We prospectively evaluated the diagnostic contribution of 123I-FP-Cit (DAT) and 123I-IBZM (IBZM) SPECT in 29 patients with Parkinson's disease (PD) (
The atypical parkinsonian diseases (APD) multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are less common than Parkinson’s disease (PD), but since APD patients share the parkinsonian symptoms, the clinical distinction between PD and APD may be difficult in early phases [
Pre- and postsynaptic dopamine SPECTs of prospectively followed and age-matched patients with similar duration of PD, MSA, and PSP were evaluated. The diagnoses were assessed after several years of clinical followup and were entirely based on established clinical criteria. Additionally, the SPECT uptake at baseline and after 3 years in a group of age-matched healthy controls (HC) was used for comparison. The uptake patterns and change over time were measured using a ROI method. The aim of this study was to investigate if, or when in the course of the disease, the addition of 123I-FP-Cit (DAT) SPECT and 123I-IBZM (IBZM) SPECT may be of use in the diagnostic workup of early idiopathic parkinsonian diseases.
The study population in the present study was selected from a large, on-going longitudinal clinical research project (main clinical project; inclusion time January 1, 2004–April 30, 2009) and imaging study (SPECT substudy) on idiopathic parkinsonism [
Twenty-eight patients that fulfilled the established clinical criteria for APD after clinical followup in the above mentioned research project were included in the present study. Additionally, 29 age-matched PD patients fulfilling the criteria for clinical definite PD and 16 age-matched HCs were selected from the same research project.
In the present study, the DAT and IBZM SPECTs were done on a hybrid gamma-camera system, an Infinia Hawkeye (General Electric, Milwaukee, WI, USA) at baseline and at sequential timepoints up to 3 years from inclusion. Gender, age at SPECT and age at symptoms’ onset are shown in Table
The number of SPECTs in patients and HC, per SPECT timepoint.
SPECT year | PD | APD | HC | ||||
---|---|---|---|---|---|---|---|
DAT | IBZM | DAT | IBZM | DAT | IBZM | ||
Number of individuals (m/f) | 0 | 29 (18/11) | 29 (18/11) | 20 (11/9) | 18 (11/7) | 14* (6/8) | 14* (6/8) |
1 | 29 (18/11) | 29 (18/11) | 20 (13/7) | 18 (13/5) | 0 | 0 | |
3 | 22 (15/7) | 17 (11/6) | 10 (7/3) | 10 (7/3) | 16 (7/9) | 16 (7/9) | |
| |||||||
Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | ||
| |||||||
Age at first symptom |
|
|
|
|
|||
Age at SPECT | 0 |
|
|
|
|
|
|
1 |
|
|
|
|
|||
3 |
|
|
|
|
|
|
The clinical follow-up time of the patients that underwent DAT SPECT and/or IBZM SPECT at each time-point, per diagnosis.
SPECT year | Diagnosis |
|
Follow-up time, years |
---|---|---|---|
Mean ± SD | |||
0 | PD | 29 |
|
MSA | 7 |
|
|
PSP | 13 |
|
|
HC | 16 |
|
|
| |||
1 | PD | 29 |
|
MSA | 8 |
|
|
PSP | 12 |
|
|
| |||
3 | PD | 23 |
|
MSA | 7 |
|
|
PSP | 5 |
|
|
HC | 16 |
|
MSA: multiple system atrophy, PSP: progressive supranuclear palsy; PD: Parkinson’s disease. SPECT year 0: baseline, 1: 1 year followup, 3: 3 years followup, and SD: 1 standard deviation.
The regional ethics committee in Västerbotten, the local radiation safety committee, and the Swedish medical products agency approved the study. Recruited patients and HC were included after written and oral consent according to the declaration of World medical Association Declaration of Helsinki.
For this paper, patients having done at least one DAT SPECT and/or IBZM SPECT on the above mentioned hybrid gamma-camera were selected. In the main clinical project, a total of 15 patients fulfilled the diagnostic criteria for MSA [
Sixteen patients in the main clinical project fulfilled the diagnostic criteria for PSP [
Several of the APD patients additionally fulfilled the UK Parkinson’s Disease Society Brain Bank (UK PDSBB) diagnostic criteria for PD [
MSA and PSP patients with SPECT: diagnoses, gender, subtype, and SPECT per timepoint.
