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.

This case report describes a patient in his 60s with peripheral-type paralysis and hemorrhage in the left thalamus-radiation crown region.

This diagnostic study evaluates the ability of multiple skin biopsies to detect prion seeding activity compared with the cerebrospinal fluid (CSF) as a diagnostic biomarker in prion diseases.

This Viewpoint advocates for the implementation of collaborative care with care navigation in the diagnosis and treatment of Alzheimer disease.

This cohort study analyzes electronic health record data for US veterans with an audiogram to determine whether hearing loss is associated with an increased risk of Parkinson disease and to gauge its effect modification by well-established prodromal conditions and hearing aids.

This case report describes a novel crossed clonus response in a 48-year-old man with compressive cervical myelopathy.

This study attempts to develop and externally validate a prognostic score to estimate the individual risk of postcerebral venous thrombosis epilepsy.

This systematic review and meta-analysis evaluates the risk of new-onset inflammatory central nervous system diseases after tumor necrosis factor–inhibitor treatment for autoimmune disease.

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.

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.

This cohort study investigates if prehospital management in a mobile stroke unit compared with standard emergency medical services management reduces the level of global disability at hospital discharge in patients with ischemic stroke who are potentially eligible for intravenous thrombolysis.

The cornerstone of acute ischemic stroke (AIS) treatment is intravenous thrombolysis (IVT). IVT with alteplase or tenecteplase administered within 4.5 hours of last known well time (LKWT) or from 4.5 to 24 hours from LKWT for select subgroups robustly improves the odds of good clinical outcomes in patients with AIS and disabling symptoms. The effect of IVT is highly time sensitive, with earlier treatment conferring greater odds of functional independence. The Mobile Stroke Unit (MSU) concept, developed in Germany in 2008, effectively brings IVT to the patient using specialized ambulances equipped with computed tomography scanners and stroke-trained personnel, thus saving transport time. MSU use has been shown in observational studies and clinical trials to increase the frequency and speed of IVT administration and thereby lead to better functional outcomes compared to standard ambulance care. This includes the Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared with Standard Management by Emergency Medical Services (BEST-MSU) trial, an alternating-week, cluster-controlled trial that enrolled 1515 patients largely in Houston, Texas, along with 6 other US cities. MSUs, when sufficiently busy, have been shown to be cost-effective in studies from both Germany and Australia. A pending analysis from the BEST-MSU trial currently under peer review should provide guidance on the case volumes required for cost-effectiveness. Starting in Houston, MSUs have proliferated in the US, and there are currently over 20 active programs representing all major geographic regions. Whether the benefits of MSUs translate into improved clinical outcomes in routine clinical practice, wherein care is less controlled and patient selection for IVT may be looser, is uncertain.

This Special Communication discusses a recent revision of the Alzheimer’s Association (AA) criteria to define Alzheimer disease (AD) as a purely biological entity, which raises concerns that if diagnosis of AD can be reduced to the sole presence of AD core 1 biomarkers, major uncertainty and variability in the clinical prognosis of patients diagnosed with AD may be introduced.

In this issue of JAMA Neurology, the International Work Group (IWG) responds to the recently published 2024 Alzheimer Association (AA) Diagnostic Framework for Alzheimer Disease (AD) with their own framework and views. Back in 2018, the National Institute on Aging (NIA)–AA group proposed a biological definition of AD stating that if a person had the biomarker evidence of brain amyloid (A) and tau (T), the pathologic hallmarks of the disease, the patient had AD irrespective of the person’s clinical state. In their recent 2024 revision, they maintain a biological definition but have extended it to incorporate more recent biomarkers for AD. They define AD by positivity on core 1 biomarkers that indicate the crossing of a specific amyloid threshold on amyloid positron emission tomography (PET), cerebrospinal fluid, and foreseeably, plasma biomarkers. A major question pertains to the requirement for tau in the definition. The AA group argues that the vast majority of individuals who have amyloid-positive PET scans have some tau pathology. Furthermore, the AA group proposes a clinical staging scheme that provides a framework to define the frequent mismatch between AD biomarker positivity (and underlying neuropathology) and the clinical expression of the disease, often an indicator of mixed pathologies or resilience. Importantly, although the AA group does base the AD diagnosis on biomarker positivity, they do not currently advise testing in asymptomatic persons in a clinical setting.

Mission Statement: The mission of JAMA Neurology is to publish and disseminate scientific information primarily important for physicians caring for people with neurologic disorders and for those interested in the structure and function of the normal and diseased human nervous system. The specific aims are to (1) publish timely original research, including clinical trials that will directly improve clinical neurologic care and that will inform efforts to improve neurological health and promote health care equity; (2) report translational research that is pertinent to the understanding of neurologic disease; (3) address topics of practice, ethics, education, and public health that are a key part of modern medicine; and (4) provide a forum for discussion and publication of important topics including bias, racism, and diversity. This information will be published only after extensive review by scientific peers and journal editors so that clarity, rigor, originality, and precision are ensured.