Timing-dependent synergies between motor cortex and posterior spinal stimulation in humans.

Volitional movement requires descending input from the motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans, it is not known whether posterior epidural spinal cord stimulation targeted at the sensorimotor interface or anterior epidural spinal cord stimulation targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord was stimulated with epidural electrodes, with muscle responses being recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, clinical signs suggest that facilitation was observed in both injured and uninjured segments of the spinal cord. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation. KEY POINTS: Pairs of stimuli designed to alter nervous system function typically target the motor system, or one targets the sensory system and the other targets the motor system for convergence in cortex. In humans undergoing clinically indicated surgery, we tested paired brain and spinal cord stimulation that we developed in rats aiming to target sensorimotor convergence in the cervical cord. Arm and hand muscle responses to paired sensorimotor stimulation were more than five times larger than brain or spinal cord stimulation alone when applied to the posterior but not anterior spinal cord. Arm and hand muscle responses to paired stimulation were more selective for targeted muscles than the brain- or spinal-only conditions, especially at latencies that produced the strongest effects of paired stimulation. Measures of clinical evidence of compression were only weakly related to the paired stimulation effect, suggesting that it could be applied as therapy in people affected by disorders of the central nervous system.

Preoperative rehabilitation optimization for spinal surgery: a narrative review of assessment, interventions, and feasibility.

PURPOSE: Postoperative physical therapy (PT) is a cornerstone of orthopedic and musculoskeletal rehabilitation, proven to provide various positive clinical benefits. However, there is a paucity of literature evaluating the utility of preoperative rehabilitation specific to spine surgery. Thus, this review article aims to provide an overview of previously published studies discussing the efficacy of preoperative rehabilitation programs and its role in spinal surgery. Special emphasis was given to preoperative frailty assessments, physical performance tests, interventional strategies, feasibility, and future directions. METHODS: We performed a literature review using PubMed, Google Scholar, EMBASE, and PubMed Central (PMC) using directed search terms. Articles that examined preoperative rehabilitation in adult spine surgery were compiled for this review. Prehabilitation programs focused on exercise, flexibility, and behavioral modifications have been shown to significantly improve pain levels and functional strength assessments in patients undergoing elective spine surgery. In addition, studies suggest that these programs may also decrease hospital stays, return to work time, and overall direct health care expenditure costs. Screening tools such as the FRAIL scale can be used to assess frailty while physical function tests like the timed-up-and go (TUGT), 5 repetition sit-to-stand test (5R-STST), and hand grip strength (HGS) can help identify patients who would most benefit from prehabilitation. CONCLUSIONS: This review illustrates that prehabilitation programs have the potential to increase quality of life, improve physical function and activity levels, and decrease pain, hospital stays, return to work time, and overall direct costs. However, there is a paucity of literature in this field that requires further study and investigation.

Innovative technologies in thoracolumbar and lumbar spine surgery failing to reach standard of care: state-of-art review.

PURPOSE: To evaluate previously popular technologies in the field of spine surgery, and to better understand their advantages and limitations to the current standards of care. Spine surgery is an ever-evolving field that serves to resolve various spinal pathologies in patients of all ages. While there are established treatments for various conditions, such as lumbar spinal stenosis, idiopathic scoliosis, and degenerative lumbar disease, there is always further research and development in these areas to produce innovative technologies that can lead to better outcomes. As this process progresses, we must remind ourselves of previously tried and tested inventions and their outcomes that have fallen short of becoming a standard to ensure we are able to learn lessons from the past. METHODS: A thorough literature review was conducted with the aim of compiling literature of previously utilized technologies in spine surgery. Biomedical databases were utilized to gather relevant articles including PubMed, MEDLINE, and EMBASE. Emphasis was placed on gathering articles with technologies or therapeutics aimed at treating common spinal pathologies including lumbar spinal stenosis (LSS), adolescent idiopathic scoliosis (AIS), and other degenerative lumbar spine diseases. The keywords used were: "failed technologies", "historical technologies", "spine surgery", "spinal stenosis", "adolescent idiopathic scoliosis", and "degenerative lumbar spine disease". A total of 47 articles were gathered after initial review. RESULTS: Different technologies pertaining to spine surgery were identified and critically evaluated. Some of these technologies included X-STOP, Vertiflex, Vertebral Body Stapling, and Dynesys. These technologies were evaluated for their strengths and limitations across their spinal pathology applications. While each type of technology had their benefits, the data tended to be mixed with various limitations across studies. CONCLUSION: These technologies have been trialed in the field of spine surgery across various spinal pathologies, but still prove of limited efficacy and shortcomings to the current standards of care.

