lumbar spinal fusion., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: Members of the Scoliosis Research Society are required to annually submit complication data regarding deaths, visual acuity loss, neurological deficit and infection (2012-1st year for this measure) for all deformity operations performed. The purpose of this study is to report the 2012 results and the differences in these complications from the years 2009-2012., Methods: The SRS M&M database is a self-reported complications registry of deformity operations performed by the members. The data from 2009-2012, inclusive, was tabulated and analyzed. Differences in frequency distribution between years were analyzed with Fisher's exact test. Significance was set at α = 0.05., Results: The total number of cases reported increased from 34,332 in 2009 to 47,755 in 2012. Overall mortality ranged from 0.07% in 2011 to 0.12% in 2009. The neuromuscular scoliosis group had the highest mortality rate (0.44%) in 2010. The combined groups' neurological deficit rate increased from 0.44% in 2009 to 0.79% in 2012. Neurological deficits were significantly lower in 2009 compared to 2012 for idiopathic scoliosis >18 years, other scoliosis, degenerative and isthmic spondylolisthesis and other groups. The groups with the highest neurological deficit rates were dysplastic spondylolisthesis and congenital kyphosis. There were no differences in vision loss rates between years. The overall 2012 infection rate was 1.14% with neuromuscular scoliosis having the highest group rate at 2.97%., Conclusion: Neuromuscular scoliosis has the highest complication rates of mortality and infection. The neurological deficit rates of all groups combined have slightly increased from 2009 to 2012 with the highest rates consistently being in the dysplastic spondylolisthesis and congenital kyphosis groups. This could be due to a number of factors, including more rigorous reporting., (Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Tobacco use has documented negative effects on perioperative complications and clinical outcomes. Smoking cessation before spinal surgery may improve clinical outcomes. The goal of this study was to determine the recidivism rate after smoking cessation before spinal fusion. A prospective observational study was performed at the University of Kansas Medical Center between 2006 and 2011. All patients with serum-confirmed nicotine cessation before spinal fusion surgery were eligible. Smoking status was determined with questionnaires at 3 months, 6 months, and 1 year postoperatively. All reported nonsmokers had confirmatory serum nicotine and cotinine tests. Two-tailed Pearson chi-square and independent t tests were conducted, and significance was set at α=0.05. A total of 42 subjects (21 women, 21 men) with confirmed preoperative serum-negative test results were prospectively enrolled over a period of 3.9 years. Of these patients, 1 opted out at 6 months and 1 died of unknown cause. The findings showed a recidivism rate (response rate) of 60% (40 of 41) at 3 months, 61% (33 of 41) at 6 months, and 68% (25 of 40) at 1 year. One case of asymptomatic pseudarthrosis occurred 1 year postoperatively in a confirmed nonsmoker. No correlation was found between smoking status at 3 months and sex, primary vs revision surgery, or complications (P>.05). Smokers who relapsed at 3 months were older than nonsmokers (55.2 vs 44.2 years, respectively; P=.03). Some patients are willing to cease smoking before spinal fusion for optimal clinical outcomes; however, the rate of recidivism is high (60%) within the first 3 months post-operatively., (Copyright 2016, SLACK Incorporated.)

