Evaluating consciousness and awareness during focal seizures: responsiveness testing versus recall testing

Objective: The current International League Against Epilepsy (ILAE) guidelines classify focal seizures based on awareness, defined as successful postictal recall of ictal experiences, and exclude the use of responsiveness during seizures for classification. One reason for this exclusion is that responsiveness was thought to not be commonly tested during seizures. Our goal was to determine whether, in at least some settings, responsiveness testing during seizures is relatively common. Methods: We assessed how often responsiveness and recall were each evaluated in patients with focal epilepsy undergoing surface and intracranial EEG-video monitoring. We performed this evaluation by retrospectively reviewing video recordings from 121 seizures from 48 patients during their stay in the epilepsy monitoring unit between September 2012 and November 2019. Results: We found that responsiveness during seizures was tested more frequently than recall of ictal events after seizures. Of 121 seizures in 48 patients, responsiveness was tested in 101 seizures, whereas recall was tested in only 38. Significance: Evaluating if consciousness is impaired during seizures is of critical importance for guiding recommendations for people with epilepsy, such as whether it is safe for them to drive or operate machinery. The ILAE classification guidelines are intended to be broadly useful, but our findings demonstrate that at least in one important clinical setting, responsiveness was used more commonly than recall to evaluate patients during focal seizures. Although our preliminary findings should be replicated in a larger sample and in other patient groups, they suggest that responsiveness testing during focal seizures might be relatively common in at least some clinical practice settings. With further study, this may lead to a re-evaluation of criteria for classifying focal seizures to include both responsiveness and recall of experiences during seizures, as both may provide important information to guide clinical care.

Granulomatous hepatitis in a patient with Crohn's disease and cholestasis.

We describe a case of a 23-year-old woman with a history of Crohn's disease (CD), who initially presented with sepsis-like symptoms, subsequently developed severe cholestasis and following extensive inpatient workup was found to have non-caseating granulomas on her liver biopsy. Infectious aetiologies were excluded and the patient was treated with oral corticosteroids, which ameliorated but did not completely reverse the cholestasis. We review the differential diagnosis of hepatic granulomas and discuss the potential difficulties in establishing their exact aetiology in patients with CD.

Progesterone modulates SERCA2a expression and function in rabbit cardiomyocytes.

We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo)plasmic reticulum Ca(2+)-ATPase type 2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca(2+)-dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes. Cardiomyocytes from neonatal (3- to 5-day-old) rabbits were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and sarcoplasmic reticulum-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca(2+) transients and Ca(2+) clearance was determined using digital imaging. Progesterone treatment increased the total pool of SERCA2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCA2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitin-tagged SERCA2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca(2+) transients. Progesterone treatment increases protein levels and activity of SERCA2a. Progesterone stabilizes SERCA2a, in part, by decreasing the ubiquitination level of SERCA2a polypeptides.