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The Patient Safety Subcommittee requested a review of the science and policy issues regarding the rapidly emerging public health epidemic of prescription opioid-related morbidity and mortality in the United States. Over 100,000 persons have died, directly or indirectly, from prescribed opioids in the United States since policies changed in the late 1990s. In the highest-risk group (age 35–54 years), these deaths have exceeded mortality from both firearms and motor vehicle accidents. Whereas there is evidence for significant short-term pain relief, there is no substantial evidence for maintenance of pain relief or improved function over long periods of time without incurring serious risk of overdose, dependence, or addiction. The objectives of the article are to review the following: (1) the key initiating causes of the epidemic; (2) the evidence for safety and effectiveness of opioids for chronic pain; (3) federal and state policy responses; and (4) recommendations for neurologists in practice to increase use of best practices/universal precautions most likely to improve effective and safe use of opioids and to reduce the likelihood of severe adverse and overdose events. Neurology® 2014;83:1277–1284

The year 2014 will see the debut of Neurology® Neuroimmunology & Neuroinflammation, a new online-only, open-access journal in the Neurology collection of publications. Many may ask whether we need a new biomedical journal. Our mission and vision statements embody why our answer is yes

I fully agree with the paper by Green et al.1 However, these strategies are not always easy for a young colleague in a busy emergency department. I have many years of positive experiences using the model presented in this short paper,2 which describes an algorithm with 3 components: the Romberg test, the horizontal smooth pursuit eye movement test, and tragal pressure. This algorithm can be used at bedside without any equipment or previous training diagnosing nystagmus. I would propose for the head impulse test, nystagmus evaluation, and test of skew (HINTS) and my proposed algorithm to be used together. The tragal pressure is only relevant in the peripheral cases; I include it because of my clinical experience of overlooked cholesteatomas, presenting as a small amount of cerumen at the top of the tympanic membrane.

In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine. Therefore, the American Academy of Neurology should advise its members against this practice, as it had done until 2018.

ObjectiveThis nationwide cohort study evaluates seizure responses to immunotherapy and antiepileptic drugs (AEDs) in patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), and anti-gamma-aminobutyric-acid B receptor (GABABR) encephalitis.MethodsAnti-LGI1, anti-NMDAR, and anti-GABABR encephalitis patients with new-onset seizures were included. Medical information about disease course, AEDs and immunotherapies used, effects, and side effects were collected. Outcome measures were (1) seizure freedom while using AEDs or immunotherapy, (2) days to seizure freedom from start of AEDs or immunotherapy, and (3) side effects.ResultsOf 153 patients with autoimmune encephalitis (AIE) (53 LGI1, 75 NMDAR, 25 GABABR), 72% (n = 110) had epileptic seizures, and 89% reached seizure freedom. At least 53% achieved seizure freedom shortly after immunotherapy, and 14% achieved seizure freedom while using only AEDs (p < 0.0001). This effect was similar in all types (p = 0.0001; p = 0.0005; p = 0.013, respectively). Median time to seizure freedom from AEDs start was 59 days (interquartile range [IQR] 27–160), and 28 days from start of immunotherapy (IQR 9–71, p < 0.0001). Side effects were psychotic behavior and suicidal thoughts by the use of levetiracetam, and rash by the use of carbamazepine. Carbamazepine was more effective than levetiracetam in reducing seizures in anti-LGI1 encephalitis (p = 0.031). Only 1 patient, of 86 surviving patients, developed epilepsy after resolved encephalitis.ConclusionEpilepsy after resolved encephalitis was rare in our cohort of patients with AIE treated with immunotherapy. In addition, seizure freedom is achieved faster and more frequently after immunotherapy. Therefore, AEDs should be considered as add-on treatment, and similar to treatment of other encephalitis symptoms, immunotherapy is crucial.

