This article is an excerpt from a natural history study published in Neurology in 2025, focusing on the sensitivity of clinical outcome measures in assessing adult patients with Becker Muscular Dystrophy (BMD) over a three-year period. Researchers aimed to identify which functional tests, such as the Rise From Floor velocity (RFFv) and the North Star Ambulatory Assessment (NSAA), were most responsive to the disease's slow and variable progression for use in clinical trials. The study concluded that RFFv was the only measure with high responsiveness across the entire cohort at three years, although selecting a subgroup based on phenotype (NSAA scores 10–32) significantly improved the sensitivity of RFFv, NSAA, and 4-stair climb velocity earlier in the follow-up. Furthermore, the analysis suggested that genotype selection did not significantly enhance responsiveness, and the decline in cardiac function occurred independently of skeletal muscle function. Overall, the findings recommend the use of NSAA in clinical trials for ambulant BMD patients due to its broad feasibility and consistent decline, especially when patients are selected based on baseline NSAA scores.

This journal article provides a practical guide to understanding and applying the International League Against Epilepsy (ILAE) updated seizure classification of 2025. It explains how the new system, which builds on the 2017 classification, enhances clarity and consistency in terminology for healthcare professionals managing epilepsy. The classification organizes seizures into four main classes—focal, generalized, unknown, and unclassified—and introduces both a basic version for general use and an expanded version with detailed semiological descriptors. A key update is the use of consciousness, defined by both awareness and responsiveness, as a critical classifier for seizures. The article includes numerous case vignettes and definitions of generalized seizure types to aid in the clinical implementation of this flexible, structured framework.

The paper provides updated 2025 management guidelines from the Association of British Neurologists (ABN) for autoimmune myasthenia gravis (MG). The document outlines several key updates from previous 2015 guidelines, emphasizing new standard practices such as prescribing daily steroids and recommending early thymectomy for certain patient groups. It extensively details the diagnosis, initial treatment (like pyridostigmine and prednisolone protocols), and long-term immunosuppression, including the recommended early use of rituximab for generalized MG. Furthermore, the guidelines introduce information on novel targeted therapies like complement inhibitors and neonatal Fc gamma receptor blockers, alongside protocols for managing MG relapses, emergencies, and myasthenia in pregnancy.

The papers summarized focus on Cerebral Amyloid Angiopathy (CAA), particularly the emerging clinical phenomenon of iatrogenic CAA (iCAA). iCAA is hypothesized to occur following the transmission of Amyloid-β (Aβ) seeds (prions) during medical procedures, such as neurosurgery involving cadaveric dura mater. Key points regarding CAA and iCAA include:• Pathogenesis and Latency: The transmission of Aβ results in symptomatic CAA decades later, with a typical latency between exposure and clinical onset ranging from 27 to 59 years.• Clinical Presentation: While initial reports focused on early-onset iCAA (typically under age 55) resulting from childhood procedures, later-onset cases (aged 65 and older) are now recognized, although differentiating them from sporadic CAA (sCAA) in this older age group remains challenging. Presenting symptoms often include spontaneous intracerebral hemorrhage (ICH), seizures, transient focal neurological episodes (TFNEs), or cognitive impairment.• Inflammatory Variant (CAA-ri): iCAA can evolve into CAA-related inflammation (CAA-ri), an acute or subacute encephalopathy characterized by features like headache, seizures, cognitive impairment, and specific MRI findings (e.g., asymmetric confluent white matter edema and leptomeningeal enhancement). CAA-ri in iCAA cases is often associated with a severe clinical course and may show a poor response to steroid treatment.• Diagnosis and Criteria: Diagnosis relies on clinical data and Magnetic Resonance Imaging (MRI) biomarkers, including lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), severe visible perivascular spaces in the centrum semiovale (CSO-PVS), and white matter hyperintensities (WMHs). The Boston Criteria version 2.0 for probable CAA incorporates these non-hemorrhagic MRI markers (like severe CSO-PVS and WMH-MS) to enhance diagnostic sensitivity without compromising specificity for sporadic CAA.

This  original article published in the New England Journal of Medicine  reports the findings of the ASSET-IT trial, a phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial. This study investigates the efficacy and safety of early tirofiban infusion after standard intravenous thrombolysis for patients experiencing acute ischemic noncardioembolic stroke. The trial's primary outcome demonstrates that early administration of tirofiban significantly increases the likelihood of an excellent functional outcome at 90 days compared to placebo. However, the study also notes a slightly higher risk of symptomatic intracranial hemorrhage in the tirofiban group. The conclusions suggest that tirofiban may be a beneficial adjunct therapy for this specific patient population, though the generalizability is limited as the trial was conducted solely in China and excluded patients eligible for thrombectomy.

