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Objective: Condylar screw fixation is a rescue technique and an alternative to the conventional configuration of occipitocervical fusion. Condylar screws are utilized when previous surgical bone removal along the supraocciput has occurred which makes anchoring of a traditional barplate technically difficult or impossible. However, the challenging dissection of C0-1 necessary for condylar screw fixation and the concerns about possible complications have, thus far, prevented the acquisition of large surgical series utilizing occipital condylar screws. In the largest case series to date, this paper aims to evaluate the safety profile and complications of condylar screw fixation for occipitocervical fusion., Methods: A retrospective safety and complication-based analysis of occipitocervical fusion via condylar screws fixation was performed., Results: A total of 250 patients underwent occipitocervical fusions using 500 condylar screws between September 2012 and September 2018. No condylar screw pullouts, or vertebral artery impingements were observed in this series. The sacrifice of condylar veins during the dissection at C0-1 did not cause any venous stroke. Hypotrophic condyles were found in 36.4% (91 of the 250) cases and did not prevent the insertion of condylar screws. Two transient hypoglossal deficits occurred at the beginning of this surgical series and were followed by recovery a few months later. Corrective strategies were effective in preventing further hypoglossal injuries., Conclusions: This surgical series suggests that the use of condylar screws fixation is a relatively safe and reliable option for OC fusion in both adult and pediatric patients. Methodical dissection of anatomical landmarks, intraoperative imaging, and neurophysiologic monitoring allowed the safe execution of the largest series of condylar screws reported to date. Separate contributions will follow in the future to provide details about the long-term clinical outcome of this series., (© 2021. The Author(s).)

Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure-a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals ( n = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended.

Background: De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia., Objectives: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations., Methods: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila -derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes., Results: We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes., Conclusion: We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)