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A.6.01.54
Dopamine transporter imaging with single-photon emission computed tomography (DaT-SPECT), using radiopharmaceutical ioflupane injection, is a neuroimaging modality being evaluated to improve the differential diagnosis of parkinsonian syndromes from non-parkinsonian tremor, as well as dementia with Lewy bodies from Alzheimer disease.
Parkinsonian Syndromes
Parkinsonian syndromes are a group of diseases that share similar cardinal signs, characterized by bradykinesia, rigidity, resting tremor, and gait disturbance. Parkinson disease (PD) is the most common cause of parkinsonism.
Despite the well-known symptoms of PD, diagnosis is challenging even for experienced clinicians, particularly in the early stages of the disease. In addition, other etiologies such as essential tremor, corticobasal degeneration, multiple system atrophy, progressive supranuclear palsy, vascular parkinsonism, and drug-induced parkinsonism can lead to a similar set of symptoms. One recent approach to improve the accuracy of clinical diagnosis of PD and other parkinsonian syndromes is to evaluate the integrity of dopaminergic pathways in the brain using dopamine transporter imaging with single-photon emission computed tomography (DaT-SPECT) imaging.
Dementia with Lewy Bodies
Dementia with Lewy bodies is a type of dementia characterized by parkinsonism, visual hallucinations, cognitive fluctuation, sleep disorders, and severe neuroleptic sensitivity. Dementia with Lewy bodies is the second most common form of degenerative dementia; Alzheimer disease, which can have similar symptoms at onset, is the most common.
Diagnosis can be challenging, particularly when patients have multiple comorbidities including cerebrovascular disease and/or Alzheimer disease. As with PD, dementia with Lewy bodies is characterized by the degeneration of nigrostriatal neurons; as such, DaT-SPECT is also proposed to differentiate dementia with Lewy bodies from Alzheimer disease.
DaT-SPECT
DaT-SPECT is based on the selective affinity of dopamine transporter (DaT) ligands for dopamine-synthesizing neurons, which allows visualization of deficits in the nigrostriatal dopaminergic pathway.
DaT ligands include iodine 123I-2β-carbomethoxy-3β-(4-iodophenyl) tropane (123I-β-CIT), which is a cocaine analogue with affinity for both dopamine and serotonin transporters. Intravenous 123I-β-CIT requires a delay between injection and scan of about 24 hours. Iodine-123 N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) is a fluoropropyl derivate of β-CIT that is selective for brain striatal DaT, but can also bind to the serotonin transporter. Intravenous 123I-FP-CIT can be injected 3 to 6 hours before the scan (DaTscan). Other SPECT ligands with affinity for dopamine transporter include technetium 99m (2β((N,N-bis(2-mercaptoethyl) ethylene diamino)methyl) and 3β-(4-chlorophenyl) tropane (99mTc-TRODAT-1).
Binding of ligands with an affinity for DaT ligands in the striatum is, in general, reduced in Parkinson disease (PD), genetic parkinsonism, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and multiple system atrophy. In contrast, striatal DaT ligand binding is expected to be within the normal range of Alzheimer disease, essential tremor, dystonic tremor, orthostatic tremor, drug-induced parkinsonism, and psychogenic parkinsonism.
Visualization of striatal dopamine transporter binding, through DaT-SPECT, permits assessment of presynaptic dopaminergic deficit. It is proposed that an abnormal DaT-SPECT scan supports the diagnosis of PD, dementia with Lewy bodies, or other neurodegenerative parkinsonian syndrome, while a normal DaT-SPECT scan in a symptomatic patient supports the diagnosis of a disease not affecting the nigrostriatal dopaminergic pathway.
Analysis of DaT-SPECT images can be visual, semiquantitative, or quantitative. In patients with PD, physical symptoms start after 30% to 50% of dopaminergic neurons have degenerated. Symptomatic patients with PD would be thus expected to have sufficient abnormality on DaT-SPECT for visual analysis to be adequate for interpretation. 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 for analysis and the development of an atlas for visual interpretation. Several research centers are developing quantitative and semiquantitative classification methods for the evaluation of DaT-SPECT images.
Anatomic variation in the brain, including vascular lesions, may interfere with the distribution of the iodine-123 tracer and could result in an abnormal scan. Dopamine agonists and levodopa may also affect DaT expression, which could influence the ability of DaT-SPECT to monitor the progression of disease unless these agents are discontinued prior to imaging. Patients with clinically diagnosed PD or dementia with Lewy bodies, who present with a normal DaT-SPECT scan, are referred to in the literature as having “scans without evidence of dopaminergic deficit.” While many of these patients are ultimately diagnosed with non-PD syndromes, a portion of patients with normal DaT-SPECT imaging are confirmed to have PD or dementia with Lewy bodies by the reference standard. In studies where clinical diagnosis is used as an endpoint, scans without evidence of dopaminergic deficit are present in 3% to 20% of PD patients. A study of patients clinically diagnosed with dementia with Lewy bodies found that 10% of these patients had normal scans. Further research may shed light on these cases.
In 2011, DaTscan™ (GE Healthcare) was approved by the U.S. Food and Drug Administration through a new drug application and is “indicated for striatal dopamine transporter visualization using single-photon emission computed tomography brain imaging to assist in the evaluation of adult patients with suspected parkinsonian syndromes. In these patients, DaTscan may be used to help differentiate essential tremor, from tremor due to parkinsonian syndromes (idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy). DaTscan is an adjunct to other diagnostic evaluations.” In 2022, DaTscan was approved for use in patients with suspected dementia with Lewy bodies.
