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Parkinsonian syndromes are a group of diseases that share similar cardinal signs, characterized by bradykinesia, rigidity, resting tremor and gait disturbance. Parkinson’s disease (PD) is the most common cause of parkinsonism; however, diagnosing PD in early stage of the disease can be difficult. In addition other etiologies such as essential tremor, corticobasal degeneration, multisystem atrophy, progressive supranuclear palsy, vascular parkinsonism, and drug-induced parkinsonism can lead to a similar set of symptoms. Even in specialized movement disorders centers, up to 25% of patients may be misclassified, and some patients, such as those with essential tremor who have been diagnosed with PD, may be erroneously treated. This has led to the development of additional tests to improve the accuracy of clinical diagnosis of PD and other parkinsonian syndromes. One recent approach is to evaluate the integrity of dopaminergic pathways in the brain with DAT-SPECT. 

DAT-SPECT detects presynaptic dopaminergic deficit by measuring dopamine transporter (DAT) binding. In general, striatal DAT binding is reduced in PD, genetic parkinsonism, dementia with Lewy bodies (DLB), corticobasal degeneration, progressive supranuclear palsy, and multiple system atrophy, while striatal DAT binding is in the normal range in Alzheimer’s disease, essential tremor, dystonic tremor, orthostatic tremor, drug-induced parkinsonism, psychogenic parkinsonism, and vascular parkinsonism. It is proposed that an abnormal DAT-SPECT supports the diagnosis of PD or other neurodegenerative parkinsonian syndrome (multisystem atrophy, progressive supranuclear palsy), while a normal DAT-SPECT in a symptomatic patient increases the likelihood of a disease not affecting the nigrostriatal dopaminergic pathway. 

Due to the degeneration of nigrostriatal neurons in DLB, DAT-SPECT is also proposed to differentiate DLB from Alzheimer’s disease. Some note a severe sensitivity to neuroleptics (potentially life-threatening) in patients with DLB. However, newer agents are usually well-tolerated, and patients with DLB may also respond to the cholinesterase inhibitors that are more commonly used to treat Alzheimer’s disease.

Analysis of DAT-SPECT images can be visual or semi-quantitative. Since patients typically do not become symptomatic before a substantial number of striatal synapses have degenerated, visual interpretation of the scan is thought to be sufficient for clinical evaluation. A variety of methods are being tested to improve the validity and reliability of ratings, including commercially available software to define the region of interest (ROI) for semi-quantitative analysis and the development of an atlas for visual interpretation. Semiquantitative interpretion may aid visual interpretation and, if performed rigorously, may increase diagnostic accuracy; however, interobserver variability tends to be high with manual ROI based semi-quantification. Semi-quantitative analysis also requires normal control values and varies across imaging systems.

Dopamine transporter ligands include 123I-β-CIT, 123I-FP-CIT, and 99mTc-TRODAT-1. (2) 123I-β-CIT requires a delay between injection and scan of about 24 hours. 123I-FP-CIT (DaTscan) is a fluoropropyl derivate of β-CIT that can be injected 3-6 hours before the scan.

DaTscan (GE Healthcare) has been in use in Europe since 2000 with a diagnostic indication for use in parkinsonian patients and with expanded use since 2006 in patients suspected of DLB. DaTscan was approved by the U.S. Food and Drug Administration (FDA) in 2011 and is “indicated for striatal dopamine transporter visualization using single photon emission computed tomography (SPECT) brain imaging to assist in the evaluation of adult patients with suspected parkinsonian syndromes (PS). In these patients, DaTscan may be used to help differentiate essential tremor from tremor due to PS (idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy). DaTscan is an adjunct to other diagnostic evaluations.”

Related medical policies are –

• Miscellaneous Applications of Positron Emission Tomography (PET)
• Deep Brain Stimulation

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