Journal of Neurology

, Volume 260, Issue 4, pp 1031–1036 | Cite as

MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy

  • Igor N. PetrovicEmail author
  • Antonio Martin-Bastida
  • Luke Massey
  • Helen Ling
  • Sean S. O’Sullivan
  • David R. Williams
  • Janice L. Holton
  • Tamas Revesz
  • James W. Ironside
  • Andrew J. Lees
  • Laura Silveira-Moriyama
Original Communication


The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis. The few patients in the literature who presented with parkinsonism and who were suspected to have progressive supranuclear palsy (PSP) all ran a malignant course and most of them died within 3 years of diagnosis. We screened the Queen Square Brain Bank database and, among 213 patients with a clinical diagnosis of PSP, we found ten patients with 3 years or less disease duration, including one patient with CJD pathology. We report this patient and review other similar cases from the literature. Ten additional cases with similar presentation were identified in the literature. The mean disease duration was 24.2 months. The classical clinical, radiological and laboratory findings for sCJD were absent in the majority of these cases. Clinical presentation of these patients consists of: early falls, prominent dementia, early vertical supranuclear gaze palsy and symmetric akinetic syndrome. In the patients who were subtyped at post-mortem, all four represented the MM2 subtype of sCJD. A rapidly progressive course of PSP with early falls, cognitive impairments and vertical supranuclear gaze palsy should raise suspicion of underlying sCJD pathology regardless of absence of supportive findings on ancillary tests. This case and the literature support the notion that biochemical properties of the prion protein can influence the clinical presentation of sCJD.


Creutzfeldt-Jakob disease Prion MM2 Progressive supranuclear palsy Neuropathology 



Dr Igor Petrovic is funded by the Ministry of Science; Republic of Serbia (projects no.175090). The Reta Lila Weston Trust for Medical Research funded this project and Dr Silveira-Moriyama and Dr Helen Ling are beneficiaries of Reta Lila Weston fellowships. Dr Luke Massey has been funded by a grant from the PSP (Europe) Association.

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

All human studies must have been approved by an ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.


