Faculty Bibliography

The American Epilepsy Society Meeting in New Orleans attracted more than 5900 attendees. There was a lively exchange of new science, innovation, education, clinical practice, and many other items related to epilepsy. Educational symposia were a major part of the meeting and explored varying topics of interest for all types of epilepsy professionals. This article reviews highlights of the meeting presented in major symposia. Topics ranged from how to treat varying aspects of epilepsy as a consultant in the hospital to finding the scientific underpinning of the interaction between sleep and epilepsy. Pros and cons of novel antiseizure medications, dietary, and stimulation treatments were discussed. Epilepsy may impair memory and we need to learn what is the pathophysiologic relationship. Febrile status epilepticus may have severe consequences for a later life with seizures. Epilepsy professionals should be very well aware of the ethical implications of devasting seizures and their associated disability. These are just a few select topics of the many that we need to study further to archive the final goal to improve the lives of patients with epilepsy.

Background/UNASSIGNED:Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson disease (PD). It has been found that different land-based rehabilitation approaches based on motor and cognitive strategies could be effective for treating FOG. At the same time, there are data about the efficacy of aquatic therapy (AT) in ameliorating this phenomenon. No 1 study has explored the combined effect of land plus AT in patients with PD who have FOG. Objective/UNASSIGNED:The objective was to investigate the effectiveness of a multidisciplinary, intensive, motor-cognitive rehabilitation treatment (MIRT) in improving FOG and whether the implementation with AT (MIRT-AT) adds further benefits. Design/UNASSIGNED:The design consisted of a single-blind, parallel group, 1:1 allocation ratio, randomized trial. Setting/UNASSIGNED:Department of Parkinson disease, Movement Disorders and Brain Injury Rehabilitation - "Moriggia-Pelascini" Hospital (Gravedona ed Uniti, Como-Italy) was used as the setting. Participants/UNASSIGNED:60 hospitalized patients with PD who had FOG in Hoehn & Yahr (H&Y) stage 2 or 5-3 were included. Intervention/UNASSIGNED:60 patients with PD + FOG were randomly assigned to 2 groups. 30 underwent a 4-week MIRT and 30 underwent a 4-week MIRT plus AT (MIRT-AT). Measurements/UNASSIGNED:The primary outcome measure was the Freezing of Gait Questionnaire (FOGQ); secondary outcome measures were total Unified Parkinson Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, Berg Balance Scale (BBS), Timed Up and Go Test (TUG) and 6-Minute Walk Test (6MWT). These measures were assessed both at admission and discharge. Results/UNASSIGNED:Patients in the two groups had similar age, gender distribution, H&Y stage, and most-affected side. At baseline, no difference in outcome measures was observed between the two groups. After treatment, a significant time effect was observed for all variables in both groups. No significant time x-group interaction was observed. A between-group analysis showed non-significant differences between values at T1 and values at T0 for all variables. Limitations/UNASSIGNED:A limitation is that control group and follow-up are lacking. Conclusions/UNASSIGNED:We showed that a multidisciplinary, intensive, and goal-based rehabilitation treatment, such as MIRT, improve FOG in patients with PD. Even though AT could be considered as a useful approach for treating FOG, it does not add further benefits to this kind of motor-cognitive rehabilitation.

Objective/UNASSIGNED:The amyotrophic lateral sclerosis (ALS) trial outcome measures are clinic based. Active and passive smartphone data can provide important longitudinal information about ALS progression outside the clinic. Methods/UNASSIGNED:We used Beiwe, a research platform for smartphone-based digital phenotyping, to collect active (self-report ALSFRS-R surveys and speech recordings) and passive (phone sensors and logs) data from patients with ALS for approximately 24 weeks. In clinics, at baseline and every 3 months, we collected vital capacity, ALSFRS-R, and ALS-CBS at enrollment, week 12, and week 24. We also collected ALSFRS-R by telephone at week 6. Results/UNASSIGNED: < 0.001). ALSFRS-R slopes were equivalent and within-subject standard deviation was smaller for smartphone-based self-report (0.26 vs. 0.56). Use of Beiwe afforded weekly collection of speech samples amenable to a variety of analyses, and we found mean pause time to increase by 0.02 sec per month across the sample. Interpretation/UNASSIGNED:Smartphone-based digital phenotyping in people with ALS is feasible and informative. Self-administered smartphone ALSFRS-R scores correlate highly with clinic-based ALSFRS-R scores, have low variability, and could be used in clinical trials. More research is required to fully analyze speech recordings and passive data, and to identify optimal digital markers for use in future ALS clinical trials.

Autoimmune encephalitis is a severe inflammatory disorder of the brain with diverse causes and a complex differential diagnosis. Recent advances in the past decade have led to the identification of new syndromes and biological markers of limbic encephalitis, the commonest presentation of autoimmune encephalitis. The successful use of serum and intrathecal antibodies to diagnose affected patients has resulted in few biopsy and postmortem examinations. In those available, there can be variable infiltrating inflammatory T cells with cytotoxic granules in close apposition to neurons, consistent with an inflammatory autoimmune basis, but true vasculitis is rarely seen. The exception is Hashimoto encephalopathy.

OBJECTIVES/OBJECTIVE:The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS:Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS:Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS:Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

Cortical responses to sensory inputs vary across repeated presentations of identical stimuli, but how this trial-to-trial variability impacts detection of sensory inputs is not fully understood. Using multi-channel local field potential (LFP) recordings in primary somatosensory cortex (S1) of the awake mouse, we optimized a data-driven cortical state classifier to predict single-trial sensory-evoked responses, based on features of the spontaneous, ongoing LFP recorded across cortical layers. Our findings show that, by utilizing an ongoing prediction of the sensory response generated by this state classifier, an ideal observer improves overall detection accuracy and generates robust detection of sensory inputs across various states of ongoing cortical activity in the awake brain, which could have implications for variability in the performance of detection tasks across brain states.

Familial dysautonomia (Riley-Day syndrome, hereditary sensory and autonomic neuropathy type III) is a rare autosomal recessive disease characterized by impaired development of primary sensory and autonomic neurons resulting in a severe neurological phenotype, which includes arterial baroreflex and chemoreflex failure with high frequency of sleep-disordered breathing and sudden death during sleep. Although a rare disease, familial dysautonomia represents a unique template to study the interactions between sleep-disordered breathing and abnormal chemo- and baroreflex function. In patients with familial dysautonomia, ventilatory responses to hypercapnia are reduced, and to hypoxia are almost absent. In response to hypoxia, these patients develop paradoxical hypoventilation, hypotension, bradycardia, and potentially, death. Impaired ventilatory control due to chemoreflex failure acquires special relevance during sleep when conscious control of respiration withdraws. Overall, almost all adult (85%) and pediatric (95%) patients have some degree of sleep-disordered breathing. Obstructive apnea events are more frequent in adults, whereas central apnea events are more severe and frequent in children. The annual incidence rate of sudden death during sleep in patients with familial dysautonomia is 3.4 per 1000 person-year, compared to 0.5-1 per 1000 person-year of sudden unexpected death in epilepsy. This review summarizes recent developments in the understanding of sleep-disordered breathing in patients with familial dysautonomia, the risk factors for sudden death during sleep, and the specific interventions that could prevent it.