Neurological Sciences

, Volume 34, Issue 7, pp 1049–1055 | Cite as

Gray matter atrophy in progressive supranuclear palsy: meta-analysis of voxel-based morphometry studies

  • Hai Cun ShiEmail author
  • Jian Guo Zhong
  • Ping Lei Pan
  • Pei Rong Xiao
  • Yuan Shen
  • Li Juan Wu
  • Hua Liang Li
  • Yuan Ying Song
  • Gui Xiang He
  • Hong Ye Li
Review Article


Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with progressive supranuclear palsy (PSP) relative to healthy controls (HC). However, not all findings have been entirely concordant. Herein, we performed a quantitative meta-analysis study in order to consistently quantify GM anomalies in PSP. We conducted a systematic search for VBM studies of PSP patients and HC using PubMed and Embase databases from January 2000 to May 2012. Meta-analysis of these VBM studies was performed using a newly improved voxel-based meta-analytic technique, effect-size signed differential mapping. A total of 9 cross-sectional VBM studies that involved 143 PSP patients and 216 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the thalamus, basal ganglia, midbrain, insular cortex, and frontal cortex. These findings remained largely unchanged following jackknife sensitivity analyses. The present meta-analysis provided evidence of PSP-specific GM atrophy. This finding might help contribute to our understanding of the neurobiological basis underlying PSP.


Voxel-based morphometry Progressive supranuclear palsy Signed differential mapping Gray matter Meta-analysis 



We thank all the authors of the included studies. We especially thank Dr. Joaquim Radua for his kind help and suggestings.

Conflict of interest

There is no actual or potential financial and other conflict of interest related to the submitted manuscript.


