Joint learning of nonlinear representation and projection for fast constrained MRSI reconstruction.

PURPOSE: To develop and evaluate a novel method for computationally efficient reconstruction from noisy MR spectroscopic imaging (MRSI) data. METHODS: The proposed method features (a) a novel strategy that jointly learns a nonlinear low-dimensional representation of high-dimensional spectroscopic signals and a neural-network-based projector to recover the low-dimensional embeddings from noisy/limited data; (b) a formulation that integrates the forward encoding model, a regularizer exploiting the learned representation, and a complementary spatial constraint; and (c) a highly efficient algorithm enabled by the learned projector within an alternating direction method of multipliers (ADMM) framework, circumventing the computationally expensive network inversion subproblem. RESULTS: The proposed method has been evaluated using simulations as well as in vivo 1 $$ {}^1 $$ H and 31 $$ {}^{31} $$ P MRSI data, demonstrating improved performance over state-of-the-art methods, with about 6 × $$ \times $$ fewer averages needed than standard Fourier reconstruction for similar metabolite estimation variances and up to 100 × $$ \times $$ reduction in processing time compared to a prior neural network constrained reconstruction method. Computational and theoretical analyses were performed to offer further insights into the effectiveness of the proposed method. CONCLUSION: A novel method was developed for fast, high-SNR spatiospectral reconstruction from noisy MRSI data. We expect our method to be useful for enhancing the quality of MRSI or other high-dimensional spatiospectral imaging data.

Increased Change in Cervical Lordosis is Associated With Decreased Rate of Recovery in Patients With C5 Palsy.

STUDY DESIGN: A retrospective chart review. OBJECTIVE: The authors aim to investigate the role of clinical and radiographic parameters in patients who underwent posterior cervical surgery, and their association with C5 palsy severity and time to recovery. BACKGROUND: Postoperative C5 palsy affects 1%-30% of patients undergoing posterior decompression, with or without fusion. Causation and avoidance of this complication remain widely debated. MATERIALS AND METHODS: A single institution review of patients who underwent posterior cervical spine surgery was focused on using specific Common Procedural Technology codes associated with the patient population of interest. Patients were excluded if they had inadequate pre and postoperative imaging, as well as a history of prior cervical spine surgery, concurrent anterior surgery, intradural pathology, spinal tumor, or spinal trauma. Radiographic measurements of the pre and postoperative images were completed with subsequent intraclass correlation coefficient analysis to confirm the precision of measurements. RESULTS: Out of 105 total patients, 35 (33%) patients developed a C5 palsy. Twenty-four (69%) of those palsies completely resolved, with a median time to recovery of 8 months. Preoperative demographics and radiographic parameters demonstrated heterogeneity among those patients who did and did not have a resolution of palsy. Patients with increased change in C2-C7 lordosis (P = 0.011) after surgery were associated with decreased likelihood of recovery. Patients without a smoking history (P = 0.009) had an increased likelihood of recovering from C5 palsy. CONCLUSIONS: The degree of increased lordosis in the treatment of degenerative cervical disease plays a role in the rate of recovery from C5 palsy. This should be considered during preoperative planning in determining the amount of lordosis desired. In addition, patients without a smoking history were associated with a higher rate of recovery. LEVEL OF EVIDENCE: Level IV.

Prediction models for risk assessment of surgical site infection after spinal surgery: A systematic review.

Background: Spinal surgeries are a common procedure, but there is significant risk of adverse events following these operations. While the rate of adverse events ranges from 8% to 18%, surgical site infections (SSIs) alone occur in between 1% and 4% of spinal surgeries. Methods: We completed a systematic review addressing factors that contribute to surgical site infection after spinal surgery. From the included studies, we separated the articles into groups based on whether they propose a clinical predictive tool or model. We then compared the prediction variables, model development, model validation, and model performance. Results: About 47 articles were included in this study: 10 proposed a model and 5 validated a model. The models were developed from 7,720 participants in total and 210 participants with SSI. Only one of the proposed models was externally validated by an independent group. The other 4 validation papers examined the performance of the ACS NSQIP surgical risk calculator. Conclusions: While some preoperative risk models have been validated, and even successfully implemented clinically, the significance of postoperative SSIs and the unique susceptibility of spine surgery patients merits the development of a spine-specific preoperative risk model. Additionally, comprehensive and stratified risk modeling for SSI would be of invaluable clinical utility and greatly improve the field of spine surgery.

