Diagnostic and Prognostic Value of Epigenetic Markers in Neurological Diseases. A Narrative Review

Neurological disorders are a leading cause of disability and death, yet sensitive and specific biomarkers remain limited. Epigenetic modifications link genetic background with environmental influences and may improve diagnosis, prognosis, and treatment stratification. The study aimed to summarise the current knowledge on epigenetics in neurological diseases, primarily focusing on their diagnostic value. We performed a narrative review with elements of systematic methodology. PubMed was searched up to November 21, 2025, using broad neurology and epigenetics terms followed by disease-specific queries. Sixty-five original studies on epigenetic markers with diagnostic or prognostic utility in neurological diseases were included. Across neurological disorders, multiple disease-associated epigenetic signatures have been reported. In neurodegenerative diseases, deoxyribonucleic acid (DNA) methylation patterns, histone modifications, and non-coding ribonucleic acid (RNA) profiles discriminate patients from controls and correlate with disease stage and clinical outcomes. In multiple sclerosis, methylation changes in genes involved in disease pathogenesis and characteristic microRNAs may distinguish relapsing from progressive forms and relate to disability. In ischemic stroke and transient ischemic attack, epigenetic alterations in vascular, metabolic, circadian, and inflammatory pathways, together with non-coding RNAs and extracellular vesicle signatures, are associated with stroke risk, severity, and outcome. Evidence in epilepsy, migraine, myasthenia gravis, dystrophies, and leukodystrophies suggests additional disease-specific epigenetic candidates. Epigenetic biomarkers across DNA methylation, histone modifications, and non-coding RNAs hold substantial potential to enhance precision neurology, from early diagnosis to prognostic stratification and therapy guidance. However, current evidence is heterogeneous and often based on small cohorts and variable methodologies. Large, longitudinal studies with standardised protocols are required before routine clinical implementation.