Secondary Logo

Journal Logo

The Impact of DaTscan in the Diagnosis of Parkinson Disease

Gayed, Isis, MD*; Joseph, Usha, MD*; Fanous, Mina, MD*; Wan, David, MD*; Schiess, Mya, MD; Ondo, William, MD; Won, Kyoung-Sook, MD

doi: 10.1097/RLU.0000000000000766
Original Articles
Open

Purpose The aim of this study was to evaluate the impact of DaTscan in a heterogeneous group of patients with movement disorders as well as the degree of confidence in scan findings between different readers.

Procedures A retrospective evaluation of consecutive patients who underwent DaTscan during 1 year was performed. The patients’ demographics, symptoms, duration, clinical diagnosis, and medications were collected. The scan findings were categorized by 2 blinded observers on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each of the caudate heads and putamina separately. A correlation of the scan findings with the clinical symptoms and diagnosis as well as interobserver agreement was performed. Disagreement was considered when a difference greater than 2 in more than 1 area of the basal ganglia was recorded. Descriptive statistics and κ test for interobserver agreement were used for data analysis.

Results Fifty-seven patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of Parkinson disease (PD) was certain in 26 and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). In 31 patients with uncertain diagnosis, 15 (48%) had markedly abnormal scans, 5 (16%) had mild abnormalities, and 11 (36%) had normal scans. Each of the sensitivity and positive predictive value of DaTscan in patients who had certain clinical diagnosis of PD (26 patients) is 92%. Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (κ = 0.82). There was also a good correlation with laterality of symptoms in 32 (82%) of 39 positive studies.

Conclusions Markedly abnormal DaTscan is confirmed as the diagnostic pattern for PD. This pattern helps confirm the diagnosis in patients with unclear clinical diagnosis. Good interobserver agreement is easily obtained in reading DaTscans.

From the *Nuclear Medicine Section, Department of Diagnostic and Interventional Imaging, and †Department of Neurology, Medical School at Houston Health Science Center, Houston, TX; and ‡Department of Nuclear Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea.

Received for publication October 31, 2014; revision accepted January 13, 2015.

Conflicts of interest and sources of funding: none declared.

Reprints: Isis W. Gayed MD, Department of Radiology, University of Texas-Houston, Medical School, 6431 Fannin, Suite 2.130b, Houston, TX 77030. E-mail: Isis.W.Gayed@uth.tmc.edu.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Since first recognized by James Parkinson in 1817, Parkinson disease (PD) has no clear diagnostic test, although it is the second most common neurodegenerative disorder.1,2 Physicians diagnose it clinically based on the presence of 2 or more cardinal signs: tremor, bradykinesia, and rigidity.3,4

Diagnosis of Parkinson disease may not be straightforward, and may be late,5 due to overlap of symptoms with other movement disorders, including essential tremor (ET), dystonic tremor, and other parkinsonian syndromes.6–8 Furthermore presence of nonmotor symptoms9 and inconsistent response to Parkinson medication10,11 makes the diagnosis more difficult, and sometimes wrong or inconclusive. Many studies have found a high rate of misdiagnosis, even among movement disorder specialist, leading to wrong prognostication and management.12–20 That, in addition to avoidance of medication adverse effects and cost, makes the need for a more accurate test indispensable.

DaTscan has been in use in Europe since 2000, and the Food and Drug Administration has approved it in the United States in 2011. The scan allows visualization of dopamine transporter (DaT) function in the striatum (caudate and putamen) using SPECT brain imaging. 123I-FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β {4-iodophenyl} nortropane), a radiopharmaceutical derived from cocaine, binds with high affinity to presynaptic DaT in the striatum.21 The dopamine reuptake inhibitor GBR 12909 inhibits binding of 123I-ioflupane to the striatum.22,23 However, the effect of different anti-Parkinson medications on DaTscan is a question that remains to be answered.

An abnormal scan suggests a diagnosis of nigrostriatal neurodegenerative parkinsonian syndrome (PD, multisystem atrophy, progressive supranuclear palsy, corticobasal degeneration, or Lewy body disease), whereas a normal scan suggests nondegenerative parkinsonism (drug-induced, vascular, or psychogenic), ET, or dystonic tremor.24–26

The present study was designed to evaluate DaTscan patterns of abnormalities in a heterogeneous group of patients with movement disorders, particularly tremors, in a routine clinical setting. We also aimed to evaluate the performance of DaTscan between different observers and the consistency of reading DaTscan between different readers. A note was also made of patient on or off their anti-Parkinson medications.