In July 2021, aducanumab (Aduhelm™; Biogen), an amyloid beta-targeted antibody, was approved for the treatment of mild cognitive impairment or mild dementia due to Alzheimer disease. In July 2023, lecanemab-irmb (Leqembi®; Esai) received FDA approval as amyloid beta-targeted antibodies for the treatment of mild cognitive impairment or mild dementia due to Alzheimer disease. A third anti-amyloid antibody product, donanemab-azbt, was approved by the FDA in July 2024. Aducanumab was subsequently discontinued by the manufacturer in 2024. The safety and efficacy of aducanumab, lecanemab, or donanemab in patients with dementia with Lewy bodies has not been established as patients with any medical or neurological condition other than Alzheimer disease that might be a contributing cause to the subject's cognitive impairment were excluded from trials. The use of DaT-SPECT for the diagnosis, management, or surveillance of Alzheimer disease is considered out of scope for this policy.
Related medical policies are –
Dopamine transporter imaging with single-photon emission computed tomography may be considered medically necessary when used for individuals with:
clinically uncertain Parkinson disease; or
clinically uncertain dementia with Lewy bodies.
Use of dopamine transporter imaging with single-photon emission computed tomography is considered investigational for all other indications not included above.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
In July 2021, aducanumab (Aduhelm™; Biogen) received FDA accelerated approval and in July, 2023, lecanemab-irmb- (Leqembi; Esai) received FDA approval as amyloid beta-targeted antibodies for the treatment of mild cognitive impairment or mild dementia due to Alzheimer disease. A third anti-amyloid antibody product, donanemab-azbt, was approved by the FDA in July 2024. Aducanumab was subsequently discontinued by the manufacturer in 2024. The safety and efficacy of aducanumab, lecanemab, or donanemab in individuals with dementia with Lewy bodies has not been established as participants with any medical or neurological condition other than Alzheimer disease that might be a contributing cause to the subject's cognitive impairment were excluded from trials. The use of dopamine transporter imaging with single-photon emission computed tomography for the diagnosis, management, or surveillance of Alzheimer disease is considered out of scope for this policy.
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
11/15/2012: Approved by Medical Policy Advisory Committee.
11/06/2013: Policy reviewed; no changes.
09/22/2014: Policy reviewed; no changes.
07/13/2015: Code Reference section updated for ICD-10.
02/10/2016: Policy description updated. The following investigational indications were updated in the policy statement: "essential tremor" changed to "distinguishing between parkinsonian syndromes and essential tremor" and "dementia with Lewy bodies" changed to "distinguishing between dementia with Lewy bodies and Alzheimer disease." Investigative definition updated in policy guidelines section.
05/31/2016: Policy number A.6.01.54 added.
11/01/2016: Policy description updated. Policy statement unchanged.
10/31/2017: Policy description updated regarding DaT-SPECT, diagnosis of Parkinson disease, and diagnosis of DLB. Policy statement unchanged.
02/01/2019: Policy description updated regarding analysis of DaT-SPECT images in patients with Parkinson disease and dementia with Lewy bodies. Policy statement changed from investigational to medically necessary. Added medically necessary statements for the use of dopamine transporter imaging with single-photon computed tomography for individuals with clinically uncertain Parkinson disease or clinically uncertain dementia with Lewy bodies. The use of dopamine transporter imaging with single-photon emission computed tomography is considered investigational for all other indications. Policy Guidelines updated to define medically necessary. Coding table changed from investigational to medically necessary. Added ICD-10 procedure code C020FZZ and ICD-10 diagnosis codes G20 and G31.83.
10/24/2019: Policy reviewed; no changes.
12/19/2019: Code Reference section updated to make note of deleted CPT code.
01/22/2021: Policy description updated regarding Parkinsonian Syndromes and Dementia with Lewy Bodies. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Code Reference section updated to add CPT code 78803. Removed deleted CPT code 78607.
01/17/2022: Policy description updated regarding treatment for mild cognitive impairment or mild dementia due to Alzheimer disease. Policy statements unchanged.
09/30/2022: Code Reference section updated to revise description for ICD-10 diagnosis code G31.83, effective 10/01/2022.
12/13/2022: Policy reviewed; no changes.
12/21/2022: Code Reference section updated to revise the description for CPT code 78803, effective 01/01/2023.
09/28/2023: Code Reference section updated to add new ICD-10 diagnosis codes G20.A1, G20.A2, G20.B1, G20.B2, and G20.2, effective 10/01/2023.
11/15/2023: Policy reviewed. Policy statements unchanged. Policy Guidelines updated regarding the safety and efficacy of aducanumab or lecanemab in individuals with dementia with Lewy bodies.
01/13/2025: Policy description updated regarding DaTscan and medications used for treatment. Policy statements unchanged. Policy Guidelines updated regarding medications used for treatment. Code Reference section updated to remove deleted ICD-10 diagnosis code G20.
Blue Cross Blue Shield Association policy # 6.01.54
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.
Code Number | Description |
CPT-4 | |
78803 | Radiopharmaceutical localization of tumor, inflammatory process or distribution of radiopharmaceutical agent(s) (includes vascular flow and blood pool imaging, when performed); tomographic (SPECT), single area (eg, head, neck, chest, pelvis) or acquisition, single day imaging |
HCPCS | |
A9584 | Iodine I-123 ioflupane, diagnostic, per study dose, up to 5 millicuries |
ICD-10 Procedure | |
C020FZZ | Tomographic (Tomo) nuclear medicine imaging of brain using Iodine 123 (I-123) |
ICD-10 Diagnosis | |
G20.A1, G20.A2 | Parkinson's disease without dyskinesia |
G20.B1, G20.B2 | Parkinson's disease with dyskinesia |
G20.C | Parkinsonism, unspecified |
G31.83 | Neurocognitive disorder with Lewy bodies |
CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.