Efficacy and safety of spironolactone versus bicalutamide in female pattern hair loss: A retrospective comparative study.

BACKGROUND: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles. OBJECTIVE: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL]. METHODS: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment. RESULTS: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139). CONCLUSIONS: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL.

Revision of Harrington rod constructs: a single-center's experience with this homogenous adult spinal deformity population at a minimum 2-year follow-up.

PURPOSE: To evaluate radiographic and clinical outcomes following revision surgery after HRC fusions. METHODS: Single-institution, retrospective study of patients revised following HRC with minimum 2-year follow-up post-revision. Demographics, perioperative information, radiographic parameters, complications, and Oswestry disability index (ODI) scores were collected. Radiographic parameters included global alignment, coronal and sagittal measurements pre and postoperatively, as well as final follow-up time points. RESULTS: 26 patients were included with a mean follow-up of 3.3 ± 1.1 years. Mean age was 55.5 ± 7.8 years, BMI 25.2 ± 5.8, and 22 (85%) were females. Instrumented levels increased from 9.7 ± 2.8 to 16.0 ± 2.2. Five (19.2%) patients underwent lumbar pedicle subtraction osteotomies, and 23 (88.4%) had interbody fusions. Patients significantly improved in all radiographic parameters at immediate and final follow-up (p < 0.005), except for thoracic kyphosis and pelvic incidence (p > 0.05). Correction was maintained from immediate postop to final follow-up (p > 0.05). 20 (76.9%) of patients experienced a complication at some point within the follow-up period with the most common being a lumbar nerve root deficit (n = 7). However, only one patient had a nerve root deficit at final follow-up, that being a 4/5 unilateral anterior tibialis function. 5 (19.2%) patients required further revision within a mean of 1.8 ± 1.1 years. On average, patients had an improvement in ODI score by final follow-up (35.6 ± 16.8 vs 25.4 ± 19.8, p = 0.035). CONCLUSION: Patients revised for HRCs significantly improve, both clinically and radiographically by final follow-up. This group did have a propensity for distal lumbar root neurological issues, which were common but all patients except for one, recovered to full strength by two-year follow-up.

Knee flexion compensation in postoperative adult spinal deformity patients: implications for sagittal balance and clinical outcomes.

PURPOSE: To determine whether maintaining good sagittal balance with significant knee flexion (KF) constitutes a suboptimal outcome after adult spinal deformity (ASD) correction. METHODS: This single-center, single-surgeon retrospective study, assessed ASD patients who underwent posterior spinal fusion between 2014 and 2020. Inclusion criteria included meeting at least one of the following: PI-LL ≥ 25°, T1PA ≥ 20°, or CrSVA-H ≥ 2 cm. Those with lower-extremity contractures were excluded. Patients were classified into four groups based on their 6-week postoperative cranio-hip balance and KF angle, and followed for at least 2 years: Malaligned with Knee Flexion (MKF+) (CrSVA-H > 20 mm + KFA > 10), Malaligned without Knee Flexion (MKF-) (CrSVA-H > 20 mm + KFA < 10), Aligned without Knee Flexion (AKF-) (CrSVA-H < 20 mm + KFA < 10), and Aligned with Knee Flexion (AKF+) (CrSVA-H < 20 mm + KFA > 10). The primary outcomes of this study included one and two year reoperation rates. Secondy outcomes included clinical and patient reported outcomes. RESULTS: 263 patients (mean age 60.0 ± 0.9 years, 74.5% female, and mean Edmonton Frailty Score 3.3 ± 0.2) were included. 60.8% (160/263 patients) exhibited good sagittal alignment at 6-week postop without KF. Significant differences were observed in 1-year (p = 0.0482) and 2-year reoperation rates (p = 0.0374) across sub-cohorts, with the lowest and highest rates in the AKF- cohort (5%, n = 8) and MKF + cohort (16.7%, n = 4), respectively. Multivariable Cox regression demonstrated the AKF- cohort exhibited significantly better reoperation outcomes compared to other groups: AKF + (HR: 5.24, p = 0.025), MKF + (HR: 31.7, p < 0.0001), and MKF- (HR: 11.8, p < 0.0001). CONCLUSION: Our findings demonstrate that patients relying on knee flexion compensation in the early postoperative period have inferior outcomes compared to those achieving sagittal balance without knee flexion. When compared to malaligned patients, those with CrSVA-H < 20 mm and KFA > 10 degrees experience fewer early reoperations but similar delayed reoperation rates. This insight emphasizes the importance of considering knee compensation perioperatively when managing sagittal imbalance in clinical practice.