On behalf of the Brain Death Working Group, Dr. Russell and colleagues have provided medical professionals and the public with formal guidance as to the definition and determination of brain death. This AAN position statement answers many lingering questions faced by neurologists, intensivists, and critical care providers about when and how to perform an assessment of brain death. Among declarations made in this guideline are that brain death is a clinical diagnosis based on the loss of function of the brain as a whole; that medical providers have no legal obligation to provide organ support to patients with brain death (applies to all US states with the exception of New Jersey); and that providers are permitted to conduct brain death testing—including the apnea test—without consent of the patient's surrogate. In response to this position paper, Dr. Nitin Sethi expresses concern regarding the rights of AAN members to recuse themselves from brain death determination or management. Such a recusal might be perceived by family members or caregivers as medical uncertainty regarding a diagnosis of brain death. However, the AAN position statement is consistent with a long-standing moral imperative that extricates AAN members from having to make a brain death determination—or provide continued care to the deceased—when such management conflicts with their own personal beliefs. In a separate comment, Dr. Calixto Machado highlights the importance of this document in that it provides a standardized definition and management strategy of brain death including the performance of the apnea test, which can be referenced by health care professionals and legal authorities. Finally, Dr. Nathaniel Robbins addresses the inherent limitations of clinical brain death determination, which is wholly reliant on motor output and an intact brain stem. Although absence of brain stem function is prognostically useful in and of itself, Robbins asserts, it should not indicate that all functions of the brain have ceased. Higher cortical functions may be preserved and are clinically untestable. In response, Dr. Russell emphasizes that injury to the “brain as a whole” is what constitutes brain death and understanding the nature of the injury limits the possibility of a false-positive declaration. As we are not required to demonstrate that all myocardial cells have died in the event of cardiac death, we need not prove that all nerve cells have died to make a determination of brain death. On behalf of the Brain Death Working Group, Dr. Russell and colleagues have provided medical professionals and the public with formal guidance as to the definition and determination of brain death. This AAN position statement answers many lingering questions faced by neurologists, intensivists, and critical care providers about when and how to perform an assessment of brain death. Among declarations made in this guideline are that brain death is a clinical diagnosis based on the loss of function of the brain as a whole; that medical providers have no legal obligation to provide organ support to patients with brain death (applies to all US states with the exception of New Jersey); and that providers are permitted to conduct brain death testing—including the apnea test—without consent of the patient's surrogate. In response to this position paper, Dr. Nitin Sethi expresses concern regarding the rights of AAN members to recuse themselves from brain death determination or management. Such a recusal might be perceived by family members or caregivers as medical uncertainty regarding a diagnosis of brain death. However, the AAN position statement is consistent with a long-standing moral imperative that extricates AAN members from having to make a brain death determination—or provide continued care to the deceased—when such management conflicts with their own personal beliefs. In a separate comment, Dr. Calixto Machado highlights the importance of this document in that it provides a standardized definition and management strategy of brain death including the performance of the apnea test, which can be referenced by health care professionals and legal authorities. Finally, Dr. Nathaniel Robbins addresses the inherent limitations of clinical brain death determination, which is wholly reliant on motor output and an intact brain stem. Although absence of brain stem function is prognostically useful in and of itself, Robbins asserts, it should not indicate that all functions of the brain have ceased. Higher cortical functions may be preserved and are clinically untestable. In response, Dr. Russell emphasizes that injury to the “brain as a whole” is what constitutes brain death and understanding the nature of the injury limits the possibility of a false-positive declaration. As we are not required to demonstrate that all myocardial cells have died in the event of cardiac death, we need not prove that all nerve cells have died to make a determination of brain death.

Objective: To examine the ethical and legal issues physicians face when evaluating and managing athletes with sports-related concussions, and to offer guidance to physicians as they navigate these situations. Results: This position paper reviews and compares the components of sports-related concussion laws, including education, removal from play, and clearance for return to play. It highlights the challenges privacy laws present relevant to providing care to concussed athletes and suggests ways to help physicians overcome these obstacles. The report also explores the ethical considerations physicians should bear in mind as they evaluate and manage concussed athletes, addressing them through a framework that includes considerations of professionalism, informed decision-making, patient autonomy, beneficence, nonmaleficence, conflicts of interest, and distributive justice. Conclusions: Physicians caring for concussed athletes have an ethical obligation to ensure that their primary responsibility is to safeguard the current and future physical and mental health of their patients. Physicians have a duty to provide athletes and their parents with information about concussion risk factors, symptoms, and the risks for postconcussion neurologic impairments. Physicians should facilitate informed and shared decision-making among athletes, parents, and medical teams while protecting athletes from potential harm. Additionally, including concussion evaluation and management training in neurology residency programs, as well as developing a national concussion registry, will benefit patients by the development of policies and clinical guidelines that optimize prevention and treatment of concussive head injury.

