BACKGROUND AND PURPOSE: Huntington disease is a devastating genetic neurodegenerative disorder for which no effective treatment is yet available. Although progressive striatal atrophy is its pathologic hallmark, concomitant cortical deterioration is assumed to occur, but it is poorly characterized. Our objective was to study the loss of cortical integrity and its association with clinical indicators throughout the course of the disease. MATERIALS AND METHODS: Using a cohort of 39 patients with Huntington disease and 25 controls with available MR imaging (T1WI and DTI), we compared cortical atrophy and intracortical diffusivity across disease stages. Intracortical diffusivity is a DTI-derived metric that has recently been suggested to detect incipient neuronal death because water can diffuse more freely in cortical regions with reduced neural density. RESULTS: We observed progressive thinning and increasing diffusivity within the cerebral cortex of patients with Huntington disease (P < .05, corrected for multiple comparisons). Most important, in the absence of pronounced atrophy, widespread increased diffusivity was already present in individuals with premanifest Huntington disease, correlating, in turn, with clinical and disease-specific progression markers. CONCLUSIONS: Intracortical diffusivity may be more sensitive than cortical thinning for tracking early neurodegeneration in Huntington disease. Moreover, our findings provide further evidence of an early cortical compromise in Huntington disease, which contributes to our understanding of its clinical phenotype and could have important therapeutic implications.

Huntington’s disease (HD) is the most common autosomal dominant neurodegenerative disorder, characterized by a triad of motor dysfunction, cognitive decline, and psychiatric disturbances. While recent efforts have focused on developing disease-modifying therapies, no treatment has yet demonstrated clinical efficacy. As a result, symptomatic treatment remains the cornerstone of care. However, high-quality evidence from large randomized trials is limited, and therapeutic decisions must rely on clinical expertise and extrapolation from other neurological or psychiatric conditions. This narrative review provides a comprehensive and practical overview of symptomatic treatment strategies for HD with emphasis on the pathophysiological underpinnings of each symptom and the molecular mechanisms of available and emerging therapies, aiming to support rational, individualized management. Finally, we highlight the critical role of non-pharmacological interventions and the need for multidisciplinary approaches to optimize patient outcomes and quality of life.

Despite the advances in the understanding of Huntington's disease (HD), there is a need for molecular biomarkers to categorize mutation carriers during the preclinical stage of the disease preceding functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological processes. Here, using an optimized method for plasma extracellular vesicles (EVs) purification and an exhaustive analysis pipeline of sRNA sequencing data, we show that EV‐sRNAs are downregulated early in mutation carriers and that this deregulation is associated with premanifest cognitive performance. Seven candidate sRNAs (tRF‐Glu‐CTC, tRF‐Gly‐GCC, miR‐451a, miR‐21‐5p, miR‐26a‐5p, miR‐27a‐3p and let7a‐5p) were validated in additional subjects, showing a significant diagnostic accuracy at premanifest stages. Of these, miR‐21‐5p was significantly decreased over time in a longitudinal study; and miR‐21‐5p and miR‐26a‐5p levels correlated with cognitive changes in the premanifest cohort. In summary, the present results suggest that deregulated plasma EV‐sRNAs define an early biosignature in mutation carriers with specific species highlighting the progression and cognitive changes occurring at the premanifest stage.

Hereditary choreas are a clinically and genetically heterogeneous group of monogenic disorders in which chorea constitutes the core or an early‐dominant feature. These conditions result from various genetic mutations affecting the structures and pathways involved in movement control, primarily the caudate and putamen, ultimately impairing the basal ganglia circuits involved in the regulation of movement, cognition, and behavior. This review focuses on the main forms of hereditary choreas, including Huntington's disease, neuroacanthocytosis syndromes, Huntington's disease phenocopies, benign hereditary chorea, and other less common genetic disorders presenting with chorea. We discuss the clinical, genetic, and pathophysiological features of each condition, alongside key aspects of phenomenology, examination, and complementary tests—including laboratory findings—to guide phenotype‐driven genetic testing. We detail the characteristic features of key disorders while also highlighting less common but emerging conditions. This review aims to assist neurologists in recognizing and diagnosing hereditary choreas efficiently, including guidance on the selection of appropriate genetic tests, thereby reducing diagnostic delays, informing accurate counseling, and facilitating access to disease‐specific interventions and clinical trials.

Hereditary ataxias are a heterogeneous group of disorders with overlapping clinical presentations but diverse genetic and molecular etiologies. Biomarkers are increasingly essential to improve diagnosis, refine prognosis, and accelerate the development of targeted therapies. Following PRISMA-ScR guidelines, we conducted a scoping review of PubMed and complementary sources (2010–2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral–pallidoluysian atrophy (DRPLA), Friedreich’s ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). Eligible evidence encompassed observational cohorts, clinical trials, case series, and case reports providing primary biomarker data, with the objective of characterizing evidence breadth and identifying knowledge gaps rather than assessing comparative effectiveness. Across modalities, converging evidence highlights subtype-specific biomarker signatures. MRI volumetry, DTI, and FDG-PET map characteristic neurodegeneration patterns. Fluid biomarkers such as neurofilament light chain are informative across several SCAs and FRDA, while frataxin levels constitute robust endpoints in FRDA trials. Pathology-specific biomarkers such as ataxin-3 are advancing as tools for target engagement and may generalize to future gene-lowering strategies. Electrophysiological and oculographic measures show sensitivity for early disease detection, and wearable technologies are emerging as scalable tools for longitudinal monitoring. This scoping review synthesizes the heterogeneous evidence on hereditary ataxia biomarkers, highlighting multimodal frameworks that link molecular mechanisms with clinical endpoints. Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias.