Background. Differentiating Parkinson’s disease (PD) from multiple system atrophy (MSA) can be challenging especially early in the course of the disease. Previous studies have shown that midbrain serotonin transporter (SERT) availability in patients with established MSA was significantly lower compared to PD. It is unknown if this is also true for early-stage patients. Methods. 77 early-stage, untreated PD patients were recruited between 1995 and 1998, underwent [123I]β-CIT SPECT imaging, and were followed for at least five years. 16 patients were lost to followup, and in 4 the diagnosis was changed to another atypical parkinsonian syndrome, but not in MSA. In 50 patients, the PD diagnosis was unchanged at followup. In seven patients, the diagnosis was changed to MSA at followup. We retrospectively assessed baseline midbrain SERT availability as well as midbrain SERT-to-striatal dopamine transporter (DAT) ratios. Results. No difference in baseline [123I]β-CIT SERT availability was found. The midbrain SERT-to-striatal DAT ratio for whole striatum was significantly lower in patients with PD compared to MSA ( ). However, when adjusting for the disease duration at imaging this difference is not significant ( ). Conclusion. Midbrain SERT availability is not different between early-stage PD and MSA. Therefore, SERT imaging is not useful to differentiate between early PD and MSA. 1. Introduction A key neuropathological characteristic of Parkinson’s disease (PD) is loss of brainstem neurons that produce dopamine [1]. This loss induces features such as bradykinesia and rigidity. The clinical diagnosis of PD is based on the combination of motor features and response to levodopa [2, 3]. Differentiating PD from multiple system atrophy (MSA) can be challenging especially early in the disease course, when signs and symptoms overlap [4, 5]. Indeed, in specialized centers, PD is misdiagnosed in 6–25% of cases [2, 3, 6, 7]. General neurologists misdiagnose PD patients in up to 35% of cases [4]. Dopamine transporter (DAT) imaging with single photon emission computed tomography (SPECT) is reliable in detecting nigrostriatal cell loss. Some studies even suggest that imaging of the DAT can provide more certainty in the differential diagnosis of PD [8, 9], although this is not supported by other studies [10–12]. However, it has become clear that PD is characterized not only by dopaminergic, but also by serotonergic degeneration [13, 14]. Although [123I] -carboxymethyoxy-3- -(4-iodophenyl) tropane ( -CIT) and its fluoropropyl variant (FP-CIT) are well-known tracers for
References
[1]
H. Bernheimer, W. Birkmayer, and O. Hornykiewicz, “Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations,” Journal of the Neurological Sciences, vol. 20, no. 4, pp. 415–455, 1973.
[2]
A. J. Hughes, S. E. Daniel, L. Kilford, and A. J. Lees, “Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases,” Journal of Neurology Neurosurgery and Psychiatry, vol. 55, no. 3, pp. 181–184, 1992.
[3]
A. J. Hughes, S. E. Daniel, and A. J. Lees, “Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease,” Neurology, vol. 57, no. 8, pp. 1497–1499, 2001.
[4]
J. Jankovic, A. H. Rajput, M. P. McDermott, and D. P. Perl, “The evolution of diagnosis in early Parkinson disease,” Archives of Neurology, vol. 57, no. 3, pp. 369–372, 2000.
[5]
E. Tolosa, G. Wenning, and W. Poewe, “The diagnosis of Parkinson's disease,” The Lancet Neurology, vol. 5, no. 1, pp. 75–86, 2006.
[6]
A. J. Hughes, S. E. Daniel, Y. Ben-Shlomo, and A. J. Lees, “The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service,” Brain, vol. 125, no. 4, pp. 861–870, 2002.
[7]
I. Litvan, A. MacIntyre, C. G. Goetz et al., “Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study,” Archives of Neurology, vol. 55, no. 7, pp. 969–978, 1998.
[8]
R. de la Fuente-Fernandez, “Role of DaTSCAN and clinical diagnosis in Parkinson disease,” Neurology, vol. 78, pp. 696–701, 2012.