Back to Top | Article Outline

PATIENTS AND METHODS

A retrospective evaluation was performed of all consecutive patients who underwent DaTscan in our nuclear medicine imaging clinic during a 1-year period from September 2011 to September 2012. Information about the patients’ demographics, symptoms and their duration, clinical diagnosis, and medications were collected. All patients underwent DaTscan according to standard imaging protocol.

Back to Top | Article Outline

DaTscan Scan

The patients were administered a supersaturated potassium iodide dose of 50 to 250 mg (1-5 drops) orally, approximately 1 hour before the injection of 123I-ioflupane. The patients were administered 5 mCi of 123I-ioflupane intravenously, and SPECT imaging was started between 3 and 5 hours postinjection. A Phillips dual-head γ-camera was placed as close to the patient’s head as physically possible. A radius of rotation of 11 to 15 cm was used for positioning. Patient’s head, arms, and legs were stabilized with straps to decrease patients’ motion during imaging. All-purpose high-resolution collimators were used with 20% energy window set around 159 KeV. The image acquisition was in a circular 360-degree orbit, 30 s/frame, 120 frames. Minimum of 1.5 million counts were obtained for optimal image quality. Images were processed using iterative reconstruction (Astonish program), with 2 iterations in 16 subsets.

Back to Top | Article Outline

DaTscan Interpretation

Two experienced nuclear medicine physicians interpreted the scans independently and without knowledge of the patients’ clinical information. The scan findings were categorized on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each caudate head and putamen separately. Correlation of the scan findings with the clinical symptoms and diagnosis, as well as interobserver agreement, was performed. Disagreement was considered when there was a difference between the 2 readers of more than 2 points on the semiquantitative scale in more than 1 area of the basal ganglia.

Back to Top | Article Outline

Statistical Analysis

Descriptive statistics were used to analyze the findings of the scans and the patients’ demographics and clinical information. Agreements between the readers in the interpretation of the scans were tested using κ test. A κ value of 0.0 means no agreement between the readers, and a value of 1 means perfect agreement.

Back to Top | Article Outline

RESULTS

A total of 57 patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of PD was certain in 26 patients and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). The 31 patients with uncertain clinical diagnosis of PD had markedly abnormal scan in 15 patients (48%), normal in 11 (36%), and mild abnormalities in 5 (16%) (Table 1). Each of the sensitivity and positive predictive value of DaTscan in the patients who had certain clinical diagnosis for the presence or absence of PD (26 patients) was 92%. The specificity and negative predictive value are difficult to evaluate because PD is usually a clinically confirmed diagnosis, and patients with no clinical suspicion for PD are not sent for a DaTscan.

TABLE 1

TABLE 1

Absence of uptake from at least one of the putamina was a consistent pattern in all patients with positive scans and clinically confirmed PD. The caudate heads were consistently less affected with DaTs dysfunction than the putamina in all patients with abnormal scans.

Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (κ = 0.82) (Table 2). Two of the patients with disagreement between the readers were clinically diagnosed PD, and the DaTscan was for confirmation of the diagnosis. One reader assigned higher degree of severity of defects in the putamina confirming the clinical diagnosis while the other reader indicated very mild defects. Another 2 patients with disagreement between the readers had bilateral hand tremors with unclear clinical diagnosis of essential versus parkinsonian tremors. Again, 1 reader interpreted more severe defects than the other, which suggested the diagnosis of PD by the first reader and ET by the second reader (Fig. 1).

TABLE 2

TABLE 2

FIGURE 1

FIGURE 1

Correlation of laterality of symptoms and side of defect or more severe defect on the DaTscan showed good results in 32 (82%) of 39 positive studies (Table 3). Specifically, DaTscan demonstrated worse symptoms on the contralateral side of the body in 30 (77%) of 39 patients or equal severity of symptoms with equal severity of basal ganglia involvement in 2 (5%) of 39 patients. Five patients had equally severe basal ganglia involvement, whereas a laterality of symptoms (13%) was indicated by history. Only 2 patients’ symptoms were on the ipsilateral side of basal ganglia defect (5%) (Fig. 2).

TABLE 3

TABLE 3

FIGURE 2

FIGURE 2

In addition, 21 of 26 patients with clinically confirmed PD were on anti-Parkinson medications, and 5 have discontinued their medications for variable periods before the DaTscan with an average of 37 days (range, 1–60 days). All 5 patients who discontinued their medication and 19 patients who were imaged while still taking their medications had findings of marked abnormalities rated as 3 and/or 4 in 1 or both putamina. Two patients who were clinically confirmed with the diagnosis of PD and had a negative scan were receiving their antiparkinsonism medications. One of these patients was on Azilect (rasagiline), and the other patient was on Stalevo (levodopa, carbidopa, entacapone) during the scan.

