The Original Investigation “Rate and Prognosis of Brain Ischemia in Patients With Lower-Risk Transient or Persistent Minor Neurologic Events,”1 published online September 23, 2019, contained an error in the Results section. The sentence “The final diagnosis (ischemic vs nonischemic cause) was unchanged after all investigations in 720 individuals (70.0%), revised from ischemic to nonischemic in 79 (7.7%), and revised from nonischemic to ischemic in 229 (22.3%)” should have said “The final diagnosis (ischemic vs nonischemic cause) was unchanged after all investigations in 720 individuals (70.0%), revised from nonischemic to ischemic in 79 (7.7%), and revised from ischemic to nonischemic in 229 (22.3%).” The article was corrected online.

A juvenile Peruvian bear, of the species Tremarctos ornatus,1 presented to the emergency department after being found unconscious at 32 Windsor Gardens, London, England.2 The bear had been struck in the left posterior head region by a returning boomerang. On assessment, he demonstrated retrograde amnesia and language-related symptoms. When offered a bun, one of the patient’s favourite things to eat, he replied by asking, “What’s a bun?” Later, he demonstrated a pattern of repetitive behavior in which he forced air through pursed lips to generate a “phew” sound. Finally, the patient attempted to request a cup of tea, but was unable to produce the name of the desired item. These deficits persisted for 24 hours and then resolved completely.

Mission Statement: The mission of JAMA Neurology is to publish scientific information primarily important for those physicians caring for people with neurologic disorders but also for those interested in the structure and function of the normal and diseased nervous system. These specific aims are (1) to make timely publication of original research of the nervous system, (2) to record observations of single patients or groups of patients that will provide new information and insights, (3) to report more basic research that is pertinent to the understanding of disease, (4) to introduce topics of practice, ethics, teaching, and history that are useful, and (5) to provide a forum for discussion on topics that may be controversial in this field. This information will be published only after extensive peer review so that originality, clarity, and precision are ensured.

In the Original Investigation titled “Interrater Reliability of Experts in Identifying Interictal Epileptiform Discharges in Electroencephalograms,” published online October 21, 2019, in JAMA Neurology,1 an author’s middle initial and second degree were missing from the byline. The 10th author’s full name and credentials should have appeared as “Carlos F. Muniz, MD, MSc.” This article was corrected online.

In Reply We agree with Popkirov that left atrial volume is a better marker of incident atrial fibrillation than atrial diameter1; however, we did not have these data available at all of the sites participating in the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial.2 Recently completed3 and ongoing4 studies will help determine if our observation has a clinical role and may provide additional data on left atrial size and function. Once all of these data are available, guidelines committees will likely make recommendations regarding the threshold values of left atrial size (if present) for which anticoagulation therapy appears beneficial for patients with embolic stroke of undetermined source. Such recommendations would have to consider how to extrapolate the clinical trial results, allowing for the many different methods for assessing left size. The clinical use of the proposed, nongated computed tomography protocol5 is interesting, but should await additional studies to define its sensitivity and specificity compared with echocardiography, particularly for detecting other potential cardioembolic causes of stroke, such as patent foramen ovale and left ventricular thrombus.6

To the Editor In a secondary analysis of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source trial, Healey and colleagues1 determined that for patients with embolic stroke of undetermined source and left atrial enlargement rivaroxaban treatment was associated with a 74% reduction in recurrent stroke.1 The authors suggest that left atrial enlargement could become a new determinant in secondary stroke prevention.

The standard of care for stroke treatment in adults changed rapidly in 2015 after results from 5 major clinical trials each showed efficacy of endovascular treatment of anterior circulation large-vessel occlusion within 6 hours of stroke onset.1-5 The positive results of these studies have since raised questions about whether endovascular therapy should be used for children who present with stroke due to large-vessel occlusion and, other than age, fit adult criteria for thrombectomy. Compared with the occurrence in adults, ischemic stroke in children is uncommon, but remains important to address because the resulting disability from a stroke in a child is costly at individual and societal levels.6 While it would be ideal to conduct a randomized trial to test efficacy of endovascular treatment in children, this type of study would be challenging owing to slow participant accrual. Few adult stroke trials have included children, and, to our knowledge, there have been no large, randomized efficacy trials of acute stroke treatment aimed specifically for children. The lack of clinical trials in pediatric stroke poses challenges to clinicians who are left to extrapolate best practices from research conducted in adults. On the strength of adult studies, in 2015, the American Heart Association/American Stroke Association guidelines suggested that mechanical thrombectomy with stent retrievers was reasonable to consider for some patients younger than 18 years with large-vessel occlusion.7

I didn’t like her when I first met her, and I definitely didn’t like her family. I was in my final year in medical school during my advanced medicine clerkship. I was full of excitement. As soon as I had walked in after winter holidays, the resident fellow had grabbed me and said, “There’s a lot for you to do. We have a new patient, a 30-year-old woman who was transferred here from a smaller hospital. She has a rare myopathy.” She didn’t know much about her disease, her treatments, anything. All our questions were answered by her mother, an extremely short woman whom I found controlling. She claimed (the mother was the only one who spoke) that she was fully satisfied by the physicians but had complaints about everything else; if she wasn’t asking for a change of room or yelling at the cleaning personnel for not meeting her cleaning standards, she was disturbing the nurses or complaining about something else to a stranger in the corridor.