Background: Cobb measurement of standing radiographs is the standard for clinical assessment of coronal spinal deformity. Angle of trunk inclination (ATI) is an accepted clinical measurement of trunk asymmetry, and has variable reported correlations with Cobb angles. Transverse plane spine deformity is most accurately measured using axial computed tomography. Aaro and Dahlbourn's technique for quantifying apical vertebral rotation with respect to the sagittal plane (RAsag) is commonly reported in the literature. To our knowledge no study has correlated ATI with RAsag. The purpose of this study was to determine the relationship between commonly used measures of trunk and spine deformity., Methods: Sixteen females that underwent preoperative apical vertebra(e) CT scans were retrospectively studied. Thoracic and thoracolumbar RAsag measurements were date-matched to clinically obtained ATI and Cobb measurements. Two-tailed Pearson correlations were calculated; α = 0.01., Results: Median patient age was 14.6 years (11-19); BMI 19.4 (16.0-25.5). Curve patterns: Lenke 1 (5); 2 (5); 3 (1); 4 (1); 5 (2): 6 (2). Twenty-six curves (15T; 11TL) with complete, date-matched data points were analyzed. In thoracic curves, ATI correlated with Cobb (r = 0.711, P < 0.004) and RAsag (r = 0.730, P <0.003). ATI was inversely correlated with Cobb flexibility (r = -0.647, P < 0.01). In thoracolumbar curves, ATI correlated with Cobb (r = 0.789, P < 0.005), and RAsag (r = 0.771, P < 0.006) but not Cobb flexibility (r = -0.452, P = 0.190)., Conclusions: Trunk and spine thoracic and thoracolumbar transverse plane deformity are correlated, as are trunk transverse plane and spine coronal plane deformity. Increasing trunk deformity limits thoracic, but not thoracolumbar spine flexibility.

Background Context: Hydroxyapatite-calcium triphosphate (HCT) biphasic compounds are known to be efficacious in filling bone voids. No large study to date has assessed their radiographic efficacy in iliac crest voids with computed tomography (CT) analysis at a 2-year follow-up., Purpose: To assess whether backfilling iliac crest defects with HCT biphasic compound decreases donor site pain and what effect backfilling has on CT appearance of the donor ilium., Study Design: Prospective randomized clinical trial., Patient Sample: Adult patients with spinal disorders undergoing spinal arthrodesis requiring posterior iliac crest bone grafting., Outcome Measures: Physician-administered visual analog scale (VAS) and pre- and postoperative CT analysis was performed., Methods: This prospective, randomized, single-blind study followed patients requiring nonstructural posterior iliac crest harvest as part of spinal disorder treatment for 2 years. The harvest technique preserved both cortical tables and their periostea. All patients were randomized to backfill of HCT or no backfill. All patients had a CT of the pelvis immediately postoperative and at the 2-year follow-up. Computed tomography analysis was performed by a board-certified neuroradiologist. Analysis included qualitative assessment of the ilia appearance and defect density quantified in Hounsfield units. All patients completed VAS of their donor site pain (0-10, from low to high) at 6 weeks and 2 years postoperatively., Results: Thirty-seven of 40 (17 women and 20 men) subjects returned for a mean 23.9-month follow-up (range, 22-29 months). The average age was 51.7 years (range, 27-79 years). Eighteen patients were in the backfill group (BF) and 19 were in the control group (C). There was no statistically significant difference in pain at 6 weeks or 2 years between the two groups. Bone density significantly decreased from postoperative to 2 years in BF (implying resorption of HCT and replacement of host bone) and significantly increased in C (implying reformation of host bone). Both groups had similar cortical defect repair. The backfill group had significantly better medullary defect repair (p<.01, Fisher exact test)., Conclusions: Backfilling iliac crest voids with HCT biphasic compound does not significantly decrease donor site pain. Both the backfilled and control defects reformed bone over the 2-year period, with BF having significantly less medullary defects than C., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We have occasionally observed clinically noticeable postoperative transverse plane pelvic rotation increase (TPPRI) in the direction of direct thoracolumbar/lumbar rotational corrective load applied during posterior instrumentation and arthrodesis for double (Lenke 3 and 6) adolescent idiopathic scoliosis (AIS) curves. Our purposes were to document this occurrence; identify its frequency, associated variables, and natural history; and determine its effect upon patient outcome., Methods: Transverse plane pelvic rotation (TPPR) can be quantified using the left/right hemipelvis width ratio as measured on standing posterior-anterior scoliosis radiographs. Descriptive statistics were done to determine means and standard deviations. Non-parametric statistical tests were used due to the small sample size and non-normally distributed data. Significance was set at P < 0.05., Results: Seventeen of 21 (81%) consecutive patients with double curves (7 with Lenke 3 curves and 10 with Lenke 6) instrumented with lumbar pedicle screw anchors to achieve direct rotation had a complete sequence of measurable radiographs. While 10 of these 17 had no postoperative TPPRI, 7 did all in the direction of the rotationally corrective thoracolumbar instrumentation load. Two preoperative variables were associated with postoperative TPPRI: more tilt of the vertebra below the lower instrumented vertebra (-23° ± 3.1° vs. -29° ± 4.6°, P = 0.014) and concurrent anterior thoracolumbar discectomy and arthrodesis (5 of 10 vs. 7 of 7, P = 0.044). Patients with a larger thoracolumbar/lumbar angle of trunk inclination or larger lower instrumented vertebra plus one to sacrum fractional/hemicurve were more likely to have received additional anterior thoracolumbar discectomy and arthrodesis (c = 0.90 and c = 0.833, respectively).Postoperative TPPRI resolved in 5 of the 7 by intermediate follow-up at 12 months. Patient outcome was not adversely affected by postoperative TPPRI, whether or not it persisted., Conclusions: Our findings suggest that TPPRI is a decompensation caused by extension of the corrective thoracolumbar rotational load into the lumbosacral hemicurve below. As posterior instrumentation of adolescent idiopathic scoliosis becomes increasingly more effective in the transverse plane, postoperative TPPRI may become more widely noticed. This study provides some assurance that recompensation usually occurs, but that in either event TPPRI does not seem to affect clinical outcome.

