nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

09.10.2023 | Original Article

In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension

verfasst von: Chenxi Xue, Xiaofeng Dou, Congcong Yu, Yan Zhong, Jing Wang, Xiang Zhang, Le Xue, Daoyan Hu, Shuang Wu, Hong Zhang, Mei Tian

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2024

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Multiple system atrophy (MSA) is a rare neurodegenerative disease, often presented with orthostatic hypotension (OH), which is a disabling symptom but has not been very explored. Here, we investigated MSA patients with OH by using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ¹¹C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (¹¹C-CFT) for in vivo evaluation of the glucose metabolism and dopaminergic function of the brain.

Methods

Totally, 51 patients with MSA and 20 healthy controls (HC) who underwent ¹⁸F-FDG PET/CT were retrospectively enrolled, among which 24 patients also underwent ¹¹C-CFT PET/CT. All patients were divided into MSA-OH(+) and MSA-OH(-) groups. Then, statistical parametric mapping (SPM) method was used to reveal the regional metabolic and dopaminergic characteristics of MSA-OH(+) compared with MSA-OH(-). Moreover, the metabolic networks of MSA-OH(+), MSA-OH(-) and HC groups were also constructed and analyzed based on graph theory to find possible network-level changes in MSA patients with OH.

Results

The SPM results showed significant hypometabolism in the pons and right cerebellar tonsil, as well as hypermetabolism in the left parahippocampal gyrus and left superior temporal gyrus in MSA-OH(+) compared with MSA-OH(-). A reduced ¹¹C-CFT uptake in the left caudate was also shown in MSA-OH(+) compared with MSA-OH(-). In the network analysis, significantly reduced local efficiency and clustering coefficient were shown in MSA-OH(+) compared with HC, and decreased nodal centrality in the frontal gyrus was found in MSA-OH(+) compared with MSA-OH(-).

Conclusion

In this study, the changes in glucose metabolism in the pons, right cerebellar tonsil, left parahippocampal gyrus and left superior temporal gyrus were found closely related to OH in MSA patients. And the decreased presynaptic dopaminergic function in the left caudate may contribute to OH in MSA. Taken together, this study provided in vivo pathophysiologic information on MSA with OH from neuroimaging approach, which is essential for a better understanding of MSA with OH.

Nur mit Berechtigung zugänglich

Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372:249–63. https://doi.org/10.1056/NEJMra1311488.CrossRefPubMed

Meissner WG, Fernagut PO, Dehay B, Péran P, Traon APL, Foubert-Samier A, et al. Multiple System Atrophy: Recent Developments and Future Perspectives. Mov Disord. 2019;34:1629–42. https://doi.org/10.1002/mds.27894.CrossRef

Poewe W, Stankovic I, Halliday G, Meissner WG, Wenning GK, Pellecchia MT, et al. Multiple system atrophy. Nat Rev Dis Primers. 2022;8:56. https://doi.org/10.1038/s41572-022-00382-6.CrossRefPubMed

Coon EA, Ahlskog JE. My Treatment Approach to Multiple System Atrophy. Mayo Clin Proc. 2021;96:708–19. https://doi.org/10.1016/j.mayocp.2020.10.005.CrossRef

Grimaldi S, Boucekine M, Witjas T, Fluchere F, Azulay JP, Guedj E, et al. Early atypical signs and insula hypometabolism predict survival in multiple system atrophy. J Neurol Neurosurg Psychiatry. 2021. https://doi.org/10.1136/jnnp-2020-324823.CrossRefPubMed

Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, et al. Diagnosis and treatment of orthostatic hypotension. Lancet Neurol. 2022;21:735–46. https://doi.org/10.1016/S1474-4422(22)00169-7.CrossRefPubMedPubMedCentral

Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic Hypotension. J Am Coll Cardiol. 2018;72:1294–309. https://doi.org/10.1016/j.jacc.2018.05.079.CrossRefPubMed

Benarroch EE. The arterial baroreflex: functional organization and involvement in neurologic disease. Neurology. 2008;71:1733–8. https://doi.org/10.1212/01.wnl.0000335246.93495.92.CrossRefPubMed

Palma JA, Benarroch EE. Neural control of the heart: recent concepts and clinical correlations. Neurology. 2014;83:261–71. https://doi.org/10.1212/wnl.0000000000000605.CrossRef

10.

