Clinical MRI Biomarkers to Differentiate Parkinson Disease from Its Mimics

The clinical discrimination of Parkinson disease (PD) from its mimics can be challenging, especially in the early stages. These mimics include atypical parkinsonian syndromes (APSs), essential tremor, drug-induced parkinsonism, and vascular parkinsonism. Moreover, differential diagnosis of PD is not exclusive; overlapping and coexisting neurodegenerative diseases are common. Most patients with suspected PD undergo standard clinical MRI (including T1- and T2-weighted sequences) as the first imaging examination, with the primary objective to exclude other diseases. Standard MRI can help detect vascular pathologic features in vascular parkinsonism or atrophy patterns in some APSs but is not sensitive for detecting PD. Dopamine transporter imaging remains the neuroimaging reference standard for specific diagnosis of PD: It can be used to detect PD and most APSs but cannot reliably be used to discriminate between them or exclude other findings, including cerebrovascular disease. Emerging MRI biomarkers of PD are nigrosome 1 (N1; the swallow tail sign at susceptibility-weighted imaging) and neuromelanin (at neuromelanin-sensitive MRI). These markers appear abnormal in PD and most APSs yet normal in essential tremor, drug-induced parkinsonism, and vascular parkinsonism. Identifying these challenging markers depends on specific technical parameters and reader experience. Although dopamine transporter imaging remains more accurate for diagnosing PD, the authors discuss how adding N1 or neuromelanin imaging to standard MRI is a practical, cost-effective, and sustainable way to help diagnose PD and PD mimics and select patients for subsequent dopamine transporter imaging.