This recently-published article touches upon the four disorders in our group.
It’s a review article is about the use of DAT-SPECT — dopamine transporter SPECT scans — in diagnosing movement disorders. The authors have done a great job in reviewing all the data and then presenting understandable one-sentence conclusions, which I will now share…
For MSA, PSP, and CBD, the authors conclude: In “clinical practice, DAT-SPECTs are not useful in differentiating between PD and atypical parkinsonian syndromes (MSA, PSP, CBD).”
For DLB, the authors conclude: “DAT-SPECT cannot discriminate between PD/PD-dementia and DLB but can be very useful in the differential diagnosis between DLB and Alzheimer disease and can also be of some value in the differential diagnosis between DLB and vascular dementia.”
I remember learning back in 2008 that there was some type of legal issue with bringing SPECT scans to the US, though they are already widely used in Europe. SPECT imaging is important for some disorders (such as DLB) so it’s been frustrating that SPECT imaging is not approved for use in the US except in a few research settings. In 2008, there was a Q&A with Dr. Mark Stacy from Duke about this:
“Question: Why are SPECT scans not available in the US?
Answer: Because of corporate changes. GE bought Amersham (sp?). Amersham wanted to bring another type of SPECT agent to market. It’s been found that the drug that GE started to bring to market in Europe is easier to use. So it got slowed down bringing this agent to the US. GE is talking to the FDA about using European trial data.”
Recently, I asked Dr. Hubert Fernandez (on NPF’s “Ask the Doctor” Forum) about the status of bringing DAT-SPECT scans to the US. He first explained what a DAT ligand is and then answered the question:
“DAT (dopamine transporter) is a type of ligand (vehicle or medium) to conduct the SPECT scan. [It] ‘tags’ dopamine. It is important that the medium used is the correct one. Good examples are altropane or B-CIT….these are ligands that are used for SPECT scans to evaluate for PD.
Yes, for now, they DAT SPECT scans are not commercially available….but soon they they will be. One of the companies that manufactures a DAT ligand has received an ‘approvable letter’ from the FDA.”
OK, that’s probably all any of you want to know about DAT-SPECT imaging.
I’ve copied the article’s abstract and a few excerpts below, if any of you want to go further…
Robin
Journal of Neurology, Neurosurgery & Psychiatry. 2010 Jan;81(1):5-12.
The role of DAT-SPECT in movement disorders.
Kägi G, Bhatia KP, Tolosa E.
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
Dopamine transporter (DAT) imaging is a sensitive method to detect presynaptic dopamine neuronal dysfunction, which is a hallmark of neurodegenerative parkinsonism. DAT imaging can therefore assist the differentiation between conditions with and without presynaptic dopaminergic deficit.
Diagnosis of Parkinson disease or tremor disorders can be achieved with high degrees of accuracy in cases with full expression of classical clinical features; however, diagnosis can be difficult, since there is a substantial clinical overlap especially in monosymptomatic tremor (dystonic tremor, essential tremor, Parkinson tremor).
The use of DAT-SPECT can prove or excludes with high sensitivity nigrostriatal dysfunction in those cases and facilitates early and accurate diagnosis.
Furthermore, a normal DAT-SPECT is helpful in supporting a diagnosis of drug-induced-, psychogenic- and vascular parkinsonism by excluding underlying true nigrostriatal dysfunction.
This review addresses the value of DAT-SPECT and its impact on diagnostic accuracy in movement disorders presenting with tremor and/or parkinsonism.
PubMed ID#: 20019219 (see pubmed.gov for abstract only)
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Excerpts (in case you didn’t get enough already):
“Atypical parkinsonism (MSA, PSP, CBD)
The differentiation of atypical parkinsonian disorders from PD and between each other can raise considerable difficulties, particularly in early disease stages. This difficulty is reflected in clinicopathological studies where atypical parkinsonism accounts for a large part of misdiagnosis in PD. MSA, especially the parkinsonian subtype (MSA-P), can initially be very difficult to distinguish from PD before more specific symptoms like pronounced autonomic involvement, laryngeal stridor or lack of response to dopaminergic therapy occur. The same is true for the parkinsonian type of PSP (PSP-P) in which the more disease-specific signs and symptoms such as supranuclear vertical gaze palsy and imbalance with falls occur. Also, corticobasal degeneration (CBD) can initially easily be mistaken as PD because of its marked asymmetrical akinetic-rigid syndrome before apraxia, myoclonus and cognitive problems occur. A faster disease progression and a poor responsiveness to levodopa are common features in atypical forms and is explained by the pre- and postsynaptic dopaminergic degeneration. However,
some responsiveness to levodopa is not uncommon in early MSA-P or PSP-P. Previously, several studies have been carried out to establish the value of DAT-SPECT for the differentiation between PD and atypical PD. It has been shown that DAT-SPECT is sensitive in detecting presynaptic nigrostriatal degeneration in PD and atypical PD but not useful in the differential diagnosis of PD and atypical PD.”