Characteristics of Spinal Morphology According to the Global Alignment and Proportion (GAP) Score in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study.

STUDY DESIGN: Multi-Ethnic Alignment Normative Study (MEANS) cohort: prospective, cross-sectional, multicenter. OBJECTIVE: To analyze the distribution of GAP scores in the MEANS cohort and compare the spinal shape via stratification by GAP alignment category, age, and country. SUMMARY OF BACKGROUND DATA: The GAP score has been used to categorize spinal morphology and prognosticate adult spinal deformity surgical outcomes and mechanical complications. We analyzed a large, multiethnic, asymptomatic cohort to assess the distribution of GAP scores. METHODS: Four hundred sixty-seven healthy volunteers without spinal disorders were recruited in five countries. Sagittal radiographic parameters were measured via the EOS imaging system. The GAP total and constituent factor scores were calculated for each patient. Kruskal-Wallis rank sum test was performed to compare variables across groups, followed by the post hoc Games-Howell test. Fisher exact test was used to compare categorical variables. The significance level was set to P <0.05. RESULTS: In the MEANS cohort, 13.7% (64/467) of volunteers were ≥60 years old, and 86.3% (403/467) were <60 years old. 76.9% (359/467) was proportioned, 19.5% (91/467) was moderately disproportioned, and 3.6% (17/467) was severely disproportioned. There was no significant difference in the frequency of proportioned, moderately, or severely disproportioned GAP between subjects from different countries ( P =0.060). Those with severely disproportioned GAP alignment were on average 14.5 years older ( P =0.016), had 23.1° lower magnitude lumbar lordosis (LL) ( P <0.001), 14.2° higher pelvic tilt ( P <0.001), 13.3° lower sacral slope ( P <0.001), and 24.1° higher pelvic-incidence (PI)-LL mismatch ( P <0.001), 18.2° higher global tilt ( P <0.001) than those with proportioned GAP; thoracic kyphosis and PI were not significantly different ( P >0.05). CONCLUSIONS: The GAP system applies to a large, multiethnic, asymptomatic cohort. Spinal alignment should be considered on a spectrum, as 19.5% of the asymptomatic volunteers were classified as moderately disproportioned and 3.6% severely disproportioned. Radiographic malalignment does not always indicate symptoms or pathology. LEVEL OF EVIDENCE: 3.

Characteristics of Spinal Morphology According to the "Current" and "Theoretical" Roussouly Classification Systems in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study (MEANS).