Dataset factors associated with age-related changes in brain structure and function in neurodevelopmental conditions.

With brain structure and function undergoing complex changes throughout childhood and adolescence, age is a critical consideration in neuroimaging studies, particularly for those of individuals with neurodevelopmental conditions. However, despite the increasing use of large, consortium-based datasets to examine brain structure and function in neurotypical and neurodivergent populations, it is unclear whether age-related changes are consistent between datasets and whether inconsistencies related to differences in sample characteristics, such as demographics and phenotypic features, exist. To address this, we built models of age-related changes of brain structure (regional cortical thickness and regional surface area; N = 1218) and function (resting-state functional connectivity strength; N = 1254) in two neurodiverse datasets: the Province of Ontario Neurodevelopmental Network and the Healthy Brain Network. We examined whether deviations from these models differed between the datasets, and explored whether these deviations were associated with demographic and clinical variables. We found significant differences between the two datasets for measures of cortical surface area and functional connectivity strength throughout the brain. For regional measures of cortical surface area, the patterns of differences were associated with race/ethnicity, while for functional connectivity strength, positive associations were observed with head motion. Our findings highlight that patterns of age-related changes in the brain may be influenced by demographic and phenotypic characteristics, and thus future studies should consider these when examining or controlling for age effects in analyses.

Chronic pain patients' evaluations of consultations: A matter of high expectations or expectations unmet?

OBJECTIVE: This study tests two hypotheses about spine pain patients' expectations for consultations and their negative evaluations. High expectations may be impractical or unachievable and can set patients up for disappointment. Unmet expectations are the absolute difference between expectations before the visit and perceptions of expectations actually enacted. METHOD: We conducted a single-site prospective study using pre- and post-consultation surveys. Patients (N = 200) were English-speaking individuals aged 18-75 presenting for an initial consultation for musculoskeletal pain. Analyses were conducted in SPSS v. 28.0 using mixed modeling to account for interdependence among cases. RESULTS: Contrary to initial predictions, higher pre-consultation expectations for shared decision-making were positively linked to post-consultation satisfaction, trust, and agreement. Exceeding expectations in shared decision-making, history-taking, examination, and interpersonal skills significantly enhanced post-consultation outcomes. CONCLUSIONS: Results support the unmet expectations hypothesis over the high expectations hypothesis. Increased expectations and exceeding these expectations in key areas of patient-physician interaction were positively associated with improved consultation outcomes. PRACTICE IMPLICATIONS: Findings highlight the importance of exceeding multifaceted patient expectations in physician evaluations. Yet, physicians must first understand the nature and source of each patient's expectations pre-consultation, which vary across individuals in aspirational and realistic dimensions.

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. METHODS: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). RESULTS: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. CONCLUSIONS: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

One- and 2-year outcomes of lumbar facet arthroplasty versus spinal fusion in young (<65 years) and old (≥65 years) patients for the treatment of degenerative spondylolisthesis and stenosis.

Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (<65 and ≥65 years) with symptomatic grade 1 degenerative spondylolisthesis with moderate to severe spinal stenosis at L2-5. Methods: Patient-reported outcomes (PROMS), including Oswestry disability index (ODI), visual analog pain scales (VAS), and Zurich claudication questionnaires (ZCQ), were assessed at baseline and multiple postoperative timepoints. Radiographic evaluation of flexion/extension range of motion (ROM) occurred at baseline, 12 months, and 24 months. Data were analyzed following an intention-to-treat model. Significance was defined as p<.05. Results: About 299 patients were included (TOPS=206, TLIF=93). The groups were similar at baseline. At 2 years, the TOPS group had a greater proportion of patients report ≥15-point improvement for ODI (93.8% versus 77.1%, p=.011) and ≥20-point improvement for VAS back (84.4% versus 61.8%, p=.014). At 1 year, TOPS group had a greater proportion of patients report clinically significant improvements in all ZCQ categories (91.6% versus 78.5%, p=.012). In patients <65 years, the TOPS group had improved PROMS compared to TLIF at 2 years; however, these differences were less pronounced in patients ≥65 years old. The TOPS groups preserved more ROM at 12 (2.8° 95%CI [1.87; 3.74], p<.0001) and 24 (2.99° 95%CI [1.82; 4.15], p<.0001) months compared to TLIF. ROM was similarly preserved in patients aged <65 and ≥65. The rate of adverse events did not differ significantly between treatment groups. Conclusions: Facet arthroplasty preserves more ROM in all ages and leads to improved PROMS compared to TLIF, particularly in younger patients.

A protocol for the formative evaluation of the implementation of patient-reported outcome measures in child and adolescent mental health services as part of a learning health system.

BACKGROUND: Mental health conditions affect one in seven young people and research suggests that current mental health services are not meeting the needs of most children and youth. Learning health systems are an approach to enhancing services through rapid, routinized cycles of continuous learning and improvement. Patient-reported outcome measures provide a key data source for learning health systems. They have also been shown to improve outcomes for patients when integrated into routine clinical care. However, implementing these measures into health systems is a challenging process. This paper describes a protocol for a formative evaluation of the implementation of patient-reported measures in a newly operational child and adolescent mental health centre in Calgary, Canada. The purpose is to optimize the collection and use of patient-reported outcome measures. Our specific objectives are to assess the implementation progress, identify barriers and facilitators to implementation, and explore patient, caregivers and clinician experiences of using these measures in routine clinical care. METHODS: This study is a mixed-methods, formative evaluation using the Consolidated Framework for Implementation Research. Participants include patients and caregivers who have used the centre's services, as well as leadership, clinical and support staff at the centre. Focus groups and semi-structured interviews will be conducted to assess barriers and facilitators to the implementation and sustainability of the use of patient-reported outcome measures, as well as individuals' experiences with using these measures within clinical care. The data generated by the patient-reported measures over the first five months of the centre's operation will be analyzed to understand implementation progress, as well as validity of the chosen measures for the centres' population. DISCUSSION: The findings of this evaluation will help to identify and address the factors that are affecting the successful implementation of patient-reported measures at the centre. They will inform the co-design of strategies to improve implementation with key stakeholders, which include patients, clinical staff, and leadership at the centre. To our knowledge, this is the first study of the implementation of patient-reported outcome measures in child and adolescent mental health services and our findings can be used to enhance future implementation efforts in similar settings.

The trajectory of depression and anxiety among children and adolescents over two years of the COVID-19 pandemic.

Longitudinal research examining children's mental health (MH) over the course of the COVID-19 pandemic is scarce. We examined trajectories of depression and anxiety over two pandemic years among children with and without MH disorders. Parents and children 2-18 years completed surveys at seven timepoints (April 2020 to June 2022). Parents completed validated measures of depression and anxiety for children 8-18 years, and validated measures of emotional/behavioural symptoms for children 2-7 years old; children ≥10 years completed validated measures of depression and anxiety. Latent growth curve analysis determined depression and anxiety trajectories, accounting for demographics, child and parent MH. Data were available on 1315 unique children (1259 parent-reports; 550 child-reports). Trajectories were stable across the study period, however individual variation in trajectories was statistically significant. Of included covariates, only initial symptom level predicted symptom trajectories. Among participants with pre-COVID data, a significant increase in depression symptoms relative to pre-pandemic levels was observed; children and adolescents experienced elevated and sustained levels of depression and anxiety during the two-year period. Findings have direct policy implications in the prioritization and of maintenance of educational, recreational, and social activities with added MH supports in the face of future events.

SCAT5 baseline values, test-retest reliability, and reliable change metrics in high school athletes.

