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PET and SPECT in the Evaluation of Patients with Central Motor Disorders

  • John P. Seibyl
Chapter

In the nearly 200 years since the first modern clinical description of the spectrum of bradykinesia, tremor, and gait disturbance by James Parkinson, tremendous progress has been made in the understanding and clinical management of movement disorders. 1 In particular, the discovery of the pathologic changes occurring in the brain in patients with these disorders directly led to the development of effective symptomatic treatments and set the current focus on the next generation of therapeutics designed to interrupt the progression of disease. Neuroimaging methods, especially positron emission tomography (PET) and single photon emission tomography (SPECT), have now assumed an important role in the refinement in understanding of differential diagnosis and clinical course by providing disease-relevant biomarkers that complement other clinical measures. Nonetheless, as scintigraphic methods are still early in the routine application to the diagnosis and management of Parkinson’s disease (PD) and related disorders, intense interest and some controversy remains as to their ultimate clinical application

Keywords

Positron Emission Tomography Multiple System Atrophy Essential Tremor Movement Disorder Specialist Diffuse Lewy Body Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    1. Yahr MD. Early recognition of Parkinson’s disease. Hosp Pract (Off Ed) 1981;16:65–7, 77–80.Google Scholar
  2. 2.
    2. Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann NY Acad Sci 2003;991:1–14.PubMedGoogle Scholar
  3. 3.
    3. Fahn S. Controversies in the therapy of Parkinson’s disease. Adv Neurol 1996;69:477–486.PubMedGoogle Scholar
  4. 4.
    4. Uitti RJ, Baba Y, Wszolek ZK,. Defining the Parkinson’s disease phenotype: initial symptoms and baseline characteristics in a clinical cohort. Parkinsonism Relat Disord 2005;11:139–145.PubMedGoogle Scholar
  5. 5.
    5. Lewis SJ, Foltynie T, Blackwell AD,. Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005;76:343–348.PubMedGoogle Scholar
  6. 6.
    6. Jankovic J Progression of Parkinson disease: are we making progress in charting the course. Arch Neurol 2005;62:351–352.PubMedGoogle Scholar
  7. 7.
    7. Olanow CW. The scientific basis for the current treatment of Parkinson’s disease. Annu Rev Med 2004;55:41–60.PubMedGoogle Scholar
  8. 8.
    8. Tetrud J. Treatment challenges in early stage Parkinson’s disease. Neurol Clin 2004;22(3 Suppl):S19–33.PubMedGoogle Scholar
  9. 9.
    9. Markham CH, Diamond SG. Long-term follow-up of early dopa treatment in Parkinson’s disease. Ann Neurol 1986;19:365–372.PubMedGoogle Scholar
  10. 10.
    10. Wermuth L. Outpatient treatment of Parkinson’s disease. Eur Neurol 1988;28:152–155.PubMedGoogle Scholar
  11. 11.
    11. Fahn S, Oakes D, Shoulson I,. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004;351(24):2498–2508.PubMedGoogle Scholar
  12. 12.
    12. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002;287:1653–1661.Google Scholar
  13. 13.
    13. Rakshi JS, Pavese N, Uema T,. A comparison of the progression of early Parkinson’s disease in patients started on ropinirole or L-dopa: an 18F-dopa PET study. J Neural Transm 2002;109:1433–1443.PubMedGoogle Scholar
  14. 14.
    14. Whone AL, Watts RL, Stoessl AJ,. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 2003;54:93–101.PubMedGoogle Scholar
  15. 15.
    15. Swope DM. Rapid treatment of “wearing off” in Parkinson’s disease. Neurology 2004;62(6 Suppl 4):S27–31.PubMedGoogle Scholar
  16. 16.
    16. Obeso JA, Rodriguez-Oroz M, Marin C,. The origin of motor fluctuations in Parkinson’s disease: importance of dopaminergic innervation and basal ganglia circuits. Neurology 2004;62(Suppl 1):S17–30.PubMedGoogle Scholar
  17. 17.
    17. Lyons KE, Pahwa R. Deep brain stimulation in Parkinson’s disease. Curr Neurol Neurosci Rep 2004;4:290–295.PubMedGoogle Scholar
  18. 18.
    18. Breit S, Schulz JB, Benabid AL. Deep brain stimulation. Cell Tissue Res 2004;318:275–288.PubMedGoogle Scholar
  19. 19.