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVE: To classify spinal morphology using the "current" and "theoretical" Roussouly systems and assess sagittal alignment in an asymptomatic cohort. METHODS: 467 asymptomatic volunteers were recruited from 5 countries. Radiographic parameters were measured via the EOS imaging system. "Current" and "theoretical" Roussouly classification was assigned with sagittal whole spine imaging using sacral slope (SS), pelvic incidence (PI), and the lumbar apex. One-way analysis of variance (ANOVA) was performed to compare subject characteristics across Roussouly types, followed by post hoc Bonferroni correction. RESULTS: Volunteers were categorized into 4 groups (Types 1-4) and 1 subgroup (Type 3 AP) using the "current" and "theoretical" Roussouly systems. The mean PI in "current" Roussouly groups was 40.8° (Type 1), 43.6° (Type 2), 52.4° (Type 3), 62.4° (Type 4), and 43.7° (Type 3AP). The mean PI in "theoretical" Roussouly groups was 36.5° (Type 1), 39.1°(Type 2), 52.5° (Type 3), 67.3° (Type 4), and 51.0° (Type 3AP). The difference in PI between "current" and "theoretical" Roussouly types was significant for Type 1 (P = .02), Type 2 (P < .001), Type 4 (P < .001), and Type 3AP (P < .001). 34.7% of subjects had a "current" Roussouly type different from the "theoretical" type. Type 3 theoretical shape had the most frequent mismatch, constituting 61.1% of the mismatched subjects. 51.5% of mismatched Type 3 become "current" Type 4. CONCLUSION: The distribution of Roussouly types differs depending on whether the "current" or "theoretical" classification are employed. A sizeable proportion of volunteers exhibited current and theoretical type mismatch, highlighting the need to interpret sagittal alignment cautiously when utilizing the Roussouly system.

Practical Methods of Assessing Coronal Alignment and Outcomes in Adult Spinal Deformity Surgery: A Comparative Analysis.

STUDY DESIGN: Asymptomatic cohort: prospective, cross-sectional, multicenter. Symptomatic: retrospective, multisurgeon, single-center. OBJECTIVE: To assess the association between cranial coronal alignment and adult spinal deformity (ASD) surgical risk and outcomes. SUMMARY OF BACKGROUND DATA: ASD leads to decreased quality of life. Studies have shown that coronal malignment (CM) is associated with worse surgical outcomes. MATERIALS AND METHODS: A total of 468 adult participants were prospectively enrolled in the asymptomatic cohort. Totally, 172 symptomatic ASD patients with 2-year follow-ups were retrospectively enrolled in the symptomatic cohort. Three cranial plumb line parameters: the positions of the plumb lines from the midpoint between the medial orbital rims (ORB-L5), the odontoid (OD-L5), and the C7 centroid (C7-L5) relative to the L5 pedicle, were measured. Each subject had plumb line medial (M), touching (T), or lateral (L) to either pedicle. The association between each group of patients and radiographic parameters, intraoperative variables, patient-reported outcomes, and clinical outcomes were analyzed. RESULTS: In the asymptomatic cohort, OD-L5 was medial to or touching the L5 pedicle in 98.3% of volunteers. In the symptomatic patients, preoperative OD-L5-L exhibited higher mean age (56.2±14.0), odontoid-coronal vertical axis (OD-CVA) (5.5±3.3 cm), Oswestry disability index (ODI) score (40.6±18.4), pelvic fixation rate (56/62, 90.3%), OR time (528.4±144.6 min), median estimated blood loss (1300 ml), and durotomy rate (24/62, 38.7%). A similar pattern of higher CVA, preoperative ODI, intraoperative pelvic fixation rate, OR time, estimated blood loss, and durotomy rate was observed in ORB-L5-L and C7-L5-L patients. Final follow-up postoperative OD-L5-L was associated with higher rates of proximal junctional kyphosis (13.0%) and pseudarthrosis (17.4%). CONCLUSION: Preoperative OD-L5, ORB-L5, and C7-L5 lateral to pedicles were associated with worse preoperative ODI and higher intraoperative complexity. Postoperative OD-L5-L was associated with higher rates of proximal junctional kyphosis and pseudarthrosis. Postoperative CM, approximated by the cranial plumb line lateral to the L5 pedicles, was associated with sagittal plane complications.

Preoperative nutritional optimization for adult spinal deformity: Review.