The use of prescription medication to augment cognitive or affective function in healthy persons—or neuroenhancement—is increasing in adult and pediatric populations. In children and adolescents, neuroenhancement appears to be increasing in parallel to the rising rates of attention-deficit disorder diagnoses and stimulant medication prescriptions, and the opportunities for medication diversion. Pediatric neuroenhancement remains a particularly unsettled and value-laden practice, often without appropriate goals or justification. Pediatric neuroenhancement presents its own ethical, social, legal, and developmental issues, including the fiduciary responsibility of physicians caring for children, the special integrity of the doctor–child–parent relationship, the vulnerability of children to various forms of coercion, distributive justice in school settings, and the moral obligation of physicians to prevent misuse of medication. Neurodevelopmental issues include the importance of evolving personal authenticity during childhood and adolescence, the emergence of individual decision-making capacities, and the process of developing autonomy. This Ethics, Law, and Humanities Committee position paper, endorsed by the American Academy of Neurology, Child Neurology Society, and American Neurological Association, focuses on various implications of pediatric neuroenhancement and outlines discussion points in responding to neuroenhancement requests from parents or adolescents. Based on currently available data and the balance of ethics issues reviewed in this position paper, neuroenhancement in legally and developmentally nonautonomous children and adolescents without a diagnosis of a neurologic disorder is not justifiable. In nearly autonomous adolescents, the fiduciary obligation of the physician may be weaker, but the prescription of neuroenhancements is inadvisable because of numerous social, developmental, and professional integrity issues.

Widespread use of opioids for chronic noncancer pain has resulted in an epidemic of misuse; prescribed opioids are currently responsible for more deaths in the United States than heroin and cocaine combined. An American Academy of Neurology (AAN) position paper questions the long-term efficacy of opioids for chronic noncancer pain, calls attention to the poor safety profile of opioids, urges regulatory guidelines in their use, and calls for more research on chronic pain management.1

The American Academy of Neurology (AAN) and American Neurological Association (ANA) position paper on the use of stem cells in biomedical research is a decision to support destruction of and experimentation on human life at its very earliest stage. The AAN and ANA justify this position by citing “a strong moral obligation to pursue research that may result in beneficial treatments.” However, using an end to justify a means is dangerous when dealing with human life and was used in the last century to justify increasing encroachment on principles that physicians should hold sacred.1 Physicians should not be saying, “This research may result in a cure, therefore it is justified.” Physicians should be saying, “If there is any, even the least chance that this research is ethically questionable, we should not go anywhere near it.” The AAN and ANA should be guardians of the traditional ethics and standards of the neurologic profession and should be conservative and cautious about any new positions they take on behalf of their members.2 It is also difficult to understand the motivation of the AAN and ANA to put out an ethical position paper which is decisive in its conclusions when there is ongoing debate and disagreement on this issue throughout the country. The journal Neurology has also not shown balance in publishing two editorials that strongly favor one side of the debate without giving a voice to neurologists who object to using embryonic human stem cells. April 4th 2005 Dear Dr. Olson: We are writing to raise a major concern about the way in which the President and Board of Directors of the American Academy of Neurology have represented its members in the recent Position Statement regarding the use of embryonic and adult human stem cells in biomedical research. The position taken …

To the Editor: As the Executive Board, and on behalf of the National Academy of Neuropsychology (NAN), we would like to comment on the report titled, "Assessment: Neuropsychological testing of adults. Considerations for neurologists,"1 of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, which was published in the August 1996 issue of Neurology . The National Academy of Neuropsychology is the only independent organization representing neuropsychologists in practice in the United States. Our membership exceeds 3,500 individuals. At our recent meeting, we had more than 1,200 neuropsychologists in attendance, and the Neurology position paper was an item of major discussion. Accordingly, we feel that the National Academy of Neuropsychology is in the best position to provide some input concerning the issues raised in the Neurology article. First, we are pleased with the endorsement that "neuropsychological assessment is accepted as appropriate by the practicing medical community"(p. 598). NAN's foremost organizational objective is devoted to improved understanding of brain-behavior relationships via neuropsychological techniques that focus on measurable behavior. In fact, the entire profession of neuropsychology is dependent on methods of neurobehavioral assessment. Neuropsychological assessment has long been an integral aspect of the comprehensive medical and psychological evaluation of patients presenting with a diverse array of neuropsychiatric symptoms, but to our knowledge, NAN's report of the subcommittee's recommendation is the first published endorsement. Likewise, we are pleased for the class II, type A designation given for neuropsychological assessment. Nonetheless, we still feel that important issues were raised that need further comment and clarification. We recognize space limitations in publishing excerpts from the report as well as our correspondence. Accordingly, we will be brief and to the point. The report was divided into four main topical areas: (1) Technical issues in neuropsychological assessment, (2) neuropsychological assessment of specific neurologic …