“The amount and pattern of reduced striatal DAT binding in MSA have been shown to be in the range of PD with a more pronounced loss of DAT binding in the posterior putamen compared with the caudate to be typical for both. Asymmetry of DAT binding loss tends to be more pronounced in PD, and progression is faster in MSA compared with PD. PET and DAT-SPECT studies have shown that even clinically pure forms of MSA-C have some decrease in DAT binding but less compared with MSA-P or PD. This finding could be of some diagnostic impact in the differential diagnosis of MSA-C to idiopathic late-onset cerebellar ataxia (ILOCA). For separating MSA from PD,
other techniques such as voxelwise analysis of DAT-SPECT combined DAT/D2 receptor SPECT (IBZM, Epidepride,
Iodolisuride and IBF) or D2 PET (raclopride) can provide more information, although D2 receptor binding imaging methods are influenced by dopaminergic therapy and are therefore most useful in drug-naive patients. In drug-naive PD, D2 binding exceeds normal levels because of D2 receptor upregulation, whereas D2 binding is reduced in MSA early on because of postsynaptic degeneration. PET studies may contribute in the differential diagnosis of these entities. Striatal metabolic studies using FDG have shown to be of value in the differential diagnosis of atypical parkinsonism with hypermetoablism in the dorsolateral putamen in PD, bilateral hypometabolism in the putamen in MSA and hypometabolism of the brainstem and the middle frontal cortex in PSP. In CBD, unlike PSP or PD,
unilateral balanced (caudate/putamen) reduction in tracer uptake has been observed. In addition, cardiac imaging with MIBG has shown changes consistent with heart denervation in patients with PD which are not present in patients with MSA or PSP.”
“DAT-SPECT is also of limited value in the differential between PD and PSP, although PSP seem to have a more
symmetrical and profound DAT loss in the whole striatum, whereas in PD the posterior part of the putamen shows more loss of DAT density compared with the anterior part and the caudate.”
“DAT loss in CBD is in the same range as it is in PD and atypical PD, although DAT loss is much more asymmetrical and less pronounced than that seen in MSA and PSP. D2 SPECT seems to be of less value compared with MSA and PSP because D2 binding in CBD is more often in normal range than it is in MSA and PSP.”
“In conclusion, DAT-SPECT imaging does not help to differentiate between the neurodegenerative parkinsonian disorders. Hence, in clinical practice, DAT-SPECTs are not useful in differentiating between PD and atypical parkinsonian syndromes (MSA, PSP, CBD).”
“Dementia with Lewy bodies
In dementia with Lewy bodies (DLB), the extent of DAT loss in the striatum is in the range of PD and therefore not useful in the differential of PD and atypical PD. Neuropathological data suggest that 5060% of dementia in people aged 65 or older is due to Alzheimer disease, with a further 1020% each attributable to DLB or vascular cognitive impairment. Operationalised clinical diagnostic criteria have been agreed for all of these syndromes, but even in specialist research settings, they have limited accuracy when compared with neuropathological autopsy findings. Distinguishing Alzheimer disease from DLB is clinically relevant in terms of prognosis and appropriate treatment. A striking biological difference between DLB and Alzheimer disease is the severe nigrostriatal degeneration and consequent DAT loss that occurs in DLB, but not to any significant extent in Alzheimer disease. Several imaging
studies have shown that DAT imaging improves diagnostic accuracy with a sensitivity of 78% and a specificity of up to 94% in the separation between DLB and AD. Most of these studies have used clinical diagnosis as the gold standard, and the results have to be taken with some caution. One study with 20 cases with pathologically proven dementias (DLB/non-DLB) and with an FP-CIT SPECT at initial clinical workup showed that the DAT imaging substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone. Abnormal DAT imaging has therefore also been included as a suggestive feature in the DLB consensus criteria in 2005.”
“In conclusion, DAT-SPECT cannot discriminate between PD/PD-dementia and DLB but can be very useful in the differential diagnosis between DLB and Alzheimer disease and can also be of some value in the differential diagnosis between DLB and vascular dementia.”
