for the Critical Care EEG Monitoring Research Consortium IMPORTANCE Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear.OBJECTIVE To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. DESIGN, SETTING, AND PARTICIPANTSWe reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. INTERVENTIONS Continuous electroencephalography.MAIN OUTCOMES AND MEASURES Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. RESULTSOf the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.

Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.

Objectives:We wanted to examine the extent to which “neurophobia” exists among medical students and determine if students’ perceptions of neurology differ by year of study while exploring the factors that contribute to the development of “neurophobia”.Methods:We used a two-phase, sequential, mixed-methods explanatory design in this single centre study. Phase 1 involved the collection and analysis of a questionnaire administered to students in the first three years of medical school. Phase 2 involved focus groups of a subgroup of students who demonstrated evidence of neurophobia in Phase 1.Results:In total, 187 (39 %) undergraduate medical trainees responded to the questionnaire (response rates of 37%, 44% and 19% for first-, second- and third-year students, respectively). 24% of respondents indicated that they were afraid of clinical neurology and 32% were afraid of the academic neurosciences. Additionally, 46% of respondents thought that clinical neurology is one of the most difficult disciplines in medicine. Phase 2 findings revealed that many students reported negative preconceptions about neurology and commented on neurology’s difficulty. Some experienced changes in these conceptions following their neurology block. Past clinical, educational, and personal experiences in neurology impacted their comfort level.Conclusions:This study shows that the level of comfort towards clinical neurology increases following students’ participation in second-year neurology blocks, but that third-year students continue to show signs of neurophobia with lower comfort levels. It provides insight into why neurophobia exists amongst medical students and sheds light on pre-existing and emerging factors contributing to this sense of neurophobia.