A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome.

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE). METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome. RESULTS: For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements. CONCLUSIONS: These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR.

Increasing Provider Utilization of a Seizure Action Plan in the Outpatient Setting.

OBJECTIVES: A seizure action plan (SAP) is a powerful tool that provides actionable information for caregivers during seizures. Guidelines have expressed the need for individualized SAPs. Our quality improvement team aimed to increase implementation of an SAP within a pediatric tertiary center, initially among epilepsy providers and expanded to all neurology providers. METHODS: Process changes were implemented using Plan-Do-Study-Act cycles and data were evaluated monthly using control charts. The team focused on tracking patients who received SAPs and identified opportunities for improvement, including reminders within the electronic medical record, and standardizing clinic processes. A secondary analysis was performed to trend emergency department (ED) use among our patient population. RESULTS: The SAP utilization rate among epilepsy providers increased from a baseline of 39% to 78% by December 2019 and reached the goal of 85% by June 2020, with a further increase to 92% by February 2022 and maintained. The SAP utilization rate among general neurology providers increased from 43% in 2018 to 85% by July 2020, and further increased to 93% by February 2022 and maintained. ED visits of established patients with epilepsy decreased from a baseline of 10.2 per 1000 to 7.5 per 1000. CONCLUSIONS: Quality improvement methodologies increased the utilization of a standardized SAP within neurology outpatient care centers. The SAP is a simplified tool that allows patients and providers to navigate a complex health care system. The utility of an SAP may potentially extend to minimizing unnecessary ED visits.

RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, we identified 24 individuals with neurodevelopmental delays from 18 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants showed reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicated that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 revealed that most disease-associated missense variants mapped to the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants had reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS ( SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.