Occipital intermittent rhythmic delta activity (OIRDA) in pediatric focal epilepsies: A case series.

In this case series, we have identified an atypical pattern of OIRDA (Occipital intermittent rhythmic delta activity) on the electroencephalograms (EEGs) of three pediatric patients with self-limited focal epilepsies, including Childhood Epilepsy with Centrotemporal Spikes (CECTS), and Panayiotopoulos syndrome (PS). Previously, OIRDA was described as a symmetric sinusoidal occipital-maximal activity, often associated with childhood idiopathic generalized epilepsies, although it was also reported among other physiologic or pathological entities including focal epilepsy. We have observed in our case series that OIRDA, without prominent field effect, is lateralized or maximal on the hemispheric side ipsilateral to the more defining epileptiform discharges in these focal epilepsies. They also exhibit a notched morphology due to the intermixed sharp wave activities, although the sharp waves are not occurring repetitively. This report provides additional evidence that OIRDA can be associated with a spectrum of idiopathic focal epilepsies and may suggest a cortical origin of OIRDA in these patients as opposed to a hypothesized subcortical generator in patients with primary generalized absence epilepsy, even though further investigation is warranted for either hypothesis.

Partial Recanalization of a Large Vessel Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator, Followed by Systemic Anticoagulation, in the Setting of COVID-19-Induced Hypercoagulability: A Case Report.

We report on the use of systemic heparinization following thrombolysis with intravenous tissue plasminogen activator (t-PA) for acute ischemic large vessel stroke, in the setting of COVID-19-induced hypercoagulability, with partial recanalization of the internal carotid artery. Off-label systemic heparinization was used within 12 hours of t-PA administration, after extensive multidisciplinary collaboration and family discussion, given evidence of severe hypercoagulability. We conclude that thrombolysis should be considered for all eligible patients with suspected or confirmed COVID-19 and acute ischemic stroke, and systemic anticoagulation, although with inherent risks, may be a useful adjunct treatment modality in selected patients who have received intravenous thrombolysis.

Central Disorders of Hypersomnolence, Restless Legs Syndrome, and Surgery With General Anesthesia: Patient Perceptions.

Introduction: The importance of obstructive sleep apnea in patients undergoing surgery with general anesthesia is well-defined, but the surgical and anesthetic implications of other sleep disorders are less clear. We sought to evaluate response to surgery with general anesthesia in patients with central disorders of hypersomnolence or restless legs syndrome. Methods: We surveyed patients on their most recent surgical procedure with general anesthesia, querying about procedure, recovery, and any changes in sleep disorder symptomatology following the procedure. Results: Forty-five patients with restless legs syndrome and 57 patients with central disorders of hypersomnolence (15 narcolepsy type 2, 1 narcolepsy type 1, 30 idiopathic hypersomnia, 1 Kleine-Levin syndrome, and 10 subjective sleepiness) completed the survey, with response rates of 45.5 and 53.8%, respectively. While patients in both groups were equally likely to report surgical complications and difficulty awakening from anesthesia, hypersomnolent patients were more likely to report worsened sleepiness (40% of the hypersomnolent group vs. 11% of the RLS group, p = 0.001) and worsening of their sleep disorder symptoms (40% of the hypersomnolent group vs. 9% of the RLS group, p = 0.0001). Conclusion: Patients with sleep disorders other than sleep apnea frequently report surgical or anesthetic complications. Patients with hypersomnolence disorders commonly perceive that their sleep disorder worsened following a procedure; whether this might be related to long term effects of general anesthesia in a particularly vulnerable clinical population requires further study.

Encouraging Student Interest in Teaching Through a Medical Student Teaching Competition.