Background and objectives.White matter hyperintensities (WMH) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal intra-individual WMH volume changes in sporadic SVD.Methods.We searched EMBASE and MEDLINE for papers up to 28 January 2022 on WMH volume changes using MRI on ≥2 time-points in adults with sporadic SVD. We classified populations (healthy/community-dwelling, stroke, cognitive, other vascular risk factors, depression) based on study characteristics. We performed random-effects meta-analyses with Knapp-Hartung adjustment to determine mean WMH volume change (change in mL, % of intracranial volume [%ICV], or mL/year), 95%CI and prediction intervals (PI, limits of increase and decrease) using unadjusted data. Risk of Bias Assessment tool for Non-randomised Studies (RoBANS) was used to assess risk of bias. We followed PRISMA guidelines.Results.Fortyone papers, 12,284 participants, met the inclusion criteria. Thirteen papers had low risk of bias across all domains. Mean WMH volume increased over time by: 1.74 mL (95% CI 1.23, 2.26; PI -1.24, 4.73 mL; 27 papers, N=7411, mean time interval 2.7 years, SD=1.65); 0.25%ICV (95% CI 0.14, 0.36; PI -0.06, 0.56; 6 papers, N=1071, mean time interval 3.5 years, SD =1.54); or 0.58 mL/year (95% CI 0.35, 0.81; PI -0.26, 1.41; 8 papers, N=3802). Additionally, 13 papers specifically mentioned and/or provided data on WMH regression, which occurred in asymptomatic, stroke, and cognitive disorders related to SVD.Discussion.Net mean WMH volume increases over time mask wide-ranging change (e.g. mean increase of 1¾mL ranging from 1¼mL decrease to 4¾ml increase), with regression documented explicitly in up to 1/3 of participants. More knowledge on underlying mechanisms, associated factors and clinical correlates is needed, as WMH regression could be an important intervention target.

ObjectiveTo present and improve understanding of patient outcomes and quality of life post-autoimmune encephalitis.BackgroundPatient outcome following encephalitis and in particular following autoimmune encephalitis is not well understood. It is only over the last 15 years that we knew, became able to test for, and identify some of these autoimmune causes of encephalitis and so there currently only a small and emerging literature about patient outcomes. Many papers that talk about or refer to patient outcome look quite early on in the patient pathway and often when they talk about outcome they mean immediate clinical outcome and not how patients are, if they survive, several months or years down the line. Therefore we don't actually have a good handle yet on autoimmune patient outcomes nor their quality of life. Yet, most papers agree that much more needs to be done to assess long-term outcome and quality of life in autoimmune encephalitis patients. One further point of importance is that some complications of AE might not appear until several months or years down the line.Design/MethodsReview of the literature accompanied by first-hand patient video testimony providing rich insight into long term outcomes and impact on quality of life post-autoimmune encephalitis.ResultsPatient outcomes post-AE can be life-changing and in some instances may occur several months and years post-acute illness. These outcomes and quality of life influence how patients understand and make sense of their experience; how they engage with recovery and rehabilitation. A range of poorly understood factors influence patient quality of life post-AE. These include a lack of easily understood index event, lack of community and collective understanding, fears of relapse, post-ICU PTSD, and a lack of accurate information and understanding of their outcomes pre and post-discharge.ConclusionsImproved understanding of patient outcomes post autoimmune encephalitis can improve patient care and engagement.

From April 1, 2011, through September 30, 2011, Neurology ® received 2,167 new and 643 revised manuscripts. During this interval, 3,909 peer reviews were received (compared to 3,758 during the same period in 2010), with the average turnaround time after assignment being 8.5 days. Average time from submission to first decision for papers chosen for review remained at 33 days. Limitations in the number of pages we can publish allow us to accept only a minority of papers submitted. Your specific comments regarding the uniqueness of study populations, novel methods, studies that are especially educational, or new strategies for diagnosing and treating neurologic disease are appreciated; these comments help us immeasurably when we make final decisions regarding which articles we believe will most benefit our authors and readers, as well as improve patient care. Manuscripts for the Resident & Fellow Section of Neurology are often submitted by trainees who have less experience in preparing articles for publication, and it is the goal of the Section to help these junior authors improve their clinical and scientific writing abilities. We especially appreciate the constructive feedback provided by reviewers of these manuscripts. We recently posted an Information for Reviewers (IFR) link on www.neurology.org. Click on this link for information on expectations of reviewers regarding confidentiality, timeliness, and reviewer conflicts of interest. The IFR also provides instructions for formatting the comments to editors and authors in order to make communication with authors most effective. In appreciation of your dedication to Neurology , we offer an hour of CME credit, if requested, for each manuscript you review for the Journal (maximum of 15 credits per year as determined by ACCME). To receive credit, it should be evident that the reviewer has read and understood the content of the manuscript, accompanying figures and tables, supplementary …

Several recent papers in Neurology ® reported cases or series of patients with various neurologic presentations associated with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this special collection, we highlight recent correspondence relating to some of these cases. Several recent papers in Neurology ® reported cases or series of patients with various neurologic presentations associated with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this special collection, we highlight recent correspondence relating to some of these cases.

Dr. Lewis et al. reviewed official national protocols for the determination of brain death or death by neurologic criteria (BD/DNC) from contacts in 83 countries and found considerable variation in these protocols, leading them to recommend that a worldwide consensus be reached on the minimum standards for BD/DNC. In response, Dr. Sethi agrees that there is a need for worldwide consensus, but cautions against compromising on the standards of BD/DNC determination to accommodate different beliefs or demands for organs. In another response, Dr. Machado notes that whereas some patients with primary posterior fossa lesions who fulfill clinical BD criteria/DNC may show preservation of electroencephalographic activity, evoked potential, and autonomic function, some isolated brainstem lesions may theoretically cause a fully apneic locked-in syndrome potentially fulfilling clinical BD criteria, despite potential preservation of some consciousness, citing the case of Jahi McMath. Dr. Machado calls for further research and discussion regarding the use of ancillary tests for BD in the presence of primary posterior fossa lesions. Responding to these comments, the authors agree that the standards for BD/DNC must be conservative and rigorous to avoid false positive determinations and to ensure that a person considered dead in one place is not considered alive in another. The authors note that the worldwide variation in the process of BD/DNC determination, demonstrated in their paper, prompted the creation of the World Brain Death Project, an international, multidisciplinary collaboration to identify the minimum criteria for BD/DNC and serve as guidance for professional societies and countries to revise or develop guidelines on BD/DNC. They hope that this project will help improve consistency in BD/DNC determination and increase public trust in BD/DNC, without compromising the stringency of the process. They note that highly publicized lawsuits related to BD/DNC, like the case of Jahi McMath, prompted the American Academy of Neurology and other stakeholders to advocate for regulatory oversight for uniformity of BD/DNC policies in US Healthcare Institutions. They also note that the World Brain Death Project will also seek to address the present variability in BD/DNC determination in complex situations such as patients with posterior fossa injuries, on extracorporeal membrane oxygenation, or treated with targeted temperature management. This exchange highlights challenging considerations that arise in the pursuit of greater worldwide uniformity in BD/DNC determination. Dr. Lewis et al. reviewed official national protocols for the determination of brain death or death by neurologic criteria (BD/DNC) from contacts in 83 countries and found considerable variation in these protocols, leading them to recommend that a worldwide consensus be reached on the minimum standards for BD/DNC. In response, Dr. Sethi agrees that there is a need for worldwide consensus, but cautions against compromising on the standards of BD/DNC determination to accommodate different beliefs or demands for organs. In another response, Dr. Machado notes that whereas some patients with primary posterior fossa lesions who fulfill clinical BD criteria/DNC may show preservation of electroencephalographic activity, evoked potential, and autonomic function, some isolated brainstem lesions may theoretically cause a fully apneic locked-in syndrome potentially fulfilling clinical BD criteria, despite potential preservation of some consciousness, citing the case of Jahi McMath. Dr. Machado calls for further research and discussion regarding the use of ancillary tests for BD in the presence of primary posterior fossa lesions. Responding to these comments, the authors agree that the standards for BD/DNC must be conservative and rigorous to avoid false positive determinations and to ensure that a person considered dead in one place is not considered alive in another. The authors note that the worldwide variation in the process of BD/DNC determination, demonstrated in their paper, prompted the creation of the World Brain Death Project, an international, multidisciplinary collaboration to identify the minimum criteria for BD/DNC and serve as guidance for professional societies and countries to revise or develop guidelines on BD/DNC. They hope that this project will help improve consistency in BD/DNC determination and increase public trust in BD/DNC, without compromising the stringency of the process. They note that highly publicized lawsuits related to BD/DNC, like the case of Jahi McMath, prompted the American Academy of Neurology and other stakeholders to advocate for regulatory oversight for uniformity of BD/DNC policies in US Healthcare Institutions. They also note that the World Brain Death Project will also seek to address the present variability in BD/DNC determination in complex situations such as patients with posterior fossa injuries, on extracorporeal membrane oxygenation, or treated with targeted temperature management. This exchange highlights challenging considerations that arise in the pursuit of greater worldwide uniformity in BD/DNC determination.