Although mechanical thrombectomy (MT) is the standard of care for anterior circulation acute large-vessel occlusion (LVO), it is not known whether MT benefits patients with National Institutes of Health Stroke Scale scores less than 6. Goyal and colleagues evaluated 364 patients with mild deficits and acute LVO treated with MT or best medical management in a retrospective pooled multicenter study over a 5-year period. The patients treated with MT experienced higher odds of asymptomatic intracerebral hemorrhage (ICH) and lower rates of 3-month functional independence compared with patients treated with best medical management. In a meta-analysis that included 843 patients from 4 studies, MT was associated with higher odds of symptomatic ICH, but no other differences, suggesting a clinical trial in this patient population is warranted. Randomized clinical trials show efficacy of endovascular recanalization for stroke treatment in adults, but it is not clear whether these results can be applied to pediatric patients with stroke with large-vessel occlusion. Sporns and coauthors found that endovascular recanalization appeared to be safe with positive interventional and neurologic outcomes in this pediatric population. The study findings showed that the rate of recanalization, complications, and neurologic outcomes were comparable with those in adult trials and therefore support endovascular recanalization in children with acute, large-vessel occlusion. Editorial perspective is provided by Fox and Dlamini. Editorial

In the Original Investigation titled “Selective Vulnerability of the Nucleus Basalis of Meynert Among Neuropathologic Subtypes of Alzheimer Disease,”1 published online October 28, 2019, the following funding information was missing from Funding/Support: “This work was supported by funding from the National Institute on Aging Mayo Clinic Alzheimer’s Disease Research Center (P50 AG016574 and P30 AG062677).” The article was corrected online.

Studies published in JAMA Neurology in 2019 featured a breadth of diverse and highly influential investigations. Here, we highlight a few of many exciting studies from the past year that illustrate major strides in neurology across fields from a lens of varied experimental approaches. Randomized clinical trials (RCTs) play a vital role in health care decision-making, so we have been particularly pleased by the increasing number of high-profile RCTs published in JAMA Neurology. Several of these in the fields of stroke, pain, and behavioral neurology promise to directly inform practice and policy—and thus quickly affect care delivery.

In Reply We recently reported that many patients who presented to level 1 trauma centers after mild traumatic brain injury (mTBI) continued to report injury-related functional limitations at 1 year postinjury.1 Our findings are from the TRACK-TBI study, one of the most comprehensive prospective investigations of civilian TBI to date. A recent Letter to the Editor suggested that our findings veer from seminal work by several of our coauthors that was published 20 or more years ago. We contend that our results reflect major advances in brain injury science over the past 2 decades, including our understanding of mTBI. Levin et al2 and Dikmen et al3 focused on cognitive outcomes, not functional limitations, and analyzed narrower and broader TBI populations, respectively. Accordingly, they were not directly informative to cite in the present study. Our findings should also not be considered interchangeable with the research from McCrea et al4 on athletes with sport-related concussion. Factors, such as preinjury physical conditioning5 and TBI severity,3 are associated with recovery after mTBI; consequently, we should not assume that the rapid recovery experienced by most healthy athletes with sport-related concussion is generalizable to expected recovery in the broader neurotrauma population.

To the Editor Nelson et al1 state that the term mild in mild traumatic brain injury misrepresents the burden of traumatic brain injury. Seminal prospective controlled studies by 3 of Nelson’s own coauthors, who are neuropsychologists, that date back to the 1980s contradict the findings of this article.1 To my knowledge, Levin et al2 were the first to conclusively show that a single uncomplicated mild head injury produces no permanent neurobehavioral impairment. A Glasgow Coma Scale score of 13 to 15 and a coma not to exceed 20 minutes was introduced earlier as a definition of mild head injury.3 Levin et al2 added normal imaging as the third defining feature to separate those with complicated mild head injury, namely acute imaging abnormalities. An earlier study3 that included patients with mild complicated injury showed cognitive and functional impairment. Dikmen et al4 published the second important article. One year post–head injury, patients who took up to an hour to follow commands did not differ cognitively from the controls. Curiously, neither of these 2 articles are cited by Nelson et al.1 The benign outcome of mild head injury seen in the civilian literature was established by McCrea et al5 in the best-characterized sports concussion sample published at that time. The cognitive effects of concussion resolve in 7 days.5

The Research Letter “Perception of Dementia Risk and Preventive Actions Among US Adults Aged 50 to 64 Years,”1 published online November 15, 2019, contained an error in the Results section. The phrase “Respondents who rated their physical or mental health as fair or poor reported a higher likelihood of developing dementia” should have said “mental health” only, omitting the mention of physical health. The article was corrected online.

