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DATSCAN
DaTSCAN for Diagnosis
Czech neurologist, Irena Rektorova explores the role
that DAT imaging can play in Parkinson’s diagnosis
Irena Rektorova is a
neurologist at the
1st Department of
Neurology, Masaryk
University and St Anne's
Hospital, Brno,
Czech Republic.
C
linico-pathological correlations in
patients diagnosed with idiopathic
Parkinson’s disease show that 10-25%
have an alternative diagnosis. Applying diagnostic
criteria increases accuracy, but even in specialised
movement disorder centres, up to 25% of patients will
be reclassified during follow-up visits.1
Current clinical criteria are based on clinicopathological correlation (PDS UK Brain Bank Criteria).2
They comprise:
• Evaluation of the cardinal motor symptoms of
Parkinson’s
• Assessment of exclusion criteria
• A favourable response to dopaminergic therapy.
However, early diagnosis may sometimes be difficult
because of the presence of atypical features and/or
an incomplete response to dopaminergic treatment.
The need for an accurate diagnosis
The EPDA Charter has acknowledged that people with
Parkinson’s have a right to receive an accurate
diagnosis. In 2003, this document became part of the
Global Declaration, Parkinson’s Disease – Moving
and Shaping, launched during the 7th World
Parkinson’s Day International Symposium in
Mumbai, India.
The need to receive an accurate diagnosis was further
supported by results of the Global Parkinson’s
Disease Survey in which the EPDA took an active role.
The study data demonstrated that “satisfaction with
the explanation of the condition at diagnosis” had a
significant impact on health-related quality of life.
Additional tests
Recently, several additional tests have been used
for identifying Parkinson’s, mostly for research
purposes. These clinical and auxiliary methods
include:
• Acute testing of dopaminergic responsiveness with
apomorphine
• Finger tapping
• Evaluation of cognitive function
• Depressive symptoms
• Visual contrast sensitivity
• Smell function
• Sleep abnormalities.
A variety of neuroimaging procedures based on
magnetic resonance imaging (MRI), positron
emission tomography (PET) and single photon
emission computed tomography (SPECT) have also
been used.3,4
DAT
Loss of striatal dopamine nerve terminal function, a
hallmark of neurodegenerative parkinsonism, is related
to decrease of dopamine transporter (DAT) density.
The DAT is a protein located on the presynaptic
dopaminergic nerve terminal. Imaging with specific
SPECT ligands for DAT enables in vivo demonstration
of striatal dopamine activity and provides a marker for
presynaptic neuronal degeneration (Figures 1 a, b; see
also the EPDA web page at http://www.epda.eu.com/
medInfo/DatSCAN/).1,3,4
There are several DAT ligands available for SPECT
scanning, including [99mTc]TRODAT, 123Iß-CIT or 123IFP-CIT.
DAT imaging and Parkinson’s: a summary
• Imaging with 123I-Ioflupane SPECT does not by itself provide a definite diagnosis in patients presenting with atypical features of the
condition and response to treatment. However, it offers valuable additional information in patients with uncertain diagnosis,
particularly early in the disease and can influence the clinician to make changes in clinical diagnosis and planned patient management.
• At present, routine visual or semi-quantitative assessment of images does not enable clinicians to differentiate between idiopathic
Parkinson’s disease and so-called ‘Parkinson plus’ degenerative syndromes, such as multiple system atrophy (MSA) or progressive
supranuclear palsy (PSP).
• FP-CIT SPECT can be of help in differentiating degenerative parkinsonism from drug-induced or psychogenic parkinsonism; young-onset
Parkinson’s disease from dopa-responsive dystonia; and dementia with Lewy bodies from Alzheimer’s disease.
• The technique may also have potential for detecting pre-clinical parkinsonism in people at risk of developing Parkinson’s and for
longitudinal monitoring of disease progression in treated people with Parkinson’s. However, these potential roles of DAT SPECT
imaging still need to be clarified and validated.
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DATSCAN
In the European Union FP-CIT (123I-Ioflupane) SPECT
(DaTSCAN) has received regulatory approval as a
diagnostic test to help differentiate essential
tremor from Parkinson’s disease in patients with
diagnostic uncertainty.
DaTSCAN is administered to the patients via slow
intravenous injection and a SPECT image is performed
3-6 hours after the injection. After its administration to
the patient, the concentration of radiopharmaceutical is
measured using a scanner called a gamma-camera.
SPECT imaging with DaTSCAN produces images of the
brain structures that are involved in the pathophysiology
of degenerative parkinsonian syndromes. The procedure
usually takes between 20 and 45 minutes depending on
the type of gamma camera used. More practical patient
information is available at http://www.epda.eu.com/
medInfo/DatSCAN/.
Image analysis typically uses quantitative region of
interest ratios and/or qualitative visual grading.
Results
Studies that aim to differentiate Parkinson’s from
essential tremor have shown that in patients with an
established clinical diagnosis, sensitivity of DAT SPECT in
the identification of nigrostriatal degeneration using
visual assessment has been as high as 97%. In patients
with uncertain parkinsonism, the specificity has been
demonstrated to be 100% (no false positive cases) with a
true negative rate of 92%.5 There is a good side specific
correlation between striatal DAT binding and global
measures of disease severity, and bradykinesia, posture,
gait, speech, facial expression, and rigidity in particular.