Friedreich’s ataxia is a rare, progressive, autosomal recessive neurodegenerative, multisystem disorder caused by a homozygous GAA repeat expansion in the frataxin gene, resulting in a deficiency of the mitochondrial protein frataxin. This core pathology impairs iron–sulfur cluster biosynthesis and mitochondrial adenosine triphosphate production, leading to mitochondrial dysfunction and increased oxidative stress. While characterized by ataxia, Friedreich’s ataxia is multisystemic, including cardiomyopathy, which represents the major determinant of reduced survival. Omaveloxolone, approved by the United States Food and Drug Administration and recommended by the Committee for Medicinal Products for Human Use of the European Medicine Agency, is the first available treatment for eligible patients, acting as a potent activator of the Nuclear factor erythroid 2-related factor 2 pathway. Clinical evaluation demonstrated a statistically significant improvement in neurological function, as measured by Friedreich Ataxia Rating Scale scores (combining Friedreich Ataxia Rating Scale and modified Friedreich Ataxia Rating Scale), and analysis also showed that drugs augmenting mitochondrial function significantly improved Left ventricular mass index. A common adverse event is the elevation of alanine aminotransferase and aspartate aminotransferase concentrations, which are generally transient, reversible, and mostly occur within the first 12 weeks of treatment and are likely related to Nuclear factor erythroid 2-related factor 2-mediated metabolic adaptations rather than drug-induced liver injury. Due to the limitations of existing outcome measures in tracking slow disease progression, future randomized controlled trials should run for at least 24 months and employ a multifaceted biomarker toolbox, such as combining Friedreich Ataxia Rating Scale scores and Left ventricular mass index assessment, to accurately capture treatment effects across different aspects of the disease.

This episode combines three papers to provide a comprehensive overview of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), emphasizing its status as the most common monogenic cerebral small vessel disorder caused by NOTCH3 gene mutations. These mutations, particularly those altering cysteine residues in the NOTCH3 receptor, lead to the accumulation of granular osmiophilic material (GOM) in blood vessel walls, although the precise disease mechanism remains unclear, with major hypotheses focusing on aberrant NOTCH3 aggregation and signaling. The research highlights the dramatic variability in disease onset and severity, noting that the prevalence of pathogenic NOTCH3 variants is higher than previously estimated, especially among Asian populations, and that the location of the mutation (e.g., in EGFRs 1–6 versus 7–34) may influence disease prognosis and the severity of the clinical phenotype. Finally, the texts discuss various diagnostic biomarkers, such as characteristic MRI features (like white matter hyperintensities in the anterior temporal lobe) and promising blood biomarkers like neurofilament light chain, which aid in diagnosis and predicting outcomes.

The two research articles reviewed here compare the clinical presentation of different variants of hereditary transthyretin-mediated amyloidosis (TTR familial amyloidosis), particularly focusing on the Val142Ile variant.

This episode reviews clinical practice guideline developed for the management of Spinal Bulbar Muscular Atrophy (SBMA), also known as Kennedy disease, in Canada. The guideline is prompted by the discovery of a substantially elevated prevalence of this rare X-linked recessive neuromuscular disorder among First Nations and Métis people in western Canada. It addresses the diagnosis and comprehensive, multidisciplinary management of SBMA, including motor, cardiac, and endocrine complications, while emphasizing the critical need for culturally appropriate care for Indigenous populations. The recommendations, which cover 41 aspects of care, were created using rigorous methodological frameworks by an interdisciplinary working group and informed by existing guidelines for SBMA (from France) and Amyotrophic Lateral Sclerosis (ALS).

This episode reviews the VasCog-2-WSO Criteria, which is the 2025 revised consensus diagnostic guidelines for Vascular Cognitive Impairment and Dementia (VCID). Developed by an international consortium of experts using a Delphi consensus process, these criteria update the previous VasCog guidelines to incorporate recent advances in neuroimaging and biomarkers. The objective was to create an operationalized international standard for diagnosing VCID across preclinical, mild, and major dementia severity levels, addressing prior inconsistencies in terminology and assessment. Key updates include defining VCID as the overarching term, refining the neuroimaging criteria for establishing a vascular etiology, and introducing a category for preclinical/at-risk VCID for preventative measures. The World Stroke Organization (WSO) endorsed these criteria, which are designed to enhance diagnostic consistency for both clinicians and researchers.