Clarifying the clinical landscape of pediatric spinal arteriovenous shunts: an institutional experience and individual patient-data meta-analysis.

BACKGROUND: Pediatric spinal arteriovenous shunts (SAVS) are rare lesions with heterogeneous pathogenesis and clinical manifestations. OBJECTIVE: To evaluate the clinical characteristics, angioarchitecture, and technical/clinical outcomes in SAVS through a large single-center cohort analysis and meta-analysis of individual patient data. METHODS: A retrospective institutional database identified children (aged 0-21 years) who underwent digital subtraction spinal angiography (DSA) for SAVS between January 1996 and July 2021. Clinical data were recorded to evaluate angioarchitecture, generate modified Aminoff-Logue gait disturbance scores (AL) and McCormick grades (MC), and assess outcomes. We then performed a systematic literature review following PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for individual patient data) guidelines, extracting similar data on individual patients for meta-analysis. RESULTS: The cohort consisted of 28 children (M:F=11:17) with 32 SAVS lesions, with a mean age of 12.8±1.1 years at diagnosis. At presentation, SAVS were most highly concentrated in the cervical region (40.6%). Children had a median AL=2 and MC=2, with thoracolumbar AVS carrying the greatest disability. Among treated cases, complete obliteration was achieved in 48% of cases and median AL scores and MC grades both improved by one point. Systematic literature review identified 161 children (M:F=96:65) with 166 SAVS lesions with a mean age of 8.7±0.4 years. Among studies describing symptom chronicity, 37/51 (72.5%) of children presented acutely. At presentation, children had a median AL=4 and MC=3, with thoracolumbar AVS carrying the highest MC grades. After intervention, median AL and MC both improved by one point. CONCLUSIONS: This study provides epidemiologic information on the location, onset, and presentation of the full spectrum of pediatric SAVS, highlighting the role of targeted treatment of high-risk features.

Comparison of multiplex cytokine assays in a pediatric cohort with epilepsy.

BACKGROUND: Multiplex analyses allow for detection of dozens of cytokines/chemokines in small sample volumes. Although several commercially available assay kits are available, there are no comparative data in plasma measurements among pediatric or epilepsy cohorts. NEW METHOD: Cohort study of 38 children with epilepsy. We evaluated plasma levels of cytokines/chemokines using three different assays: Luminex® xMAP high-sensitivity (HS) and standard-sensitivity (SS) assays, and Meso-Scale Discovery (MSD). We calculated recovery rates of each analyte, correlation coefficients between assays, and level of agreement between measurements. We repeated analyses in a subset of samples after a single freeze-thaw cycle. RESULTS: Among ten analytes common to all assays, HS had high recovery (<15% of values extrapolated or out-of- range [OOR]) for all analytes, SS for 50%, and MSD for 40%. While several analytes had a high correlation between assays, Bland-Altman plots demonstrated assays were not interchangeable. For most analytes, a single freeze-thaw cycle decreased cytokines/chemokine measurements. There was good correlation of measurements after a freeze-thaw cycle with acceptable agreement between measurements for six of 13 (46%) analytes using HS, one of 9 (11%) for SS, and none for MSD. COMPARISON WITH EXISTING METHODS: HS assays may optimize yield in plasma for proteins of particular interest in epilepsy research, limit values extrapolated beyond the standard curve, and improve precision compared to other SS and MSD assays. CONCLUSION: Our results demonstrate assay choice may be critical to study results and support the need for a standardized approach to biomarker assessment across epilepsy research and other domains.