BACKGROUND Although many clinical risk factors of spastic cerebral palsy (CP) have been identified, the genetic basis of spastic CP is largely unknown. Here, using whole-genome genetic information linked to a deidentified electronic health record (BioVU) with replication in the UK Biobank and FinnGen, we perform the first genome-wide association study (GWAS) for spastic CP. OBJECTIVE To define the genetic basis of spastic CP. METHODS Whole-genome data were obtained using the multi-ethnic genotyping array (MEGA) genotyping array capturing single-nucleotide polymorphisms (SNPs), minor allele frequency (MAF) > 0.01, and imputation quality score (r2) > 0.3, imputed based on the 1000 genomes phase 3 reference panel. Threshold for genome-wide significance was defined after Bonferroni correction for the total number of SNPs tested (P < 5.0 × 10–8). Replication analysis (defined as P < .05) was performed in the UK Biobank and FinnGen. RESULTS We identify 1 SNP (rs78686911) reaching genome-wide significance with spastic CP. Expression quantitative trait loci (eQTL) analysis suggests that rs78686911 decreases expression of GRIK4, a gene that encodes a high-affinity kainate glutamatergic receptor of largely unknown function. Replication analysis in the UK Biobank and FinnGen reveals additional SNPs in the GRIK4 loci associated with CP. CONCLUSION To our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.
OBJECTIVE Anterior-to-psoas lumbar interbody fusion (ATP-LIF), more commonly referred to as oblique lateral interbody fusion, and lateral transpsoas lumbar interbody fusion (LTP-LIF), also known as extreme lateral interbody fusion, are the two commonly used lateral approaches for performing a lumbar fusion procedure. These approaches help overcome some of the technical challenges associated with traditional approaches for lumbar fusion. In this systematic review and indirect meta-analysis, the authors compared operative and patient-reported outcomes between these two select approaches using available studies. METHODS Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, the authors conducted an electronic search using the PubMed, EMBASE, and Scopus databases for studies published before May 1, 2019. Indirect meta-analysis was conducted on fusion rate, cage movement (subsidence plus migration), permanent deficits, and transient deficits; results were depicted as forest plots of proportions (effect size [ES]). RESULTS A total of 63 studies were included in this review after applying the exclusion criteria, of which 26 studies investigated the outcomes of ATP-LIF, while 37 studied the outcomes of LTP-LIF. The average fusion rate was found to be similar between the two groups (ES 0.97, 95% CI 0.84–1.00 vs ES 0.94, 95% CI 0.91–0.97; p = 0.561). The mean incidence of cage movement was significantly higher in the ATP-LIF group compared with the LTP-LIF group (stand-alone: ES 0.15, 95% CI 0.06–0.27 vs ES 0.09, 95% CI 0.04–0.16 [p = 0.317]; combined: ES 0.18, 95% CI 0.07–0.32 vs ES 0.02, 95% CI 0.00–0.05 [p = 0.002]). The mean incidence of reoperations was significantly higher in patients undergoing ATP-LIF than in those undergoing LTP-LIF (ES 0.02, 95% CI 0.01–0.03 vs ES 0.04, 95% CI 0.02–0.07; p = 0.012). The mean incidence of permanent deficits was similar between the two groups (stand-alone: ES 0.03, 95% CI 0.01–0.06 vs ES 0.05, 95% CI 0.01–0.12 [p = 0.204]; combined: ES 0.03, 95% CI 0.01–0.06 vs ES 0.03, 95% CI 0.00–0.08 [p = 0.595]). The postoperative changes in visual analog scale (VAS) and Oswestry Disability Index (ODI) scores were both found to be higher for ATP-LIF relative to LTP-LIF (VAS: weighted average 4.11 [SD 2.03] vs weighted average 3.75 [SD 1.94] [p = 0.004]; ODI: weighted average 28.3 [SD 5.33] vs weighted average 24.3 [SD 4.94] [p < 0.001]). CONCLUSIONS These analyses indicate that while both approaches are associated with similar fusion rates, ATP-LIF may be related to higher odds of cage movement and reoperations as compared with LTP-LIF. Furthermore, there is no difference in rates of permanent deficits between the two procedures.
Background: While many clinical risk factors of trigeminal neuralgia (TN) have been identified, the genetic basis of TN is largely unknown. Here, we perform the first genome-wide association study (GWAS) for TN using three independent DNA biobanks: BioVU, the UK Biobank, and Finngen. Objective: To elucidate the genetic basis of TN. Methods: Using GWAS summary statistics generated from BioVU, the UK Biobank, and Finngen, we performed fixed-effect meta-analysis across 490,912 individuals (1,188 TN cases and 489,724 controls) to identify genetic risk factors for TN. Genome-wide significance was defined as p < 5.0x10-8. Results: We identify an intergenic locus on chromosome 1p22.2 flanked by ZNF326 and SNORD3G containing 5 SNPs (rs77449572, rs543311093, rs35117749, rs71666259, and rs116010656) reaching genome-wide significance (p < 5.0 x 10-8), where rs77449572 is the sentinel variant (p = 1.72 x 10-9). The SNP rs77449572 overlaps an enhancer element in cortex-derived neurospheres. In addition, rs71666259 and rs116010656 are located in enhancer elements in embryonic stem cells (HUES48), suggesting potential functional consequences of this locus. We also identify a second locus on chromosome 5q35.1 containing sentinel variant rs62376947 reaching genome-wide significance (p = 2.49 x 10-8). Conclusions: To our knowledge, we perform the first GWAS of TN. Future studies should be aimed at understanding the extent to which genetic variation stratifies response to neuropathic pain medication and whether genetic information may be used to identify patients who are likely to benefit (or not) from surgical intervention.
OBJECTIVE Craniosynostosis (CS) affects about 1 in 2500 infants and is predominantly treated by surgical intervention in infancy. Later in childhood, many of these children wish to participate in sports. However, the safety of participation is largely anecdotal and based on surgeon experience. The objective of this survey study was to describe sport participation and sport-related head injury in CS patients. METHODS A 16-question survey related to child/parent demographics, CS surgery history, sport history, and sport-induced head injury history was made available to patients/parents in the United States through a series of synostosis organization listservs, as well as synostosis-focused Facebook groups, between October 2019 and June 2020. Sports were categorized based on the American Academy of Pediatrics groupings. Pearson’s chi-square test, Fisher’s exact test, and the independent-samples t-test were used in the analysis. RESULTS Overall, 187 CS patients were described as 63% male, 89% White, and 88% non-Hispanic, and 89% underwent surgery at 1 year or younger. The majority (74%) had participated in sports starting at an average age of 5 years (SD 2.2). Of those participating in sports, contact/collision sport participation was most common (77%), and 71% participated in multiple sports. Those that played sports were less frequently Hispanic (2.2% vs 22.9%, p < 0.001) and more frequently had undergone a second surgery (44% vs 25%, p = 0.021). Only 9 of 139 (6.5%) sport-participating CS patients suffered head injuries; 6 (67%) were concussions and the remaining 3 were nondescript but did not mention any surgical needs. CONCLUSIONS In this nationwide survey of postsurgical CS patients and parents, sport participation was exceedingly common, with contact sports being the most common sport category. Few head injuries (mostly concussions) were reported as related to sport participation. Although this is a selective sample of CS patients, the initial data suggest that sport participation, even in contact sports, and typically beginning a few years after CS correction, is safe and commonplace.
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