Gender | Diagnosis | Motor Subtype | SPECT timepoint | ||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | First year | Third year | |||||||
DAT | IBZM | DAT | IBZM | DAT | IBZM | ||||
MSA | Male | MSA prob. (+ |
PIGD | * | * | * | * | X | X |
Female | MSA prob. | PIGD | * | * | * | * | X | X | |
Male | MSA prob. | PIGD | * | * | X | X | X | X | |
Male | MSA prob. (+ |
PIGD | * | * | X | X | X | X | |
Male | MSA prob. | PIGD | * | * | X | X | X | ||
Female | MSA poss. (+ |
Indeterm. | X | X | X | X | |||
Female | MSA prob. | PIGD | X | X | |||||
Male | MSA prob. | PIGD | X | X | X | X | |||
Female | MSA prob. | PIGD | X | X | |||||
Male | MSA poss. (+ |
Tremor | X | X | X | X | |||
Male | MSA poss. (+ |
PIGD | X | X | X | X | X | X | |
Male | MSA prob. (+ |
Tremor | X | X | X | X | |||
| |||||||||
Total (male/female) | 12 (8/4) | 7 (4/3) | 6 (4/2) | 8 (7/1) | 8 (7/1) | 7 (5/2) | 5 (4/1) | ||
| |||||||||
PSP | Female | PSP poss. | Indeterm. | * | * | X | X | ||
Male | PSP poss. | PIGD | * | * | X | X | |||
Female | PSP prob. | PIGD | * | * | X | X | X | ||
Female | PSP PAGF | PIGD | X | X | X | X | X | ||
Male | PSP poss. | PIGD | X | X | X | X | X | X | |
Male | PSP prob. | PIGD | X | X | X | X | X | X | |
Male | PSP poss. | Indeterm. | X | X | X | X | X | ||
Female | PSP poss. (+ |
PIGD | X | X | X | ||||
Male | PSP poss. (+ |
PIGD | X | X | X | X | |||
Female | PSP prob. | PIGD | X | X | |||||
Male | PSP prob. | PIGD | X | X | |||||
Female | PSP prob. | PIGD | X | X | X | X | |||
Female | PSP prob. | PIGD | X | X | X | X | |||
Male | PSP poss. | Tremor | X | X | X | X | |||
Male | PSP prob. | PIGD | X | X | |||||
Female | PSP prob. | PIGD | X | ||||||
| |||||||||
Total (male/female) | 16 (8/8) | 13 (7/6) | 12 (7/5) | 12 (6/6) | 10 (6/4) | 3 (2/1) | 5 (3/2) |
The patients fulfilled the established criteria for diagnosis of MSA according to Gilman et al., 1999 [
Clinical data on patients with SPECT shown per SPECT time-point.
PD | MSA | PSP | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SPECT |
DAT | IBZM | DAT | IBZM | DAT | IBZM | |||||||
|
|
|
|
|
|
||||||||
Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | ||
Age | 0 | 74.4 | 72.8–76.0 | 74.5 | 72.9–76.1 | 71.3 | 60.7–81.9 | 69.9 | 57.4–82.3 | 75.9 | 71.3–80.6 | 75.3 | 70.4–80.2 |
1 | 75.5 | 73.9–77.1 | 75.5 | 73.9–77.1 | 76.3 | 73.3–79.2 | 76.2 | 73.4–79.0 | 74.3 | 70.5–78.1 | 73.8 | 69.2–78.5 | |
3 | 77.3 | 75.5–79.1 | 77.5 | 75.8–79.3 | 78.7 | 75.9–81.5 | 77.5 | 74.7–80.3 | 72.5 | 61–84 | 75.9 | 68.1–83.7 | |
Duration | 0 | 1.5 | 1.2–1.8 | 1.6 | 1.2–1.9 | 1.3 | 0.6–2.0 | 1.5 | 0.7–2.3 | 1.9 | 1.1–2.7 | 1.8 | 1.0–2.7 |
1 | 2.6 | 2.3–3.0 | 2.6 | 2.3–3.0 | 3.1 | 2.2–4.0 | 3.0 | 2.1–3.9 | 2.9 | 1.9–3.9 | 2.8 | 1.6–4.0 | |
3 | 4.5 | 4.1–4.9 | 4.4 | 3.9–4.8 | 5.1 | 4.1–6.2 | 5.5 | 4.1–6.8 | 4.6 | 0.3–9.0 | 5.0 | 3.1–6.9 | |
LED | 0 | 0.0 | 0.0–0.0 | 0.0 | 0.0–0.0 | 0.0 | 0.0–0.0 | 0.0 | 0.0–0.0 | 0.0 | 0.0–0.0 | 0.0 | 0.0–0.0 |
1 | 335 | 273–397 | 335 | 273–397 | 312 | 160–465 | 312 | 160–465 | 340 | 157–522 | 287 | 108–467 | |
3 | 507.4 | 419–595 | 439 | 352–526 | 582 | 404–761 | 620 | 398–842 | 708 | 202–1214 | 515 | 92–938 | |
| |||||||||||||
