Faculty Bibliography

Two studies examined genetic and environmental influences on traits proposed by the revised Reinforcement Sensitivity Theory (rRST) of personality. Both quantitative and molecular behavioral genetic methods were applied considering the effects of COMT, DRD2, HTR1A and TPH2 single nucleotide polymorphisms (SNPs). Study one included 274 monozygotic and 154 dizygotic twins for the quantitative behavioral study; and in study two there were 431 twins for the molecular genetic study. The Reinforcement Sensitivity Questionnaire was used to assess basic personality traits defined by the rRST. Univariate biometric modeling suggested that genetic influences accounted for 34-44% of variance of Behavioral Approach System (BAS), Behavioral Inhibition System (BIS) and Fight-Fligh-Freeze System. Molecular genetic analyses proposed the significant main effect of COMT SNP on the BAS and TPH2 SNP on the BIS, and pointed out epistatic effects of COMT x DRD2 on BAS and HTR1A x TPH2 on Fight. Results demonstrated substantial heritability for all rRST constructs, as well as for differences in the molecular genetic basis of both approach-related and avoidance-related dimensions.

PURPOSE OF REVIEW/OBJECTIVE:Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue. RECENT FINDINGS/RESULTS:An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic.

The Uniform Determination of Death Act (UDDA), the recommended legal statute for determination of death in the United States, was initially formulated in 1981. Forty years later, because of the concerns of experts in medicine, law, ethics, and philosophy, the Uniform Law Commission (ULC) created a drafting committee to update the UDDA. The drafting committee, which has until 2023 to propose revisions to the ULC Executive Committee, will need to determine how to address the following key questions about the UDDA: (1) Should the term "irreversible" be replaced by the term "permanent"? (2) Is absence of hypothalamic-pituitary-axis-induced antidiuretic hormone secretion included in "all functions of the entire brain," and if so, how can we reconcile the fact that this is not tested in the medical standards for determination of death by neurologic criteria published by the American Academy of Neurology and the Society of Critical Care Medicine, American Academy of Pediatrics, and Child Neurology Society? (3) What are the accepted medical standards for determination of death? (4) Is consent needed to determine death? and (5) How should objections to the use of neurologic criteria to declare death be handled? Once the ULC finalizes revisions to the UDDA, individual states will have the opportunity to decide whether to adopt the revisions in whole or in part. Hopefully, the revised UDDA will provide clarity and consistency about the legal distinction between life and death for physicians, lawyers, and the public at large. The events that led to the formation of the drafting committee and the potential consequences of revising the UDDA are discussed herein.

Hearing one's own voice is critical for fluent speech production as it allows for the detection and correction of vocalization errors in real time. This behavior known as the auditory feedback control of speech is impaired in various neurological disorders ranging from stuttering to aphasia; however, the underlying neural mechanisms are still poorly understood. Computational models of speech motor control suggest that, during speech production, the brain uses an efference copy of the motor command to generate an internal estimate of the speech output. When actual feedback differs from this internal estimate, an error signal is generated to correct the internal estimate and update necessary motor commands to produce intended speech. We were able to localize the auditory error signal using electrocorticographic recordings from neurosurgical participants during a delayed auditory feedback (DAF) paradigm. In this task, participants hear their voice with a time delay as they produced words and sentences (similar to an echo on a conference call), which is well known to disrupt fluency by causing slow and stutter-like speech in humans. We observed a significant response enhancement in auditory cortex that scaled with the duration of feedback delay, indicating an auditory speech error signal. Immediately following auditory cortex, dorsal precentral gyrus (dPreCG), a region that has not been implicated in auditory feedback processing before, exhibited a markedly similar response enhancement, suggesting a tight coupling between the 2 regions. Critically, response enhancement in dPreCG occurred only during articulation of long utterances due to a continuous mismatch between produced speech and reafferent feedback. These results suggest that dPreCG plays an essential role in processing auditory error signals during speech production to maintain fluency.

