Revisiting cirrhosis-related parkinsonism: a comprehensive review

Cirrhosis-related Parkinsonism is a frequent but often overlooked neurological complication of chronic liver disease, primarily driven by manganese (Mn) accumulation in the basal ganglia resulting from portosystemic shunting. Clinically, it presents as an atypical Parkinsonian syndrome characterized by bilateral and symmetrical motor features, early postural instability, and poor responsiveness to dopaminergic therapy, which distinguishes it from idiopathic Parkinson's disease. The underlying pathophysiology involves a complex cascade of Mn-induced neuroinflammation, mitochondrial dysfunction, and 𝛂-synuclein misfolding, particularly affecting the globus pallidus. While T1-weighted MRI typically reveals characteristic bilateral hyperintensities in the globus pallidus, its low specificity remains a significant diagnostic challenge, as these findings can occur in asymptomatic cirrhotic patients. Orthotopic liver transplantation stands as the only definitive treatment, offering potential for reversal of neurological deficits by restoring hepatic detoxification. Alternative strategies include interventional radiological shunt obliteration and symptomatic pharmacological therapies, though evidence for the latter remains inconsistent. This review synthesizes current knowledge on the epidemiology, pathogenesis, and management of this neurohepatic syndrome, highlighting the urgent need for standardized diagnostic criteria and validated biomarkers to improve clinical recognition and patient outcomes.