Study Design: Cross-sectional mail questionnaire., Objective: Examination of the underlying construct validity of the Scoliosis Research Society-22r (SRS-22r) Health-Related Quality of Life (HRQoL) Questionnaire using factor analysis., Summary of Background Data: The original SRS-24 HRQoL questionnaire has undergone a series of modifications in an effort to further improve its psychometric properties and validate its use in patients from 10 years of age until well into adulthood. The SRS-22r questionnaire is the result of this effort. To date, the underlying construct validity of the original English version has not been analyzed by factor analysis., Methods: A questionnaire including all questions on the SRS-24, -23, -22, and -22r questionnaires (49 total questions) was mailed to a consecutive series of 235 patients who had received primary posterior or anterior instrumentation and arthrodesis. Domain structure of the SRS-22r questions was analyzed using iterated principal factor analysis with orthogonal rotation., Results: One hundred twenty-one (51%) of the patients, age 23.34 +/- 4.52 years (range, 14.16-34.57 years), returned the questionnaire at 8.63 +/- 4.00 years (range, 2.32-15.94 years) following surgery. Factor analysis using all 22 questions resulted in 3 factors with many shared items because of significant collinearity of the satisfaction/dissatisfaction with management questions with the others. After 18 iterations, factor analysis using the 20 nonmanagement questions revealed 4 factors that explained 98% of the variance. These factors parallel the assigned domains of the SRS-22r questionnaire. Three questions (2 self-image and 1 function) were identified that had high loading in 2 factors. However, internal consistency was best when 2 of the questions (1 self-image and 1 function) were retained in their assigned SRS-22r domains and the third decreased self-image internal consistency by only 0.01%. The internal consistencies (Cronbach alpha) of the assigned SRS-22r nonmanagement domains were excellent or very good: function 0.83, pain 0.87, self-image 0.80, and mental health 0.90. For the management domain it was good: 0.73., Conclusion: Factor analysis of the SRS-22r HRQoL confirms placement of the 20 nonmanagement domain questions in the assigned 4 domains, all with excellent or very good internal consistency.