  1. 1.
    Ironside JW, Ghetti B, Head MW, Piccardo P, Will RG (2008) Prion diseases. In: Ellison DW, Louis DN, Love S (eds) Greenfield’s neuropathology. Arnold, LondonGoogle Scholar
  2. 2.
    Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233PubMedCrossRefGoogle Scholar
  3. 3.
    Will RG, Lees AJ, Gibb W, Barnard RO (1988) A case of progressive subcortical gliosis presenting clinically as Steele-Richardson-Olszewski syndrome. J Neurol Neurosurg Psychiatry 51:1224–1227PubMedCrossRefGoogle Scholar
  4. 4.
    Shimamura M, Uyama E, Hirano T, Murakami T, Mita S, Kitamoto T, Uchino M (2003) A unique case of sporadic Creutzfeldt-Jacob disease presenting as progressive supranuclear palsy. Intern Med 42:195–198PubMedCrossRefGoogle Scholar
  5. 5.
    Rowe DB, Lewis V, Needham M, Rodriguez M, Boyd A, McLean C, Roberts H, Masters CL, Collins SJ (2007) Novel prion protein gene mutation presenting with subacute PSP-like syndrome. Neurology 68:868–870PubMedCrossRefGoogle Scholar
  6. 6.
    Revesz T, Daniel SE, Lees AJ, Will RG (1995) A case of progressive subcortical gliosis associated with deposition of abnormal prion protein (PrP). J Neurol Neurosurg Psychiatry 58:759–760PubMedCrossRefGoogle Scholar
  7. 7.
    Prasad S, Ko MW, Lee EB, Gonatas NK, Stern MB, Galetta S (2007) Supranuclear vertical gaze abnormalities in sporadic Creutzfeldt-Jakob disease. J Neurol Sci 253:69–72PubMedCrossRefGoogle Scholar
  8. 8.
    Kawasaki K, Wakabayashi K, Kawakami A, Higuchi M, Kitamoto T, Tsuji S, Takahashi H (1997) Thalamic form of Creutzfeldt-Jakob disease or fatal insomnia? Report of a sporadic case with normal prion protein genotype. Acta Neuropathol 93:317–322PubMedCrossRefGoogle Scholar
  9. 9.
    Josephs KA, Tsuboi Y, Dickson DW (2004) Creutzfeldt-Jakob disease presenting as progressive supranuclear palsy. Eur J Neurol 11:343–346PubMedCrossRefGoogle Scholar
  10. 10.
    Huber FM, Bour F, Sazdovitch V, Hauw JJ, Heinemann U, Zanini F, Droste DW, Diederich NJ (2007) Creutzfeldt-Jakob disease with slow progression. A mimickry of progressive supranuclear palsy. Bull Soc Sci Med Grand Duche Luxemb 2:125–130PubMedGoogle Scholar
  11. 11.
    Hamaguchi T, Kitamoto T, Sato T, Mizusawa H, Nakamura Y, Noguchi M, Furukawa Y, Ishida C, Kuji I, Mitani K, Murayama S, Kohriyama T, Katayama S, Yamashita M, Yamamoto T, Udaka F, Kawakami A, Ihara Y, Nishinaka T, Kuroda S, Suzuki N, Shiga Y, Arai H, Maruyama M, Yamada M (2005) Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease. Neurology 64:643–648PubMedCrossRefGoogle Scholar
  12. 12.
    Josephs KA, Dickson DW (2003) Diagnostic accuracy of progressive supranuclear palsy in the society for progressive supranuclear palsy brain bank. Mov Disord 18:1018–1026PubMedCrossRefGoogle Scholar
  13. 13.
    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 47:1–9PubMedCrossRefGoogle Scholar
  14. 14.
    Matěj R, Kovacs GG, Johanidesová S, Keller J, Matějčková M, Nováková J, Sigut V, Keller O, Rusina R (2012) Genetic Creutzfeldt-Jakob disease with R208H mutation presenting as progressive supranuclear palsy. Mov Disord 27:476–479PubMedCrossRefGoogle Scholar
  15. 15.
    Williams DR, Lees AJ (2009) Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 8:270–279PubMedCrossRefGoogle Scholar
  16. 16.
    Kertesz A, McMonagle P (2010) Behavior and cognition in corticobasal degeneration and progressive supranucler palsy. J Neurol Sci 289:138–143PubMedCrossRefGoogle Scholar
  17. 17.
    Millar D, Griffiths P, Zermansky AJ, Burn DJ (2006) Characterizing behavioral and cognitive dysexecutive changes in progressive supranuclear palsy. Mov Disord 21:199–207PubMedCrossRefGoogle Scholar
  18. 18.
    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 128:1247–1258PubMedCrossRefGoogle Scholar
  19. 19.
    Bertoni JM, Brown P, Goldfarb LG, Rubenstein R, Gajdusek DC (1992) Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy. JAMA 268:2413–2415PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Igor N. Petrovic
    • 1
    • 2
    Email author
  • Antonio Martin-Bastida
    • 3
  • Luke Massey
    • 1
    • 4
  • Helen Ling
    • 1
  • Sean S. O’Sullivan
    • 1
  • David R. Williams
    • 5
  • Janice L. Holton
    • 6
  • Tamas Revesz
    • 6
  • James W. Ironside
    • 7
  • Andrew J. Lees
    • 1
    • 4
    • 6
  • Laura Silveira-Moriyama
    • 1
    • 8
  1. 1.Reta Lila Weston Institute of Neurological StudiesUCL Institute of NeurologyLondonUK
  2. 2.Neurology Clinic, CCSBelgradeSerbia
  3. 3.University Hospital Virgen MacarenaSevillaSpain
  4. 4.Sarah Koe PSP Research CentreUCL Institute of NeurologyLondonUK
  5. 5.Van Cleef Roet Centre for Nervous DiseaseMonash UniversityMelbourneAustralia
  6. 6.Queen Square Brain Bank, Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK
  7. 7.National Creutzfeldt-Jakob Disease Research and Surveillance UnitUniversity of Edinburgh, Western General HospitalEdinburghUK
  8. 8.Child Neurology Unit, Department of NeurologyUniversity of Campinas, UNICAMPCampinasBrazil

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