OBJECTIVE: In the United States, more than 1 million sport-related concussions afflict children annually, with many cases undetected or unreported. The Sport Concussion Assessment Tool (SCAT) is widely used to detect concussions in high school, collegiate, and professional sports. The objective of this study was to establish baseline values for the SCAT version 5 (SCAT5) in high school athletes. METHODS: Baseline SCAT5 evaluations were conducted in students (ages 14-19 years) from 19 high schools in central Illinois who were participating in various school-sponsored sports. The SCAT5 evaluations were retrospectively extracted from the electronic medical record system for analysis. Statistical analyses included the Wilcoxon rank-sum test for continuous variables and the chi-square test for categorical variables, considering significance at p < 0.05. Test-retest reliability at < 6 months, 10-14 months, and 16-20 months was computed using intraclass correlation and Spearman's rho (ρ). Reliable change indices are provided using the Iverson formula. RESULTS: A total of 2833 unique athletes were included, and the average age was 15.5 ± 1.14 (SD) years. There were 721 female (25.5%) and 2112 male (74.5%) athletes. Students ≥ 15 years old had more prior concussions (p < 0.001), and male athletes were more frequently hospitalized for head injury (p = 0.013). Female athletes exhibited a significantly higher prevalence of mood disorders (14.7% vs 4.6%, p < 0.001), whereas attention-deficit/hyperactivity disorder was more common in male athletes (5.2% vs 13.2%, p < 0.001). Symptom number and severity were significantly greater in female athletes (3.17 ± 4.39 vs 2.08 ± 3.49, p < 0.001; 5.47 ± 9.21 vs 3.52 ± 7.26, p < 0.001, respectively), with mood-related symptoms representing the largest differences. Female athletes and students ≥ 15 years old performed better on most cognitive assessments. Female athletes and students < 15 years old performed better on the modified Balance Error Scoring System (p < 0.001). Test-retest reliability was poor to moderate for most assessment components. Reliable change index cutoff values differed slightly by sex, with female athletes often having a greater cutoff value. CONCLUSIONS: This study underscores the variability of SCAT5 baseline values influenced by age, sex, and medical history among adolescent athletes. It provides a robust dataset, delineating baseline values stratified by sex and age within this demographic. Additionally, the results provide enhanced guidance to clinicians for interpretation of change and reliability of baselines.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Patient-Reported and Clinical Outcomes of Surgically Treated Patients With Symptomatic Spinal Metastases: Results From Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO), a Prospective, Multi-Institutional and International Study.

BACKGROUND AND OBJECTIVES: The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS: The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS: Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION: Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.

Patients May Return to Work Sooner After Laminoplasty: Occupational Outcomes of the Cervical Spondylotic Myelopathy Surgical Trial.

BACKGROUND AND OBJECTIVES: Return-to-work (RTW) is an important outcome for employed patients considering surgery for cervical spondylotic myelopathy (CSM). We conducted a post hoc analysis of patients as-treated in the Cervical Spondylotic Myelopathy Surgical Trial, a prospective, randomized trial comparing surgical approaches for CSM to evaluate factors associated with RTW. METHODS: In the trial, patients were randomized (2:3) to either anterior surgery (anterior cervical decompression/fusion [ACDF]) or posterior surgery (laminoplasty [LP], or posterior cervical decompression/fusion [PCDF], at surgeon's discretion). Work status was recorded at 1, 3, 6, and 12 months postoperatively. For patients working full-time or part-time on enrollment, time to RTW was compared across as-treated surgical groups using discrete-time survival analysis. Multivariate logistic regression was used to assess predictors of RTW. Clinical outcomes were compared using a linear mixed-effects model. RESULTS: A total of 68 (42%) of 163 patients were working preoperatively and were analyzed. In total, 27 patients underwent ACDF, 29 underwent PCDF, and 12 underwent LP. 45 (66%) of 68 patients returned to work by 12 months. Median time to RTW differed by surgical approach (LP = 1 month, ACDF = 3 months, PCDF = 6 months; P = .02). Patients with longer length-of-stay were less likely to be working at 1 month (odds ratio 0.51; 95% CI, 0.29-0.91; P = .022) and 3 months (odds ratio 0.39; 95% CI, 0.16-0.96; P = .04). At 3 months, PCDF was associated with lower Short-Form 36 physical component summary scores than ACDF (estimated mean difference [EMD]: 6.42; 95% CI, 1.4-11.4; P = .007) and LP (EMD: 7.98; 95% CI, 2.7-13.3; P = .003), and higher Neck Disability Index scores than ACDF (EMD: 12.48; 95% CI, 2.3-22.7; P = .01) and LP (EMD: 15.22; 95% CI, 2.3-28.1; P = .014), indicating worse perceived physical functioning and greater disability, respectively. CONCLUSION: Most employed patients returned to work within 1 year. LP patients resumed employment earliest, while PCDF patients returned to work latest, with greater disability at follow-up, suggesting that choice of surgical intervention may influence occupational outcomes.