Coon EA, Cutsforth-Gregory JK, Benarroch EE. Neuropathology of autonomic dysfunction in synucleinopathies. Mov Disord. 2018;33:349–58. https://doi.org/10.1002/mds.27186.CrossRefPubMed

11.

Benarroch EE, Smithson IL, Low PA, Parisi JE. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure. Ann Neurol. 1998;43:156–63. https://doi.org/10.1002/ana.410430205.CrossRefPubMed

12.

Benarroch EE. Depletion of ventromedullary NK-1 receptor-immunoreactive neurons in multiple system atrophy. Brain. 2003;126:2183–90. https://doi.org/10.1093/brain/awg220.CrossRefPubMed

13.

Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969;32:28–34. https://doi.org/10.1136/jnnp.32.1.28.CrossRefPubMedPubMedCentral

14.

Gray F, Vincent D, Hauw JJ. Quantitative study of lateral horn cells in 15 cases of multiple system atrophy. Acta Neuropathol. 1988;75:513–8. https://doi.org/10.1007/bf00687140.CrossRef

15.

Kennedy PG, Duchen LW. A quantitative study of intermediolateral column cells in motor neuron disease and the Shy-Drager syndrome. J Neurol Neurosurg Psychiatry. 1985;48:1103–6. https://doi.org/10.1136/jnnp.48.11.1103.CrossRefPubMedPubMedCentral

16.

Oppenheimer DR. Lateral horn cells in progressive autonomic failure. J Neurol Sci. 1980;46:393–404. https://doi.org/10.1016/0022-510x(80)90064-7.CrossRefPubMed

17.

Sakajiri K, Makifuchi T, Fukuhara N, Nakajima T. Quantitative study of intermediolateral column cell counts in Machado-Joseph disease. J Neurol Sci. 1996;144:156–9. https://doi.org/10.1016/s0022-510x(96)00221-3.CrossRef

18.

Critchley HD, Mathias CJ, Josephs O, O’Doherty J, Zanini S, Dewar BK, et al. Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. Brain. 2003;126:2139–52. https://doi.org/10.1093/brain/awg216.CrossRef

19.

Papapetropoulos S, Mash DC. Insular pathology in Parkinson’s disease patients with orthostatic hypotension. Parkinsonism Relat Disord. 2007;13:308–11. https://doi.org/10.1016/j.parkreldis.2006.06.009.CrossRefPubMed

20.

Cersosimo MG, Benarroch EE. Central control of autonomic function and involvement in neurodegenerative disorders. Handb Clin Neurol. 2013;117:45–57. https://doi.org/10.1016/b978-0-444-53491-0.00005-5.CrossRefPubMed

21.

Pazo JH, Belforte JE. Basal ganglia and functions of the autonomic nervous system. Cell Mol Neurobiol. 2002;22:645–54. https://doi.org/10.1023/a:1021844605250.CrossRefPubMed

22.

van den Buuse M. Pressor responses to brain dopaminergic stimulation. Clin Exp Pharmacol Physiol. 1997;24:764–9. https://doi.org/10.1111/j.1440-1681.1997.tb02129.x.CrossRefPubMed

23.

Volkow ND, Wang GJ, Fowler JS, Molina PE, Logan J, Gatley SJ, et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology. 2003;166:264–70. https://doi.org/10.1007/s00213-002-1340-7.CrossRefPubMed

24.

