Sottotipi motor
3. TABELLE E FIGURE Tabella
Caratteristiche cliniche dei pazienti con Malattia di Parkinson
EOPD LOPD
Numero di pazienti 35 41
Sesso (M/F) 16; 19 30; 11
Età di esordio (anni, media)
46,51 73,95
Durata sintomi (mesi, media)
12,25 10,48
Lato di esordio (numero) Destro Sinistro Bilaterale 19 14 2 17 11 13 Sintomatologia all’esordio (numero) Rigidità/Bradicinesia Tremore Misto 14 16 5 15 26 0 Stadio UPDRS III alla
prima valutazione (puteggio, media) 14,84 19,09 Terapie (numero) SSRI Antipsicotici BDZ Stabilizzanti dell’umore 4 0 4 1 11 2 6 2
Tabella II
Risultati delle immagini SPECT con FP-CIT
EOPD LOPD Media caudato 2,957402754 2,30635002 Deviazione standard caudato 0,52678216 0,40694803 Media putamen 2,41289075 2,4446104 Deviazione standard putamen 0,32358489 0,3839679 Z-scores caudato -1,229039709 -1,050086744 Z-scores putamen -2,716579524 -1,715940033
Grafico I
Grafico II
Grafico III
Grafico IV
Grafico V
Grafico VI
4. BIBLIOGRAFIA
Aharon-Peretz, J., S. Badarny, H. Rosenbaum, and R. Gershoni-Baruch. 2005. 'Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype-genotype correlation', Neurology, 65: 1460-1.
Ahlskog, J. E., and M. D. Muenter. 2001. 'Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature', Mov Disord, 16: 448-58.
Ascherio, A., and M. A. Schwarzschild. 2016. 'The epidemiology of Parkinson's disease: risk factors and prevention', Lancet Neurol, 15: 1257-72.
Athauda, D., K. Maclagan, S. S. Skene, M. Bajwa-Joseph, D. Letchford, K. Chowdhury, S. Hibbert, N. Budnik, L. Zampedri, J. Dickson, Y. Li, I. Aviles-Olmos, T. T. Warner, P. Limousin, A. J. Lees, N. H. Greig, S. Tebbs, and T. Foltynie. 2017. 'Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial', Lancet, 390: 1664-75.
Bayliss, J. A., M. B. Lemus, V. V. Santos, M. Deo, J. S. Davies, B. E. Kemp, J. D. Elsworth, and Z. B. Andrews. 2016. 'Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons', PLoS One, 11: e0159381.
Bellou, V., L. Belbasis, I. Tzoulaki, E. Evangelou, and J. P. Ioannidis. 2016. 'Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses', Parkinsonism Relat Disord, 23: 1-9.
Benamer, H. T. S., J. Patterson, D. G. Grosset, J. Booij, K. de Bruin, E. van Royen, J. D. Speelman, Mhim Horstink, Hjwa Sips, R. A. Dierckx, J. Versijpt, D. Decoo, C. Van Der Linden, D. M. Hadley, M. Doder, A. J. Lees, D. C. Costa, S. Gacinovic, W. H. Oertel, O. Pogarell, H. Hoeffken, K. Joseph, K. Tatsch, J. Schwarz, and V. Ries. 2000. 'Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123 I]-FP-CIT SPECT imaging: The [123 I]-FP-CIT study group', Mov Disord, 15: 503-10.
Bernheimer, H., W. Birkmayer, O. Hornykiewicz, K. Jellinger, and F. Seitelberger. 1973. 'Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations', J Neurol Sci, 20: 415-55.
Bezard, E., C. E. Gross, and J. M. Brotchie. 2003. 'Presymptomatic compensation in Parkinson's disease is not dopamine-mediated', Trends Neurosci, 26: 215-21.
Bibbiani, F., L. C. Costantini, R. Patel, and T. N. Chase. 2005. 'Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates', Exp Neurol, 192: 73-8.
Blandini, F., and M. T. Armentero. 2012. 'Animal models of Parkinson's disease', FEBS J, 279: 1156-66.