PURPOSE: The main objective of this review article is to examine the role that nutrition has on adult spinal deformity. The information presented in this review aims to provide spine surgeons with a broad overview of screening, assessment, and interventional strategies that may be used for presurgical nutritional optimization. METHODS: A comprehensive literature review utilizing three biomedical databases was performed to generate articles of interest. Published articles related to nutrition, adult spinal deformity, spine surgery and orthopaedics were reviewed for the composition of this article. Nutrition may play a role in optimizing postoperative outcomes following adult spinal deformity surgeries, such as limiting delirium, length of stay, blood transfusion, and other medical complications. The use of screening tools, such as the PNI and CONUT score can assess preoperative nutritional status and may provide some utility in evaluating nutrition status in patients undergoing deformity surgery. Balancing both macronutrients and micronutrients, notably, carbohydrates, protein, albumin, and vitamin D can play a role in preoperative optimization. CONCLUSION: Adult spinal deformity patients are at an increased risk for malnutrition. These patients should be assessed for nutrition status to prime them for surgery, minimize complications, and maximize their outcomes. However, further studies are needed to determine how nutrition ultimately affects adult spinal deformity patients in the postoperative period and to establish specific nutritional recommendations for this unique population.

Impact of Teriparatide on Complications and Patient-Reported Outcomes of Patients Undergoing Long Spinal Fusion According to Bone Density.

BACKGROUND: Surgery for adult spinal deformity (ASD) poses substantial risks, including the development of symptomatic pseudarthrosis, which is twice as prevalent among patients with osteoporosis compared with those with normal bone mineral density (BMD). Limited data exist on the impact of teriparatide, an osteoanabolic compound, in limiting the rates of reoperation and pseudarthrosis after treatment of spinal deformity in patients with osteoporosis. METHODS: Osteoporotic patients on teriparatide (OP-T group) were compared with patients with osteopenia (OPE group) and those with normal BMD. OP-T patients were matched with OPE patients and patients with normal BMD at a 1:2:2 ratio. All patients had a minimum 2-year follow-up and underwent posterior spinal fusion (PSF) involving >7 instrumented levels. The primary outcome was the 2-year reoperation rate. Secondary outcomes included pseudarthrosis with or without implant failure, proximal junctional kyphosis (PJK), and changes in patient-reported outcomes (PROs). Clinical outcomes were analyzed using conditional logistic regression. Changes in PROs were analyzed using a mixed-effects model. RESULTS: Five hundred and forty patients (52.6% normal BMD, 32.9% OPE, 14.4% OP-T) were included. In the unmatched cohort, 2-year reoperation rates (odds ratio [OR] = 0.45 [95% confidence interval (CI): 0.20 to 0.91]) and pseudarthrosis rates (OR = 0.25 [95% CI: 0.08 to 0.61]) were significantly lower in the OP-T group than the OPE group. Seventy-eight patients in the OP-T group were matched to 156 patients in the OPE group. Among these matched patients, at 2 years, 23.1% (36) in the OPE group versus 11.5% (9) in the OP-T group had a reoperation (OR = 0.45, p = 0.0188), 21.8% (34) versus 6.4% (5) had pseudarthrosis with or without implant failure (OR = 0.25, p = 0.0048), and 6.4% (10) versus 7.7% (6) had PJK (OR = 1.18, p = 0.7547), respectively. At 2 years postoperatively, PROs were better among OP-T patients than OPE patients. Subsequently, 78 patients in the OP-T group were matched to 156 patients in the normal BMD group. Among these matched patients, there was no significant difference in 2-year reoperation (OR = 0.85 [95% CI: 0.37 to 1.98]), pseudarthrosis (OR = 0.51 [95% CI: 0.181 to 1.44]), and PJK rates (OR = 0.77 [95% CI: 0.28 to 2.06). CONCLUSIONS: Osteoporotic patients on teriparatide demonstrated lower reoperation and symptomatic pseudarthrosis rates 2 years postoperatively compared with osteopenic patients. Moreover, patient-reported and clinical outcomes for osteoporotic patients on teriparatide were not different from those for patients with normal BMD. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Do adult spinal deformity patients who achieve and maintain PI-LL < 10 have better patient-reported and clinical outcomes compared to patients with PI-LL ≥ 10? A propensity score-matched analysis.