Metzger JM, Emborg ME. Autonomic dysfunction in Parkinson disease and animal models. Clin Auton Res. 2019;29:397–414. https://doi.org/10.1007/s10286-018-00584-7.CrossRefPubMedPubMedCentral

25.

Tian M, Civelek AC, Carrio I, Watanabe Y, Kang KW, Murakami K, et al. International consensus on the use of tau PET imaging agent (18)F-flortaucipir in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2022;49:895–904. https://doi.org/10.1007/s00259-021-05673-w.CrossRefPubMedPubMedCentral

26.

Tian M, Zuo C, Civelek AC, Carrio I, Watanabe Y, Kang KW, et al. International Nuclear Medicine Consensus on the Clinical Use of Amyloid Positron Emission Tomography in Alzheimer’s Disease. Phenomics. 2022. https://doi.org/10.1007/s43657-022-00068-9.CrossRefPubMedPubMedCentral

27.

Tian M, He X, Jin C, He X, Wu S, Zhou R, et al. Transpathology: molecular imaging-based pathology. Eur J Nucl Med Mol Imaging. 2021;48:2338–50. https://doi.org/10.1007/s00259-021-05234-1.CrossRefPubMedPubMedCentral

28.

Tian M, Watanabe Y, Kang KW, Murakami K, Chiti A, Carrio I, et al. International consensus on the use of [(18)F]-FDG PET/CT in pediatric patients affected by epilepsy. Eur J Nucl Med Mol Imaging. 2021;48:3827–34. https://doi.org/10.1007/s00259-021-05524-8.CrossRefPubMed

29.

Verger A, Grimaldi S, Ribeiro MJ, Frismand S, Guedj E. Single Photon Emission Computed Tomography/Positron Emission Tomography Molecular Imaging for Parkinsonism: A Fast-Developing Field. Ann Neurol. 2021;90:711–9. https://doi.org/10.1002/ana.26187.CrossRefPubMedPubMedCentral

30.

Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009;10:186–98. https://doi.org/10.1038/nrn2575.CrossRefPubMed

31.

Attwell D, Iadecola C. The neural basis of functional brain imaging signals. Trends Neurosci. 2002;25:621–5. https://doi.org/10.1016/s0166-2236(02)02264-6.CrossRefPubMed

32.

Mihaescu AS, Kim J, Masellis M, Graff-Guerrero A, Cho SS, Christopher L, et al. Graph theory analysis of the dopamine D2 receptor network in Parkinson’s disease patients with cognitive decline. J Neurosci Res. 2021;99:947–65. https://doi.org/10.1002/jnr.24760.CrossRefPubMed

33.

Lu CF, Soong BW, Wu HM, Teng S, Wang PS, Wu YT. Disrupted cerebellar connectivity reduces whole-brain network efficiency in multiple system atrophy. Mov Disord. 2013;28:362–9. https://doi.org/10.1002/mds.25314.CrossRefPubMed

34.

Bu LL, Liu FT, Jiang CF, Guo SS, Yu H, Zuo CT, et al. Patterns of dopamine transporter imaging in subtypes of multiple system atrophy. Acta Neurol Scand. 2018;138:170–6. https://doi.org/10.1111/ane.12932.CrossRefPubMed

35.

Jia XZ, Wang J, Sun HY, Zhang H, Liao W, Wang Z, et al. RESTplus: an improved toolkit for resting-state functional magnetic resonance imaging data processing. Sci Bull (Beijing). 2019;64:953–4. https://doi.org/10.1016/j.scib.2019.05.008.CrossRefPubMed

36.

Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15:273–89. https://doi.org/10.1006/nimg.2001.0978.CrossRefPubMed

37.

Lee R, Shin JH, Choi H, Kim HJ, Cheon GJ, Jeon B. Variability of FP-CIT PET Patterns Associated With Clinical Features of Multiple System Atrophy. Neurology. 2021;96:e1663–71. https://doi.org/10.1212/WNL.0000000000011634.CrossRefPubMed

38.