Blin, J., B. Dubois, A. M. Bonnet, M. Vidailhet, M. Brandabur, and Y. Agid. 1991. 'Does ageing aggravate parkinsonian disability?', J Neurol Neurosurg Psychiatry, 54: 780-2.
Booij, J., P. Bergmans, A. Winogrodzka, J. D. Speelman, and E. C. Wolters. 2001. 'Imaging of dopamine transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease', Synapse, 39: 101-8.
Booij, J., J. de Jong, K. de Bruin, R. Knol, M. M. de Win, and B. L. van Eck- Smit. 2007. 'Quantification of striatal dopamine transporters with 123I-FP- CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects', J Nucl Med, 48: 359-66.
Booij, J., and P. Kemp. 2008. 'Dopamine transporter imaging with [(123)I]FP-CIT SPECT: potential effects of drugs', Eur J Nucl Med Mol Imaging, 35: 424- 38.
Boyce, S., N. M. Rupniak, M. J. Steventon, and S. D. Iversen. 1990. 'Nigrostriatal damage is required for induction of dyskinesias by L-DOPA in squirrel monkeys', Clin Neuropharmacol, 13: 448-58.
Braak, H., K. Del Tredici, U. Rub, R. A. de Vos, E. N. Jansen Steur, and E. Braak. 2003. 'Staging of brain pathology related to sporadic Parkinson's disease', Neurobiol Aging, 24: 197-211.
Brooks, D. J. 2010. 'Imaging approaches to Parkinson disease', J Nucl Med, 51: 596-609.
Bruck, A., S. Aalto, E. Rauhala, J. Bergman, R. Marttila, and J. O. Rinne. 2009. 'A follow-up study on 6-[18F]fluoro-L-dopa uptake in early Parkinson's disease shows nonlinear progression in the putamen', Mov Disord, 24: 1009-15.
Calvini, P., G. Rodriguez, F. Inguglia, A. Mignone, U. P. Guerra, and F. Nobili. 2007. 'The basal ganglia matching tools package for striatal uptake semi- quantification: description and validation', Eur J Nucl Med Mol Imaging, 34: 1240-53.
Cenci, M. A. 2014. 'Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications', Front Neurol, 5: 242.
Cheng, H. C., C. M. Ulane, and R. E. Burke. 2010. 'Clinical progression in Parkinson disease and the neurobiology of axons', Ann Neurol, 67: 715-25. Coelho, M., and J. J. Ferreira. 2012. 'Late-stage Parkinson disease', Nat Rev
Neurol, 8: 435-42.
Connolly, B. S., and A. E. Lang. 2014. 'Pharmacological treatment of Parkinson disease: a review', JAMA, 311: 1670-83.
Cummings, J. L., C. Henchcliffe, S. Schaier, T. Simuni, A. Waxman, and P. Kemp. 2011. 'The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration', Brain, 134: 3146- 66.
da Silva-Junior, F. P., P. Braga-Neto, F. Sueli Monte, and V. M. de Bruin. 2005. 'Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study', Parkinsonism Relat Disord, 11: 449-52.
'DATATOP: a multicenter controlled clinical trial in early Parkinson's disease. Parkinson Study Group'. 1989. Arch Neurol, 46: 1052-60.
De La Fuente-Fernandez, R., A. S. Lim, V. Sossi, M. J. Adam, T. J. Ruth, D. B. Calne, A. J. Stoessl, and C. S. Lee. 2003. 'Age and severity of nigrostriatal damage at onset of Parkinson's disease', Synapse, 47: 152-8.
de la Fuente-Fernandez, R., J. Q. Lu, V. Sossi, S. Jivan, M. Schulzer, J. E. Holden, C. S. Lee, T. J. Ruth, D. B. Calne, and A. J. Stoessl. 2001. 'Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover', Ann Neurol, 49: 298-303.
de la Fuente-Fernandez, R., M. Schulzer, L. Kuramoto, J. Cragg, N. Ramachandiran, W. L. Au, E. Mak, J. McKenzie, S. McCormick, V. Sossi, T. J. Ruth, C. S. Lee, D. B. Calne, and A. J. Stoessl. 2011. 'Age-specific progression of nigrostriatal dysfunction in Parkinson's disease', Ann Neurol, 69: 803-10.