    19. Elm JJ, Goetz CG, Ravina B,. A responsive outcome for Parkinson’s disease neuroprotection futility studies. Ann Neurol 2005;57:197–203.PubMedGoogle Scholar
  20. 20.
    20. Calne D, Schulzer M, Mak E,. Treatment for the progression of Parkinson’s disease. Lancet Neurol 2005;4:206.PubMedGoogle Scholar
  21. 21.
    21. Schapira AH, Olanow CW. Neuroprotection in Parkinson disease: mysteries, myths, and misconceptions. JAMA 2004;291:358–364.PubMedGoogle Scholar
  22. 22.
    22. Schapira AH. Disease modification in Parkinson’s disease. Lancet Neurol 2004;3:362–368.PubMedGoogle Scholar
  23. 23.
    23. Lang AE, Obeso JA. Challenges in Parkinson’s disease: restoration of the nigrostriatal dopamine system is not enough. Lancet Neurol 2004;3:309–316.PubMedGoogle Scholar
  24. 24.
    24. Koller WC, Cersosimo MG. Neuroprotection in Parkinson’s disease: an elusive goal. Curr Neurol Neurosci Rep 2004;4:277–283.PubMedGoogle Scholar
  25. 25.
    25. Johnston TH, Brotchie JM. Drugs in development for Parkinson’s disease. Curr Opin Investig Drugs 2004;5:720–726.PubMedGoogle Scholar
  26. 26.
    26. Drucker-Colin R, Verdugo-Diaz L. Cell transplantation for Parkinson’s disease: present status. Cell Mol Neurobiol 2004;24:301–316.PubMedGoogle Scholar
  27. 27.
    27. Dlamini Z, Mbita Z, Zungu M. Genealogy, expression, and molecular mechanisms in apoptosis. Pharmacol Ther 2004;101:1–15.PubMedGoogle Scholar
  28. 28.
    28. Clarke CE. Neuroprotection and pharmacotherapy for motor symptoms in Parkinson’s disease. Lancet Neurol 2004;3:466–474.PubMedGoogle Scholar
  29. 29.
    29. Siderowf A, Newberg A, Chou KL,. [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 2005;64:1716–1720.PubMedGoogle Scholar
  30. 30.
    30. Brooks DJ, Ibanez V, Sawle GV,. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 1990;28:547–555.PubMedGoogle Scholar
  31. 31.
    31. Boja JW, Patel A, Carroll FI,. [125I]RTI-55: a potent ligand for dopamine transporters. Eur J Pharmacol 1991;194:133–134.PubMedGoogle Scholar
  32. 32.
    32. Brooks DJ. Functional imaging in relation to parkinsonian syndromes. J Neurol Sci 1993;115:1–17.PubMedGoogle Scholar
  33. 33.
    33. Brucke T, Kornhuber J, Angelberger P, SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain. J Neural Transm Gen Sect 1993;94:137–146.PubMedGoogle Scholar
  34. 34.
    34. Innis RB, Seibyl JP, Scanley BE,. Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci USA 1993;90:11965–11969.PubMedGoogle Scholar
  35. 35.
    35. Wilson AA, DaSilva JN, Houle S. In vivo evaluation of [11C]- and [18F]-labelled cocaine analogues as potential dopamine transporter ligands for positron emission tomography. Nucl Med Biol 1996;23:141–146.PubMedGoogle Scholar
  36. 36.
    36. Scheffel U, Steinert C, Kim SE,. Effect of dopaminergic drugs on the in vivo binding of [3H]WIN 35,428 to central dopamine transporters. Synapse 1996;23:61–69.PubMedGoogle Scholar
  37. 37.
    37. Haaparanta M, Bergman J, Laakso A,. [18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: biodistribution in rats. Synapse 1996;23:321–327.PubMedGoogle Scholar
  38. 38.
    38. Brownell AL, Elmaleh DR, Meltzer PC,. Cocaine congeners as PET imaging probes for dopamine terminals. J Nucl Med 1996;37:1186–1192.PubMedGoogle Scholar
  39. 39.
    39. Volkow ND, Ding YS, Fowler JS,. A new PET ligand for the dopamine transporter: studies in the human brain. J Nucl Med 1995;36:2162–2168.PubMedGoogle Scholar
  40. 40.
    40. Malison RT, Vessotskie JM, Kung MP,. Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT. J Nucl Med 1995;36:2290–2297.PubMedGoogle Scholar
  41. 41.
    41. Lundkvist C, Halldin C, Swahn CG,. [O-methyl-11C]beta-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.PubMedGoogle Scholar
  42. 42.
    42. Laruelle M, Wallace E, Seibyl JP,. Graphical, kinetic, and equilibrium analyses of in vivo [123I] beta-CIT binding to dopamine transporters in healthy human subjects. J Cereb Blood Flow Metab 1994;14:982–994.PubMedGoogle Scholar
  43. 43.
    43. Innis R, Baldwin R, Sybirska E,. Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [123I]CIT. Eur J Pharmacol 1991;200:369–370.PubMedGoogle Scholar
  44. 44.
    44. Frey KA, Koeppe RA, Kilbourn MR. Imaging the vesicular monoamine transporter. Adv Neurol 2001;86:237–247.PubMedGoogle Scholar
  45. 45.
    45. Best SE, Sarrel PM, Malison RT,. Striatal dopamine transporter availability with [(123)I]beta-CIT SPECT is unrelated to gender or menstrual cycle. Psychopharmacology (Berl) 2005;183:181–189.Google Scholar
  46. 46.
    46. Mozley PD, Schneider JS, Acton PD,. Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson’s disease and in healthy volunteers. J Nucl Med 2000;41:584–589.PubMedGoogle Scholar
  47. 47.
    47. Huang WS, Chiang YH, Lin JC,. Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson’s disease patients. J Nucl Med 2003;44:999–1005.PubMedGoogle Scholar
  48. 48.
    48. Brooks DJ. Detection of preclinical Parkinson’s disease with PET. Geriatrics 1991;46(Suppl 1):25–30.PubMedGoogle Scholar
  49. 49.
    49. Seibyl JP, Marek KL, Quinlan D,. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Ann Neurol 1995;38:589–598.PubMedGoogle Scholar
  50. 50.
    50. Hilker R, Schweitzer K, Coburger S,. Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity. Arch Neurol 2005;62:378–382.PubMedGoogle Scholar
  51. 51.
    51. Au WL, Adams JR, Troiano AR,. Parkinson’s disease: in vivo assessment of disease progression using positron emission tomography. Brain Res Mol Brain Res 2005;134:24–33.PubMedGoogle Scholar
  52. 52.
    52. Sossi V, de la Fuente-Fernandez R, Holden JE,. Changes of dopamine turnover in the progression of Parkinson’s disease as measured by positron emission tomography: their relation to disease-compensatory mechanisms. J Cereb Blood Flow Metab 2004;24:869–876.PubMedGoogle Scholar
  53. 53.
    Seibyl JP. Single-photon emission computed tomography and positron emission tomography evaluations of patients with central motor disorders. Semin Nucl Med 2008;38:274–286.Google Scholar
  54. 54.
    54. Pirker W, Holler I, Gerschlager W,. Measuring the rate of progression of Parkinson’s disease over a 5-year period with beta-CIT SPECT. Mov Disord 2003;18:1266–1272.PubMedGoogle Scholar
  55. 55.
    55. Morrish PK REAL and CALM: what have we learned. Mov Disord 2003;18:839–840.PubMedGoogle Scholar
  56. 56.
    56. Ito K, Morrish PK, Rakshi JS,. Statistical parametric mapping with 18F-dopa PET shows bilaterally reduced striatal and nigral dopaminergic function in early Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;66:754–758.PubMedGoogle Scholar
  57. 57.
    57. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999;56:33–39.PubMedGoogle Scholar
  58. 58.
    58. Quinn N. Parkinsonism—recognition and differential diagnosis. BMJ 1995;310:447–452.PubMedGoogle Scholar
  59. 59.
    59. Meara J, Bhowmick BK, Hobson P. Accuracy of diagnosis in patients with presumed Parkinson’s disease. Age Ageing 1999;28:99–102.PubMedGoogle Scholar
  60. 60.
    60. Hughes AJ, Daniel SE, Kilford L,. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.PubMedGoogle Scholar
  61. 61.
    61. Rajput DR. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1993;56:938–939.PubMedGoogle Scholar
  62. 62.
    62. Weng YH, Yen TC, Chen MC,. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson’s disease from healthy subjects. J Nucl Med 2004;45:393–401.PubMedGoogle Scholar
  63. 63.
    63. Chou KL, Hurtig HI, Stern MB,. Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson’s disease. Parkinsonism Relat Disord 2004;10:375–379.PubMedGoogle Scholar
  64. 64.
    64. Tzen KY, Lu CS, Yen TC,. Differential diagnosis of Parkinson’s disease and vascular parkinsonism by (99m)Tc-TRODAT-1. J Nucl Med 2001;42:408–413.PubMedGoogle Scholar
  65. 65.
    65. 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.PubMedGoogle Scholar
  66. 66.
    66. Group PS. A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in parkinsonism. Parkinson Study Group. Neurology 2000;55:1540–1547.Google Scholar
  67. 67.
    67. Burn DJ, O’Brien JT. Use of functional imaging in Parkinsonism and dementia. Mov Disord 2003;18(Suppl 6):S88–95.PubMedGoogle Scholar
  68. 68.
    68. Jennings DL, Seibyl JP, Oakes D,. (123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 2004;61:1224–1229.PubMedGoogle Scholar
  69. 69.
    69. Seibyl J, Jennings D, Tabamo R,. The role of neuroimaging in the early diagnosis and evaluation of Parkinson’s disease. Minerva Med 2005;96:353–364.PubMedGoogle Scholar
  70. 70.
    70. Varrone A, Marek KL, Jennings D,. [(123)I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Mov Disord 2001;16:1023–1032.PubMedGoogle Scholar
  71. 71.
    71. Kim YJ, Ichise M, Ballinger JM,. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord 2002;17:303–312.PubMedGoogle Scholar
  72. 72.
    72. Walker Z, Costa DC, Walker RW,. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology 2004;62:1568–1572.PubMedGoogle Scholar
  73. 73.
    73. Small GW. Neuroimaging as a diagnostic tool in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2004;17(Suppl 1):25–31.PubMedGoogle Scholar
  74. 74.
    74. O’Brien JT, Colloby S, Fenwick J,. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 2004;61:919–925.PubMedGoogle Scholar
  75. 75.
    75. Schwarz J, Storch A, Koch W,. Loss of dopamine transporter binding in Parkinson’s disease follows a single exponential rather than linear decline. J Nucl Med 2004;45:1694–1697.PubMedGoogle Scholar
  76. 76.
    76. de la Fuente-Fernandez R, Sossi V, Huang Z,. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias. Brain 2004;127(Pt 12):2747–2754.PubMedGoogle Scholar
  77. 77.
    77. Snow B. Objective measures for the progression of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:287.PubMedGoogle Scholar
  78. 78.
    78. Marshall V, Grosset D. Role of dopamine transporter imaging in routine clinical practice. Mov Disord 2003;18:1415–1423.PubMedGoogle Scholar
  79. 79.
    79. van Dyck CH, Seibyl JP, Malison RT,. Age-related decline in dopamine transporters: analysis of striatal subregions, nonlinear effects, and hemispheric asymmetries. Am J Geriatr Psychiatry 2002;10:36–43.PubMedGoogle Scholar
  80. 80.
    80. van Dyck CH, Malison RT, Jacobsen LK,. Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. J Nucl Med 2005;46:745–751.PubMedGoogle Scholar
  81. 81.
    A randomized controlled trial comparing pramipexole with levodopa in early Parkinson’s disease: design and methods of the CALM-PD Study. Parkinson Study Group. Clin Neuropharmacol 2000;23:34–44.Google Scholar
  82. 82.
    82. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004;61:561–566.Google Scholar
  83. 83.
    83. Marek KL, Seibyl JP, Zoghbi SS,. [123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson’s disease. Neurology 1996;46:231–237.PubMedGoogle Scholar
  84. 84.
    84. Braak H, Del Tredici K, Rub U,. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.PubMedGoogle Scholar
  85. 85.
    85. Braak H, Rub U, Gai WP,. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003;110:517–536.PubMedGoogle Scholar
  86. 86.
    86. Kim SE, Choi JY, Choe YS,. Serotonin transporters in the midbrain of Parkinson’s disease patients: a study with 123I-beta-CIT SPECT. J Nucl Med 2003;44:870–876.PubMedGoogle Scholar
  87. 87.
    87. Murai T, Muller U, Werheid K,. In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2001;13:222–228.PubMedGoogle Scholar
  88. 88.
    88. Dewey RB Jr. Autonomic dysfunction in Parkinson’s disease. Neurol Clin 2004;22(3 Suppl):S127–139.PubMedGoogle Scholar
  89. 89.
    89. Kaufmann H, Nahm K, Purohit D,. Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies. Neurology 2004;63:1093–1095.PubMedGoogle Scholar
  90. 90.
    90. Schrag A. Psychiatric aspects of Parkinson’s disease—an update. J Neurol 2004;251:795–804.PubMedGoogle Scholar
  91. 91.