[9]
A. M. M. Vlaar, M. J. P. G. van Kroonenburgh, A. G. H. Kessels, and W. E. J. Weber, “Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes,” BMC Neurology, vol. 7, article 27, 2007.
[10]
A. Antonini, R. Benti, R. De Notaris et al., “123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy,” Neurological Sciences, vol. 24, no. 3, pp. 149–150, 2003.
[11]
A. Varrone, K. L. Marek, D. Jennings, R. B. Innis, and J. P. Seibyl, “[123I]β-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson's disease and multiple system atrophy,” Movement Disorders, vol. 16, no. 6, pp. 1023–1032, 2001.
[12]
L. Farde, C. Halldin, L. Muller, T. Suhara, P. Karlsson, and H. Hall, “PET study of [11C]β-CIT binding to monoamine transporters in the monkey and human brain,” Synapse, vol. 16, no. 2, pp. 93–103, 1994.
[13]
E. C. Hirsch, G. Orieux, M.-P. Muriel, C. Francois, and J. Feger, “Nondopaminergic neurons in Parkinson's disease,” Advances in Neurology, vol. 91, pp. 29–37, 2003.
[14]
S. J. Kish, J. Tong, O. Hornykiewicz et al., “Preferential loss of serotonin markers in caudate versus putamen in Parkinson's disease,” Brain, vol. 131, no. 1, pp. 120–131, 2008.
[15]
F. Roselli, N. M. Pisciotta, M. Pennelli, et al., “Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study,” Movement Disorders, vol. 25, pp. 1853–1859, 2010.
[16]
C. Scherfler, K. Seppi, E. Donnemiller et al., “Voxel-wise analysis of [123I]β-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease,” Brain, vol. 128, no. 7, pp. 1605–1612, 2005.
[17]
W. Pirker, S. Asenbaum, M. Hauk et al., “Imaging serotonin and dopamine transporters with 123I-β-CIT SPECT: binding kinetics and effects of normal aging,” Journal of Nuclear Medicine, vol. 41, no. 1, pp. 36–44, 2000.
[18]
M. M. L. de Win, J. B. A. Habraken, L. Reneman, W. Van Den Brink, G. J. Den Heeten, and J. Booij, “Validation of [123I]β-CIT SPECT to serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram,” Neuropsychopharmacology, vol. 30, no. 5, pp. 996–1005, 2005.
[19]
M. Laruelle, R. M. Baldwin, R. T. Malison et al., “SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates,” Synapse, vol. 13, no. 4, pp. 295–309, 1993.
[20]
J. L. Neumeyer, S. Wang, Y. Gao et al., “N-ω-fluoroalkyl analogs of (1R)-2β-carbomethoxy-3β-(4-iodophenyl)-tropane (β-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters,” Journal of Medicinal Chemistry, vol. 37, no. 11, pp. 1558–1561, 1994.
[21]
W. R. G. Gibb and A. J. Lees, “The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease,” Journal of Neurology Neurosurgery and Psychiatry, vol. 51, no. 6, pp. 745–752, 1988.
[22]
A. J. Hughes, Y. Ben-Shlomo, S. E. Daniel, and A. J. Lees, “What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study,” Neurology, vol. 42, no. 6, pp. 1142–1146, 1992.
[23]
D. Stoffers, J. Booij, L. Bosscher, A. Winogrodzka, E. C. Wolters, and H. W. Berendse, “Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 32, no. 6, pp. 689–695, 2005.
[24]
G. Tissingh, P. Bergmans, J. Booij et al., “Drug-naive patients with Parkinson's disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT,” Journal of Neurology, vol. 245, no. 1, pp. 14–20, 1998.
[25]
E. Boot, J. Booij, G. Hasler et al., “AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 7, pp. 1350–1356, 2008.
[26]
R. B. Innis, V. J. Cunningham, J. Delforge et al., “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 9, pp. 1533–1539, 2007.
[27]
W. Pirker, S. Djamshidian, S. Asenbaum et al., “Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: a longitudinal β-CIT SPECT study,” Movement Disorders, vol. 17, no. 1, pp. 45–53, 2002.