de la Fuente-Fernandez, R., M. Schulzer, E. Mak, D. B. Calne, and A. J. Stoessl. 2004. 'Presynaptic mechanisms of motor fluctuations in Parkinson's disease: a probabilistic model', Brain, 127: 888-99.
de la Fuente-Fernandez, R., M. Schulzer, E. Mak, and V. Sossi. 2010. 'Trials of neuroprotective therapies for Parkinson's disease: problems and limitations', Parkinsonism Relat Disord, 16: 365-9.
Delamarre, A., and W. G. Meissner. 2017. 'Epidemiology, environmental risk factors and genetics of Parkinson's disease', Presse Med, 46: 175-81. Deleu, D., Y. Hanssens, and M. G. Northway. 2004. 'Subcutaneous apomorphine :
an evidence-based review of its use in Parkinson's disease', Drugs Aging, 21: 687-709.
Di Monte, D. A., A. McCormack, G. Petzinger, A. M. Janson, M. Quik, and W. J. Langston. 2000. 'Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model', Mov Disord, 15: 459-66.
Diederich, N. J., C. G. Moore, S. E. Leurgans, T. A. Chmura, and C. G. Goetz. 2003. 'Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset', Arch Neurol, 60: 529-33.
Dorsey, E. R., R. Constantinescu, J. P. Thompson, K. M. Biglan, R. G. Holloway, K. Kieburtz, F. J. Marshall, B. M. Ravina, G. Schifitto, A. Siderowf, and C. M. Tanner. 2007. 'Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030', Neurology, 68: 384-6. Doudet, D. J., G. L. Chan, J. E. Holden, E. G. McGeer, T. A. Aigner, R. J. Wyatt,
and T. J. Ruth. 1998. '6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys', Synapse, 29: 225-32.
Dunnett, S. B., and A. Bjorklund. 1999. 'Prospects for new restorative and neuroprotective treatments in Parkinson's disease', Nature, 399: A32-9. Durso, R., K. Isaac, L. Perry, M. Saint-Hilaire, and R. G. Feldman. 1993. 'Age
influences magnitude but not duration of response to levodopa', J Neurol Neurosurg Psychiatry, 56: 65-8.
Eggers, C., D. J. Pedrosa, D. Kahraman, F. Maier, C. J. Lewis, G. R. Fink, M. Schmidt, and L. Timmermann. 2012. 'Parkinson subtypes progress differently in clinical course and imaging pattern', PLoS One, 7: e46813. Fabbrini, G., M. M. Mouradian, J. L. Juncos, J. Schlegel, E. Mohr, and T. N.
Chase. 1988. 'Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I', Ann Neurol, 24: 366-71.
Fahn, S. 2000. 'The spectrum of levodopa-induced dyskinesias', Ann Neurol, 47: S2-9; discussion S9-11.
———. 2006. 'A new look at levodopa based on the ELLDOPA study', J Neural Transm Suppl: 419-26.
Fearnley, J. M., and A. J. Lees. 1991. 'Ageing and Parkinson's disease: substantia nigra regional selectivity', Brain, 114 ( Pt 5): 2283-301.
Ferreira, J. J., R. Katzenschlager, B. R. Bloem, U. Bonuccelli, D. Burn, G. Deuschl, E. Dietrichs, G. Fabbrini, A. Friedman, P. Kanovsky, V. Kostic, A. Nieuwboer, P. Odin, W. Poewe, O. Rascol, C. Sampaio, M. Schupbach, E. Tolosa, C. Trenkwalder, A. Schapira, A. Berardelli, and W. H. Oertel. 2013. 'Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease', Eur J Neurol, 20: 5-15.
Gauthier, S., and L. Gauthier. 1987. 'Current status of levodopa therapy in idiopathic Parkinson's disease', Can J Neurol Sci, 14: 452-4.