Mijalkov M, Kakaei E, Pereira JB, Westman E, Volpe G. BRAPH: A graph theory software for the analysis of brain connectivity. PLoS One. 2017;12:e0178798. https://doi.org/10.1371/journal.pone.0178798.CrossRefPubMedPubMedCentral

39.

Xia M, Wang J, He Y. BrainNet Viewer: a network visualization tool for human brain connectomics. PLoS One. 2013;8:e68910. https://doi.org/10.1371/journal.pone.0068910.CrossRefPubMedPubMedCentral

40.

Crossley NA, Mechelli A, Scott J, Carletti F, Fox PT, McGuire P, et al. The hubs of the human connectome are generally implicated in the anatomy of brain disorders. Brain. 2014;137:2382–95. https://doi.org/10.1093/brain/awu132.CrossRefPubMedPubMedCentral

41.

Rubinov M, Sporns O. Complex network measures of brain connectivity: Uses and interpretations. Neuroimage. 2010;52:1059–69. https://doi.org/10.1016/j.neuroimage.2009.10.003.CrossRefPubMed

42.

Lyoo CH, Jeong Y, Ryu YH, Lee SY, Song TJ, Lee JH, et al. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy. Brain. 2008;131:438–46. https://doi.org/10.1093/brain/awm328.CrossRef

43.

Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries JJ, et al. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord. 2010;25:2395–404. https://doi.org/10.1002/mds.23291.CrossRefPubMed

44.

Pasquini J, Firbank MJ, Ceravolo R, Silani V, Pavese N. Diffusion Magnetic Resonance Imaging Microstructural Abnormalities in Multiple System Atrophy: A Comprehensive Review. Mov Disord. 2022;37:1963–84. https://doi.org/10.1002/mds.29195.CrossRefPubMedCentral

45.

Baker J, Kimpinski K. Evidence of Impaired Cerebellar Connectivity at Rest and During Autonomic Maneuvers in Patients with Autonomic Failure. Cerebellum. 2020;19:30–9. https://doi.org/10.1007/s12311-019-01076-8.CrossRefPubMed

46.

Kimmerly DS, O’Leary DD, Menon RS, Gati JS, Shoemaker JK. Cortical regions associated with autonomic cardiovascular regulation during lower body negative pressure in humans. J Physiol. 2005;569:331–45. https://doi.org/10.1113/jphysiol.2005.091637.CrossRefPubMedCentral

47.

Nemmi F, Pavy-Le Traon A, Phillips OR, Galitzky M, Meissner WG, Rascol O, et al. A totally data-driven whole-brain multimodal pipeline for the discrimination of Parkinson’s disease, multiple system atrophy and healthy control. Neuroimage Clin. 2019;23:101858. https://doi.org/10.1016/j.nicl.2019.101858.CrossRefPubMedPubMedCentral

48.

Yang H, Wang N, Luo X, Lv H, Liu H, Li Y, et al. Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy. Neuroimage Clin. 2019;23:101891. https://doi.org/10.1016/j.nicl.2019.101891.CrossRefPubMedCentral

49.

Laosiripisan J, Tarumi T, Gonzales MM, Haley AP, Tanaka H. Association between cardiovagal baroreflex sensitivity and baseline cerebral perfusion of the hippocampus. Clin Auton Res. 2015;25:213–8. https://doi.org/10.1007/s10286-015-0296-8.CrossRefPubMed

50.

Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage. 2005;26:912–21. https://doi.org/10.1016/j.neuroimage.2005.03.012.CrossRefPubMed

51.

Wenning GK, Granata R, Krismer F, Dürr S, Seppi K, Poewe W, et al. Orthostatic Hypotension Is Differentially Associated with the Cerebellar Versus the Parkinsonian Variant of Multiple System Atrophy: a Comparative Study. The Cerebellum. 2011;11:223–6. https://doi.org/10.1007/s12311-011-0299-5.CrossRef

52.