How Chronic Pain Patients' and Physicians' Communication Influences Patients' Uncertainty: A Pre- and Post-Consultation Study.

Chronic pain is a health problem that is difficult to diagnose, treat, and manage, partly owing to uncertainty surrounding ambiguous causes, few treatment options, and frequent misunderstandings in clinical encounters. Pairing uncertainty management theory with medical communication competence, we predicted that both physicians and patients are influential to patients' uncertainty appraisals and uncertainty management. We collected pre- and post-consultation data from 200 patients with chronic neck and spine/back pain and their physicians. Patients' reports of their physician's communication were a consistent predictor of their post-consultation uncertainty outcomes. Physicians' reports of both their own and patients' communication competence were associated with patients' positive uncertainty appraisals. Physicians' reports of patients' communication competence were also associated with reductions in patients' uncertainty. Findings illustrate how both interactants' perceptions of communication competence-how they view their own (for physicians) and the other's-are associated with patients' post-consultation outcomes.

Altered Error Monitoring and Decreased Flanker Task Accuracy in Pediatric Obsessive-Compulsive Disorder.

The error-related negativity (ERN) and error positivity (Pe) are components of the event-related potential following an error that are potential mechanistic biomarkers of obsessive-compulsive disorder (OCD). The study examined the ERN, Pe, flanker task accuracy, and clinical measures in 105 OCD cases and 105 matched healthy controls (HC) ages 8-18 years. Higher flanker task accuracy in all participants was associated with an increased ERN amplitude and increased difference between Pe and correct positivity amplitudes (ΔPe). Compared to HC, OCD cases had an increased ERN but decreased ΔPe and flanker task accuracy. Those differences were also significant in tic-related and non-tic-related OCD cases compared to HC. A lower ΔPe was associated in cases with an earlier age at OCD symptom onset. The results support the hypothesis that OCD involves defects in an error monitoring system and suggest a reduced ΔPe may compromise error signaling and cause uncertainty about the correctness of a response.

Postoperative C5 Palsy after Anterior or Posterior Decompression for Degenerative Cervical Myelopathy: A Subgroup Analysis of the Multicenter, Prospective, Randomized, Phase III, CSM-Protect Clinical Trial.

STUDY DESIGN: Retrospective cohort study of prospectively accrued data. OBJECTIVE: To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach. SUMMARY OF BACKGROUND DATA: The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data. METHODS: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. RESULTS: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. CONCLUSION: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. LEVEL OF EVIDENCE: Therapeutic Level-II.

Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts.

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist - Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = -0.97; FC feature vectors, rPOND-HBN = -0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = -0.99; FC feature vectors, rPOND-HBN = -0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

Posterior-only 2-level vertebrectomy and fusion in a medically complex patient with lumbar metastasis: illustrative case.

