Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders.

PURPOSE: Missense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability. METHODS: By international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro. RESULTS: In accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well. CONCLUSION: By identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders.

Curriculum Innovations: A Podcast-Based Neurologic Emergency Flipped Classroom Curriculum for Neurology Residents.

Introduction: Education on the management of neurologic emergencies is vital for neurology residents, and effective educational methods are needed. This study aims to implement and evaluate the impact of a podcast-based flipped classroom curriculum in neurologic emergencies. "Flipped classroom" instructional methods have been used in GME and informed by experiential learning theory. Curriculum Objectives: The objectives of this curriculum were to (1) compare the clinical phenomena discussed in the neurologic emergencies podcast(s) with your own clinical experience; (2) discuss the pitfalls in the management of the neurologic emergencies discussed in the podcast(s); and (3) develop a management plan for the neurologic emergencies discussed in the podcast(s). Methods: At 10 neurology residency programs, we implemented a 3-session flipped classroom curriculum covering topics in acute stroke, movement disorder emergencies, and status epilepticus. Each session consisted of a Neurology® podcast followed by content discussion with a clinical expert. Assessment of the curriculum included presession and postsession surveys focused on learners' confidence and attitudes toward podcast-based education. Results: Our data sample consisted of survey responses from residents, with response volumes ranging from 29-111 across all surveys. Podcasts are already highly used by neurology residents in their self-directed education. Confidence increased among learners in the management of movement disorder emergencies (18% confident before vs 79% confident after, p < 0.001) and status epilepticus (72% confident before vs 91% confident after, p = 0.014) among those who completed the curriculum. A change in confidence in acute stroke management was not found (p = 0.15). Podcasts were consistently preferred over lectures and reading-based instructional methods while less preferred compared with simulation-based learning and case-based discussion with faculty. The podcast-based curriculum studied here showed high levels of enjoyment and perceived utility. Conclusions: We present a 3-part curriculum to help build learners' familiarity and confidence in 3 neurologic emergency categories. The educational impact is established in Level 1 of the Kirkpatrick paradigm. Future studies can explore a higher-level impact of this curriculum. Evolution in neurology education is shifting increasingly toward immediately accessible information via digital media. This curriculum can be useful to neurology educators who need to be increasingly agile and facile with multiple educational techniques to meet learners' needs.

Burnout, career satisfaction, and well-being among US neurology residents and fellows in 2016.

OBJECTIVE: To study prevalence of and factors contributing to burnout, career satisfaction, and well-being in US neurology residents and fellows. METHODS: A total of 938 US American Academy of Neurology member neurology residents and fellows were surveyed using standardized measures of burnout, career satisfaction, and well-being from January 19 to March 21, 2016. RESULTS: Response rate was 37.7% (354/938); about 2/3 of responders were residents and 1/3 were fellows. Median age of participants was 32 years and 51.1% were female. Seventy-three percent of residents and 55% of fellows had at least one symptom of burnout, the difference largely related to higher scores for depersonalization among residents. For residents, greater satisfaction with work-life balance, meaning in work, and older age were associated with lower risk of burnout; for fellows, greater satisfaction with work-life balance and effective support staff were associated with lower risk of burnout. Trainees experiencing burnout were less likely to report career satisfaction. Career satisfaction was more likely among those reporting meaning in work and more likely for those working in the Midwest compared with the Northeast region. CONCLUSIONS: Burnout is common in neurology residents and fellows. Lack of work-life balance and lack of meaning in work were associated with reduced career satisfaction and increased risk of burnout. These results should inform approaches to reduce burnout and promote career satisfaction and well-being in US neurology trainees.

Trouble crossing the bridge: altered interhemispheric communication of emotional images in anxiety.

Worry is thought to involve a strategy of cognitive avoidance, in which internal verbalization acts to suppress threatening emotional imagery. This study tested the hypothesis that worry-prone individuals would exhibit patterns of between-hemisphere communication that reflect cognitive avoidance. Specifically, the hypothesis predicted slower transfer of threatening images from the left to the right hemisphere among worriers. Event-related potential (ERP) measures of interhemispheric transfer time supported this prediction. Left-to-right hemisphere transfer times for angry faces were relatively slower for individuals scoring high in self-reported worry compared with those scoring low, whereas transfer of happy and neutral faces did not differ between groups. These results suggest that altered interhemispheric communication may constitute one mechanism of cognitive avoidance in worry.

Anxiety and error monitoring: increased error sensitivity or altered expectations?

This study tested the prediction that the error-related negativity (ERN), a physiological measure of error monitoring, would be enhanced in anxious individuals, particularly in conditions with threatening cues. Participants made gender judgments about faces whose expressions were either happy, angry, or neutral. Replicating prior studies, midline scalp negativities were greater following errors than following correct responses. In addition, state anxiety interacted with facial expression to predict ERN amplitudes. Counter to predictions, participants high in state anxiety displayed smaller ERNs for angry-face blocks and larger ERNs for happy-face blocks, compared to less anxious participants. These results are inconsistent with the simple notion that anxiety enhances error sensitivity globally. Rather, we interpret the findings within an expectancy violation framework, in which anxious participants have altered expectations for success and failure in the context of happy and angry facial cues, with greater ERN amplitudes when expectations are violated.