Repeat Pediatric Trisomy 21 Radiographic Exam: Does Atlantoaxial Instability Develop Over Time?

BACKGROUND: Atlantoaxial instability (AAI) is common in pediatric patients with Trisomy 21 and can lead to spinal cord injury during sports, trauma, or anesthetized neck manipulation. Children with Trisomy 21 therefore commonly undergo radiographic cervical spine screening, but recommendations on age and timing vary. The purpose of this study was to determine if instability develops over time. METHODS: We performed a retrospective review for all pediatric Trisomy 21 patients receiving at least 2 cervical spine radiographic series between 2008 and 2020 at our institution. Atlantodens interval (ADI) and space available for the cord at C1 (SAC) were measured; bony abnormalities such as os odontoidium, and age and time between radiographs were noted. AAI was determined by ADI ≥6 mm or SAC ≤14 mm based on our groups' prior study. Those who developed instability were compared with those who did not. RESULTS: A total of 437 cervical spine radiographic series from 192 patients were evaluated, with 160 included. Mean age at first radiograph was 7.4±4.4 years, average ADI was 3.1 mm (±1.2), and SAC was 18.1 mm (±2.6). The average time between first and last radiographs was 4.3 years (±1.8), with average final ADI 3.2 mm (±1.4) and SAC 18.9 mm (±2.9). Seven patients (4%) had instability: 4 were unstable on their initial studies and 3 (1.6%) on subsequent imaging. Os odontoideum was found in 5 (71%) unstable spines and 3 (2%) stable spines (P<0.0001); only 1 patient that became unstable on subsequent radiograph did not have an os. There was no specific age cut-off or surveillance time period after which one could be determined no longer at risk. CONCLUSIONS: Trisomy 21 patients have a 4.4% overall rate of AAI in our series with a 1.6% rate of progression to instability over ∼4 years. Given this nearly 1 in 23 risk of instability, we recommend initial surveillance radiograph for all children over 3 years with Trisomy 21; repeat asymptomatic surveillance should continue in those with os odontoideum given their high instability risk. LEVEL OF EVIDENCE: Level II-diagnostic study.

Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid.

Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.