Considerable evidence indicates that cholinomimetic-induced tremulous jaw movements in rats share many characteristics with human Parkinsonian tremor, and several antiparkinsonian drugs suppress cholinomimetic-induced tremulous jaw movements. The present study investigated three different types of dopamine agonists, which have known antiparkinsonian characteristics, for their ability to suppress the tremulous jaw movements induced by tacrine (5.0 mg/kg). The non-selective dopamine agonist pergolide, a widely used antiparkinsonian drug, was highly potent at suppressing tacrine-induced jaw movements (e.g. 0.125-1.0 mg/kg). The selective D2 agonist ropinirole, which also is used clinically as an antiparkinsonian drug, suppressed jaw movements in the dose range of 2.5-20.0 mg/kg. The D1 agonist CY 208-243, which has been reported to suppress tremor, also reduced jaw movement activity (4.0 mg/kg). Across several studies, the rank order of potency for suppressing cholinomimetic-induced jaw movements in rats is related to the potency for producing antiparkinsonian effects in humans. Together with previous studies, the present results suggest that cholinomimetic-induced jaw movements in rats can be used to characterize dopaminergic antiparkinsonian agents and to investigate the basal ganglia circuits involved in the generation of tremulous movements.

Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.

Traditional approaches in the treatment of Parkinson's disease have typically been directed at restoring dopaminergic tone in the neostriatum of the basal ganglia. Nevertheless, the vast majority of neostriatal efferent projections use GABA as their neurotransmitter. Substantia nigra pars reticulata (SNr) is a major basal ganglia output area that is a target of these GABAergic projections, and research from animal models has indicated that stimulation of GABA receptors in SNr can produce motor effects consistent with an antiparkinsonian action. In the present study, implantation of engineered GABA-releasing cells into SNr reduced tremulous movements in an animal model of parkinsonian tremor. These results suggest that implantation of GABA cells into SNr, or possibly into other basal ganglia structures, could provide an alternative transplantation strategy for the treatment of Parkinsonism.

Rationale: Atypical antipsychotics such as clozapine and olanzapine have a low liability for producing motor side effects. In addition to being D2 antagonists, these drugs have a complex binding profile that includes affinity for muscarinic, alpha, H1, and various serotonin receptors. Previous work in rats has shown that atypical antipsychotics suppress tremulous jaw movements induced by the anticholinesterase tacrine in rats. Cholinomimetic-induced jaw movements are a putative model of parkinsonian tremor, and the ability of antipsychotic drugs to suppress these movements in rats is correlated with motor side-effect liability in humans., Objective: The present work was undertaken to study the role of central serotonin receptors in the generation of cholinomimetic-induced jaw movements., Results: Systemic injections of the serotonin antagonist mianserin suppressed tacrine-induced jaw movements, with an ED(50) of 2.77 mg/kg. Local injections of mianserin directly into substantia nigra pars reticulata (SNr) also suppressed tacrine-induced jaw movements. Injections into ventrolateral neostriatum, or a control site dorsal to SNr, failed to have any effects on jaw movement activity., Conclusions: These studies suggest that atypical antipsychotics may act both on striatal muscarinic receptors and nigral serotonin receptors to suppress jaw movement activity. It is possible that the unique motor properties of atypical antipsychotics result from actions on multiple receptors in several brain areas. The precise serotonin receptor subtype involved in these effects is unknown, and future work will examine the effects of drugs that act selectively on 5-HT(2A) and 5-HT(2C) receptors.

