Intra-arterial Urokinase After Incomplete Mechanical Thrombectomy
Complete and rapid revascularization can dramatically reduce disability after large-vessel occlusion (LVO) acute ischemic stroke (AIS). 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 al 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 quantifiab...
Source: JAMA Neurology - December 9, 2019 Category: Neurology Source Type: research

Pharmacologic Acute and Preventive Treatment for Migraine in Children and Adolescents
This guideline summary provides a review of the American Academy of Neurology and the American Headache Society ’s guidelines on Acute Treatment of Migraine in Children and Adolescents and Pharmacologic Treatment for Pediatric Migraine Prevention. (Source: JAMA Neurology)
Source: JAMA Neurology - December 9, 2019 Category: Neurology Source Type: research

Association Between Breastfeeding and Postpartum Multiple Sclerosis Relapses
This systematic review and meta-analysis examines the occurrence of multiple sclerosis relapses in women who are breastfeeding (Source: JAMA Neurology)
Source: JAMA Neurology - December 9, 2019 Category: Neurology Source Type: research

Intra-arterial Rescue With Urokinase
This cohort study assesses whether administration of intra-arterial urokinase is safe and improves reperfusion among patients who have undergone failed or incomplete mechanical thrombectomy. (Source: JAMA Neurology)
Source: JAMA Neurology - December 9, 2019 Category: Neurology Source Type: research

Active Immunotherapy to Prevent Alzheimer Disease —A DNA Amyloid β 1-42 Trimer Vaccine
This Viewpoint argues that there is a possibility of finding a path forward in Alzheimer disease prevention with the DNA amyloid β 1-42 timer vaccine that warrants its evaluation in a clinical trial. (Source: JAMA Neurology)
Source: JAMA Neurology - December 9, 2019 Category: Neurology Source Type: research

Dopamine-Mediated Yawning-Fatigue Syndrome With Specific Recurrent Initiation and Responsiveness to Opioids
This case report describes a man with recurrent attacks of yawning and fatigue that were mediated by dopamine and responsive to opioid treatment. (Source: JAMA Neurology)
Source: JAMA Neurology - December 2, 2019 Category: Neurology Source Type: research

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol
This randomized clinical trial investigates whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were already taking stiripentol-inclusive regimens. (Source: JAMA Neurology)
Source: JAMA Neurology - December 2, 2019 Category: Neurology Source Type: research

Hail Mary
This essay describes an interaction the author had with a patient ’s family members in deciding whether to pursue surgey for the patient. (Source: JAMA Neurology)
Source: JAMA Neurology - December 2, 2019 Category: Neurology Source Type: research

The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke
This narrative review summarizes randomized clinical trials with negative (vs neutral) outcomes to study why previous acute stroke interventions appeared to cause harm. (Source: JAMA Neurology)
Source: JAMA Neurology - December 2, 2019 Category: Neurology Source Type: research

Errors in Table and Supplemental Figure
This article was correcte d online. (Source: JAMA Neurology)
Source: JAMA Neurology - December 1, 2019 Category: Neurology Source Type: research

December 2019 Issue Highlights
(Source: JAMA Neurology)
Source: JAMA Neurology - December 1, 2019 Category: Neurology Source Type: research

JAMA Neurology
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, a...
Source: JAMA Neurology - December 1, 2019 Category: Neurology Source Type: research

Episodic Visual Snow Associated With Migraine Attacks
This case series describes 3 individuals with episodic visual snow, co-occurring with migraines. (Source: JAMA Neurology)
Source: JAMA Neurology - November 25, 2019 Category: Neurology Source Type: research

Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease
The AMARANTH and DAYBREAK-ALZ randomized clinical trials assess whether lanabecestat slows the progression of Alzheimer disease compared with placebo in patients with early Alzheimer disease or mild Alzheimer disease dementia. (Source: JAMA Neurology)
Source: JAMA Neurology - November 25, 2019 Category: Neurology Source Type: research

Microgravity and Cosmic Radiations During Space Exploration as a Window Into Neurodegeneration on Earth
This Viewpoint encourages researchers to take the opportunity to investigate brain adaptation to long-term spaceflight as a model of aging. (Source: JAMA Neurology)
Source: JAMA Neurology - November 25, 2019 Category: Neurology Source Type: research

Pragmatic Trials and Repurposed Drugs for Alzheimer Disease
Howard and colleagues report a randomized clinical trial in which 554 patients clinically diagnosed with early Alzheimer disease were randomized to 200 mg/d or 400 mg/d of the broad-spectrum antibiotic minocycline or to placebo and followed up for 24 months. Clinical outcomes were a structured Mini-Mental State Examination (MMSE) and the Bristol Activities of Daily Living scale. About 62% of the 200 mg/d minocycline –treated group compared with 64% of the placebo-treated group completed 2 years of treatment; only 29% of the group receiving 400 mg/d of minocycline completed the trial. There was no evidence for efficac...
Source: JAMA Neurology - November 18, 2019 Category: Neurology Source Type: research

Minocycline vs Placebo for Patients With Mild Alzheimer Disease
This randomized clinical trial examines whether 24 months of minocycline treatment can modify cognitive and functional decline in patients with mild Alzheimer disease. (Source: JAMA Neurology)
Source: JAMA Neurology - November 18, 2019 Category: Neurology Source Type: research

Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers
This systematic review and meta-analysis examines prognostic factors in c9 amyotrophic lateral sclerosis, c9 frontotemporal dementia, c9 amyotrophic lateral sclerosis and frontotemporal dementia, and atypical phenotypes. (Source: JAMA Neurology)
Source: JAMA Neurology - November 18, 2019 Category: Neurology Source Type: research

The Patient I Didn ’t Like
This essay describes lessons the author learned through treating a difficult patient. (Source: JAMA Neurology)
Source: JAMA Neurology - November 18, 2019 Category: Neurology Source Type: research

Insidious Cerebrovascular Disease —the Uncool Iceberg
This Viewpoint describes the clinical and public health implications of emerging information on subclinical cases of cerebrovascular disease. (Source: JAMA Neurology)
Source: JAMA Neurology - November 18, 2019 Category: Neurology Source Type: research

Perception of Dementia Risk and Preventive Actions Among US Adults Aged 50 to 64 Years
This study examines the perception of US individuals about their likelihood of developing dementia and their strategies to improve or maintain memory. (Source: JAMA Neurology)
Source: JAMA Neurology - November 15, 2019 Category: Neurology Source Type: research

Error in Text
This article was corrected online. (Source: JAMA Neurology)
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Developmental Venous Anomaly Inside a Glioblastoma
This case report details an unusual developmental venous anomaly within a glioblastoma. (Source: JAMA Neurology)
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Left Atrial Enlargement Could Be Detected on Extended Computed Tomography Angiography
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 colleagues 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. The authors suggest that left atrial enlargement could become a new determinant in secondary stroke prevention. (Source: JAMA Neurology)
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Left Atrial Enlargement Could Be Detected on Extended Computed Tomography Angiography —Reply
In Reply We agree with Popkirov that left atrial volume is a better marker of incident atrial fibrillation than atrial diameter; 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. Recently completed and ongoing 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 recommendat...
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With AD, PSP, and CBS
This parallel-design, double-blind randomized clinical trial assesses the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 in patients with Alzheimer disease or the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome. (Source: JAMA Neurology)
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Spatial and Temporal Pattern of Ischemia and Abnormal Vascular Function Following Traumatic Brain Injury
This single-center observational cohort study aims to comprehensively characterize the spatiotemporal changes in cerebral physiology after traumatic brain injury by comparing a cohort of affected patients with healthy control participants. (Source: JAMA Neurology)
Source: JAMA Neurology - November 11, 2019 Category: Neurology Source Type: research

Error in Affiliation
The Review “Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review,” 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 anoth er institutional name that should have come after “IRCCS.” The name, “Istituti Clinici Scientifici Maugeri,” has been added to correct the error. (Source: JAMA Neurology)
Source: JAMA Neurology - November 4, 2019 Category: Neurology Source Type: research

Prevention of Dementia —Thinking Beyond the Age and Amyloid Boxes
It is increasingly recognized that the declines in brain structure and function in persons with no clinical brain disease that we call brain aging and the 2 brain diseases that most frequently affect older adults (dementia and stroke) are the theoretically predictable consequences of a lifetime of injury that overcomes genetically and environmentally determined reserve and resilience, a concept encapsulated in the shorthand phrase life-course illness. Despite this insight, details of the various factors that adversely affect the brain health of older adults (and clarity on which times during life have the greatest effect a...
Source: JAMA Neurology - November 4, 2019 Category: Neurology Source Type: research

Distinctive Magnetic Resonance Imaging Findings in IgLON5 Antibody Disease
This case report describes distinctive magnetic resonance imaging findings in a Chinese woman with IgLON5 antibody disease. (Source: JAMA Neurology)
Source: JAMA Neurology - November 4, 2019 Category: Neurology Source Type: research

Associations Between Vascular Risk Across Adulthood and Brain Pathology in Late Life
This longitudinal cohort study assesses the associations between vascular risk in early adulthood, midlife, and late life with late-life brain structure and β-amyloid load and white matter hyperintensity, whole-brain, and hippocampal volumes. (Source: JAMA Neurology)
Source: JAMA Neurology - November 4, 2019 Category: Neurology Source Type: research

Are Daylight Saving Time Changes Bad for the Brain?
This Viewpoint reviews data associated with the US daylight saving time transition. (Source: JAMA Neurology)
Source: JAMA Neurology - November 4, 2019 Category: Neurology Source Type: research

Trends in Prices, Market Share, and Spending on Disease-Modifying Therapies in Medicare Part D
This cohort study assesses trends in prices, market share, and spending on self-administered disease-modifying therapies for multiple sclerosis in Medicare Part D from 2006 through 2016. (Source: JAMA Neurology)
Source: JAMA Neurology - November 1, 2019 Category: Neurology Source Type: research

November 2019 Issue Highlights
(Source: JAMA Neurology)
Source: JAMA Neurology - November 1, 2019 Category: Neurology Source Type: research