  1. 1.
    Steele JC, Richardson JC, Olszewski J (1964) Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol 10:333–359PubMedCrossRefGoogle Scholar
  2. 2.
    Morris HR, Gibb G, Katzenschlager R, Wood NW, Hanger DP, Strand C, Lashley T, Daniel SE, Lees AJ, Anderton BH, Revesz T (2002) Pathological, clinical and genetic heterogeneity in progressive supranuclear palsy. Brain 125(Pt 5):969–975PubMedCrossRefGoogle Scholar
  3. 3.
    Barsottini OG, Felicio AC, Aquino CC, Pedroso JL (2010) Progressive supranuclear palsy: new concepts. Arq Neuropsiquiatr 68(6):938–946PubMedCrossRefGoogle Scholar
  4. 4.
    Burn DJ, Lees AJ (2002) Progressive supranuclear palsy: where are we now? Lancet Neurol 1(6):359–369PubMedCrossRefGoogle Scholar
  5. 5.
    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 128(Pt 6):1247–1258. doi: 10.1093/brain/awh488 PubMedCrossRefGoogle Scholar
  6. 6.
    Williams DR, Lees AJ (2009) Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 8(3):270–279. doi: 10.1016/s1474-4422(09)70042-0 PubMedCrossRefGoogle Scholar
  7. 7.
    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):2015–2019PubMedCrossRefGoogle Scholar
  8. 8.
    Santacruz P, Uttl B, Litvan I, Grafman J (1998) Progressive supranuclear palsy: a survey of the disease course. Neurology 50(6):1637–1647PubMedCrossRefGoogle Scholar
  9. 9.
    Josephs KA, Dickson DW (2003) Diagnostic accuracy of progressive supranuclear palsy in the society for progressive supranuclear palsy brain bank. Mov Disord 18(9):1018–1026. doi: 10.1002/mds.10488 PubMedCrossRefGoogle Scholar
  10. 10.
    Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11(6 Pt 1):805–821. doi: 10.1006/nimg.2000.0582 PubMedCrossRefGoogle Scholar
  11. 11.
    Brenneis C, Seppi K, Schocke M, Benke T, Wenning GK, Poewe W (2004) Voxel based morphometry reveals a distinct pattern of frontal atrophy in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 75(2):246–249PubMedGoogle Scholar
  12. 12.
    Price S, Paviour D, Scahill R, Stevens J, Rossor M, Lees A, Fox N (2004) Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson’s disease. Neuroimage 23(2):663–669. doi: 10.1016/j.neuroimage.2004.06.013 PubMedCrossRefGoogle Scholar
  13. 13.
    Cordato NJ, Duggins AJ, Halliday GM, Morris JG, Pantelis C (2005) Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy. Brain 128(Pt 6):1259–1266. doi: 10.1093/brain/awh508 PubMedCrossRefGoogle Scholar
  14. 14.
    Boxer AL, Geschwind MD, Belfor N, Gorno-Tempini ML, Schauer GF, Miller BL, Weiner MW, Rosen HJ (2006) Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol 63(1):81–86. doi: 10.1001/archneur.63.1.81 PubMedCrossRefGoogle Scholar
  15. 15.
    Padovani A, Borroni B, Brambati SM, Agosti C, Broli M, Alonso R, Scifo P, Bellelli G, Alberici A, Gasparotti R, Perani D (2006) Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 77(4):457–463. doi: 10.1136/jnnp.2005.075713 PubMedCrossRefGoogle Scholar
  16. 16.
    Agosta F, Kostic VS, Galantucci S, Mesaros S, Svetel M, Pagani E, Stefanova E, Filippi M (2010) The in vivo distribution of brain tissue loss in Richardson’s syndrome and PSP-parkinsonism: a VBM-DARTEL study. Eur J Neurosci 32(4):640–647. doi: 10.1111/j.1460-9568.2010.07304.x PubMedCrossRefGoogle Scholar
  17. 17.
    Lehericy S, Hartmann A, Lannuzel A, Galanaud D, Delmaire C, Bienaimee MJ, Jodoin N, Roze E, Gaymard B, Vidailhet M (2010) Magnetic resonance imaging lesion pattern in Guadeloupean parkinsonism is distinct from progressive supranuclear palsy. Brain 133(Pt 8):2410–2425. doi: 10.1093/brain/awq162 PubMedCrossRefGoogle Scholar
  18. 18.
    Takahashi R, Ishii K, Kakigi T, Yokoyama K, Mori E, Murakami T (2011) Brain alterations and mini-mental state examination in patients with progressive supranuclear palsy: voxel-based investigations using f-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging. Dement Geriatr Cogn Dis Extra 1(1):381–392. doi: 10.1159/000333368 PubMedCrossRefGoogle Scholar
  19. 19.
    Ghosh BC, Calder AJ, Peers PV, Lawrence AD, Acosta-Cabronero J, Pereira JM, Hodges JR, Rowe JB (2012) Social cognitive deficits and their neural correlates in progressive supranuclear palsy. Brain. doi: 10.1093/brain/aws128 PubMedGoogle Scholar
  20. 20.
    Whitwell JL, Avula R, Master A, Vemuri P, Senjem ML, Jones DT, Jack CR Jr, Josephs KA (2011) Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study. Parkinsonism Relat Disord 17(8):599–605. doi: 10.1016/j.parkreldis.2011.05.013 PubMedCrossRefGoogle Scholar
  21. 21.
    Saini J, Bagepally BS, Sandhya M, Pasha SA, Yadav R, Pal PK (2011) In vivo evaluation of white matter pathology in patients of progressive supranuclear palsy using TBSS. Neuroradiology. doi: 10.1007/s00234-011-0983-7 Google Scholar
  22. 22.
    Radua J, Mataix-Cols D (2009) Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder. Br J Psychiatry 195(5):393–402. doi: 10.1192/bjp.bp.108.055046 PubMedCrossRefGoogle Scholar
  23. 23.
    Radua J, Mataix-Cols D, Phillips ML, El-Hage W, Kronhaus DM, Cardoner N, Surguladze S (2011) A new meta-analytic method for neuroimaging studies that combines reported peak coordinates and statistical parametric maps. Eur Psychiatry. doi: 10.1016/j.eurpsy.2011.04.001 PubMedGoogle Scholar
  24. 24.
    Li J, Pan P, Huang R, Shang H (2012) A meta-analysis of voxel-based morphometry studies of white matter volume alterations in Alzheimer’s disease. Neurosci Biobehav Rev 36(2):757–763. doi: 10.1016/j.neubiorev.2011.12.001 PubMedCrossRefGoogle Scholar
  25. 25.
    Pan PL, Song W, Shang HF (2012) Voxel-wise meta-analysis of gray matter abnormalities in idiopathic Parkinson’s disease. Eur J Neurol 19(2):199–206. doi: 10.1111/j.1468-1331.2011.03474.x PubMedCrossRefGoogle Scholar
  26. 26.