BACKGROUND: Spinal metastases are commonly seen in patients with cancer and often indicate a poor prognosis. Treatment can include curative or palliative surgery, chemotherapy, and radiation therapy. The surgical approach varies widely on the basis of the affected region of the spine, the location of the tumor (anterior versus posterior), the goal of surgery, the health of the patient, and surgeon preference. OBSERVATIONS: The authors present a case of a 68-year-old male with intractable lower-back pain and substantially diminished ambulation. Diagnostic imaging revealed a lumbar metastasis from a cholangiocarcinoma primary at L2-3 (4.5 cm anteroposterior × 5.7 cm transverse × 7.0 cm craniocaudal). The patient underwent a 2-level vertebrectomy with expandable cage placement and T10 to S2 fusion via a posterior-only approach. The patient regained much of his mobility and quality of life after the surgery. LESSONS: Although this was a high-risk surgery, the authors show that a posterior-only approach can be used for lumbar vertebrectomies and fusion when necessary. Palliative surgeries carrying a high risk, especially in the setting of a limited prognosis, should include multidisciplinary deliberations and a thorough discussion of the risks and outcome expectations with the patient.

Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population.

While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.

Racial/Ethnic Disparities in Psychiatric Traits and Diagnoses within a Community-based Sample of Children and Youth: Disparités raciales/ethniques dans les traits et diagnostics psychiatriques au sein d'un échantillon communautaire d'enfants et de jeunes.

OBJECTIVE: Racial/ethnic disparities in the prevalence of psychiatric disorders have been reported, but have not accounted for the prevalence of the traits that underlie these disorders. Examining rates of diagnoses in relation to traits may yield a clearer understanding of the degree to which racial/ethnic minority youth in Canada differ in their access to care. We sought to examine differences in self/parent-reported rates of diagnoses for obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders after adjusting for differences in trait levels between youth from three racial/ethnic groups: White, South Asian and East Asian. METHOD: We collected parent or self-reported ratings of OCD, ADHD and anxiety traits and diagnoses for 6- to 17-year-olds from a Canadian general population sample (Spit for Science). We examined racial/ethnic differences in trait levels and the odds of reporting a diagnosis using mixed-effects linear models and logistic regression models. RESULTS: East Asian (N = 1301) and South Asian (N = 730) youth reported significantly higher levels of OCD and anxiety traits than White youth (N = 6896). East Asian and South Asian youth had significantly lower odds of reporting a diagnosis for OCD (odds ratio [OR]East Asian = 0.08 [0.02, 0.41]; ORSouth Asian = 0.05 [0.00, 0.81]), ADHD (OREast Asian = 0.27 [0.16, 0.45]; ORSouth Asian = 0.09 [0.03, 0.30]) and anxiety (OREast Asian = 0.21 [0.11, 0.39]; ORSouth Asian = 0.12 [0.05, 0.32]) than White youth after accounting for psychiatric trait levels. CONCLUSIONS: These results suggest a discrepancy between trait levels of OCD, ADHD and anxiety and rates of diagnoses for East Asian and South Asian youth. This discrepancy may be due to increased barriers for ethnically diverse youth to access mental health care. Efforts to understand and mitigate these barriers in Canada are needed.

We know that there is there are differences in the prevalence of childhood mental illnesses by race/ethnic group, which may be related to disproportionate access to mental health care. What is unknown is whether there this difference in prevalence is related to differences in the presence of symptoms for mental illness or whether children and youth from marginalized racial/ethnic groups have symptoms but are not getting diagnosed. This information is needed to understand the degree to which children and youth from marginalized race/ethnicity groups are accessing mental health care in Canada. We tested the differences in reported symptoms and diagnosis of three common and impairing childhood-onset disorders (obsessive-compulsive disorder­OCD), attention-deficit/hyperactivity disorder­ADHD and anxiety disorders) in children and youth (6­17 years of age) living in Canada that were from three racial/ethnic groups: White, South Asian and East Asian. East Asian and South Asian youth reported significantly higher levels of OCD and anxiety traits than White youth. However, East Asian and South Asian youth were significantly less likely than White youth to have a reported diagnosis of OCD, ADHD or anxiety even after accounting for symptom levels for each disorder. Our findings suggest that East and South Asian children are less likely than White children to get a diagnosis for common mental illness even if they have symptoms of that mental illness. This gap in receiving a diagnosis might be because of more barriers to mental health care for children and youth from marginalized racial/ethnic groups but we need more research to pinpoint the cause.