Gelb, D. J., E. Oliver, and S. Gilman. 1999. 'Diagnostic criteria for Parkinson disease', Arch Neurol, 56: 33-9.
Gibb, W. R., and A. J. Lees. 1988. 'A comparison of clinical and pathological features of young- and old-onset Parkinson's disease', Neurology, 38: 1402-6.
Giovannini, P., I. Piccolo, S. Genitrini, P. Soliveri, F. Girotti, G. Geminiani, G. Scigliano, and T. Caraceni. 1991. 'Early-onset Parkinson's disease', Mov Disord, 6: 36-42.
Gomez Arevalo, G., R. Jorge, S. Garcia, O. Scipioni, and O. Gershanik. 1997. 'Clinical and pharmacological differences in early- versus late-onset Parkinson's disease', Mov Disord, 12: 277-84.
Granerus, A. K., G. Steg, and A. Svanborg. 1972. 'Clinical analyses of factors influencing L-dopa treatment of Parkinson's syndrome', Acta Med Scand, 192: 1-11.
Guttman, M., D. Stewart, D. Hussey, A. Wilson, S. Houle, and S. Kish. 2001. 'Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD', Neurology, 56: 1559-64.
Harrington, K. A., S. J. Augood, A. E. Kingsbury, O. J. Foster, and P. C. Emson. 1996. 'Dopamine transporter (Dat) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson's disease', Brain Res Mol Brain Res, 36: 157-62.
Hauser, R. A., and D. G. Grosset. 2012. '[123I]FP-CIT (DaTscan) SPECT brain imaging in patients with suspected parkinsonian syndromes', J Neuroimaging, 22: 225-30.
Hauser, R. A., M. P. McDermott, and S. Messing. 2006. 'Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease', Arch Neurol, 63: 1756-60.
Hauser, R. A., M. Panisset, G. Abbruzzese, L. Mancione, N. Dronamraju, A. Kakarieka, and First-Step Study Group. 2009. 'Double-blind trial of
levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease', Mov Disord, 24: 541-50.
Hauser, R. A., O. Rascol, A. D. Korczyn, A. Jon Stoessl, R. L. Watts, W. Poewe, P. P. De Deyn, and A. E. Lang. 2007. 'Ten-year follow-up of Parkinson's disease patients randomized to initial therapy with ropinirole or levodopa', Mov Disord, 22: 2409-17.
Hely, M. A., J. G. Morris, W. G. Reid, D. J. O'Sullivan, P. M. Williamson, G. A. Broe, and M. A. Adena. 1995. 'Age at onset: the major determinant of outcome in Parkinson's disease', Acta Neurol Scand, 92: 455-63.
Hernandez, D. G., X. Reed, and A. B. Singleton. 2016. 'Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance', J Neurochem, 139 Suppl 1: 59-74.
Hilker, R., K. Schweitzer, S. Coburger, M. Ghaemi, S. Weisenbach, A. H. Jacobs, J. Rudolf, K. Herholz, and W. D. Heiss. 2005. 'Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity', Arch Neurol, 62: 378-82. Hirsch, E. C., A. M. Graybiel, C. Duyckaerts, and F. Javoy-Agid. 1987. 'Neuronal
loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy', Proc Natl Acad Sci U S A, 84: 5976-80. Hitri, A., Y. L. Hurd, R. J. Wyatt, and S. I. Deutsch. 1994. 'Molecular, functional and biochemical characteristics of the dopamine transporter: regional differences and clinical relevance', Clin Neuropharmacol, 17: 1-22.
Hobson, D. E. 2003. 'Clinical manifestations of Parkinson's disease and parkinsonism', Can J Neurol Sci, 30 Suppl 1: S2-9.
Hughes, A. J., S. E. Daniel, and A. J. Lees. 2001. 'Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease', Neurology, 57: 1497-9. Hughes, T. A., H. F. Ross, S. Musa, S. Bhattacherjee, R. N. Nathan, R. H.
Mindham, and E. G. Spokes. 2000. 'A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease', Neurology, 54: 1596-602.