    Via E, Radua J, Cardoner N, Happe F, Mataix-Cols D (2011) Meta-analysis of gray matter abnormalities in autism spectrum disorder: should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder? Arch Gen Psychiatry 68(4):409–418. doi: 10.1001/archgenpsychiatry.2011.27 PubMedCrossRefGoogle Scholar
  27. 27.
    Li J, Pan P, Song W, Huang R, Chen K, Shang H (2011) A meta-analysis of diffusion tensor imaging studies in amyotrophic lateral sclerosis. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2011.04.007 Google Scholar
  28. 28.
    Bora E, Fornito A, Yucel M, Pantelis C (2010) Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry 67(11):1097–1105. doi: 10.1016/j.biopsych.2010.01.020 PubMedCrossRefGoogle Scholar
  29. 29.
    Pan P, Song W, Yang J, Huang R, Chen K, Gong QY, Zhong JG, Shi HC, Shang HF (2012) Gray matter atrophy in behavioral variant frontotemporal dementia: a meta-analysis of voxel-based morphometry studies. Dement Geriatr Cogn Disord 33(2–3):141–148PubMedCrossRefGoogle Scholar
  30. 30.
    Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47(1):1–9PubMedCrossRefGoogle Scholar
  31. 31.
    Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) Movement disorders society scientific issues committee report: SIC task force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 18(5):467–486. doi: 10.1002/mds.10459 PubMedCrossRefGoogle Scholar
  32. 32.
    Herrero MT, Barcia C, Navarro JM (2002) Functional anatomy of thalamus and basal ganglia. Childs Nerv Syst 18(8):386–404. doi: 10.1007/s00381-002-0604-1 PubMedCrossRefGoogle Scholar
  33. 33.
    Warren NM, Piggott MA, Perry EK, Burn DJ (2005) Cholinergic systems in progressive supranuclear palsy. Brain 128(Pt 2):239–249. doi: 10.1093/brain/awh391 PubMedGoogle Scholar
  34. 34.
    Matsumoto R, Nakano I, Arai N, Suda M, Oda M (1996) Progressive supranuclear palsy with asymmetric lesions in the thalamus and cerebellum, with special reference to the unilateral predominance of many torpedoes. Acta Neuropathol 92(6):640–644PubMedCrossRefGoogle Scholar
  35. 35.
    Dickson DW, Rademakers R, Hutton ML (2007) Progressive supranuclear palsy: pathology and genetics. Brain Pathol 17(1):74–82. doi: 10.1111/j.1750-3639.2007.00054.x PubMedCrossRefGoogle Scholar
  36. 36.
    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 25(14):2395–2404. doi: 10.1002/mds.23291 PubMedCrossRefGoogle Scholar
  37. 37.
    Messina D, Cerasa A, Condino F, Arabia G, Novellino F, Nicoletti G, Salsone M, Morelli M, Lanza PL, Quattrone A (2011) Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord 17(3):172–176. doi: 10.1016/j.parkreldis.2010.12.010 PubMedCrossRefGoogle Scholar
  38. 38.
    Hanyu H, Asano T, Sakurai H, Takasaki M, Shindo H, Abe K (2001) Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson’s disease with and without dementia and in progressive supranuclear palsy. Neuroradiology 43(7):542–546PubMedCrossRefGoogle Scholar
  39. 39.
    Schulz JB, Skalej M, Wedekind D, Luft AR, Abele M, Voigt K, Dichgans J, Klockgether T (1999) Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson’s syndrome from multiple system atrophy and progressive supranuclear palsy. Ann Neurol 45(1):65–74PubMedCrossRefGoogle Scholar
  40. 40.
    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 27(1):151–155PubMedCrossRefGoogle Scholar
  41. 41.
    Zwergal A, la Fougere C, Lorenzl S, Rominger A, Xiong G, Deutschenbaur L, Linn J, Krafczyk S, Dieterich M, Brandt T, Strupp M, Bartenstein P, Jahn K (2011) Postural imbalance and falls in PSP correlate with functional pathology of the thalamus. Neurology 77(2):101–109. doi: 10.1212/WNL.0b013e318223c79d PubMedCrossRefGoogle Scholar
  42. 42.
    Goffinet AM, De Volder AG, Gillain C, Rectem D, Bol A, Michel C, Cogneau M, Labar D, Laterre C (1989) Positron tomography demonstrates frontal lobe hypometabolism in progressive supranuclear palsy. Ann Neurol 25(2):131–139. doi: 10.1002/ana.410250205 PubMedCrossRefGoogle Scholar
  43. 43.
    Karbe H, Grond M, Huber M, Herholz K, Kessler J, Heiss WD (1992) Subcortical damage and cortical dysfunction in progressive supranuclear palsy demonstrated by positron emission tomography. J Neurol 239(2):98–102PubMedCrossRefGoogle Scholar
  44. 44.
    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 PubMedCrossRefGoogle Scholar
  45. 45.
    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 PubMedCrossRefGoogle Scholar
  46. 46.
    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):67–71PubMedCrossRefGoogle Scholar
  47. 47.
    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 PubMedCrossRefGoogle Scholar
  48. 48.
    Augustine JR (1996) Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Brain Res Rev 22(3):229–244PubMedCrossRefGoogle Scholar
  49. 49.
    Liakakis G, Nickel J, Seitz RJ (2011) Diversity of the inferior frontal gyrus—a meta-analysis of neuroimaging studies. Behav Brain Res 225(1):341–347. doi: 10.1016/j.bbr.2011.06.022 PubMedCrossRefGoogle Scholar
  50. 50.
    Colosimo C, Morgante L, Antonini A, Barone P, Avarello TP, Bottacchi E, Cannas A, Ceravolo MG, Ceravolo R, Cicarelli G, Gaglio RM, Giglia L, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Del Dotto P, Simoni L, Marconi R (2010) Non-motor symptoms in atypical and secondary parkinsonism: the PRIAMO study. J Neurol 257(1):5–14. doi: 10.1007/s00415-009-5255-7 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Hai Cun Shi
    • 1
    Email author
  • Jian Guo Zhong
    • 1
  • Ping Lei Pan
    • 1
  • Pei Rong Xiao
    • 1
  • Yuan Shen
    • 1
  • Li Juan Wu
    • 1
  • Hua Liang Li
    • 1
  • Yuan Ying Song
    • 1
  • Gui Xiang He
    • 1
  • Hong Ye Li
    • 1
  1. 1.Department of Neurology, Yancheng Third People’s HospitalThe affiliated Yancheng hospital of Southeast University medical collegeYanChengPeople’s Republic of China

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