Median | Min–Max | Median | Min–Max | Median | Min–Max | Median | Min–Max | Median | Min–Max | Median | Min–Max | ||
| |||||||||||||
UPDRS-III | 0 | 27 | 8–46 | 27 | 8–46 | 22 | 9–48 | 22.5 | 21–48 | 30 | 12–64 | 29 | 12–64 |
1 | 25 | 3–48 | 25 | 3–48 | 24 | 14–44 | 24 | 14–44 | 36† | 18–54 | 35.5†† | 18–54 | |
3 | 25 | 3–48 | 23 | 6–54 | 41* | 31–65 | 41.0* | 33–49 | 48† |
|
43†† | 38–55 | |
| |||||||||||||
UPDRS% Change during first year |
( |
( |
( |
||||||||||
| |||||||||||||
H&Y | 0 | 2 | 1–3 | 2 | 1–3 | 2 | 2–5 | 2 | 2–5 | 2.5 | 1.5–5 | 2.5 | 1.5–5 |
1 | 2 | 1–3 | 2 | 1–3 | 2 | 2–3 | 2 | 2–3 | 2.75† | 1.5–5 | 2.75†† | 2–5 | |
3 | 2 | 2–4 | 2 | 2–3 | 3* | 2–5 | 3* | 2–4 | 4† | 2–5 | 2.5† | 2–5 | |
ADL% | 0 | 90 | 60–95 | 90 | 60–95 | 90 | 60–100 | 90 | 60–100 | 80 | 70–95 | 80 | 70–95 |
1 | 90 | 60–95 | 90 | 60–95 | 90 | 70–90 | 90 | 70–90 | 80† | 50–95 | 80†† | 50–95 | |
3 | 90 | 40–100 | 90 | 40–100 | 80* | 40–80 | 80* | 70–80 | 70 | 30–90 | 70 | 30–90 |
Mann-Whitney
PD patients were selected if (i) the diagnostic criteria of clinically definitive PD [
HCs with ages within the age range of the patients and with a clinical followup time of 5 years were selected. These had at least one DAT SPECT or IBZM SPECT at baseline as well as follow-up SPECTs after 3 years. The selection resulted in a group of 16 individuals (m/f 7/9). HCs were clinically evaluated at baseline and followup according to a detailed neurological and physical protocol. None of the HCs had any clinical signs of parkinsonism or other clinical signs of neurological disease at baseline or followup. The number of HC and age at SPECT is shown in Table
The clinical data on the selected patients in this study are presented in Table
Median UPDRS-III sub score in the PD, MSA and PSP patients at baseline, and after 1 and 3 years of follow-up.
As shown in Table
Drop-off in the APD group was attributable to inability to sustain temporary pharmacological withdrawal, disease severity, (making it too demanding to lie still in the SPECT camera) refusal, or death. There were no statistical differences between the APD patients with and without SPECT at the third year follow-up timepoint with respect to disease severity (as measured with UPDRS III points and H&Y score), neither age at onset or age at inclusion. The APD patients remaining in the SPECT group at followup (i.e., individuals with either DAT- or IBZM SPECT or both,
In PD, symptoms are typically asymmetrical in the early phase of the disease, reflecting an asymmetrical degree of dopamine degeneration between hemispheres, with the most affected side in the brain contralateral to the most affected limb or body-half. Still, symptoms at presentation were symmetrical or without any specific laterality (e.g., global bradykinesia as the main presenting symptom) in half of the patients in this study. The majority of the APD patients presented with postural instability and gait difficulty (PIGD) motor subtype at baseline without specific laterality (Table
PD and APD patients with SPECT: clinical laterality versus DAT uptake in putamen and clinical subtype at baseline. The ratio between left and right DAT SPECT uptake in putamen at baseline.