Huot, P., T. H. Johnston, J. B. Koprich, S. H. Fox, and J. M. Brotchie. 2013. 'The pharmacology of L-DOPA-induced dyskinesia in Parkinson's disease', Pharmacol Rev, 65: 171-222.
Hwang, O. 2013. 'Role of oxidative stress in Parkinson's disease', Exp Neurobiol, 22: 11-7.
Jankovic, J. 2008. 'Parkinson's disease: clinical features and diagnosis', J Neurol Neurosurg Psychiatry, 79: 368-76.
Jankovic, J., M. McDermott, J. Carter, S. Gauthier, C. Goetz, L. Golbe, S. Huber, W. Koller, C. Olanow, I. Shoulson, and et al. 1990. 'Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group', Neurology, 40: 1529-34.
Joyce, J. N., G. Smutzer, C. J. Whitty, A. Myers, and M. J. Bannon. 1997. 'Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease', Mov Disord, 12: 885-97. Kaasinen, V., J. Joutsa, T. Noponen, J. Johansson, and M. Seppanen. 2015.
'Effects of aging and gender on striatal and extrastriatal [123I]FP-CIT binding in Parkinson's disease', Neurobiol Aging, 36: 1757-63.
Kempster, P. A., S. S. O'Sullivan, J. L. Holton, T. Revesz, and A. J. Lees. 2010. 'Relationships between age and late progression of Parkinson's disease: a clinico-pathological study', Brain, 133: 1755-62.
Khan, N. L., D. J. Brooks, N. Pavese, M. G. Sweeney, N. W. Wood, A. J. Lees, and P. Piccini. 2002. 'Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study', Brain, 125: 2248-56. Kish, S. J., K. Shannak, A. Rajput, J. H. Deck, and O. Hornykiewicz. 1992.
'Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease', J Neurochem, 58: 642- 8.
Kitada, T., S. Asakawa, N. Hattori, H. Matsumine, Y. Yamamura, S. Minoshima, M. Yokochi, Y. Mizuno, and N. Shimizu. 1998. 'Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism', Nature, 392: 605- 8.
Klingelhoefer, L., and H. Reichmann. 2015. 'Pathogenesis of Parkinson disease-- the gut-brain axis and environmental factors', Nat Rev Neurol, 11: 625-36. Koller, W. C., and A. E. Lang. 1987. 'Age of onset of Parkinson's disease', Can J
Neurol Sci, 14: 179-80.
Korchounov, A., H. I. Schipper, I. S. Preobrazhenskaya, K. R. Kessler, and N. N. Yakhno. 2004. 'Differences in age at onset and familial aggregation between clinical types of idiopathic Parkinson's disease', Mov Disord, 19: 1059-64.
Kordower, J. H., C. W. Olanow, H. B. Dodiya, Y. Chu, T. G. Beach, C. H. Adler, G. M. Halliday, and R. T. Bartus. 2013. 'Disease duration and the integrity of the nigrostriatal system in Parkinson's disease', Brain, 136: 2419-31. Kostic, V., S. Przedborski, E. Flaster, and N. Sternic. 1991. 'Early development of
levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease', Neurology, 41: 202-5.
Kumar, N., J. A. Van Gerpen, J. H. Bower, and J. E. Ahlskog. 2005. 'Levodopa- dyskinesia incidence by age of Parkinson's disease onset', Mov Disord, 20: 342-4.
Langston, J. W., P. Ballard, J. W. Tetrud, and I. Irwin. 1983. 'Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis', Science, 219: 979-80.
Lee, A., and R. M. Gilbert. 2016. 'Epidemiology of Parkinson Disease', Neurol Clin, 34: 955-65.
Lee, C. S., A. Samii, V. Sossi, T. J. Ruth, M. Schulzer, J. E. Holden, J. Wudel, P. K. Pal, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl. 2000. 'In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease', Ann Neurol, 47: 493-503.
Levy, G. 2007. 'The relationship of Parkinson disease with aging', Arch Neurol, 64: 1242-6.
Levy, G., M. X. Tang, L. J. Cote, E. D. Louis, B. Alfaro, H. Mejia, Y. Stern, and K. Marder. 2000. 'Motor impairment in PD: relationship to incident dementia and age', Neurology, 55: 539-44.
Lewis, S. J., T. Foltynie, A. D. Blackwell, T. W. Robbins, A. M. Owen, and R. A. Barker. 2005. 'Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach', J Neurol Neurosurg Psychiatry, 76: 343-8.
Liu, S. Y., J. J. Wu, J. Zhao, S. F. Huang, Y. X. Wang, J. J. Ge, P. Wu, C. T. Zuo, Z. T. Ding, and J. Wang. 2015. 'Onset-related subtypes of Parkinson's disease differ in the patterns of striatal dopaminergic dysfunction: A positron emission tomography study', Parkinsonism Relat Disord, 21: 1448-53.
Marin, C., E. Aguilar, G. Mengod, R. Cortes, and J. A. Obeso. 2009. 'Effects of early vs. late initiation of levodopa treatment in hemiparkinsonian rats', Eur J Neurosci, 30: 823-32.
Marras, C., and A. Lang. 2013. 'Parkinson's disease subtypes: lost in translation?', J Neurol Neurosurg Psychiatry, 84: 409-15.
Marsden, C. D., and J. D. Parkes. 1976. '"On-off" effects in patients with Parkinson's disease on chronic levodopa therapy', Lancet, 1: 292-6.
Marshall, V. L., C. B. Reininger, M. Marquardt, J. Patterson, D. M. Hadley, W. H. Oertel, H. T. Benamer, P. Kemp, D. Burn, E. Tolosa, J. Kulisevsky, L. Cunha, D. Costa, J. Booij, K. Tatsch, K. R. Chaudhuri, G. Ulm, O. Pogarell, H. Hoffken, A. Gerstner, and D. G. Grosset. 2009. '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, 24: 500-8.
Martin, W. R., M. R. Palmer, C. S. Patlak, and D. B. Calne. 1989. 'Nigrostriatal function in humans studied with positron emission tomography', Ann Neurol, 26: 535-42.
McCormack, A. L., M. Thiruchelvam, A. B. Manning-Bog, C. Thiffault, J. W. Langston, D. A. Cory-Slechta, and D. A. Di Monte. 2002. 'Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat', Neurobiol Dis, 10: 119-27.
Mozley, P. D., P. D. Acton, E. D. Barraclough, K. Plossl, R. C. Gur, A. Alavi, A. Mathur, J. Saffer, and H. F. Kung. 1999. 'Effects of age on dopamine transporters in healthy humans', J Nucl Med, 40: 1812-7.
Nandhagopal, R., L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, J. McKenzie, S. McCormick, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, and A. J. Stoessl. 2011. 'Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease', Brain, 134: 3290-8.
Nissen, T., N. Malek, K. A. Grosset, E. J. Newman, J. Patterson, D. Hadley, and D. G. Grosset. 2014. 'Baseline [(123) I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease', Acta Neurol Scand, 129: 204-8.
Nyholm, D. 2012. 'Duodopa(R) treatment for advanced Parkinson's disease: a review of efficacy and safety', Parkinsonism Relat Disord, 18: 916-29. Obeso, J. A., M. C. Rodriguez-Oroz, C. G. Goetz, C. Marin, J. H. Kordower, M.
Rodriguez, E. C. Hirsch, M. Farrer, A. H. Schapira, and G. Halliday. 2010. 'Missing pieces in the Parkinson's disease puzzle', Nat Med, 16: 653-61. Olanow, C. W., R. A. Hauser, J. Jankovic, W. Langston, A. Lang, W. Poewe, E.
Tolosa, F. Stocchi, E. Melamed, E. Eyal, and O. Rascol. 2008. 'A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): rationale, design, and baseline characteristics', Mov Disord, 23: 2194-201.
Pagano, G., N. Ferrara, D. J. Brooks, and N. Pavese. 2016. 'Age at onset and Parkinson disease phenotype', Neurology, 86: 1400-7.
Park, E. 2012. 'A new era of clinical dopamine transporter imaging using 123I- FP-CIT', J Nucl Med Technol, 40: 222-8.