DAT binding declines with increasing disability.6
Although marked asymmetry in reduction of
putaminal DaTSCAN uptake is typical for Parkinson’s
when compared to other degenerative disorders with
parkinsonian syndrome, the method does not help to
differentiate between the neurodegenerative
parkinsonian disorders (Parkinson’s versus multiple
system atrophy (MSA), progressive supranuclear
palsy (PSP) etc.). Recently, the whole brain voxelbased analysis of DAT SPECT using statistical
parametric mapping was employed by Scherfler et al7,
who were able to correctly classify 95% of MSA
patients (presenting with parkinsonism) and
Parkinson’s patients. However, the technique has so
far been used for research purposes only.
Sometimes, it may be difficult to differentiate druginduced (caused by antipsychotic and centrally acting
antiemetic medications) or psychogenic parkinsonism
from Parkinson’s. In these cases, FP-CIT SPECT seems
to be really helpful – it will show normal DAT
1a
1b
References
Figure 1a:
In normal cases a
transverse slice through
the striatum shows a
“crescent” or “comma”
shaped putamen on
each side and a circular
"full stop" shaped
caudate anteriorly
Figure 1b:
Loss of uptake in the
putamen is regarded as
abnormal. Uptake in the
caudate is initially
preserved leaving just a
circular image
distribution. Normal scans may also be suggestive of
dopa-responsive dystonia in young patients (quite a
rare disorder that may present with parkinsonism in
addition to dystonia and occurs in childhood,
adolescence and young adulthood).1,4
When parkinsonism is preceded by dementia and/or
visual hallucinations, the diagnosis of dementia with
Lewy bodies is considered. In uncertain dementia
cases, DAT imaging may help to differentiate
Alzheimer’s disease (normal SPECT) from dementia
with Lewy bodies (pathological DAT distribution).8
Indeed, the loss of DAT binding in the asymptomatic
striatum of hemiparkinson patients and the
measurable rate of decline in binding with Parkinson’s
progression suggest that loss of dopamine terminals
can be detected by DAT imaging well before clinical
symptoms emerge. Recently, some non-motor
symptoms of Parkinson’s, such as hyposmia (impaired
smell function), REM sleep behavioural disorder,
depression or specific cognitive deficits have attracted
special attention, since they may also precede typical
motor symptoms of Parkinson’s.
We have found that functional imaging with 123I-FP-IT
SPECT might also be a sensitive tool for detecting
dopaminergic deficit associated with depressive
symptoms and specific cognitive dysfunction in
symptomatic Parkinson’s patients.9
Also of note, Ponsen et al10 found that 10% of
asymptomatic hyposmic relatives of Parkinson’s
patients had abnormal scans at baseline and
developed Parkinson’s at two years. However, so far we
have no effective treatment for at-risk individuals and
we do not know how to best identify those at risk for
Parkinson’s. Therefore, at the moment, widespread
pre-clinical DAT SPECT testing cannot be justified.
WINTER 2007
1. Scherfler C, Schwarz J,
Antonini A et al. Role of
DAT-SPECT in the
diagnostic work up of
Parkinsonism. Mov Disord
2007; 22(9): 1229-38.
2. Hughes AJ, Daniel SE,
Kilford L et al. Accuracy
of clinical diagnosis of
idiopathic Parkinson’s
disease. J Neurol
Neurosurg Psychiatry
1992; 55(3): 181-84.
3. Leenders KL, Salmon EP,
Tyrrel P et al. The
nigrostriatal dopaminergic
system assessed in vivo
by positron emission
tomography in healthy
volunteers and patients
with Parkinson’s disease.
Arch Neurol 1990; 47(12):
1290-98.
4. Marshall VL, Grosset DG.
The role of radiotracer
imaging in Parkinson
disease. Neurology 2005;
65(7): 1144-45.
5. Catafau AM and Tolosa E.
Impact of dopamine
transporter SPECT using
123I-Ioflupane on
diagnosis and
management of patients
with clinically uncertain
parkinsonian syndromes.
Mov Disord 2004; 19(10):
1175-82.
6. Pirker W. Correlation of
dopamine transporter
imaging with
parkinsonian motor
handicap. Mov Disord
2003; 18(Suppl 7): S43-51.
7. Scherfler C, Seppi K,
Donnemiller E et al. Voxelwise analysis of [123I]betaCIT SPECT differentiates
the Parkinson variant of
multiple system atrophy
from idiopathic
Parkinson's disease. Brain.
2005; 128(Pt 7): 1605-12.
8. O'Brien JT, Colloby S,
Fenwick J et al. Dopamine
transporter loss visualized
with FP-CIT SPECT in the
differential diagnosis of
dementia with Lewy
bodies. Arch Neurol 2004;
61(6): 919-25.
9. Rektorova I, Srovnalova
H, Kubikova R et al.
Striatal dopamine
transporter imaging
correlates with
depressive symptoms
and Tower of London task
performance in
Parkinson’s disease.
Mov Disord 2007; 22
(Suppl.16): S227.
10.Ponsen MM, Stoffers B,
Booij J et al. Idiopathic
hyposmia as a preclinical
sign of Parkinson’s
disease. Ann Neurol
2004; 56(2): 173-81.
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