The role of molecular imaging in assessing degenerative parkinsonism – an updated review

Diagnosing degenerative forms of parkinsonism still relies on a thorough clinical assessment, which in Parkinson's disease involves the presence of an asymmetric bradykinesia with rest tremor and/or rigidity that respond substantially to levodopa. Conversely, atypical forms, including multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, exhibit additional features (cerebellar or pyramidal signs, early postural instability), a poor response to dopamine replacement therapy and a bad prognosis. Consensus diagnostic criteria have excellent specificity, but lack sensitivity, and a clear diagnosis solely based on clinical evaluation is not always accurate, hence the need for diagnostic biomarkers. Nuclear medicine imaging is definitely one of them, allowing a qualitative and quantitative evaluation of in vivo functional integrity of monoaminergic (e.g., dopaminergic) pathways, brain metabolism and protein deposition and representing a unique window into these complex diseases. It has proved useful for early and accurate diagnosis, and possibly represents a valid biomarker of disease pathogenesis, progression and response to neuroprotective therapies. This review focuses on the nigrostriatal pathway dysfunctions (demonstrated with presynaptic dopamine positron emission tomography [PET] and single photon emission computed tomography [SPECT] ligands) that confirm a degenerative form of parkinsonism. In addition, 123Imetaiodobenzylguanidine cardiac scintigraphy can unveil postganglionic autonomic failure specifically encountered in Parkinson's disease. Brain 18F-fluorodeoxyglucose PET may also show a distinct hypometabolism for each degenerative form of parkinsonism. Since a few years ago, the proteins that aggregate in the brain of subjects with neurodegenerative diseases (tau and alpha-synuclein) can be evaluated in vivo by novel radioligands. These developments open new perspectives both as diagnostic tools and to understand the regional topography and burden of protein deposition on motor impairment and cognitive decline. The last part of the review proposes a strategic workup in the practical evaluation of a patient with parkinsonis