Considerable evidence indicates that nucleus accumbens dopamine (DA) is involved in the regulation of instrumental response output, and that interference with DA transmission disrupts the ability of rats to overcome work-related response costs. The present experiments were conducted to assess the effects of accumbens DA depletions on the performance of variable interval schedules, to determine if the intermittence of a schedule, in itself, is an important determinant of sensitivity to accumbens DA depletions. For this purpose, two variable interval 30 s lever pressing schedules were used, each with different response requirements added to the interval requirement. For one of the schedules, the animals were reinforced for the first response after the interval elapsed (tandem variable interval/fixed ratio 1: VI/FR1). On the other schedule an additional work requirement was attached by requiring the rats to make five responses after the interval in order to receive reinforcement (tandem variable interval/fixed ratio 5: VI/FR5). Attachment of the additional work requirement led to greater response rates during baseline training. After training, rats were injected with either ascorbate vehicle or 6-hydroxydopamine (6-OHDA) into the nucleus accumbens. The effects of DA depletion on responding were highly schedule-dependent. DA depletions had no significant effect on lever pressing under the condition with low response requirement (VI/FR1), but these depletions substantially disrupted responding on the schedule with the higher response requirement (VI/FR5). The disruption of responding on the schedule with the high response requirement showed recovery over the 4 weeks of post-surgical testing. In a second experiment, the effect of 6-OHDA on spontaneous locomotion in an open field was assessed. The DA-depleted animals had impairments in locomotion and rearing compared with the vehicle treated rats when tested 8 days after surgery, but not when tested 29 days after surgery, which demonstrates recovery of locomotor function after the accumbens DA depletions. The results of these experiments support the hypothesis that nucleus accumbens DA is involved in regulating behavioral activation. The lever pressing experiment indicates that depletions of DA in the accumbens interfere with the processes that enable rats to overcome behavioral constraints such as work-related response costs, and suggest that the intermittence of reinforcement per se is not the most critical factor in determining sensitivity to accumbens DA depletions.

Although interference with dopamine (DA) systems can suppress lever pressing for food reinforcement, it is not clear whether this effect occurs because of a general disruption of food motivation. One way of assessing this has been a choice procedure in which a rat responds on an fixed ratio 5 (FR5) schedule for preferred Bioserve pellets while a less preferred lab chow is concurrently available in the operant chamber. Untreated rats consume little of the chow, preferring to respond for the Bioserve pellets. Previous studies have shown that depleting DA in the accumbens substantially decreased lever pressing while increasing chow consumption. In the present study, low doses (0.0625-1.0 microg) of the D1 antagonist SCH 23390 or the D2 antagonist raclopride were injected into the either the core or shell subregions of nucleus accumbens, and rats were tested on the concurrent lever pressing/feeding task. Analysis of the dose response curves showed that injections of SCH 23390 into the core were more potent than injections into the shell for suppressing lever pressing (i.e., the ED(50) was lower in the core). Nevertheless, injections of either drug into either site suppressed lever pressing and increased intake of the concurrently available chow. Across both drugs and at both sites, the amount of chow consumed was negatively correlated with the total number of responses. Neither drug significantly increased response duration, suggesting that accumbens DA antagonism did not produce the type of motor impairment that leads to severe alterations in the form of lever pressing. In summary, the blockade of D1 or D2 receptors in nucleus accumbens core or shell decreased lever pressing for food reinforcers, but rats remained directed toward the acquisition and consumption of food. These results indicate that accumbens D1 antagonism does not decrease lever pressing because of a general reduction in food motivation. Nevertheless, interference with accumbens DA does appear to set constraints upon which responses are selected for obtaining food, and may impair the ability of animals to overcome work-related response costs in order to obtain food.

Rationale: Considerable evidence indicates that dopaminergic drugs, including drugs that act on D1 receptors, exert their effects by actions on forebrain dopamine terminal regions. Nevertheless, anatomical studies also have demonstrated that there is a high concentration of D1 receptors in the substantia nigra pars reticulata (SNr). The D1 receptors in SNr are located largely on the terminals of gamma-aminobutyric acid (GABA)-ergic striatonigral neurons. The present studies were undertaken to determine whether the D1 antagonist SCH 23390 was effective if locally injected into SNr and to compare the results of SNr injections with those obtained from other brain sites. Fixed ratio 5 (FR5) lever pressing and open-field locomotion were used as the behavioral tests because these tasks are sensitive to systemic SCH 23390., Methods: Rats received bilateral implantations of guide cannulae into either nucleus accumbens, neostriatum, SNr, or control sites in the cortex or brainstem. Rats in the FR5 study were trained prior to surgery. All rats received one of the following local injections (0.5 microl per side): vehicle, 0.25, 0.5, 1.0, or 2.0 microg SCH 23390., Results: In the FR5 study, the SNr was by far the most potent site for suppression of lever pressing, with an ED50 (dose that produces half maximal response) of 0.33 microg per side. Nucleus accumbens and neostriatum injections were less potent than those in SNr, but more potent than injections into the control regions. With open-field locomotion, the SNr, nucleus accumbens, and neostriatum were approximately equipotent sites, and all three were more potent than the control sites., Conclusions: SNr was a very potent site for suppression of lever pressing and open-field locomotion. These data suggest that D1 antagonists have multiple sites of action, including not only the forebrain dopamine terminal regions but also the SNr. It is possible that blockade of SNr D1 receptors modulates GABA release from striatonigral neurons.