PURPOSE: To investigate whether patients with spinopelvic mismatch (PI-LL ≥ 10) report worse patient-reported outcomes (PROs) compared to patients who achieve PI-LL < 10 at 2-year postop. METHODS: In this retrospective study, propensity score matching (PSM) was used to analyze patients who underwent posterior spinal fusion due to deformity, as defined by one or more of the following criteria: PI-LL ≥ 25°, T1 pelvic angle ≥ 30°, sagittal vertical axis ≥ 15 cm, thoracic scoliosis ≥ 70°, thoracolumbar scoliosis ≥ 50°, coronal malalignment ≥ 7 cm, or those who underwent a three-column osteotomy or fusion with ≥ 12 levels. Key outcomes were total Scoliosis Research Society-22r, Oswestry Disability Index (PROs), and reoperation at 1- and 2-year postop. Patients were dichotomized based on their 2-year alignment: PI-LL ≥ 10° and PI-LL < 10°. A multivariable logistic regression model identified factors associated with achieving PI-LL < 10°, and independent predictors were matched using propensity score matching. Binary outcomes within matched cohorts were analyzed using the McNemar test, while continuous outcomes were analyzed using the Wilcoxon rank-sum test. RESULTS: One hundred sixty-four patients with 2-year follow-up were included; mean age was 50.5 (standard error mean (SEM): 1.4) years, body mass index was 24.1(SEM 1.0), and number of operative levels was 13.5 (SEM 0.3). 84 (51.2%) and 80 (48.8%) patients achieved PI-LL < 10 and PI-LL ≥ 10 at 2-year follow-up, respectively. Baseline pelvic incidence [odds ratio (OR): 0.96 (95% CI 0.92-0.99)] and baseline PI-LL [OR: 0.95 (95% CI 0.9-0.99)] were independent predictors of achieving PI-LL < 10 at 2 years. When comparing propensity matched pairs, no significant differences were found in baseline PROs. At both 1- and 2-year follow-up, outcomes on the SRS-22r scale were nearly identical for both groups (function [4.1(0.1) vs 4.0 (0.1), P = 0.75] ,Pain [3.9 (0.2) vs 3.9 (0.2), P = 0.86], appearance [4.2 (0.2) vs 3.8 (0.2), P = 0.08], mental health [4.1 (0.2) vs 4.1 (0.1), P = 0.96], satisfaction [4.4 (0.2) vs 4.4 (0.2), P = 0.72], and total [90.2 (2.5) vs 88.1 (2.5), P = 0.57]). Additionally, ODI scores at 2 years were comparable [18.1 (2.9) vs 22.4 (2.9), P = 0.30]. The 90-day reoperation rate was 2.6% (one patient) in both matched cohorts (P > 0.99). There was no significant difference in 1-year (P > 0.9999) or 2-year (P = 0.2207) reoperation rates between the groups. CONCLUSION: Patients who achieve and maintain PI-LL < 10 2-years postop following adult spinal deformity surgery have nearly identical SRS-22r and ODI outcomes, and comparable 2-year reoperation rates as compared to patients who have PI-LL ≥ 10.

The Importance of Pelvic Obliquity in Assessing Spinal Coronal Alignment: Normative Values, Demographic, and Radiographic Correlations.

