Abstract
<title>Abstract</title> <p>Background Major neurological disorders—including Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, epilepsy, and multiple sclerosis (MS)—represent a leading cause of global disability and mortality. Rapid developments in diagnostic technology and target-directed therapeutics aim to move clinical practice from late-stage symptomatic management toward early detection and disease modification. Objective This systematic literature review evaluates the effectiveness, clinical performance, and implementation limits of modern diagnostic (artificial intelligence, advanced neuroimaging, fluid biomarkers) and therapeutic interventions (disease-modifying therapies, neurostimulation, advanced neurorehabilitation) for major neurological disorders. Methods Conducted in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, a comprehensive systematic search was executed across PubMed/MEDLINE, Web of Science, and Embase through August 2026. Studies were selected via binary inclusion criteria using the Population, Intervention, Comparator, Outcome, and Study Design (PICOS) framework. Methodological quality and risk of bias were formally appraised using QUADAS-2 (diagnostic accuracy), ROBINS-I (non-randomized studies), and RoB 2 (randomized controlled trials). Data extraction was independently performed. Results From 464 identified records, 30 peer-reviewed primary studies met all eligibility criteria following the exclusion of low-quality sources and unindexed preprints. Machine learning models, particularly deep convolutional neural networks applied to brain MRI and EEG, demonstrated diagnostic accuracies ranging from 91.2% to 96.4% across multi-class neurodegenerative conditions. Ultra-sensitive fluid biomarkers—notably plasma p-tau217, p-tau181, and cerebrospinal fluid alpha-synuclein seed amplification assays (alphaSyn RT-QuIC)—exhibited high diagnostic sensitivity (> 90%) and specificity (> 92%) for early AD and PD pathology. On therapeutic fronts, anti-amyloid monoclonal antibodies (Lecanemab, Donanemab) slowed cognitive decline in early AD by 27% to 35% on the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Repetitive Transcranial Magnetic Stimulation (rTMS) and advanced neurorehabilitation (robotics, vagus nerve stimulation) yielded statistically significant functional recovery in post-stroke motor deficits and treatment-resistant epilepsy. Conclusions Modern diagnostic and therapeutic modalities demonstrate substantial clinical efficacy, shifting clinical neurology toward biomarker-driven precision medicine. However, widespread clinical adoption remains constrained by algorithmic bias, lack of multi-centric data standardization, high intervention costs, and health system infrastructure barriers.</p>