Several studies have shown that a number of pharmacological and neurochemical conditions in rats can induce jaw movements that are described as "vacuous" or "tremulous". For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevertheless, considerable evidence now indicates that the non-directed, chewing-like movements induced by cholinomimetics have many of the characteristics of parkinsonian tremor. These movements are characterized largely by vertical deflections of the jaw, which occur in the same 3-7 Hz peak frequency that is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropinirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M4 receptors in the ventrolateral neostriatum in the generation of tremulous jaw movements. Mice also show cholinomimetic-induced jaw movements, and M4 receptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are consistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor.

It has been suggested that dopamine in nucleus accumbens is involved in the process of enabling organisms to overcome work-related response costs. One way of controlling work costs with operant schedules is to use fixed ratio schedules with different ratio requirements. In the present study, the effects of nucleus accumbens dopamine depletions were investigated using six schedules: fixed ratio 5, 20, 50, 100, 200, and 300. In the first three schedules the food reinforcement consisted of one 45 mg food pellet per ratio completed. In the remaining schedules the food reinforcement per ratio completed was increased to two pellets for fixed ratio 100, four pellets for fixed ratio 200, and six pellets for fixed ratio 300. All rats were trained extensively prior to surgery, and rats were able to maintain high levels of responding on all schedules up to the fixed ratio 300. After training, rats were injected with either ascorbate vehicle or 6-hydroxydopamine into the nucleus accumbens. Rats were tested post-surgically on each of the schedules, with 3 days of testing per schedule. Rats with nucleus accumbens dopamine depletions exhibited behavioral deficits that were highly dependent upon the ratio value. There were small and transient effects of dopamine depletion on fixed ratio 5 lever pressing, but as the ratio value got larger the impairment became greater. On the fixed ratio 20 and 50 schedules, response rates were partially reduced in dopamine-depleted rats. Responding on the fixed ratio 200 and 300 schedules was severely impaired, and on the last day of fixed ratio 300 testing no dopamine-depleted rats obtained a single reinforcer. These data are consistent with previous reports that accumbens dopamine depletions enhance 'ratio strain', making rats more sensitive to high ratio values. The induction of ratio strain by dopamine depletions does not appear to be related to a loss of appetite, and seems to be relatively independent of the baseline rate of responding and the overall density of food reinforcement across the session. We conclude that dopamine in nucleus accumbens may be important for enabling rats to overcome behavioral constraints such as work-related response costs, and may be critical for the behavioral organization and conditioning processes that enable animals to emit large numbers of responses in the absence of primary reinforcement.