STUDY DESIGN: Prospective, cross-sectional study. OBJECTIVE: In a geographically diverse population of asymptomatic volunteers, we sought to report the incidence of pelvic obliquity (PO), establish normative values of PO across patient factors, and assess the correlation of PO with radiographic parameters. SUMMARY OF BACKGROUND DATA: PO is defined as the misalignment of the pelvis and can be assessed through several anatomic landmarks. Significant PO, whether caused by leg-length discrepancy or not, can lead to coronal malalignment which causes severe pain and disability. Significant emphasis has been placed on achieving appropriate sagittal alignment in recent decades; however, a greater understanding of coronal alignment is needed, and PO is a crucial aspect of evaluating the coronal plane in adult spinal deformity patients. METHODS: Asymptomatic adult volunteers, ages 18-80 years, enrolled patients from 5 countries (France, Japan, Singapore, Tunisia, and the United States) in the "multiethnic alignment normative study" cohort (IRB 201812144). The included volunteers had no known spinal disorder(s), no significant neck or back pain (Visual Analog Scale: ≤2; Oswestry Disability Index: ≤20), and no abnormal alignment (Cobb ≤20°). PO was measured in the frontal plane as the distance between the highest points of each acetabulum, calculated along the vertical axis in millimeters (mm). The incidence of PO was defined as PO ≥10 mm. Kruskal-Wallis, Wilcoxon rank-sum, Pearson correlation, and linear regression were used. RESULTS: A total of 467 patients were included, and PO values by age, sex, body mass index, and country were provided. The overall incidence of PO ≥10 mm was 4.3%, and a nonsignificant trend toward increased PO with age was seen ( P = 0.077). No significant differences were seen in PO between sex, ethnicity, or body mass index groups. No significant correlation existed between PO and other commonly used coronal radiographic measurements. CONCLUSION: PO ≥10 mm occurred in 4.3% of asymptomatic volunteers. Despite the importance of recognizing PO in preventing coronal malalignment, PO did not seem to be associated with other radiographic and demographic information, which underscores the importance of intentionally assessing for any PO before surgery. These results in an asymptomatic population provide a foundation for studying PO in patients with spinal pathology.

Risk factors for proximal junctional kyphosis in a multicenter study of Lenke type 5 and 6 adolescent idiopathic scoliosis patients.

PURPOSE: In Lenke type 5 and 6 curves, a major thoracolumbar or lumbar curve, the rates of PJK are reported as high as 50%. The purpose of this study was to confirm the rate of PJK, investigate possible risk factors, and evaluate surgical complications and the long-term effects of PJK on patient outcomes. METHODS: A retrospective review of multicenter data identified 192 with patients with 2 year and 94 with 5-year follow-up. Included patients had a Lenke type 5 or 6 curve and underwent a selective thoracolumbar or lumbar curve fusion. All radiographs preoperatively and postoperatively (1 year, 2 years, and 5 years) were evaluated. Demographic and radiographic data was analyzed as risk factors for PJK using a multi-variate regression. Outcomes scores and complications were compared between groups. RESULTS: 17 patients (8.9%) developed radiographic PJK; 1 at 1 year, 7 at 2 years, and another 9 at 5 years. All 17 patients had an upper instrumented vertebra (UIV) within 3 levels or less caudal of the thoracic kyphosis apex (the most horizontal vertebra on the sagittal); no patient with a UIV 4 or more levels from the thoracic apex (n = 96) developed PJK (X2 = 13.03, p < 0.001). In addition, PJA > 8° was found to significantly increase the risk of PJK (p = 0.039). SRS scores were significantly worse for PJK patients at 5 years in the self-image and function (p < 0.01). CONCLUSION: In Lenke 5/6 curves, no patient with a UIV 4 or more levels caudal to the thoracic kyphosis apex had PJK up to 5 years postoperatively. PJA greater than 8° was identified as a risk factor for PJK. Patients with radiographic PJK had worse SRS scores 5 years postoperatively.

Immune and oxidative stress biomarkers in pediatric psychosis and psychosis-risk: Meta-analyses and systematic review.

OBJECTIVE: While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents. METHODS: We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker. RESULTS: The systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge's g = 0.40, 95 % CI 0.17 - 0.64), tumor necrosis factor (Hedge's g = 0.38, 95 % CI 0.06 - 0.69), C-reactive protein (Hedge's g = 0.38, 95 % CI 0.05 - 0.70), interleukin-6 (Hedge's g = 0.35; 95 % CI 0.11 - 0.64), and total white blood cell count (Hedge's g = 0.29, 95 % CI 0.12 - 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous. CONCLUSION: Results from several studies are consistent with the hypothesis that signals often classified as "proinflammatory" are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.

Optimizing Preoperative Chronic Pain Management in Elective Spine Surgery Patients: A Narrative Review of Outcomes with Opioid and Adjuvant Pain Therapies.