Clinical laterality at baseline | |||||
---|---|---|---|---|---|
No reported laterality | Left | Right | Symmetrical | Total | |
Side with lowest DAT uptake in putamen | |||||
Right | 1 | 11 | 3 | 11 |
|
Left | 5 | 0 | 10 | 8 |
|
Total |
|
|
|
|
|
Parkinsonism type | |||||
PIGD | 6 | 5 | 6 | 15 |
|
Tremor | 0 | 1 | 6 | 3 |
|
Indeterminate | 0 | 5 | 1 | 1 |
|
Total |
|
|
|
|
|
PIGD: postural instability and gait difficulty and 95% CI: 95% confidence interval.
Parkinsonism motor subtype |
|
Mean left/right ratio | 95% CI |
---|---|---|---|
PIGD | 32 | 1.00 | 0.95–1.05 |
Tremor | 10 | 0.93 | 0.82–1.03 |
Indeterminate | 7 | 1.15 | 0.99–1.30 |
Total |
|
|
|
PIGD: postural instability and gait difficulty and 95% CI: 95% confidence interval.
In patients with the PIGD subtype of parkinsonism, the mean difference between the DAT uptake in the right and left putamens was very small at baseline (Table
The SPECT examination timepoints coincided with the clinical evaluation at baseline and reevaluation after 1 and 3 years (HCs were only examined at baseline and after 3 years). The SPECT studies of the patients were retrospectively related to the prospectively updated clinical diagnosis.
All baseline SPECTs in patients were performed in drug naïve state (i.e., no dopaminergic drugs). The follow-up SPECT examinations were made in “pharmacological off” state: 123I-FP-Cit SPECT (DAT) was made after a 12 h withdrawal of possible interacting drugs, and the IBZM SPECT was made after a withdrawal of 6 T1/2 for each possible interacting drug. Not less than 7 days and not more than 3 months were allowed between the DAT SPECT and the IBZM SPECT at each survey timepoint.
The DAT SPECT was performed 180 minutes after an intravenous bolus dose of 185 MBq of 123I-FP-Cit, and the IBZM SPECT was performed 90 minutes after an intravenous bolus dose of 185 MBq of 123I-IBZM. For thyroid protection, an oral dose of 200 mg potassium perchlorate was given before and after SPECT. The effective dose for 123I-FP-Cit is 4.3 mSv and 6.3 mSv for 123I-IBZM. The effective dose from the low dose CT of the head is 0.1 mSv.
The specifications of the two-headed Infinia Hawkeye gamma-camera and the collection of image data were the same as was described in an earlier publication [
Evaluation of the dopamine SPECT examinations of the patients and HC were made blinded to clinical diagnosis and clinical condition. Semiquantitative evaluation of the SPECT images was made by one of the authors (SJM) using an earlier described ROI method using the occipital region as reference [
Continuous data are presented as mean with a 95% confidence interval unless otherwise is stated. Ordinal data is presented as median with minimum and maximum values. For continuous data comparison ANOVA was used with the Bonferroni post-hoc test when comparing more than 2 groups. The Mann Whitney
The mean of right and left DAT and IBZM uptake in patients and HC is presented in Table
DAT and IBZM SPECT uptake in HC, PD, MSA, and PSP by region and SPECT timepoint.