Parkinson Study Group, Calm Cohort Investigators. 2009. 'Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease', Arch Neurol, 66: 563-70.
Pavese, N., N. L. Khan, C. Scherfler, L. Cohen, D. J. Brooks, N. W. Wood, K. P. Bhatia, N. P. Quinn, A. J. Lees, and P. Piccini. 2009. 'Nigrostriatal
dysfunction in homozygous and heterozygous parkin gene carriers: an 18F-dopa PET progression study', Mov Disord, 24: 2260-6.
Pirker, W. 2003. 'Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it?', Mov Disord, 18 Suppl 7: S43-51.
Polymeropoulos, M. H., C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E. S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W. G. Johnson, A. M. Lazzarini, R. C. Duvoisin, G. Di Iorio, L. I. Golbe, and R. L. Nussbaum. 1997. 'Mutation in the alpha-synuclein gene identified in families with Parkinson's disease', Science, 276: 2045-7.
Quinn, N., P. Critchley, and C. D. Marsden. 1987. 'Young onset Parkinson's disease', Mov Disord, 2: 73-91.
Rajput, A. H., A. Voll, M. L. Rajput, C. A. Robinson, and A. Rajput. 2009. 'Course in Parkinson disease subtypes: A 39-year clinicopathologic study', Neurology, 73: 206-12.
'A randomized controlled trial comparing pramipexole with levodopa in early Parkinson's disease: design and methods of the CALM-PD Study. Parkinson Study Group'. 2000. Clin Neuropharmacol, 23: 34-44.
Rascol, O. 2000. 'The pharmacological therapeutic management of levodopa- induced dyskinesias in patients with Parkinson's disease', J Neurol, 247 Suppl 2: II51-7.
Rascol, O., U. Sabatini, F. Chollet, N. Fabre, J. M. Senard, J. L. Montastruc, P. Celsis, J. P. Marc-Vergnes, and A. Rascol. 1994. 'Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa', J Neurol Neurosurg Psychiatry, 57: 567-71.
Ravina, B., K. Marek, S. Eberly, D. Oakes, R. Kurlan, A. Ascherio, F. Beal, J. Beck, E. Flagg, W. R. Galpern, J. Harman, A. E. Lang, M. Schwarzschild, C. Tanner, and I. Shoulson. 2012. 'Dopamine transporter imaging is associated with long-term outcomes in Parkinson's disease', Mov Disord, 27: 1392-7.
Reeve, A., E. Simcox, and D. Turnbull. 2014. 'Ageing and Parkinson's disease: why is advancing age the biggest risk factor?', Ageing Res Rev, 14: 19-30. Rektorova, I., H. Srovnalova, R. Kubikova, and J. Prasek. 2008. 'Striatal
dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease', Mov Disord, 23: 1580-7.
Rodriguez, M., C. Rodriguez-Sabate, I. Morales, A. Sanchez, and M. Sabate. 2015. 'Parkinson's disease as a result of aging', Aging Cell, 14: 293-308. Rossi, C., D. Genovesi, P. Marzullo, A. Giorgetti, E. Filidei, G. U. Corsini, U.
Bonuccelli, and R. Ceravolo. 2017. 'Striatal Dopamine Transporter Modulation After Rotigotine: Results From a Pilot Single-Photon Emission Computed Tomography Study in a Group of Early Stage Parkinson Disease Patients', Clin Neuropharmacol, 40: 34-36.
Sacks, O. W., M. Kohl, W. Schwartz, and C. Messeloff. 1970. 'Side-effects of L- dopa in postencephalic parkinsonism', Lancet, 1: 1006.
Salat, D., and E. Tolosa. 2013. 'Levodopa in the treatment of Parkinson's disease: current status and new developments', J Parkinsons Dis, 3: 255-69.