In several previous studies, tremulous jaw movements in rats have been used to assess the effects of antiparkinsonian drugs and atypical antipsychotics. Because antihistamines such as diphenhydramine are used as antiparkinsonian agents, and atypical antipsychotic drugs such as clozapine and olanzapine have high affinity for histamine H1 receptors, the present study investigated the effects of H1 antagonists on cholinomimetic-induced jaw movements. Diphenhydramine, doxepin, and mepyramine (all injected IP 2.5-20.0 mg/kg) were assessed for their ability to block the jaw movements induced by 5.0 mg/kg of the anticholinesterase tacrine. Within this dose range, only diphenhydramine produced a robust and significant reduction in jaw movement activity. Thus, diphenhydramine was subjected to further testing, which employed procedures previously used to assess the effects of other antitremorogenic drugs, such as clozapine. Diphenhydramine did not induce jaw movement activity. In addition to suppressing jaw movement activity after acute injections, diphenhydramine also suppressed tacrine-induced jaw movements after repeated (14-day) administration. In summary, the present results show that diphenhydramine suppresses cholinomimetic-induced jaw movements, an effect that is similar to other antiparkinsonian or antitremor drugs such as anticholinergics, L-DOPA, DA antagonists, and clozapine. Nevertheless, doxepin produced only mild effects, and mepyramine, which has a higher affinity and selectivity than diphenhydramine for H1 receptors, failed to suppress cholinomimetic-induced jaw movements. These results suggest that diphenhydramine suppresses tremulous movements through a mechanism that does not depend upon antagonism of histamine H1 receptors.

Two experiments were conducted to determine the effects of accumbens dopamine (DA) depletions on progressive ratio responding for food reinforcement. In one version of this schedule, ratio requirement increased by one response after each reinforcer was obtained (PROG1). In the other version, ratio requirement increased by five responses after each reinforcer was obtained (PROG5). For both versions, 60-min sessions were conducted. Accumbens DA depletions produced by local injections of 6-OHDA substantially decreased the number of responses on both schedules. The deficits in the response number induced by DA depletions persisted through the two weeks of postsurgical testing for both the PROG1 and PROG5 schedules. However, there were differences between the effects of DA depletions on the two schedules in terms of the time to complete the last ratio. Although time to complete the last ratio was significantly reduced by DA depletions only in the first week of testing on the PROG1 schedule, rats recovered on this measure by the second week after surgery. In contrast, DA-depleted rats on the PROG5 schedule showed a more persistent suppression of the time to complete the last ratio, which lasted through both weeks of postsurgical testing. Performance on schedules that generate low baseline rates of responding (e.g., continuous, fixed, and variable interval) is relatively unaffected by accumbens DA depletions; nevertheless, accumbens DA depletions substantially impair progressive ratio response output. The high work output necessary for responding on the PROG5 schedule may make these animals more sensitive to the effects of accumbens DA depletions.

Rationale: Previous work has shown that clozapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing., Objective: The novel atypical antipsychotic olanzapine was assessed in these behavioral tests., Methods: The effect of acute olanzapine on the suppression of tacrine-induced tremulous jaw movements was examined. In order to determine the relative potency of this effect compared with other behavioral effects of olanzapine, suppression of lever pressing also was studied. In a second series of experiments, rats received olanzapine for 14 consecutive days to study the effects of repeated injections of this drug on jaw movements and lever pressing., Results: Acute olanzapine administration decreased tacrine-induced jaw movements (ED50: 0.4 mg/kg), and also reduced lever pressing (ED50: 1.12 mg/kg). The ratio of the ED50 for suppression of jaw movements to that for suppression of lever pressing was used as an index of liability to produce extrapyramidal side effects, and the present results demonstrate that olanzapine has a ratio similar to that previously shown for clozapine. In the repeated administration studies, rats were observed on day 13 of drug treatment for the ability of olanzapine to induce jaw movements, and olanzapine failed to induce jaw movements. On day 14, olanzapine reduced tacrine-induced tremulous jaw movements (ED50: 1.12 mg/kg). In a separate experiment, olanzapine significantly suppressed lever pressing, and this effect showed sensitization with repeated administration (day 14, ED50: 0.76 mg/kg). Thus, repeated injections of olanzapine reduced tacrine-induced jaw movements in a dose range similar to or slightly higher than that which suppressed lever pressing., Conclusions: On tests of jaw-movement activity and lever pressing after both acute and repeated drug administration, olanzapine demonstrated a profile somewhat similar to clozapine, and both of these drugs differ substantially from the typical antipsychotic haloperidol.