Nilotinib hydrochloride, an Abelson tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia, has been in the neurology news since the results of the open-label, phase 1 study in a small group of patients with advanced Parkinson disease (PD) and dementia with Lewy bodies was reported at the Society for Neuroscience in Chicago in October 2015. The extensive media coverage that followed, supported by videos of nilotinib-treated participants getting up and walking from their wheelchairs, suggested that disease modification in PD was within reach with this drug. The corresponding publication documented that, at 150 and 300 mg/d, doses lower than required for treating leukemia, nilotinib was detectable in the cerebrospinal fluid (CSF), increased CSF homovanillic acid levels, seemed to engage the target Abelson, and was relatively safe and well tolerated at 24 weeks.1 Although the authors emphasized that “motor and cognitive outcomes suggest a possible beneficial effect on clinical outcomes,”1(p503) the accompanying editorial noted that, owing to the small sample size and lack of a control group, it was impossible to rule out a placebo effect.2

Complete and rapid revascularization can dramatically reduce disability after large-vessel occlusion (LVO) acute ischemic stroke (AIS).1 With modern mechanical thrombectomy (MT), we now have a safe and effective method to recanalize occluded cerebral vessels, and in this issue of JAMA Neurology, Kaesmacher et al2 move the field 1 step closer to achieving the goal of complete revascularization. Cohort studies have demonstrated that even among patients who achieve substantial reperfusion, defined as a Thrombolysis in Cerebral Infarction grade of 2b or greater, those who achieve the highest grades of reperfusion have quantifiably improved outcomes, but only a minority are able to achieve these highest grades.3 As such, one of the primary targets for improvement in MT is finding reliable means of achieving near-perfect reperfusion.

Immunotherapy directed to reduce amyloid levels in the brains of patients with Alzheimer disease (AD) and provide clinical benefit has not definitely been successful using either passive immunizations with preformed antiamyloid (anti-Aβ42 as the toxic processed form of amyloid β protein), monoclonal antibodies (moabs), or active immunization with amyloid peptides. A recent press release by Biogen1 has indicated that their moab aducanumab has shown clinical benefit after reanalysis of larger data panels of a phase 3 clinical trial that ended in March 2019. This reanalysis has not been published or reproduced, but it is potentially an important finding and supportive of immunotherapy for AD. Thus, antiamyloid immunotherapy still holds promise for clinical benefit, as amyloid (Aβ) accumulation in the brain can be detected decades before the onset of symptoms and amyloid accumulation is a trigger for many downstream pathologies, such as loss of neuronal plasticity, tau hyperphosphorylation, and frank neuronal death. Targeting more than one pathology with a single therapy, as we have shown for the DNA Aβ42 trimer vaccine, might be the path forward in finding an option for AD prevention or delay of disease progression.2

Mission Statement: The mission of JAMA Neurology is to publish scientific information primarily important for those physicians caring for people with neurologic disorders but also for those interested in the structure and function of the normal and diseased nervous system. These specific aims are (1) to make timely publication of original research of the nervous system, (2) to record observations of single patients or groups of patients that will provide new information and insights, (3) to report more basic research that is pertinent to the understanding of disease, (4) to introduce topics of practice, ethics, teaching, and history that are useful, and (5) to provide a forum for discussion on topics that may be controversial in this field. This information will be published only after extensive peer review so that originality, clarity, and precision are ensured.

In the Original Investigation entitled “Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo,”1 there were errors in the article’s Table and in eFigure 2 of the Supplement. The cell for “≥4 Rims” and “Sex, Female, No. (%)” was left empty, and it should be “28 (67).” This article was corrected online.

The Review “Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review,”1 published in October 2019, had an error in an affiliation. Dr Nolano’s affiliation was reported as “Skin Biopsy Laboratory, Department of Neurology, IRCCS, SpA SB, Telese Terme, Italy,” omitting another institutional name that should have come after “IRCCS.” The name, “Istituti Clinici Scientifici Maugeri,” has been added to correct the error.

In the Clinical Challenge titled “A Case of Muscle Twitching With Psoriasis,”1 published online July 15, 2019, Dr Qin’s affiliation was listed as the Department of Medicine at the University of Massachusetts Medical School, but the correct affiliation is the Department of Neurology. This article was corrected online.