Baseline | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HC |
PD |
MSA |
PSP |
Mann-Whitney | ||||||||||
Mean | 95% CI | Mean | 95% CI | PD |
Mean | 95% CI | MSA |
Mean | 95% CI | PSP |
PD |
PD |
MSA | |
|
|
|
|
|
|
|||||||||
Caudate DAT | 4.47 | 4.14–4.80 | 3.18 | 2.94–3.42 | <0.001 | 3.19 | 2.43–3.95 | <0.001 | 2.83 | 2.50–3.15 | <0.001 | ns | ns | (0.075) |
Putamen DAT | 4.09 | 3.83–4.36 | 2.47 | 2.32–2.63 | <0.001 | 2.74 | 2.16–3.31 | <0.001 | 2.31 | 2.01–2.61 | <0.001 | ns | ns | (0.075) |
Striate DAT | 4.27 | 3.98–4.56 | 2.80 | 2.61–2.98 | <0.001 | 2.95 | 2.31–3.59 | <0.001 | 2.55 | 2.25–2.85 | <0.001 | ns | ns | (0.063) |
| ||||||||||||||
Striate IBZM | 1.82 | 1.74–1.91 | 1.79 | 1.73–1.85 | 1.00 | 1.84 | 1.66–2.03 | 1.00 | 1.79 | 1.70–1.88 | 1.00 | ns | ns | ns |
Year 1 | |||||||||
---|---|---|---|---|---|---|---|---|---|
PD |
MSA |
PSP |
Mann-Whitney | ||||||
Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | PD |
PD |
MSA | |
|
|
| |||||||
Caudate DAT | 2.96 | 2.70–3.22 | 3.58 | 3.13–4.02 | 2.78 | 2.43–3.13 | 0.024 | ns | 0.007 |
Putamen DAT | 2.28 | 2.13–2.43 | 2.56 | 2.25–2.87 | 2.17 | 1.89–2.46 | (0.060) | ns | 0.025 |
Striate DAT | 2.59 | 2.40–2.79 | 3.02 | 2.67–3.38 | 2.45 | 2.15–2.76 | 0.029 | ns | 0.014 |
| |||||||||
Striate IBZM | 1.73 | 1.67–1.78 | 1.88 | 1.71–2.05 | 1.64 | 1.49–1.78 | (0.051) | ns | 0.026 |
Year 3 | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HC |
PD |
MSA |
PSP |
Mann-Whitney | ||||||||||
Mean | 95% CI | Mean | 95% CI | PD |
Mean | 95% CI | MSA |
Mean | 95% CI | PSP |
PD |
PD |
MSA | |
|
|
|
|
|
|
|||||||||
Caudate DAT | 4.35 | 4.06–4.63 | 2.83 | 2.55–3.12 | <0.001 | 2.70 | 2.28–3.12 | <0.001 | 2.38 | 1.80–2.96 | <0.001 | ns | ns | ns |
Putamen DAT | 3.96 | 3.71–4.21 | 2.13 | 1.97–2.30 | <0.001 | 2.03 | 1.80–2.26 | <0.001 | 1.92 | 1.50–2.34 | <0.001 | ns | ns | ns |
Striate DAT | 4.14 | 3.88–4.40 | 2.45 | 2.24–2.67 | <0.001 | 2.33 | 2.03–2.63 | <0.001 | 2.12 | 1.64–2.61 | <0.001 | ns | ns | ns |
| ||||||||||||||
Striate IBZM | 1.70 | 1.65–1.75 | 1.66 | 1.61–1.72 | 1.0 | 1.92 | 1.71–2.13 | 0.003 | 1.70 | 1.57–1.83 | 1.00 | 0.002 | ns | 0.016 |
Left and right uptake ratios are averaged.*One way ANOVA, Bonferroni post-hoc test
Mean DAT uptake ratios in PD, MSA, and PSP patients and healthy controls in (a) caudate, (b) putamen, (c) striate. Left and right uptake ratios are averaged. Whiskers represent 95% confidence interval of mean.
Mean IBZM uptake ratio in PD, MSA, and PSP patients and healthy controls in the striate. Left and right uptake ratios are averaged. Whiskers represent 95% confidence interval of mean. SPECT: single photon emission computed tomography; IBZM: D2/D3 dopamine receptor imaging with 123I-IBZM; MSA: multiple system atrophy, PSP: progressive supranuclear palsy; PD: Parkinson’s disease; Healthy: healthy controls.
At the first year followup, mean DAT and IBZM uptake ratios were significantly higher in MSA compared to PSP,
The third year, the mean DAT uptake was significantly higher in HC compared to the patients,
In Table
There were no significant differences in DAT uptake between baseline and followup after 1 year in MSA or PSP patients. In MSA patients, the averaged putamen uptake as well as the striate DAT was significantly lower at the third year followup compared to baseline,
In the PSP patients, the DAT uptake in the putamen at the 3-year follow-up was low compared to baseline; however, the difference did not reach significance. In the group of HCs the mean DAT uptake was not significantly different at baseline compared to 3-year followup.
