Volume 25, Issue 6, 2010, Pages 679-686
Authors: Ioannis U. Isaias, MD,[1,2]* Giorgio Marotta, MD, Shigeki Hirano, MD, PhD, Margherita Canesi, MD, Riccardo Benti, MD, Andrea Righini, MD, Chengke Tang, MD, Roberto Cilia, MD, Gianni Pezzoli, MD, David Eidelberg, MD,[4,6] and Angelo Antonini, MD, PhD[2,7]
1 Department of Human Physiology, University of Milano, Milano, Italy
2 Parkinson Institute, Istituti Clinici di Perfezionamento, Milano, Italy
3 Nuclear Medicine Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
4 Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA
5 Neuroradiology Department, V. Buzzi Hospital, Milano, Italy
6 Departments of Neurology and Medicine, North Shore University Hospital, North Shore-LIJ Health System, Manhasset, New York, USA
7 Institute of Neurology, IRCCS San Camillo, Venice and University of Padua, Italy
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To investigate over time changes in striatal dopamine transporter (DAT), we performed two sequential N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane single photon computed tomography (SPECT) scans in 20 subjects with essential tremor (ET), in 13 with Parkinson disease (PD) and in 23 healthy controls (HC, one scan only). We also performed an [(99m)Tc]ethyl cysteinate dimer bicisate SPECT exam for regional brain network analysis in 9 ET, in a second group of 18 PD (9 with tremor, tPD and 9 akinetic-rigid dominant, arPD) and in 8 HC. PD subjects had a reduced DAT binding in comparison to ET and HC with an annual decline rate of 7.3% in the contralateral putamen. There were no mean uptake differences between ET and HC at baseline and no uptake loss over time in ET. A discriminant analysis grouped 30% (first scan) and 5% (second scan) of ET as PD and a partition analysis showed overlap between ET and PD for caudate nucleus uptake. Spatial covariance analysis revealed that the expression of the PD-related regional pattern separated both tPD and arPD from ET and HC. In conclusion, PD and ET do not share a common pattern of dopaminergic loss over time. However, mild impairment of dopamine transporter in the caudate nucleus may contribute to tremor onset in ET.
© 2010 Movement Disorder Society
Summary and Review by Dr. Joseph Jankovic, MD, Baylor College of Medicine, Houston, Texas
Isaias et al 1 used FP-CIT single photon computed tomography (SPECT) to image dopamine transporter (DAT) in patients with Parkinson's disease (PD), essential tremor (ET) and healthy controls (HC). They concluded that PD patients had an annual decline of 7.3% of DAT binding, which is consistent with other studies using different imaging techniques. Because only baseline and one follow-up scans were available, the study did not address whether the dopaminergic decline in PD is linear or, as suggested by some, more rapid initially and then slows down as the disease advances.2
Another important finding was that while PD and ET show different pattern of dopaminergic loss over time, both disorders exhibit impairment of DAT in the caudate nucleus. This latter observation is consistent with the growing evidence of overlap between ET and PD, based on shared clinical features in some patients as well as on epidemiologic, genetic, imaging, and pathologic studies.3
Furthermore, since medial substantia nigra (that predominantly projects to the caudate nucleus) is particularly involved in the tremor-dominant PD and is associated with more robust caudate loss of DAT4 than non-tremor PD, it is possible that tremor-dominant PD and ET share a selective dopaminergic loss in the caudate nucleus. This, in turn, may lead to a dysfunction of the caudate-thalamic pathway and disinhibition of the thalamic autorhythmic pacemakers, clinically expressed as tremor. Indeed, beta-CIT SPECT, which mainly reflects serotonin transporters, is lower in the thalamus of patients with tremor-dominant PD as compared to those with non-tremor PD.5
In addition, caudate projects not only to thalamus but also to inferior olive and cerebellum, both structures implicated in the pathophysiology of ET. Furthermore, cerebellar involvement is also supported by growing evidence or cerebellar pathology in ET.6 In contrast to PD, ET patients showed little or no progressive loss of dopaminergic innervation, suggesting different pathophysiologic mechanisms for the two disorders, also supported by differences between the two disorders in the brain network analysis.
The overall number of repeated scans in the ET subjects was too small to address the question whether some ET patients are predisposed to develop PD later in the course. The clinical overlap between the two disorders undoubtedly contributes to the 10-15% frequency of patients diagnosed with mild PD who have Scans Without Evidence of Dopamine Deficiency (SWEDD).7 Since pathological studies of PD and ET usually exclude subjects who had both disorders, the imaging studies reported by Isaias et al1 provide important insights into the selective caudate dopaminergic deficit as a possible link between the two common disorders.
Isaias IU, Marotta G, Hirano S, et al. Imaging essential tremor. Mov Disord. 2010;25:679-86.
Jankovic J: Progression of Parkinson's disease: Are we making progress in charting the course? Arch Neurol 2005;62:351-352.
Shahed J, Jankovic J. Exploring the relationship between essential tremor and Parkinson's disease. Parkinsonism Relat Disord 2007;13:67-76.
Isaias IU, Canesi M, Benti R, et al. Striatal dopamine transporter abnormalities in patients with essential tremor. Nucl Med Commun 2008;29:349-53.
Caretti V, Stoffers D, Winogrodzka A, et al. Loss of thalamic serotonin transporters in early drug-naïve Parkinson's disease patients is associated with tremor: an [(123)I]beta-CIT SPECT study. J Neural Transm 2008;115(5):721-9.
Louis ED, Faust PL, Vonsattel JP, et al. Torpedoes in Parkinson's disease, Alzheimer's disease, essential tremor, and control brains. Mov Disord 2009;24:1600-5.
Stoessl AJ. Scans without evidence of dopamine deficiency: the triumph of careful clinical assessment. Mov Disord 2010;25:529-30.
About Dr. Joseph Jankovic, MD
Dr. Jankovic is Professor of Neurology, and Director, Parkinson Disease Center and Movement Disorders Clinic, and holds the Distinguished Chair in Movement Disorders, Department of Neurology, Baylor College of Medicine, Houston, Texas. Past president of The Movement Disorder Society and a recipient of the 2007 American Academy of Neurology Movement Disorders Research Award and the 2008 Guthrie Family Humanitarian Award, Dr. Jankovic has been elected an Honorary Member of the American Neurological Association, the French Neurological Society and other prestigious organizations. Listed in ISIHighlyCited.com, Dr. Jankovic has authored over 750 articles and chapters, and has edited or co-edited 35 books, including several standard textbooks such as "Neurology in Clinical Practice," "Parkinson's Disease and Movement Disorders," and "Principles and Practice of Movement Disorders." Dr. Jankovic has trained numerous fellows, many of whom have become internationally recognized leaders in the field of Movement Disorders. His seminal research in botulinum toxin and tetrabenazine paved the way for the approval of these drugs by the Food and Drug Administration. (www.jankovic.org)