PROBLEM: Clinician educators have realized the value not only of assigning teaching roles to medical students but also of offering explicit training in how to teach effectively. Despite this interest in the development of medical students' teaching skills, formal teaching instruction and opportunities for practice are lacking. APPROACH: To encourage medical student interest in teaching, the authors developed and implemented a medical student teaching competition (MSTC) at Emory University School of Medicine during the summers of 2014, 2015, and 2016. Each year, eight student finalists were each paired with a physician "teaching coach" and given one month to prepare for the MSTC. During the competition, each finalist delivered an eight-minute presentation to a panel of seven physician and resident judges. The authors describe the development, implementation, and assessment of the MSTC. OUTCOMES: Approximately 150 medical students and faculty members attended the MSTC each year. The students in attendance felt that the MSTC made them more likely to seek out opportunities to learn how to teach effectively and to practice teaching. Additionally, some students are now more interested in learning about a career in academic medicine than they were before the MSTC. NEXT STEPS: Given the need for more formal initiatives dedicated to improving the teaching skills of doctors-in-training, including medical students, innovative solutions such as the MSTC may enhance a medical school's existing curriculum and encourage student interest in teaching. The MSTC model may be generalizable to other medical schools.

Flumazenil for the Treatment of Refractory Hypersomnolence: Clinical Experience with 153 Patients.

STUDY OBJECTIVES: Patients with central disorders of hypersomnolence sometimes do not achieve satisfactory symptom control with currently available wake-promoting medications. Based on the finding that the cerebrospinal fluid from some patients with hypersomnolence demonstrates potentiation of gamma-aminobutyric acid (GABA)-A receptors in excess of that of controls, a finding that reverses with flumazenil, we initiated prescribing compounded flumazenil to carefully selected, treatment-refractory hypersomnolent patients. METHODS: This retrospective chart review evaluated the first 153 consecutive patients treated with transdermal and/or sublingual flumazenil by physicians at our center from 2013 through January 2015. RESULTS: Patients were 35.5 y old (± 14.4) and 92 (60.1%) were women. Mean Epworth Sleepiness Scale scores prior to flumazenil were 15.1 (± 4.5) despite prior or current treatment with traditional wake-promoting therapies. Symptomatic benefit was noted by 96 patients (62.8%), with a mean reduction in Epworth Sleepiness Scale score of 4.7 points (± 4.7) among responders. Of these, 59 remained on flumazenil chronically, for a mean of 7.8 mo (± 6.9 mo). Female sex and presence of reported sleep inertia differentiated flumazenil responders from nonresponders. Adverse events were common, but often did not result in treatment discontinuation. Serious adverse events included a transient ischemic attack and a lupus vasculopathy, although whether these events occurred because of flumazenil administration is unknown. CONCLUSIONS: This chart review demonstrates that sublingual and transdermal flumazenil provided sustained clinical benefit to 39% of patients with treatment-refractory hypersomnolence. Prospective, controlled studies of this GABA-A receptor antagonist for the treatment of hypersomnolence are needed. COMMENTARY: A commentary on this article appears in this issue on page 1321.

Interaction between troponin and myosin enhances contractile activity of myosin in cardiac muscle.

Ca(2+) signaling in striated muscle cells is critically dependent upon thin filament proteins tropomyosin (Tm) and troponin (Tn) to regulate mechanical output. Using in vitro measurements of contractility, we demonstrate that even in the absence of actin and Tm, human cardiac Tn (cTn) enhances heavy meromyosin MgATPase activity by up to 2.5-fold in solution. In addition, cTn without Tm significantly increases, or superactivates sliding speed of filamentous actin (F-actin) in skeletal motility assays by at least 12%, depending upon [cTn]. cTn alone enhances skeletal heavy meromyosin's MgATPase in a concentration-dependent manner and with sub-micromolar affinity. cTn-mediated increases in myosin ATPase may be the cause of superactivation of maximum Ca(2+)-activated regulated thin filament sliding speed in motility assays relative to unregulated skeletal F-actin. To specifically relate this classical superactivation to cardiac muscle, we demonstrate the same response using motility assays where only cardiac proteins were used, where regulated cardiac thin filament sliding speeds with cardiac myosin are >50% faster than unregulated cardiac F-actin. We additionally demonstrate that the COOH-terminal mobile domain of cTnI is not required for this interaction or functional enhancement of myosin activity. Our results provide strong evidence that the interaction between cTn and myosin is responsible for enhancement of cross-bridge kinetics when myosin binds in the vicinity of Tn on thin filaments. These data imply a novel and functionally significant molecular interaction that may provide new insights into Ca(2+) activation in cardiac muscle cells.