Abstract
The 4-repeat (4R)-tauopathies can be clinically heterogeneous and difficult to diagnose. An FDG-PET pattern of hypometabolism has been previously reported in clinically suspected 4R-tauopathies. Considering that pathological confirmation has not been used as inclusion criteria in these studies, however, the possibility exists that atypical cases were excluded. We studied pathologically confirmed cases of 4R-tauopathies to determine if FDG-PET patterns of hypometabolism different than those previously described exist. We identified all autopsy confirmed 4R-tauopathies with FDG-PET imaging performed between 2010 and 2013 within the Mayo Clinic database. Clinical features and FDG-PET imaging were compared to a group of normal controls. Ten patients, seven of which had autopsy-confirmed progressive supranuclear palsy (PSP), were identified. We also identified two cases with globular glial tauopathy (GGT) and one case of corticobasal degeneration (CBD). The overall predominant imaging findings included bilateral caudate hypometabolism in nine cases, mild asymmetric thalamic hypometabolism in eight, midbrain hypometabolism in seven, and bilateral hypometabolism in the supplementary motor area in seven. No differences were observed between PSP and GGT. The one CBD case had asymmetric parietal hypometabolism that was not seen in the PSP and GGT cases. As previously described, 4R-tauopathies are associated with frontal, caudate, midbrain and thalamic hypometabolism on FDG-PET. This is the first report of FDG-PET in GGT, and although our series was limited, no features distinguish GGT from PSP. There was some evidence that parietal hypometabolism may be suggestive of CBD.
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Schneider JA, Watts RL, Gearing M, Brewer RP, Mirra SS (1997) Corticobasal degeneration: neuropathologic and clinical heterogeneity. Neurology 48(4):959–969
Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, McKee A, Tabaton M, Litvan I (1994) Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 44(11):2015–2019
Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ (2005) Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism. Brain J Neurol 128(Pt 6):1247–1258. doi:10.1093/brain/awh488
Ahmed Z, Bigio EH, Budka H, Dickson DW, Ferrer I, Ghetti B, Giaccone G, Hatanpaa KJ, Holton JL, Josephs KA, Powers J, Spina S, Takahashi H, White CL 3rd, Revesz T, Kovacs GG (2013) Globular glial tauopathies (GGT): consensus recommendations. Acta Neuropathol. doi:10.1007/s00401-013-1171-0
Coulier IM, de Vries JJ, Leenders KL (2003) Is FDG-PET a useful tool in clinical practice for diagnosing corticobasal ganglionic degeneration? Mov Disord Off J Mov Disord Soc 18(10):1175–1178. doi:10.1002/mds.10498
Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, Eidelberg D (2005) FDG PET in the differential diagnosis of parkinsonian disorders. NeuroImage 26(3):912–921. doi:10.1016/j.neuroimage.2005.03.012
Foster NL, Gilman S, Berent S, Morin EM, Brown MB, Koeppe RA (1988) Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography. Ann Neurol 24(3):399–406. doi:10.1002/ana.410240308
Foster NL, Minoshima S, Johanns J, Little R, Heumann ML, Kuhl DE, Gilman S (2000) PET measures of benzodiazepine receptors in progressive supranuclear palsy. Neurology 54(9):1768–1773
Garraux G, Salmon E, Peigneux P, Kreisler A, Degueldre C, Lemaire C, Destee A, Franck G (2000) Voxel-based distribution of metabolic impairment in corticobasal degeneration. Mov Disord Off J Mov Disord Soc 15(5):894–904
Hellwig S, Amtage F, Kreft A, Buchert R, Winz OH, Vach W, Spehl TS, Rijntjes M, Hellwig B, Weiller C, Winkler C, Weber WA, Tuscher O, Meyer PT (2012) [(1)(8)F]FDG-PET is superior to [(1)(2)(3)I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology 79(13):1314–1322. doi:10.1212/WNL.0b013e31826c1b0a
Hosaka K, Ishii K, Sakamoto S, Mori T, Sasaki M, Hirono N, Mori E (2002) Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration. J Neurol Sci 199(1–2):67–71