JAMA Neurology
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, a...
Source: JAMA Neurology - November 1, 2019 Category: Neurology Source Type: research

The Mask Sign —An Imaging Marker of Traumatic Spinal Cord Hemorrhage
This case report describes an unusual sign on magnetic resonance imaging that characterizes a particular type of injury. (Source: JAMA Neurology)
Source: JAMA Neurology - October 28, 2019 Category: Neurology Source Type: research

Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies in Adult and Pediatric Patients
This study characterizes the frequency and sex ratio of positive test results for myelin oligodendrocyte glycoprotein –IgG and aquaporin-4–IgG in adult and pediatric patient populations in a single center. (Source: JAMA Neurology)
Source: JAMA Neurology - October 28, 2019 Category: Neurology Source Type: research

Epidemiology of Dementia and Alzheimer Disease in Individuals With Down Syndrome
This cohort study uses Medicare data to examine the incidence and prevalence of Alzheimer disease and all forms of dementia in individuals with Down syndrome. (Source: JAMA Neurology)
Source: JAMA Neurology - October 28, 2019 Category: Neurology Source Type: research

Vulnerability of the Nucleus Basalis of Meynert Among Neuropathologic Subtypes of Alzheimer Disease
This cross-sectional study using tissue from the Florida Autopsied Multi-Ethnic cohort assesses whether an association exists between neuropathologic subtypes of Alzheimer disease and neurofibrillary tangle accumulation or neuron loss in the nucleus basalis of Meynert, a major source of brain cholinergic innervation. (Source: JAMA Neurology)
Source: JAMA Neurology - October 28, 2019 Category: Neurology Source Type: research

Development of Expert-Level Automated Detection of Epileptiform Discharges
This diagnostic study aims to evaluate and validate a deep neural network trained to detect epileptiform discharges during electroencephalogram interpretation in comparison with expert physicians with subspecialty training. (Source: JAMA Neurology)
Source: JAMA Neurology - October 21, 2019 Category: Neurology Source Type: research

A Rare Form of Lipid Metabolic Encephalopathy
A 27-year-old Asian man was found with painless masses of about 5.1 cm in diameter that appeared on both Achilles tendons 10 years ago. What is your diagnosis? (Source: JAMA Neurology)
Source: JAMA Neurology - October 21, 2019 Category: Neurology Source Type: research

Error in Byline
This article was corrected online. (Source: JAMA Neurology)
Source: JAMA Neurology - October 21, 2019 Category: Neurology Source Type: research

Incorrect Affiliation
This article was corrected online. (Source: JAMA Neurology)
Source: JAMA Neurology - October 21, 2019 Category: Neurology Source Type: research

Interrater Reliability of Experts in Identifying Interictal Epileptiform Discharges in EEGs
This study assesses the reliability of subspecialty-trained clinical neurophysiologists in detecting interictal epileptiform discharges in routine electroencephalograms (EEGs) recorded from 2012 to 2016. (Source: JAMA Neurology)
Source: JAMA Neurology - October 21, 2019 Category: Neurology Source Type: research

Risk, Informed Consent, and Posttrial Responsibilities in Human Research With Neural Devices
This narrative review discusses analysis of risk, informed consent, and posttrial responsibilities to research participants in neural devices research. (Source: JAMA Neurology)
Source: JAMA Neurology - October 17, 2019 Category: Neurology Source Type: research

Endovascular Therapy for Childhood Stroke —Working Together to Reach Prime Time
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. 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 disabili...
Source: JAMA Neurology - October 14, 2019 Category: Neurology Source Type: research

Cautious Interpretation of Observational Data
To the Editor We read the article by Harding and colleagues regarding escalation vs early intensive approaches in treating patients with multiple sclerosis (MS). We agree that treating MS early and aggressively to halt disease from the start sounds attractive. In fact, there are clinical trial data that find an association of an early vs delayed start of a higher-efficacy therapy with sustained relapse rate reductions. However, there are limitations in interpreting observational data, especially in MS cohorts, that were not fully addressed in the article. (Source: JAMA Neurology)
Source: JAMA Neurology - October 14, 2019 Category: Neurology Source Type: research

Cautious Interpretation of Observational Data —Reply
In Reply We thank Soares-dos-Reis and Messina for their comments on our article. We agree that clinical observational data are often limited and require cautious interpretation. For this reason, we have used our preliminary observational data to collaborate with other centers and establish a prospective trial to address this important question (NCT03535298). (Source: JAMA Neurology)
Source: JAMA Neurology - October 14, 2019 Category: Neurology Source Type: research

Association of Endovascular Treatment With Ischemic Stroke and Clinical Outcome in Pediatric Patients
This cohort study examines the use of endovascular recanalization in pediatric patients with arterial ischemic stroke and clinical outcomes. (Source: JAMA Neurology)
Source: JAMA Neurology - October 14, 2019 Category: Neurology Source Type: research

Risk of Developing Parkinson Disease in Bipolar Disorder
This systematic review and meta-analysis assesses the association of bipolar disorder with a later diagnosis of idiopathic Parkinson disease. (Source: JAMA Neurology)
Source: JAMA Neurology - October 14, 2019 Category: Neurology Source Type: research