    91. Lemke MR, Fuchs G, Gemende I, Depression and Parkinson’s disease. J Neurol 2004;251(Suppl 6):VI/24–27.Google Scholar
  92. 92.
    92. Burghaus L, Schutz U, Krempel U,. Loss of nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the cerebral cortex of Parkinson patients. Parkinsonism Relat Disord 2003;9:243–246.PubMedGoogle Scholar
  93. 93.
    93. Martin-Ruiz C, Lawrence S, Piggott M,. Nicotinic receptors in the putamen of patients with dementia with Lewy bodies and Parkinson’s disease: relation to changes in alpha-synuclein expression. Neurosci Lett 2002;335:134–138.PubMedGoogle Scholar
  94. 94.
    94. Pimlott SL, Piggott M, Owens J,. Nicotinic acetylcholine receptor distribution in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and vascular dementia: in vitro binding study using 5-[(125)i]-a-85380. Neuropsychopharmacology 2004;29:108–116.PubMedGoogle Scholar
  95. 95.
    95. Frederickson RD, Brunden KK. New opportunities in AD research—roles of immunoinflammatory responses and glia. Alzheimer Dis Assoc Disord 1994;8:159–165.PubMedGoogle Scholar
  96. 96.
    96. Rogers J, Webster S, Lue LF,. Inflammation and Alzheimer’s disease pathogenesis. Neurobiol Aging 1996;17:681–686.PubMedGoogle Scholar
  97. 97.
    97. McGeer EG, McGeer PL. The role of the immune system in neurodegenerative disorders. Mov Disord 1997;12:855–858.PubMedGoogle Scholar
  98. 98.
    98. Hirsch EC, Breidert T, Rousselet E,. The role of glial reaction and inflammation in Parkinson’s disease. Ann NY Acad Sci 2003;991:214–228.PubMedGoogle Scholar
  99. 99.
    99. McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann NY Acad Sci 2004;1035:104–116.PubMedGoogle Scholar
  100. 100.
    100. McGeer PL, Schwab C, Parent A,. Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol 2003;54:599–604.PubMedGoogle Scholar
  101. 101.
    101. Langston JW, Forno LS, Tetrud J,. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 1999;46:598–605.PubMedGoogle Scholar
  102. 102.
    102. Teismann P, Schulz JB. Cellular pathology of Parkinson’s disease: astrocytes, microglia and inflammation. Cell Tissue Res 2004;318:149–161.PubMedGoogle Scholar
  103. 103.
    103. Chen H, Zhang SM, Hernan MA,. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 2003;60:1059–1064.PubMedGoogle Scholar
  104. 104.
    104. Asanuma M, Miyazaki I, Ogawa N. Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases. Curr Pharm Des 2004;10:695–700.PubMedGoogle Scholar
  105. 105.
    105. Cagnin A, Brooks DJ, Kennedy AM,. In-vivo measurement of activated microglia in dementia. Lancet 2001;358:461–467.PubMedGoogle Scholar
  106. 106.
    106. Gerhard A, Banati RB, Goerres GB,. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology 2003;61:686–689.PubMedGoogle Scholar
  107. 107.
    107. Gerhard A, Watts J, Trender-Gerhard I, In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord 2004; 19(10):1221–1226.Google Scholar
  108. 108.
    108. Ouchi, Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T, Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 2005;57(2):168–175.PubMedGoogle Scholar
  109. 109.
    109. Turner MR, Cagnin A, Turkheimer FE,. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis 2004;15:601–609.PubMedGoogle Scholar
  110. 110.
    110. Huang WS, Lin SZ, Lin JC,. Evaluation of early-stage Parkinson’s disease with 99mTc-TRODAT-1 imaging. J Nucl Med 2001;42:1303–1308.PubMedGoogle Scholar
  111. 111.
    111. Schwarz J, Linke R, Kerner M,. Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson’s disease: implications for a preclinical diagnosis. Arch Neurol 2000;57:205–208.PubMedGoogle Scholar
  112. 112.
    Reed J, Huang Z. Apoptosis pathways and drug targets. Nat Rev Drug Dis/Mol Cell Biol November 2004, www.nature.com/nrm/posters/apoptosis/index.html .
  113. 113.
    113. Marek K, Seibyl J. A molecular map for neurodegeneration. Science 2000;289:409–411. PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • John P. Seibyl
    • 1
  1. 1.Imaging DivisionInstitute for Neurodegenerative DisordersCT

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