Juh R, Kim J, Moon D, Choe B, Suh T (2004) Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET. Eur J Radiol 51(3):223–233. doi:10.1016/s0720-048x(03)00214-6
Juh R, Pae CU, Kim TS, Lee CU, Choe B, Suh T (2005) Cerebral glucose metabolism in corticobasal degeneration comparison with progressive supranuclear palsy using statistical mapping analysis. Neurosci Lett 383(1–2):22–27. doi:10.1016/j.neulet.2005.03.057
Klein RC, de Jong BM, de Vries JJ, Leenders KL (2005) Direct comparison between regional cerebral metabolism in progressive supranuclear palsy and Parkinson’s disease. Mov Disord Off J Mov Disord Soc 20(8):1021–1030. doi:10.1002/mds.20493
Mishina M, Ishii K, Mitani K, Ohyama M, Yamazaki M, Ishiwata K, Senda M, Kobayashi S, Kitamura S, Katayama Y (2004) Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy. Acta Neurol Scand 110(2):128–135. doi:10.1111/j.1600-0404.2004.00293.x
Srulijes K, Reimold M, Liscic RM, Bauer S, Dietzel E, Liepelt-Scarfone I, Berg D, Maetzler W (2012) Fluorodeoxyglucose positron emission tomography in Richardson’s syndrome and progressive supranuclear palsy-parkinsonism. Mov Disord Off J Mov Disord Soc 27(1):151–155
Tang CC, Poston KL, Eckert T, Feigin A, Frucht S, Gudesblatt M, Dhawan V, Lesser M, Vonsattel JP, Fahn S, Eidelberg D (2010) Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol 9(2):149–158. doi:10.1016/s1474-4422(10)70002-8
Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries JJ, van Oostrom JC, Leenders KL (2010) Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord Off J Mov Disord Soc 25(14):2395–2404. doi:10.1002/mds.23291
Tripathi M, Dhawan V, Peng S, Kushwaha S, Batla A, Jaimini A, D’Souza MM, Sharma R, Saw S, Mondal A (2013) Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography. Neuroradiology 55(4):483–492. doi:10.1007/s00234-012-1132-7
Turaga SP, Mridula R, Borgohain R (2013) Cerebral glucose metabolism, clinical, neuropsychological, and radiological profile in patients with corticobasal syndrome. Neurol India 61(1):7–11. doi:10.4103/0028-3886.107916
Zhao P, Zhang B, Gao S (2012) 18F-FDG PET study on the idiopathic Parkinson’s disease from several parkinsonian-plus syndromes. Parkinsonism Relat Disord 18(Suppl 1):S60–S62. doi:10.1016/s1353-8020(11)70020-7
Dickson DW, Ahmed Z, Algom AA, Tsuboi Y, Josephs KA (2010) Neuropathology of variants of progressive supranuclear palsy. Curr Opin Neurol 23(4):394–400. doi:10.1097/WCO.0b013e32833be924
Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ, Boeve BF, Knopman DS, Dickson DW, Jack CR Jr, Petersen RC (2006) Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain J Neurol 129(Pt 6):1385–1398. doi:10.1093/brain/awl078
Josephs KA, Katsuse O, Beccano-Kelly DA, Lin WL, Uitti RJ, Fujino Y, Boeve BF, Hutton ML, Baker MC, Dickson DW (2006) A typical progressive supranuclear palsy with corticospinal tract degeneration. J Neuropathol Exp Neurol 65(4):396–405
Botha H, Whitwell JL, Madhaven A, Senjem ML, Lowe V, Josephs KA (2013) The pimple sign of progressive supranuclear palsy syndrome. Parkinsonism Relat Disord. doi: 10.1016/j.parkreldis.2013.10.023 [Epub ahead of print]
Conflicts of interest
N. L. Zalewski: none. H. Botha: none. J. Whitwell: none. V. Lowe: none. Dr. Lowe: Received personal compensation for consulting from Bayer Pharmaceuticals; Research Grants from: GE Health Care, Siemens Molecular Imaging, AVID Radiopharmaceuticals, INC. D. Dickson: Consultant, Neotope, Inc., South San Francisco, CA. K. Josephs: none.
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The study was approved by the Mayo Clinic Institutional Review Board. All patients consented for their data to be used for research.
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Zalewski, N., Botha, H., Whitwell, J.L. et al. FDG-PET in pathologically confirmed spontaneous 4R-tauopathy variants. J Neurol 261, 710–716 (2014). https://doi.org/10.1007/s00415-014-7256-4
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DOI: https://doi.org/10.1007/s00415-014-7256-4