Faculty Bibliography

The declaration of brain death (BD), or death by neurological criteria (DNC), is medically and legally accepted throughout much of the world. However, inconsistencies in national and international policies have prompted efforts to harmonize practice and central concepts, both between and within countries. The World Brain Death Project was published in 2020, followed by notable revisions to the Canadian and US guidelines in 2023. The mission of these initiatives was to ensure accurate and conservative determination of BD/DNC, as false-positive determinations could have major negative implications for the medical field and the public's trust in our ability to accurately declare death. In this Review, we review the changes that were introduced in the 2023 US BD/DNC guidelines and consider how these guidelines compare with those formulated in Canada and elsewhere in the world. We address controversies in BD/DNC determination, including neuroendocrine function, consent and accommodation of objections, summarize the legal status of BD/DNC internationally and discuss areas for further BD/DNC research.

OBJECTIVE/UNASSIGNED:A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS/UNASSIGNED:Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS/UNASSIGNED:Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS/UNASSIGNED:Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS:tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS:≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION/CONCLUSIONS:SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.

In collaboration with the American Academy of Pediatrics, Child Neurology Society, and Society for Critical Care Medicine, the American Academy of Neurology formulated an updated, evidence-informed consensus-based guideline for pediatric and adult brain death/death by neurologic criteria (BD/DNC) determination. In comparison with the prior guidelines, the revisions and additions in this guideline, which are summarized in this review, are intended to (1) ensure recommendations are conservative, yet practical, and emphasize circumstances in which BD/DNC determination should be delayed or deferred, so as to minimize the risk of a false-positive BD/DNC determination; and (2) provide guidance about aspects of BD/DNC determination that clinicians find challenging and/or controversial. We hope that clinicians throughout the United States will use this information to revise their hospital BD/DNC determination policies to conform to the standardized process for BD/DNC determination described in the new guideline, to ensure that every BD/DNC evaluation is consistent and accurate.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The purpose of this guideline is to update the 2010 American Academy of Neurology (AAN) brain death/death by neurologic criteria (BD/DNC) guideline for adults and the 2011 American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine guideline for infants and children and to clarify the BD/DNC determination process by integrating guidance for adults and children into a single guideline. Updates in this guideline include guidance related to conducting the BD/DNC evaluation in the context of extracorporeal membrane oxygenation, targeted temperature management, and primary infratentorial injury. METHODS:A panel of experts from multiple medical societies developed BD/DNC recommendations. Because of the lack of high-quality evidence on the subject, a novel, evidence-informed formal consensus process was used. This process relied on the panel experts' review and detailed knowledge of the literature surrounding BD/DNC to guide the development of preliminary recommendations. Recommendations were formulated and voted on, using a modified Delphi process, according to the 2017 AAN Clinical Practice Guideline Process Manual. MAJOR RECOMMENDATIONS/CONCLUSIONS:Eighty-five recommendations were developed on the following: (1) general principles for the BD/DNC evaluation, (2) qualifications to perform BD/DNC evaluations, (3) prerequisites for BD/DNC determination, (4) components of the BD/DNC neurologic examination, (5) apnea testing as part of the BD/DNC evaluation, (6) ancillary testing as part of the BD/DNC evaluation, and (7) special considerations for BD/DNC determination.

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

There is a need for the neuroscience community to advocate for uniformity in the determination of brain death/death by neurologic criteria (BD/DNC). Engagement with state medical societies is one example of this type of advocacy. After determining that her hospital policy on determination of BD/DNC was unclear and inconsistent with accepted standards, the principal author submitted a resolution to the Illinois State Medical Society (ISMS) in an attempt to encourage consistency in institutional policies on the determination of BD/DNC across the state. ISMS ultimately approved a resolution on this topic, but it has some shortcomings, so its impact is unclear. Nonetheless, other neuroscience clinicians are encouraged to engage with their state medical societies to advocate for uniformity in the determination of BD/DNC.

Although the fundamental principle behind the Uniform Determination of Death Act (UDDA), the equivalence of death by circulatory-respiratory and neurologic criteria, is accepted throughout the United States and much of the world, some families object to brain death/death by neurologic criteria. Clinicians struggle to address these objections. Some objections have been brought to court, particularly in the United States, leading to inconsistent outcomes and discussion about potential modifications to the UDDA to minimize ethical and legal controversies related to the determination of brain death/death by neurologic criteria.