Although the Uniform Determination of Death Act (UDDA) has served as a model statute for 40 years, there is a growing recognition that the law must be updated. One issue being considered by the Uniform Law Commission's Drafting Committee to revise the UDDA is whether the text "all functions of the entire brain, including the brainstem" should be changed. Some argue that the absence of diabetes insipidus indicates that some brain functioning continues in many individuals who otherwise meet the "accepted medical standards" like the American Academy of Neurology's. The concern is that the legal criteria and the medical standards used to determine death by neurological criteria are not aligned. We argue for the revision of the UDDA to more accurately specify legal criteria which align with the medical standards: brain injury leading to permanent loss of a) the capacity for consciousness, b) the ability to breathe spontaneously, and c) brainstem reflexes. We term these criteria "neuro-respiratory criteria" and show that they are well-supported in the literature for physiological and social reasons justifying their use in the law.

In memory, our continuous experiences are broken up into discrete events. Boundaries between events are known to influence the temporal organization of memory. However, how and through which mechanism event boundaries shape temporal order memory (TOM) remains unknown. Across four experiments, we show that event boundaries exert a dual role: improving TOM for items within an event and impairing TOM for items across events. Decreasing event length in a list enhances TOM, but only for items at earlier local event positions, an effect we term the local primacy effect. A computational model, in which items are associated to a temporal context signal that drifts over time but resets at boundaries captures all behavioural results. Our findings provide a unified algorithmic mechanism for understanding how and why event boundaries affect TOM, reconciling a long-standing paradox of why both contextual similarity and dissimilarity promote TOM.

Purpose/UNASSIGNED:To report 3 otherwise healthy patients with Herpes zoster reactivation shortly after administration of a mRNA vaccine against the novel COVID-19 virus. Observations/UNASSIGNED:Patient 1 is a 54 year old who presented with Herpes zoster meningitis complicated by enhancing nodular leptomeningeal lesions of the spinal cord. The subsequent two patients had Herpes zoster ophthalmicus of the cornea (Case 2) and eyelid (Case 3). All three presented within 2 weeks of receiving the Pfizer/BioNTech COVID-19 vaccine. Conclusions/UNASSIGNED:Herpes zoster may be a side effect of m RNA vaccination against the Sars-CoV2 vaccine and requires further investigation.

BACKGROUND:To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS:Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS:A total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome. CONCLUSION/CONCLUSIONS:There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.

OBJECTIVE:Chronic subdural hematoma (CSDH) is a serious problem with an incidence of 20.6/100,000/year in North America and is posited to grow as the population ages. Middle Meningeal Artery (MMA) embolization is an upcoming therapy for treatment of CSDH. Among patients with CSDH who undergo MMA embolization outcomes are no different in patients who resume the antithrombotic (AT) after MMA embolization as compared to patients who don't resume AT. METHODS:We did retrospective review of all cases of MMA embolization in the setting of CSDH done over 2.5 years in 2 centers. Comparison of cases in which AT was resumed vs controls with no AT was performed. A successful outcome was defined as reduction of at least 50% volume in CSDH. Univariate analysis regarding all outcome measures for baseline variables was performed using Fisher exact test or t-test. Multivariate logistic regression with controlling for age, surgical evacuation of the hematoma. RESULTS:There were a total of 56 MMA embolization cases, 33 of them had no AT started and 23 of them had AT resumption at a mean of 2.4 days. About 40% of patients had surgical evacuation done prior to MMA embolization. There was no significant difference in hematoma reduction or volume even after adjusting for surgical evacuation (OR 1.00 95%CI 0.60- 1.67). Patients who had AT resumption had more CAD (71%vs 21% p= 0.001) and Afib (58% vs 18% p=0.002) necessitating AT. CONCLUSION/CONCLUSIONS:AT therapy can be safely resumed in CSDH after MMA embolization as there is no significant difference in CSDH volume reduction and recurrence.

Early-onset parkinsonism (EO parkinsonism), defined as subjects with disease onset before the age of 40 or 50 years, can be the main clinical presentation of a variety of conditions that are important to differentiate. Although rarer than classical late-onset Parkinson's disease (PD) and not infrequently overlapping with forms of juvenile onset PD, a correct diagnosis of the specific cause of EO parkinsonism is critical for offering appropriate counseling to patients, for family and work planning, and to select the most appropriate symptomatic or etiopathogenic treatments. Clinical features, radiological and laboratory findings are crucial for guiding the differential diagnosis. Here we summarize the most important conditions associated with primary and secondary EO parkinsonism. We also proposed a practical approach based on the current literature and expert opinion to help movement disorders specialists and neurologists navigate this complex and challenging landscape.