Autoimmune parkinsonism: Emerging clinical and therapeutic perspectives

Abstract Autoimmune parkinsonism is an uncommon but increasingly recognized cause of parkinsonian syndromes resulting from immune-mediated damage to the basal ganglia and related networks. Unlike idiopathic Parkinson’s disease, it usually presents with subacute onset, rapid progression, atypical clinical features, including early cognitive or autonomic involvement, and a poor or fluctuating response to levodopa. However, patients may respond favorably to immunotherapy, making early recognition essential. In recent years, several antibodies have been implicated in autoimmune parkinsonism, including anti-immunoglobulin-like cell adhesion molecule 5, anti-dopamine-2 receptor, and collapsin response mediator protein 5, each associated with distinct clinical phenotypes. Diagnosis relies on a combination of clinical suspicion, antibody testing, cerebrospinal fluid analysis, and neuroimaging, including magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. Treatment typically involves immunotherapy in the form of corticosteroids, intravenous immunoglobulin, plasma exchange, or B-cell-depleting agents, with variable responses depending on the type of antibody and the timing of intervention. This review summarizes the current knowledge on the epidemiology, pathophysiology, clinical presentation, and management strategies, while emphasizing current gaps in knowledge. Future research and further studies are needed to define diagnostic criteria, discover novel autoantigens, and optimize therapeutic strategies. Relevant literature was identified through a comprehensive search of MEDLINE, Embase, and Scopus databases up to July 31, 2025. Eligible case reports, series, and original studies describing autoimmune parkinsonism were reviewed, and data on clinical features, antibodies, and treatment outcomes were qualitatively synthesized