La radiologia medica

, Volume 122, Issue 5, pp 369–385 | Cite as

Neuroradiology of human prion diseases, diagnosis and differential diagnosis

  • Simona GaudinoEmail author
  • Emma Gangemi
  • Raffaella Colantonio
  • Annibale Botto
  • Emanuela Ruberto
  • Rosalinda Calandrelli
  • Matia Martucci
  • Maria Gabriella Vita
  • Carlo Masullo
  • Alfonso Cerase
  • Cesare Colosimo


Human transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal conditions associated with a range of clinical presentations. TSEs are classified as sporadic [e.g. sporadic Creutzfeldt–Jakob disease (sCJD), which is the most frequent form], genetic (e.g. Gerstmann–Straussler–Scheinker disease, fatal familial insomnia, and inherited CJD), and acquired or infectious (e.g. Kuru, iatrogenic CJD, and variant CJD). In the past, brain imaging played a supporting role in the diagnosis of TSEs, whereas nowadays magnetic resonance imaging (MRI) plays such a prominent role that MRI findings have been included in the diagnostic criteria for sCJD. Currently, MRI is required for all patients with a clinical suspicion of TSEs. Thus, MRI semeiotics of TSEs should become part of the cultural baggage of any radiologist. The purposes of this update on the neuroradiology of CJD are to (i) review the pathophysiology and clinical presentation of TSEs, (ii) describe both typical and atypical MRI findings of CJD, and (iii) illustrate diseases mimicking CJD, underlining the MRI key findings useful in the differential diagnosis.


Creutzfeldt–Jakob disease Diffusion-weighted imaging Neurodegenerative diseases Differential diagnosis 


Compliance with Ethical Standards


This study is not funded.

