Pharmacoresponsiveness of spontaneous recurrent seizures and the comorbid sleep disorder of epileptic Kcna1-null mice.

Drug resistant epilepsy affects ∼30% of people with epilepsy and is associated with epilepsy syndromes with frequent and multiple types of seizures, lesions or cytoarchitectural abnormalities, increased risk of mortality and comorbidities such as cognitive impairment and sleep disorders. A limitation of current preclinical models is that spontaneous seizures with comorbidities take time to induce and test, thus making them low-throughput. Kcna1-null mice exhibit all the characteristics of drug resistant epilepsy with spontaneous seizures and comorbidities occurring naturally; thus, we aimed to determine whether they also demonstrate pharmacoresistanct seizures and the impact of medications on their sleep disorder comorbidity. In this exploratory study, Kcna1-null mice were treated with one of four conventional antiseizure medications, carbamazepine, levetiracetam, phenytoin, and phenobarbital using a moderate throughput protocol (vehicle for 2 days followed by 2 days of treatment with high therapeutic doses selected based on published data in the 6 Hz model of pharmacoresistant seizures). Spontaneous recurrent seizures and vigilance states were recorded with video-EEG/EMG. Carbamazepine, levetiracetam and phenytoin had partial efficacy (67%, 75% and 33% were seizure free, respectively), whereas phenobarbital was fully efficacious and conferred seizure freedom to all mice. Thus, seizures of Kcna1-null mice appear to be resistant to three of the drugs tested. Levetiracetam failed to affect sleep architecture, carbamazepine and phenytoin had moderate effects, and phenobarbital, as predicted, restored sleep architecture. Data suggest Kcna1-null mice may be a moderate throughput model of drug resistant epilepsy useful in determining mechanisms of pharmacoresistance and testing novel therapeutic strategies.

A mixed methods study of physical activity and quality of life in adolescents with Turner syndrome.

Women with Turner syndrome (TS) have a high morbidity from both medical and psychological conditions with a negative impact on quality of life (QoL). Physical activity is a modifiable behavior shown to reduce risk for these chronic medical and mental health conditions and enhance QoL in other populations. Limited research suggests that adolescents and women with TS are less likely to engage in or enjoy physical activity than peers. This mixed methods study aimed to document physical activity levels in a sample of youth with TS and explore how factors unique to TS contribute to and are affected by physical activity. A cross-sectional sample of 21 girls (12-21 years) with TS and their parents (n = 21) completed standardized questionnaires to quantify habitual physical activity (3-day physical activity recall) and QoL (PROMIS) and participated in individual interviews focused on their experience with physical activity. Quantitative and qualitative results were synthesized using a phenomenological mixed methods approach. Results indicate that our sample engaged in less physical activity than peers and only 19% met recommendations for 1 hr per day of moderate-to-vigorous physical activity. Parents reported significant problems with peer relationships and psychological stress, and peer relationships scores correlated with physical activity. Reported barriers to physical activity included physical and psychosocial complications related to TS as well as unique developmental considerations specific to adolescence. Quantitative and qualitative results supported that structured fitness options embedded into routines enhanced activity levels. Results were compiled into specific recommendations for clinical care and areas of future research.