title: Molecular imaging of movement disorders.
abstract: Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington's disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette's syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson's disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.
authors.affiliation: Karlo J Lizarraga, Department of Neurology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors.forename: Karlo J
authors.initials: KJ
authors.lastname: Lizarraga
authors.affiliation: Karlo J Lizarraga, Department of Neurology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gorgulho
authors.affiliation: Karlo J Lizarraga, Department of Neurology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Karlo J Lizarraga, Department of Neurology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors.forename: Antonio A
authors.initials: AA
authors.lastname: De Salles
keywords: Dystonia; Essential tremor; Huntington’s disease; Movement disorders; Parkinsonism; Parkinson’s disease; Positron emission tomography; Single photon emission computerized tomography; Tourette’s syndrome