Back to Top | Article Outline

DISCUSSION

Our study was conducted immediately after the approval of DaTscan by Food and Drug Administration in the United States during the initial heightened enthusiasm of neurologists to test the performance of DaTscan in patients with previously confirmed clinical diagnosis of PD for long periods. This has provided us with a unique population where the confirmed clinical diagnosis as PD for many years was used as the criterion standard because there is no other imaging modality or biomarker presently available that can be used as a criterion standard for the diagnosis of PD. This group of patients (26/53) showed severe defects (grade 3-4) in 1 or both putamina of all the patients.18,27 Our study demonstrated a sensitivity of 92% in detection of PD, which is comparable results to the previously reported sensitivity of 95% and 93% by Benamer et al28 and Plotkin et al,29 respectively. Establishing the pattern of abnormalities in clinically confirmed PD patients and demonstrating high sensitivity was invaluable in imaging the second group of patients with uncertain clinical diagnoses. We were able to decide with confidence in these patients if their symptoms are due to PD or other movement disorders.29

DaTscan, with variability in basal ganglia appearance in normal brains and/or with any minimal head motion during the acquisition, can occasionally be difficult to interpret. Thus, we evaluated the interobserver variability in reading DaTscan to evaluate the differences between different interpreters’ readings. The 2 blinded readers in this study demonstrated good agreement in differentiating a mild versus severe defects in DaTs uptake with a κ value of 0.82. This also increased our confidence in the interpretation of scans regardless of minor variability or acquisition difficulties in some patients. Similar results were found by Papathanasiou et al30 who reported a κ value of 0.89 between 3 blinded observers at different levels of experience and with a simpler semiquantitative scale of only 3 levels of uptake where 2 is normal, 1 is reduced, and 0 is no uptake. We used a 5-step semiquantitative scale to be able to differentiate mild, moderate, or markedly abnormal degrees of tracer uptake. However, a disagreement between readers was considered only when there is significant difference between the readers of more than 2 points on the semiquantitative scale in more than 1 area in the basal ganglia. A disagreement occurred in 5 of 57 patients; this would change the patient diagnosis from PD to non-PD.

Good correlation of symptom laterality and scan findings was an impressive finding on DaTscans, which increased the confidence in validity of the results and the relevance to the clinical presentation and diagnosis. Only 2 patients (5%) showed more severe defect in the basal ganglia on the ipsilateral side of the symptoms. One of these patients had prior stroke with right-sided hemiplegia and left upper extremity tremor, and DaTscan showing bilateral absent tracer uptake in the bilateral putamina and left caudate. Although the left basal ganglia defect was greater in extent, the lack of laterality correlation with the right side of the body was likely due to the prior stroke-induced hemiplegia. The other patient with discrepant laterality had right arm tremor and bilateral marked defects of the bilateral putamina and of the right caudate head. There was no clear reason for the discrepant laterality findings; however, it could be due to incomplete history or a poor historian patient.

Most of the patients in our study were on anti-Parkinson medication during the time of DaTscan. However, we analyzed only the group with clinically confirmed PD (26 patients) to evaluate the effect of anti-Parkinson medication on scan findings. The scans showed marked abnormalities in 19 of 21 patients that were on the medications and 5 of 5 patients that have discontinued their medications before the DaTscan. The 19 patients on medications were divided into 10 on Sinemet (carbidopa-levodopa), 3 on Azilect (rasagiline), and 6 on both. In the 2 patients with normal scans, one was on Stalevo (levodopa, carbidopa, entacapone), and the other was on Azilect (rasagiline). Because a larger number of patients were on medication yet had a markedly abnormal scan, it is unlikely that the 2 patients with clinically confirmed PD but normal scans reflected medications effect. The data regarding effects of medication on DaTscan are very sparse at the present time and are assumed based on mechanism of action of medications. Further studies specially designed to evaluate the effect of commonly used anti-PD medications on DaTscan are warranted.

Back to Top | Article Outline

CONCLUSIONS

Markedly abnormal DaTscan in 1 or both putamina is the diagnostic pattern for PD in patients with clinically confirmed PD. This pattern helps confirm the diagnosis in patients with unclear clinical presentations. Good interobserver agreement is easily obtained in reading DaTscans.