¼ Chronic preoperative opioid use negatively affects outcomes after spine surgery, with increased complications and reoperations, longer hospital stays, decreased return-to-work rates, worse patient-reported outcomes, and a higher risk of continued opioid use postoperatively.¼ The definition of chronic opioid use is not consistent across studies, and a more specific and consistent definition will aid in stratifying patients and understanding their risk of inferior outcomes.¼ Preoperative weaning periods and maximum dose thresholds are being established, which may increase the likelihood of achieving a meaningful improvement after surgery, although higher level evidence studies are needed.¼ Spinal cord stimulators and intrathecal drug delivery devices are increasingly used to manage chronic back pain and are equivalent or perhaps even superior to opioid treatment, although few studies exist examining how patients with these devices do after subsequent spine surgery.¼ Further investigation is needed to determine whether a true mechanistic explanation exists for spine-related analgesia related to spinal cord stimulators and intrathecal drug delivery devices.

Comparison of the Odontoid and Orbital-Coronal Vertical Axis Lines in Evaluating Coronal Alignment and Outcomes in Adult Spinal Deformity Surgery.

STUDY DESIGN: Asymptomatic Multi-Ethnic Alignment Normative Study (MEANS) cohort: cross-sectional, multi-center. Symptomatic cohort: retrospective, multi-surgeon, single-center. OBJECTIVE: To assess the association of odontoid-coronal vertical axis (OD-CVA) and orbital-coronal vertical axis (ORB-CVA) with radiographic parameters, patient-reported outcomes (PROs), and clinical outcomes. SUMMARY OF BACKGROUND DATA: Previous literature studied the OD-CVA in an asymptomatic cohort and ORB-CVA in a symptomatic cohort, demonstrating their correlations with radiographic parameters and ORB-CVA with outcomes. METHODS: 468 asymptomatic adult participants were prospectively enrolled in the MEANS cohort. 174 symptomatic ASD patients with 6 fused levels and 2-year follow-ups were retrospectively enrolled in the symptomatic cohort. The association between OD-CVA and ORB-CVA, and radiographic parameters, perioperative variables, PROs, and outcomes were analyzed. Pearson's correlation was used to assess correlation and logistic regression odds of outcomes. RESULTS: In the MEANS cohort, the ORB-CVA correlated with C7-CVA (r=0.58) and OD-CVA (r=0.74). In the symptomatic cohort, preoperative ORB-CVA correlated better with leg length discrepancy (LLD) (r=0.17, P=0.029) while preoperative OD-CVA correlated better with C7-CVA (r=0.90, P<0.001). Postoperative ORB-CVA correlated with postoperative C7-CVA (r=0.66, P<0.001) and postoperative OD-CVA correlated stronger with postoperative C7-CVA (r=0.81, P<0.001). Both preoperative OD-CVA (r=0.199) and ORB-CVA (r=0.208) correlated with preoperative Oswestry Disability Index (ODI). ORB-CVA correlated better than OD-CVA in the preoperative SRS-22r pain category but worse in total and other subcategories. Preoperative ORB-CVA was associated with increased odds of intraoperative complication (OR=1.28, 1.01-1.22), like OD-CVA (OR=1.30, 1.12-1.53). Neither preoperative ORB-CVA nor OD-CVA was associated with reoperations and readmissions after multivariate analysis. Preoperative OD-ORB mismatch >1.5 cm was not associated with increased odds of intraoperative and postoperative complications, reoperations, or readmissions. CONCLUSION: ORB-CVA and OD-CVA correlated with radiographic parameters, PROs, and intraoperative complications. ORB-CVA and OD-CVA can be used interchangeably as cranial coronal parameters in ASD surgery.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment.

OBJECTIVE: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. METHODS: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20-79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). RESULTS: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7-S1 sagittal vertical axis (SVA) (p < 0.001), C2-7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). CONCLUSION: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2-7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans.

Volitional movement requires descending input from motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans it is not known whether dorsal epidural SCS targeted at the sensorimotor interface or anterior epidural SCS targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord with epidural electrodes while muscle responses were recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, paired stimulation effects were present regardless of the severity of myelopathy as measured by clinical signs or spinal cord imaging. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation.