Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson's Disease

Jörg Spiegel, Dirk Hellwig, Wolfgang H Jost, Georgios Farmakis, Samuel Samnick, Klaus Fassbender, Carl M Kirsch, Ulrich Dillmann, Jörg Spiegel, Dirk Hellwig, Wolfgang H Jost, Georgios Farmakis, Samuel Samnick, Klaus Fassbender, Carl M Kirsch, Ulrich Dillmann

Abstract

In idiopathic Parkinson's disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [(123)I]FP-CIT SPECT - to quantify cerebral nigrostriatal dopaminergic degeneration - and myocardial [(123)I]MIBG scintigraphy - to quantify extracranial myocardial sympathetic degeneration - were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function.

Keywords: FP-CIT SPECT; MIBG scintigraphy; Parkinson’s disease.

Figures

Fig. (1)
Fig. (1)
Correlation between putamen FP-CIT SPECT and MIBG scintigraphy. Each patient is represented by one symbol (patients with Hoehn and Yahr stage 1: yellow triangles, patients H&Y stage 2: red squares, patients H&Y stages 3 + 4: blue rhombs).

References

    1. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci. 1973;20(4):415–55.
    1. Deuschl G, Krack P. Morbus Parkinson. In: Hopf HC, Deuschl G, Diener HC, Reichmann H, editors. Neurologie in Praxis und Klinik. 3rd. Vol. 2. Stuttgart New York: Georg Thieme Verlag; 1999. pp. 49–69.
    1. Booij J, Bergmans P, Winogrodzka A, Speelman JD, Wolters EC. Imaging of dopamine transporters with [123I]FP-CIT does not suggest a significant effect on age on the symptomatic threshold of disease in Parkinson’s disease. Synapse. 2001;39(2):101–8.
    1. Edwards LL, Quigley EM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology. 1992;42(4):726–32.
    1. Iwanaga K, Wakabayashi K, Yoshimoto M, et al. Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases. Neurology. 1999;52(6):1269–71.
    1. Kaufmann H, Nahm K, Purohit D, Wolfe D. Autonomic failure as the initial presentation of Parkinson’s disease and dementia with Lewy bodies. Neurology. 2004;63(6):1093–5.
    1. Micieli G, Tosi P, Marcheselli S, Cavallini A. Autonomic dysfunction in Parkinson’s disease. Neurol Sci. 2003;24(1):S32–4.
    1. Okada Y, Ito Y, Aida J, Yasuhara M, Ohkawa SI, Hirokawa K. Lewy bodies in the sinoatrial nodal ganglion: clinicopathological studies. Pathol Intern. 2004;54(9):682–7.
    1. Wakabayashi K, Takahashi H. Neuropathology of autonomous nervous system in Parkinson’s disease. Eur Neurol. 1997;38(2):2–7.
    1. Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with [123I]iodobenzylguanidine. J Nucl Med. 1980;21(4):349–53.
    1. Braune S. The role of cardiac metaiodobenzylguanidine in the differential diagnosis of parkinsonian syndromes. Clin Auton Res. 2001;11(6):351–5.
    1. Hamada K, Hirayama M, Watanabe H, et al. Onset age and severity of motor impairment are associated with reduction of myocar-dial (123I)-MIBG uptake in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2003;74(4):423–6.
    1. Yoshita M, Hayashi M, Hirai S. Decreased myocardial accumulation of I123-meta-iodobenzylguanidine in Parkinson’s disease. Nucl Med Commun. 1998;19(2):137–42.
    1. Benamer HTS, Patterson J, Wyper DJ, Hadley DM, MacPhee GJA, Grosset DG. Correlation of Parkinson’s disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov Disord. 2000;15(4):692–8.
    1. Hughes A, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181–4.
    1. Laruelle M, Baldwin RM, Malison RT, et al. SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in non-human primates. Synapse. 1993;13(4):295–309.
    1. Ahlskog JE, Uitti RJ, O’Connor MK, et al. The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson’s disease. Mov Disord. 1999;14(6):940–6.
    1. Guttman M, Stewart D, Hussey D, Wilson A, Houle S, Kish S. Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology. 2001;56(11):1559–64.
    1. Innis RB, Marek KL, Sheff K, et al. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]β-CIT. Mov Disord. 1999;14(3):436–42.
    1. Nurmi E, Bergman J, Eskola O, et al. Reproducibility and effect of levodopa on dopamine transporter function measurements: a [18F]CFT PET study. J Cereb Blood Flow Metab. 2000;20(11):1604–9.
    1. Satoh A, Serita T, Seto M, et al. Loss of 123I-MIBG uptake by the heart in Parkinson’s disease: Assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med. 1999;40(3):371–5.
    1. The Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson’s disease progression. JAMA. 2002;287(13):1653–61.
    1. Spiegel J, Hellwig D, Samnick S, et al. Striatal FP-CIT uptake differs in the subtypes of early Parkinson’s disease. J Neural Transm. 2007;114(3):331–5.
    1. Spiegel J, Möllers MO, Jost WH, et al. FP-CIT and MIBG scinti-graphy in early Parkinson’s disease. Mov Disord. 2005;20(5):552–61.
    1. Turner B. Pathology of paralysis agitans. In: Vinken PJ, Bruyn GW, editors. Handbook of Clinical Neurology. Vol. 6. Amsterdam, New York: North-Holland Publishing Company, John Wiley& Sons Inc; 1968. pp. 212–7.
    1. Braak H, Ghebremedhin E, Rüb U, Bratzke HJ, Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318(1):121–34.
    1. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17(5):427–42.
    1. Fahn S, Elton RL, members of the UPDRS Development Committee . Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, editors. Recent developments in Parkinson’s disease. Florham Park, HJ: Macmillan Healthcare Information; 1987. pp. 153–64.

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