ImportanceData from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae.ObjectivesTo describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E).Design, Setting, and ParticipantsSecondary data collection from

ImportanceImmunoglobulin G4 (IgG4)–related disease is an increasingly recognized fibroinflammatory condition that can involve multiple organs, including the pachymeninges. The understanding of IgG4-related pachymeningitis (IgG4-RP) remains limited because of its rarity and the predominance of knowledge derived from case reports and case series.ObjectiveTo systematically review and synthesize the clinical

ImportanceAn accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.ObjectiveTo clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the

This Viewpoint challenges conventional clinical practice that eschews pharmacological intervention for comatose patients with epileptiform abnormalities after cardiac arrest using evidence from the Treatment of Electroencephalographic Status Epilepticus after Cardiopulmonary Resuscitation (TELSTAR) trial.

ImportanceInterventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target.ObjectiveTo investigate whether the brain-permeable iron chelator deferiprone slows cognitive decline in people with AD

This essay describes the microaggressions and burnout faced by physicians and the importance of boundaries to preserve physicians’ humanity and well-being.

ImportanceSince 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers

This Viewpoint describes the advent of neonatal neurocritical care training, the data supporting the need and its efficacy, and the ways this training can optimize outcomes for vulnerable patients and their families.

ImportanceClinical trials have suggested that prehospital management in a mobile stroke unit (MSU) improves functional outcomes in patients with acute ischemic stroke who are potentially eligible for intravenous thrombolysis, but there is a paucity of real-world evidence from routine clinical practice on this topic.ObjectiveTo determine the association between prehospital management in an MSU vs standard

This essay describes the efforts patients might make to hold onto their humanity in the midst of an absurd world: being in the emergency department with a neurological injury.

ImportanceThe risk of developing Parkinson disease (PD) after objective hearing loss is unknown. PD studies using self-reported hearing loss are insensitive, and objective data are lacking.ObjectiveTo examine the association of hearing loss with incident PD in US veterans and its effect modification by well-established prodromal conditions and hearing aids.Design, Setting, and ParticipantsThis cohort

ImportanceTumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents.ObjectiveTo evaluate the risk of inflammatory

This cohort study examined the yield and use of genome sequencing after nondiagnostic exome sequencing for pediatric patients with unexplained epilepsy between August 2018 and May 2023.

ImportanceRecent studies have revealed that autopsy skin samples from cadavers with prion diseases (PRDs) exhibited a positive prion seeding activity similar to cerebrospinal fluid (CSF). It is worthwhile to validate the findings with a large number of biopsy skin samples and compare the clinical value of prion seeding activity between skin biopsies and concurrent CSF specimens.ObjectiveTo compare

ImportanceProgressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment.ObjectiveTo determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus–specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent.Design, Setting, and ParticipantsA

This Viewpoint advocates for the accelerated adoption of tofersen therapy to treat patients with variant SOD1-mediated amyotrophic lateral sclerosis (ALS) and describes the current barriers to treatment.

ImportanceHow epilepsy may promote cardiovascular disease remains poorly understood.ObjectiveTo estimate the odds of new-onset cardiovascular events (CVEs) over 6 years in older people with vs without epilepsy, exploring how enzyme-inducing antiseizure medications (EIASMs) and traditional cardiovascular risk factors mediate these odds.Design, Setting, and ParticipantsThis was a prospective cohort study

ImportanceDrug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation trials, suggest conceptualizing TLE as a network disorder

This Viewpoint describes the potential harms associated with increased coverage of carotid artery stenting by the Centers for Medicare & Medicaid Services.

ImportanceAntiseizure medications (ASMs) are frequently prescribed for acute symptomatic seizures and epileptiform abnormalities (EAs; eg, periodic or rhythmic patterns). There are limited data on factors associated with ASM use and their association with outcomes.ObjectivesTo determine factors associated with ASM use in patients with confirmed or suspected acute symptomatic seizures undergoing continuous

ImportanceParticipation in American-style football (ASF) has been linked to chronic traumatic encephalopathy neuropathological change (CTE-NC), a specific neuropathologic finding that can only be established at autopsy. Despite being a postmortem diagnosis, living former ASF players may perceive themselves to have CTE-NC. At present, the proportion and clinical correlates of living former professional

ImportanceMultiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant

This cross-sectional study examines the frequency of increased intracranial pressure and its association with myelin oligodendrocyte glycoprotein antibody-associated disease in patients of various ages.

ImportanceWhile the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed.ObservationsThere are unique biological factors in children younger than 18 years and in adults older than

ImportancePatients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH.ObjectiveTo assess erenumab efficacy and safety in patients with nonopioid CM-MOH.Design, Settings, and ParticipantsThis randomized, double-blind

ImportanceThe X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.ObjectivesTo perform the first large-scale X chromosome–wide association study (XWAS) of AD.Design, Setting, and ParticipantsThis was a

ImportanceA proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti–myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion

This Viewpoint describes the evidence for iatrogenic disease based on amyloid-β prions and the possibility that Alzheimer disease has an iatrogenic form wherein amyloid β and tau behave as prions that transmit the disease.

ImportanceCerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.ObjectiveTo investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.Design, Setting, and ParticipantsThis single-masked randomized

ImportanceAnti-β-amyloid immunotherapy using lecanemab is becoming increasingly available to patients with Alzheimer disease (AD). Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD.ObjectiveTo investigate the binding properties of lecanemab in the brains of people with DS, in anticipation of their inclusion

This Viewpoint advocates for Medicare coverage of driving assessments for older individuals.

This case report describes a 67-year-old woman who had received adoptive immunotherapy with chimeric antigen receptor T cells for multiple myeloma and was experiencing parkinsonism-like symptoms.

ImportanceApproximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke.ObjectiveTo compare apixaban vs aspirin for the prevention

ImportanceRecently, 6 randomized clinical trials—RESCUE-Japan-LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism—Japan Large Ischemic Core Trial), ANGEL-ASPECT (Trial of Endovascular Therapy for Acute Ischemic Stroke With Large Infarct), SELECT2 (Trial of Endovascular Thrombectomy for Large Ischemic Strokes), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation

This Viewpoint cautions against premature adoption of the α-synuclein seed amplification assay as a biomarker test for Parkinson disease in general neurology practice.

ImportanceMaternal epilepsy is associated with adverse pregnancy and neonatal outcomes. A better understanding of this condition and the associated risk of mortality and morbidity at the time of delivery could help reduce adverse outcomes.ObjectiveTo determine the risk of severe maternal and perinatal morbidity and mortality among women with epilepsy.Design, Setting, ParticipantsThis prospective population-based

ImportanceFunctional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients’ quality of life.ObjectiveTo assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs.Design, Setting

This cohort study assesses the association of pain phenotypes and pain multimorbidity with cerebral palsy subtypes among Medicare beneficiaries.

ImportanceUnilateral magnetic resonance–guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused

ImportanceDysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.ObjectiveTo assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.Design, Setting, and ParticipantsThis was a double-blind, placebo-controlled, randomized clinical trial conducted between

The lack of an in vivo measure for α-synuclein (α-syn) pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages.

ImportancePhase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy in people with less severe disease. Plasma biomarkers will be essential for efficient screening of participants in future primary prevention clinical trials testing antiamyloid therapies in cognitively unimpaired (CU) individuals with initially low brain β-amyloid (Aβ)

This case report describes use of high-intensity focused ultrasound as a method to create spatially precise thermal lesions in the brain without a craniotomy.

ImportanceEpilepsy is a highly treatable condition for many people, but there are large treatment gaps with suboptimal seizure control in minoritized groups. The sexual and gender minority (SGM) community is at risk for health disparities, yet the burden of epilepsy in this community is not known.ObjectiveTo estimate the prevalence of active epilepsy among SGM people in the United States.Design, Setting

ImportanceItching is common in geriatric populations and is frequently linked to dermatological or systemic conditions. Itching engages specific brain regions that are implicated in the pathogenesis of frontotemporal lobar degeneration spectrum disorders (FTLD-SD). Thus, itching of undetermined origin (IUO) may indicate the presence of a neurodegenerative process.ObjectiveTo compare the frequency of

This Viewpoint discusses the ambiguity of amyloid positron emission tomography coverage in the era of anti-amyloid therapeutics and the considerations and consequences of narrow coverage.

ImportanceParkinsonism is associated with traumatic brain injury and chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impact (RHI) exposure, but the neuropathologic substrates that underlie parkinsonism in individuals with CTE are yet to be defined.ObjectiveTo evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI

This Viewpoint cautions against the premature adoption and implementation of biological definitions for Parkinson disease proposed in February 2024.

ImportanceDirect-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.ObjectiveTo assess the rates of thromboembolic

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development.

This case report describes a patient experiencing involuntary contractions in his right pectoralis muscles with anti-Tr antibodies in his serum, which is characteristic of myorhythmia.

ImportanceClaims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population.ObjectiveTo develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare

This essay discusses the author’s experience after her father was diagnosed with amyotrophic lateral sclerosis.

ImportanceSleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. For effective AD prevention, it is essential to pinpoint the specific disturbances in sleep and the underlying 24-hour activity rhythms that confer the highest risk of Aβ deposition.ObjectiveTo determine the associations of 24-hour activity

This case report describes a man with multiple sclerosis and insomnia who noticed improved motor function during nocturnal awakenings compared with daytime.

ImportancePatients with atrial fibrillation (AF) can have an ischemic stroke (IS) despite oral anticoagulant (OAC) treatment. Knowledge regarding the association between OAC discontinuation and the subsequent risk of recurrent IS in patients with AF is limited.ObjectivesTo determine the risk of recurrent IS in patients with AF receiving OAC and to evaluate the association between OAC discontinuation

ImportanceStudies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and lower gray matter volumes.ObjectiveTo characterize maternal vs paternal history of memory impairment in terms of brain Aβ-positron emission tomography (Aβ-PET) and baseline cognition among a large sample

ImportanceAnimal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking.ObjectiveTo evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.Design, Setting,

This Viewpoint discusses the importance of developing medical forecasting skills to improve clinician/patient/family communications regarding prognosis.

ImportanceA third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae.ObjectiveTo compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher.Design