Back to Top | Article Outline

REFERENCES

1. Parkinson J. An Essay on the Shaking Palsy. London, England: Sherwood Neely & James; 1817; 66.
2. Kasten M, Chade A, Tanner CM. Epidemiology of Parkinson’s disease. Handb Clin Neurol. 2007; 83: 129–151.
3. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008; 79: 368–376.
4. Hughes AJ, Daniel SE, Blankson S, et al. A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol. 1993; 50: 140–148.
5. Hughes AJ, Daniel SE, Ben-Shlomo Y, et al. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002; 125: 861–870.
6. Kägi G, Schwingenschuh P, Bhatia K, et al. Arm swing is reduced in idiopathic cervical dystonia. Mov Disord. 2008; 23: 1784–1787.
7. Marshall VL, Reininger CB, Marquardt M, et al. Parkinson’s disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]-FP-CIT SPECT. Mov Disord. 2009; 24: 500–508.
8. Cohen O, Pullman S, Jurewicz E, et al. Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiological characteristics. Arch Neurol. 2003; 60: 405–410.
9. Chaudhuri KR, Healy DG, Anthony Schapira AH. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006; 5: 235–245
10. Marjama-Lyons J, Koller W. Tremor-predominant Parkinson’s disease. Approaches to treatment. Drugs Aging. 2000; 16: 273–278.
11. Koller WC, Vetere-Overfield B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology. 1989; 39: 1587–1588
12. Meara J, Bhowmick BK, Hobson P. Accuracy of diagnosis in patients with presumed Parkinson’s disease. Age Ageing. 1989; 28: 99–102.
13. Rajput AH, Rozdilsky B, Rajput A. Accuracy of clinical diagnosis in parkinsonism—a prospective study. Can J Neurol Sci. 1991; 18: 275–278.
14. Taylor KS, Counsell CE, Harris CE, et al. Screening for undiagnosed parkinsonism in people aged 65 years and over in the community. Parkinsonism Relat Disord. 2006; 12: 79–85.
15. Caslake R, Taylor KS, Counsell CE. Parkinson’s disease misdiagnosed as stroke. BMJ Case Rep. 2009. Epub 2009 Feb 2.
16. Jankovic J, Rajput AH, McDermott MP, et al. The evolution of diagnosis in early Parkinson’s disease. Parkinson study group. Arch Neurol. 2000; 57: 369–372.
17. Quinn N. Parkinsonism-recognition and differential diagnosis. BMJ. 1995; 310: 447–452.
18. Bajaj NP, Gontu V, Birchall J, et al. Accuracy of clinical diagnosis in tremulous parkinsonian patients: a blinded video study. J Neurol Neurosurg Psychiatry. 2010; 81: 1223–1228.
19. Newman EJ, Breen K, Patterson J, et al. Accuracy of Parkinson’s disease diagnosis in 610 general practice patients in the West of Scotland. Mov Disord. 2009; 24: 2379–2385.
20. Schrag A, Ben-Shlomo Y, Quinn N. How valid is the clinical diagnosis of Parkinson’s disease in the community? J Neurol Neurosurg Psychiatry. 2002; 73: 529–534.
21. Booij J, Andringa G, Rijks LJM, et al. [123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys. Synapse. 1997; 27: 183–190.
22. Gunther I, Hall H, Halldin C, et al. [125I]β-CIT-FE and [125I]β- CIT-FP are superior to [125I]β-CIT for dopamine transporter visualization: autoradiographic evaluation in the human brain. Nucl Med Biol. 1997; 24: 629–634.
23. Lundkvist C, Halldin C, Swahn CG, et al. [O-methyl-11C]β- CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations. Nucl Med Biol. 1995; 22: 905–913.
24. Kemp PM. Imaging the dopaminergic system in suspected parkinsonism, drug induced movement disorders, and Lewy body dementia. Nucl Med Commun. 2005; 26: 87–96.
25. Vlaar AM, van Kroonenburgh MJ, Kessels AG, et al. Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes. BMC Neurol. 2007; 7: 27
26. Booij J, Speelman JD, Horstnink MWIM, et al. The clinical benefit of imaging striatal dopamine transporters with 123I-FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med. 2001; 28: 266–272.
27. Seifert KD, Wiener JI. The impact of DaTscan on the diagnosis and management of movement disorders: a retrospective study. Am J Neurodegener Dis. 2013; 2: 29–34.
28. Benamer TS, Patterson J, Grosset DG. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord. 2000; 15: 503–510.
29. Plotkin M, Amthauer H, Klaffke S, et al. Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm. 2005; 112: 677–92.
30. Papathanasiou N, Rondogianni P, Chroni P, et al. Interobserver variability, and visual and quantitative parameters of (123)I-FP-CIT SPECT (DaTSCAN) studies. Ann Nucl Med. 2012; 26: 234–240.
Keywords:

Parkinson disease; essential tremor; Parkinson medication; 123I-ioflupane; DaTscan; interobserver agreement; laterality of symptoms

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.