When considering the whole group of APD patients, the mean DAT uptake in the caudate was significantly lower at the 3-year followup (2.6, 2.31–2.90, and
In Table
No significant change in IBZM uptake was observed after one year compared to baseline in patients with PD, MSA, and PSP.
When comparing the IBZM uptake at 3-year followup with the uptake at baseline, the IBZM uptake was significantly lower in patients with PD,
In PD the relative reduction in the striate DAT uptake at the first year followup was significantly more pronounced compared to HC,
Yearly change (%) in uptake between baseline and 1-year followup: DAT and IBZM ratios.
|
Mean | 95% CI | Mann-Whitney | ||||||
---|---|---|---|---|---|---|---|---|---|
HC versus PD | HC versus MSA | HC versus PSP | PD versus MSA | PD versus PSP | MSA versus | ||||
|
|
|
|
|
|
||||
Contralateral∞ | |||||||||
|
|||||||||
PD | 27 | −8.0 | −11.6–−4.5 | 0.005 | ns | 0.006 | 0.013 | ns | 0.017 |
MSA | 4 | 5.3 | −4.8–15.4 | ||||||
PSP | 8 | −11.8 | −21.0–−2.7 | ||||||
HC* | 14 | −0.5 | −2.2–1.3 | ||||||
|
|||||||||
PD | 27 | −6.5 | −10.8–−2.2 | ns | ns | 0.006 | ns | ns | ns |
MSA | 4 | −3.3 | −14.4–7.8 | ||||||
PSP | 8 | −13.9 | −23.0–−4.7 | ||||||
HC* | 13 | −1.0 | −2.9–0.8 | ||||||
|
|||||||||
PD | 27 | −7.2 | −10.6–−3.9 | 0.006 | ns | 0.004 | ns | ns | 0.042 |
MSA | 4 | 0.8 | −10.4–11.9 | ||||||
PSP | 8 | −12.8 | −21.6–−4.0 | ||||||
HC* | 14 | −0.7 | −2.4–0.9 | ||||||
Ipsilateral∞ | |||||||||
|
|||||||||
PD | 27 | −7.7 | −12.1–−3.4 | 0.045 | ns | 0.006 | 0.045 | ns | ns |
MSA | 4 | 4.3 | −12.3–21.0 | ||||||
PSP | 8 | −11.9 | −24.8–1.1 | ||||||
HC* | 14 | −0.5 | −2.2–1.3 | ||||||
|
|||||||||
PD | 27 | −8.5 | −12.0–−4.9 | 0.006 | ns | 0.005 | ns | (0.054) | ns |
MSA | 4 | −8.2 | −28.0–11.5 | ||||||
PSP | 8 | −13.4 | −26.9–0.1 | ||||||
HC* | 13 | −1.0 | −2.9–0.8 | ||||||
|
|||||||||
PD | 27 | −8.3 | −11.7–−5.0 | 0.002 | ns | 0.004 | ns | ns | ns |
MSA | 4 | −1.9 | −19.2–15.4 | ||||||
PSP | 8 | −12.8 | −25.5–0.0 | ||||||
HC* | 14 | −0.7 | −2.4–0.9 | ||||||
| |||||||||
Mean | |||||||||
|
|||||||||
PD | 29 | −3.1 | −6.2–0.0 | ns | ns | ns | ns | ns | ns |
MSA | 5 | −4.7 | −8.7–−0.7 | ||||||
PSP | 8 | −8.3 | −19.8–3.3 | ||||||
HC* | 14 | −2.1 | −3.5–−0.8 |
∞Patients with same laterality as baseline.
At baseline the UPDRS-III score and the DAT uptake were significantly correlated in PD patients (Pearson’s correlation coefficients for contralateral caudate: −0.390,
The LED index was significantly correlated to presynaptic uptake in PD patients at baseline (mean caudate:
Age at the time of SPECT was not significantly correlated with either DAT or IBZM uptake, except in PD patients where, at the third year followup, a positive linear relationship was seen between age and the IBZM uptake (Pearson’s correlation coefficient: 0.567,
In this study, we found no significant differences between PD and APS in presynaptic uptake at baseline, which is in line with previous studies. However after one year, PD and PSP patients had significantly lower DAT uptake in contralateral striate compared to MSA patients. After three years the difference was also significant for the ipsilateral striatum. A lower presynaptic uptake in PSP compared to MSA was also seen in a recent positron emission tomography (PET) study using 18F-FP-Cit [
Typically, the presynaptic reduction rate was higher in patients than in HC but the difference between APS and PD was small. In the present study, most of the PD patients presented with a PIGD subtype and the disease onset was late, factors which are associated with a higher rate of progression compared to early onset and tremor dominant PD [
The decrease in DAT uptake was most pronounced in PSP patients during the first year, and the decrease slope was similar between the first and third year followup (the difference in DAT uptake ratios between baseline and the third year may not have reached significance due to the large variance at baseline and a small number of PSP patients at the last followup). The mean DAT uptake in especially the caudate in the group of MSA patients tended to increase during the first year after diagnosis. This finding is hard to explain. However, after 3 years the DAT uptake in MSA patients was within levels of the uptake in PD and PSP patients.
The correlation between the UPDRS-III score and presynaptic uptake, seen at baseline in PD patients but not after initiation of medication, is probably explained by the fact that follow-up clinical examination was made in “pharmacological on” state. Supposedly, due to less pharmacological alleviation of symptoms, there was still a correlation between the UPDRS-III score and the DAT uptake in APD patients at followup. The correlation between a longer disease duration and a less decrease in DAT uptake is in line with earlier studies as is reviewed by Brücke et al. [
There were no significant differences in IBZM uptake between patients and HC at baseline, nor between HC and PD and PSP patients after 3 years. In the group of MSA patients, the mean IBZM uptake was significantly higher compared to the PD and PSP patients as well as compared to the group of HCs at followup, which will be discussed further in the following.
A slightly unexpected finding, to our knowledge not reported elsewhere, was that the relative annual decrease rate in IBZM uptake was not significantly different between HCs and patients during the first follow-up year. The HCs in this material are followed clinically and shows no signs of parkinsonism over time and the decline in presynaptic uptake was not excessive, thus probably reflecting an essentially age dependent decline.
In previous studies, APD patients have typically exhibited lower dopamine receptor uptake compared to PD patients [
A persistent relatively high IBZM uptake despite initiated medication with L-Dopa somewhat contrast to the upregulation of postsynaptic receptors seen in untreated PD patients [
There are some important limitations to this study. First of all, the patient groups are small, and statistics have to be interpreted with caution. The drop-off in the APD group is substantial at the 3-year followup. However, we did not find any obvious systematic bias in the drop-off in this study, since there were no significant differences in clinical parameters between the patients presented here and the group of patients without follow-up SPECT. Secondly, we are aware of the problems with diagnostic accuracy of different forms of idiopathic parkinsonism [
In this study, the discriminative ability of 123I-FP-Cit SPECT was high in the first phase of symptomatic and untreated idiopathic parkinsonian disease against healthy individuals in the same age since PD, MSA, and PSP patients all had significantly lower DAT uptake compared to HCs both at baseline and at the followup. The DAT uptake was overlapping between patients with PD, MSA, and PSP; thus 123I-FP-Cit SPECT could not reliably separate these diagnostic entities at an early stage of disease. The PSP patients in this study did not have faster decrease in DAT uptake compared to PD patients. However, compared to MSA patients, the decrease rate in PSP during the first year was faster in the contralateral caudate and entire striatum, and the mean DAT uptake in caudate, putamen, and striatum was lower in PSP compared with MSA patients one year after baseline, thus offering a possibility to discriminate between the two diagnoses.
In this study, the discrimination between PD, MSA, and PSP was not possible with 123I-IBZM SPECT in the newly diagnosed, early and untreated stage of clinical disease, since the uptake in PD, MSA and PSP patients was overlapping. Neither were there any difference in IBZM uptake between PD and PSP patients after 1- and 3-year of followup. However, during the follow-up period in this study, the IBZM uptake remained relatively high in the MSA patients despite poor response to medication. In this study, the tendency towards a difference in DAT and IBZM uptake between patients with MSA and PSP was seen over the first years of clinical disease, a finding that may contribute to the discrimination between these diagnoses.
The authors declare that there are no conflict of interests.
The work was supported by grants from Västerbotten County Council (ALF), the Medical Faculty of Umeå University, and the Swedish Medical Research Council, the Parkinson Foundation in Sweden, and King Gustaf V’s and Queen Victoria’s Foundation.