Pavy-Le Traon A, Piedvache A, Perez-Lloret S, Calandra-Buonaura G, Cochen-De Cock V, Colosimo C, et al. New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study. J Neurol Neurosurg Psychiatry. 2016;87:554–61. https://doi.org/10.1136/jnnp-2014-309999.CrossRefPubMed

53.

Lazzeri G, Franco G, Difonzo T, Carandina A, Gramegna C, Vergari M, et al. Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study. Front Neurol. 2022;13:912820. https://doi.org/10.3389/fneur.2022.912820.CrossRefPubMedPubMedCentral

54.

Robertson AD, Messner MA, Shirzadi Z, Kleiner-Fisman G, Lee J, Hopyan J, et al. Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders. Parkinsonism Relat Disord. 2016;22:80–6. https://doi.org/10.1016/j.parkreldis.2015.11.019.CrossRef

55.

Wood SJ, Ramsdell CD, Mullen TJ, Oman CM, Harm DL, Paloski WH. Transient cardio-respiratory responses to visually induced tilt illusions. Brain Res Bull. 2000;53:25–31. https://doi.org/10.1016/s0361-9230(00)00305-1.CrossRefPubMed

56.

Ryu HS, Oh M, Oh JS, Moon H, Park KW, Lee C, et al. Distinct clinical features of predominant pre-synaptic and trans-synaptic nigrostriatal dysfunction in multiple system atrophy. J Neurol Sci. 2019;402:100–6. https://doi.org/10.1016/j.jns.2019.05.017.CrossRefPubMed

57.

van Deursen DN, van den Heuvel OA, Booij J, Berendse HW, Vriend C. Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies. J Neurol. 2020;267:1922–30. https://doi.org/10.1007/s00415-020-09785-5.CrossRefPubMedPubMedCentral

58.

Kitagawa T, Umehara T, Oka H, Shiraishi T, Sato T, Takatsu H, et al. Association between heart rate variability and striatal dopamine depletion in Parkinson’s disease. J Neural Transm (Vienna). 2021;128:1835–40. https://doi.org/10.1007/s00702-021-02418-9.CrossRefPubMed

59.

Bailey ES, Hooshmand SJ, Badihian N, Sandroni P, Benarroch EE, Bower JH, et al. Sex and Gender Influence Urinary Symptoms and Management in Multiple System Atrophy. J Mov Disord. 2023;16:196–201. https://doi.org/10.14802/jmd.23016.CrossRefPubMedCentral

60.

Coon EA, Nelson RM, Sletten DM, Suarez MD, Ahlskog JE, Benarroch EE, et al. Sex and gender influence symptom manifestation and survival in multiple system atrophy. Auton Neurosci. 2019;219:49–52. https://doi.org/10.1016/j.autneu.2019.04.002.CrossRefPubMedPubMedCentral

Titel: In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension
verfasst von: Chenxi Xue
Xiaofeng Dou
Congcong Yu
Yan Zhong
Jing Wang
Xiang Zhang
Le Xue
Daoyan Hu
Shuang Wu
Hong Zhang
Mei Tian
Publikationsdatum: 09.10.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06443-6

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2024

Toward individualized dosimetry for radiopharmaceutical therapy in day-to-day clinical practice of nuclear oncology: overcoming heterogeneity of radiation-absorbed dose to tumor and critical organs

Comparison of parametric imaging and SUV imaging with [68 Ga]Ga-PSMA-11 using dynamic total-body PET/CT in prostate cancer

Abdelhamid H. Elgazzar, Synopsis of Pathophysiology in Nuclear Medicine, Second Edition

Analysis of image data from the EuroNet PHL-C2 trial indicates a potential reduction in injected F-18 FDG activities in children: a proposal to update the EANM Paediatric Dosage Card

Controversies of [68Ga]Ga-FAPI-46 and 2-[18F]FDG findings in metastatic melanoma

ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers