Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet.

BACKGROUND: Children on the ketogenic diet must limit carbohydrate intake to maintain ketosis and reduce seizure burden. Patients on ketogenic diet are vulnerable to harm in the hospital setting where carbohydrate-containing medications are commonly prescribed. We developed clinical decision support to reduce inappropriate prescription of carbohydrate-containing medications in hospitalized children on ketogenic diet. METHODS: A clinical decision support alert was developed through formative and summative usability testing. The alert warned prescribers when they entered an order for a carbohydrate-containing medication in patients on ketogenic diet. The alert was implemented using a quasi-experimental design with sequential crossover from control to intervention at two tertiary care pediatric hospitals within a single health system. The primary outcome was carbohydrate-containing medication orders per patient-day. RESULTS: During the study period, there were 280 ketogenic diet patient admissions totaling 1219 patient-days. The carbohydrate-containing medication order rate declined from 0.69 to 0.35 orders per patient-day (absolute rate reduction 0.34, 95% confidence interval 0.25-0.43), corresponding to 256 inappropriate orders prevented. The alert fired 398 times and was accepted (i.e., the order was removed) 227 times for an overall acceptance rate of 57%. CONCLUSIONS: Implementation of a clinical decision support alert at order-entry resulted in a sustained reduction in carbohydrate-containing medication orders for hospitalized patients on ketogenic diet without an increase in alert burden. Clinical decision support developed with user-centered design principles can improve patient safety for children on ketogenic diet by influencing prescriber behavior.

Epileptic Encephalopathy and Cerebellar Atrophy Resulting from Compound Heterozygous CACNA2D2 Variants.

CACNA2D2 encodes an auxiliary subunit of the voltage-dependent calcium channel. To date, there have only been two reports of individuals with early-infantile epileptic encephalopathy due to CACNA2D2 mutations. In both reports, patients were homozygous for the identified variants. Here, we report a patient with epileptic encephalopathy and cerebellar atrophy who was found to have two novel variants in the CACNA2D2 gene: c.782C>T (p.Pro261Leu) and c.3137T>C (p.Leu1046Pro), by whole-exome sequencing. The variants were shown to be inherited in trans and the unaffected parents were confirmed to be heterozygous carriers. This is the third report of recessive CACNA2D2 variants associated with disease and the first report of compound heterozygous variants. The clinical description of this new case highlights the phenotypic similarities amongst individuals with CACNA2D2-related disease and suggests that CACNA2D2 should be considered as a differential diagnosis in individuals with cerebellar dysfunction and multiple seizure types that begin in the first year of life.

Topiramate loading for refractory status epilepticus in children.

PURPOSE: To describe three cases of refractory status epilepticus (RSE) in children responsive to topiramate (TPM). METHODS: Patients with SE refractory to therapeutic doses of at least two antiepileptic medications were given TPM, 10 mg/kg/d, for 2 consecutive days, followed by maintenance doses of 5 mg/kg/d. RESULTS: This protocol has been used in three cases of RSE at our institution. In each case, SE was aborted within 21 h of the initial dose of TPM. Two patients avoided pharmacologic coma, and one was rapidly weaned from continuous benzodiazepine infusion. CONCLUSIONS: Our experience indicates that TPM loading can be effective in the treatment of RSE in children.

Screening for autoantibodies in children with opsoclonus-myoclonus-ataxia.

Various paraneoplastic autoantibodies have been linked to discrete neurologic syndromes and tumors in adults, but little is known about their incidence in children. We report a cross-sectional study of known paraneoplastic antibodies in 59 children with opsoclonus-myoclonus-ataxia, 86% of whom were moderately or severely symptomatic, and 68% of whom had relapsed at the time of testing. This total number of patients includes 18 children with low-stage neuroblastoma (tested after tumor resection), six of whom had never been treated with immunosuppressants. All were seronegative for anti-Hu, anti-Ri, and anti-Yo, the three paraneoplastic antibodies most associated with opsoclonus-myoclonus or ataxia in adults. These data contrast with reports of anti-Hu-positive sera in children with high-stage tumors and suggest that anti-Hu, anti-Ri, and anti-Yo do not explain relapses in pediatric opsoclonus-myoclonus-ataxia. They underscore the need to search for unique autoantibodies, as well as cellular mechanisms of pediatric paraneoplastic disease.