Samii, A., K. Markopoulou, Z. K. Wszolek, V. Sossi, T. Dobko, E. Mak, D. B. Calne, and A. J. Stoessl. 1999. 'PET studies of parkinsonism associated with mutation in the alpha-synuclein gene', Neurology, 53: 2097-102. Santangelo, G., C. Vitale, M. Picillo, S. Cuoco, M. Moccia, D. Pezzella, R. Erro,
K. Longo, C. Vicidomini, M. T. Pellecchia, M. Amboni, A. Brunetti, M. Salvatore, P. Barone, and S. Pappata. 2015. 'Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients', Parkinsonism Relat Disord, 21: 489-93.
Schrag, A., Y. Ben-Shlomo, R. Brown, C. D. Marsden, and N. Quinn. 1998. 'Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality', Mov Disord, 13: 885-94.
Schrag, A., and J. M. Schott. 2006. 'Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism', Lancet Neurol, 5: 355-63.
Sharma, J. C., L. Macnamara, M. Hasoon, M. Vassallo, and I. Ross. 2006. 'Cascade of levodopa dose and weight-related dyskinesia in Parkinson's disease (LD-WD-PD cascade)', Parkinsonism Relat Disord, 12: 499-505. Shih, M. C., L. A. Franco de Andrade, E. Amaro, Jr., A. C. Felicio, H. B. Ferraz,
J. Wagner, M. Q. Hoexter, L. F. Lin, Y. K. Fu, J. J. Mari, S. Tufik, and R. A. Bressan. 2007. 'Higher nigrostriatal dopamine neuron loss in early than late onset Parkinson's disease?--a [99mTc]-TRODAT-1 SPECT study', Mov Disord, 22: 863-6.
Shingai, Y., A. Tateno, R. Arakawa, T. Sakayori, W. Kim, H. Suzuki, and Y. Okubo. 2014. 'Age-related decline in dopamine transporter in human brain using PET with a new radioligand [(1)(8)F]FE-PE2I', Ann Nucl Med, 28: 220-6.
Siepel, F. J., K. S. Bronnick, J. Booij, B. M. Ravina, A. V. Lebedev, J. B. Pereira, R. Gruner, and D. Aarsland. 2014. 'Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease', Mov Disord, 29: 1802-8.
Singleton, A. B., M. Farrer, J. Johnson, A. Singleton, S. Hague, J. Kachergus, M. Hulihan, T. Peuralinna, A. Dutra, R. Nussbaum, S. Lincoln, A. Crawley, M. Hanson, D. Maraganore, C. Adler, M. R. Cookson, M. Muenter, M. Baptista, D. Miller, J. Blancato, J. Hardy, and K. Gwinn-Hardy. 2003. 'alpha-Synuclein locus triplication causes Parkinson's disease', Science, 302: 841.
Smith, L. A., M. J. Jackson, G. Al-Barghouthy, S. Rose, M. Kuoppamaki, W. Olanow, and P. Jenner. 2005. 'Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates', Mov Disord, 20: 306-14.
Sossi, V., R. de La Fuente-Fernandez, J. E. Holden, D. J. Doudet, J. McKenzie, A. J. Stoessl, and T. J. Ruth. 2002. 'Increase in dopamine turnover occurs early in Parkinson's disease: evidence from a new modeling approach to PET 18 F-fluorodopa data', J Cereb Blood Flow Metab, 22: 232-9.
Sossi, V., R. de la Fuente-Fernandez, M. Schulzer, J. Adams, and J. Stoessl. 2006. 'Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications', Brain, 129: 1050-8.
Spiegel, J., D. Hellwig, S. Samnick, W. Jost, M. O. Mollers, K. Fassbender, C. M. Kirsch, and U. Dillmann. 2007. 'Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease', J Neural Transm (Vienna), 114: 331-5.
Stachowiak, M. K., J. P. Bruno, A. M. Snyder, E. M. Stricker, and M. J. Zigmond. 1984. 'Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats', Brain Res, 291: 164-7. Stefanis, L. 2012. 'alpha-Synuclein in Parkinson's disease', Cold Spring Harb
Perspect Med, 2: a009399.
Stocchi, F., O. Rascol, K. Kieburtz, W. Poewe, J. Jankovic, E. Tolosa, P. Barone, A. E. Lang, and C. W. Olanow. 2010. 'Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the