Conflict of interest

We have no conflict of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Heiseke A, Aguib Y, Riemer C, Baier M, Schatzl HM (2009) Lithium induces clearance of protease resistant prion protein in prion-infected cells by induction of autophagy. J Neurochem 109:25–34CrossRefPubMedGoogle Scholar
  2. 2.
    Sim VL, Caughey B (2009) Recent advances in prion chemotherapeutics. Infect Disord Drug Targets 9:81–91CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Panegyres PK, Armari E (2013) Therapies for human prion diseases. Am J Neurodegener Dis 2(3):176–186PubMedPubMedCentralGoogle Scholar
  4. 4.
    Zou WQ, Puoti G, Xiao X, Yuan J, Qing L, Cali I et al (2010) Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein. Ann Neurol 68:162–172CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rinne ML, McGinnis SM, Samuels MA, Katz JT, Loscalzo J (2012) Clinical problem-solving. A startling decline. N Engl J Med 366(9):836–842CrossRefPubMedGoogle Scholar
  6. 6.
    Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin MG et al (2012) Sustained translational repression by elF2α-P mediates prion neurodegeneration. Nature 485:507–511PubMedPubMedCentralGoogle Scholar
  7. 7.
    Macfarlane RG, Wroe SJ, Collinge J, Yousry TA, Jager HR (2007) Neuroimaging findings in human prion disease. J Neurol Neurosurg Psychiatry 78:664–670CrossRefPubMedGoogle Scholar
  8. 8.
    Vitali P, Maccagnano E, Caverzasi E, Henry RG, Haman A, Torres-Chae C et al (2011) Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 76:1711–1719CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Newey CR, Sarwal A, Wisco D, Alam S, Lederman RJ (2013) Variability in diagnosing Creutzfeldt–Jakob disease using standard and proposed diagnostic criteria. J Neuroimaging 23(1):58–63CrossRefPubMedGoogle Scholar
  10. 10.
    Gibbons RV, Holman RC, Belay ED, Schonberger LB (2000) Creutzfeldt–Jakob disease in the United States: 1979–1998. JAMA 284(18):2322–2323CrossRefPubMedGoogle Scholar
  11. 11.
    Klug GM, Boyd A, Lewis V, Douglass SL, Argent R, Lee JS, Australian National Creutzfeldt–Jakob Disease Registry et al (2006) Creutzfeldt–Jakob disease: Australian surveillance update to December 2005. Commun Dis Intell Q Rep 30(1):144–147Google Scholar
  12. 12.
    Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S et al (2005) Mortality from Creutzfeldt–Jakob disease and related disorders in Europe, Australia, and Canada. Neurology 64(9):586–591Google Scholar
  13. 13.
    Appleby BS, Appleby KK, Crain BJ, Onyike CU, Wallin MT, Rabins PV (2009) Characteristics of established and proposed sporadic Creutzfeldt–Jacob disease variants. Arch Neurol 66(2):208–215CrossRefPubMedGoogle Scholar
  14. 14.
    Del Barrio-Manso I, Toribio-García A, Cordero-Coma M, Tuñón L, Baragaño E (2010) Creutzfeldt–Jakob presenting with isolated visual symptoms: the Heidenhain variant. Arch Soc Esp Oftalmo 85(10):341–344CrossRefGoogle Scholar
  15. 15.
    Meissner B, Kallenger K, Sanchez-Juan P, Collie D, Summers DM, Almonti S et al (2009) MRI lesions profiles in sporadic Creutzfeldt–Jacob disease. Neurology 72:1994–2001CrossRefPubMedGoogle Scholar
  16. 16.
    Parchi P, de Boni L, Saverioni D, Cohen ML, Ferrer I, Gambetti P et al (2012) Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA. Acta Neuropathol 124(4):517–529CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wadsworth JD, Collinge J (2011) Molecular pathology of human prion disease. Acta Neuropathol 121:69–77CrossRefPubMedGoogle Scholar
  18. 18.
    Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U et al (2009) Updated clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Brain 132:2659–2668CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chohan G, Pennington C, Mackenzie JM, Andrews M, Everington D, Will RG et al (2010) The role of cerebrospinal fluid 14-3-3 and other proteins in the diagnosis of sporadic Creutzfeldt–Jakob disease in the UK: a 10-year review. J Neurol Neurosurg Psychiatry 81:1243–1248CrossRefPubMedGoogle Scholar
  20. 20.
    Muayqil T, Gronseth G, Camicioli R (2012) Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt–Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 79(14):1499–1506CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Orrù CD, Wilham JM, Vascellari S, Hughson AG, Caughey B (2012) New generation QuIC assays for prion seeding activity. Prion 6(2):147–52Google Scholar
  22. 22.
    Zanusso G, Monaco S, Pocchiari M, Caughey B (2016) Advanced tests for early and accurate diagnosis of Creutzfeldt–Jakob disease. Nat Rev Neurol 12(6):325–333CrossRefPubMedGoogle Scholar
  23. 23.
    Luk C, Jones S, Thomas C, Fox NC, Mok TH, Mead S et al (2016) Diagnosing sporadic Creutzfeldt–Jakob disease by the detection of abnormal prion protein in patient urine. JAMA Neurol 73(12):1454–1460CrossRefPubMedGoogle Scholar
  24. 24.
    Sharma S, Mukherjee M, Kedage V, Muttigi MS, Rao A, Rao S (2009) Sporadic Creutzfeldt–Jacob disease—a review. Int J Neurosci 119:1981–1994CrossRefPubMedGoogle Scholar
  25. 25.
    Kovács GG, Puopolo M, Ladogana A, Pocchiari M, Budka H, van Duijn C, EUROCJD et al (2005) Genetic prion disease: the EUROCJD experience. Hum Genet 118(2):166–174CrossRefPubMedGoogle Scholar
  26. 26.
    Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I et al (2000) Iatrogenic Creutzfeldt–Jakob disease at the millennium. Neurology 55(8):1075–1081CrossRefPubMedGoogle Scholar
  27. 27.
    Lee J, Kim SY, Hwang KJ, Ju YR, Woo HJ (2013) Prion diseases as transmissible zoonotic diseases. Osong Public Health Res Perspect 4(1):57–66CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Brandel JP, Peckeu L, Haïk S (2013) The French surveillance network of Creutzfeldt–Jakob disease. Epidemiological data in France and worldwide. Transfus Clin Biol 20(4):395–397CrossRefPubMedGoogle Scholar
  29. 29.
    Hill AF, Butterworth RJ, Joiner S, Jackson G, Rossor MN, Thomas DJ et al (1999) Investigation of variant Creutzfeldt–Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353(9148):183–189CrossRefPubMedGoogle Scholar
  30. 30.
    García Santos JM, López Corbalán JA, Martínez-Lage JF, Sicilia Guillén J (1996) CT and MRI in iatrogenic and sporadic Creutzfeldt–Jakob disease: as far as imaging perceives. Neuroradiology 38(3):226–231CrossRefPubMedGoogle Scholar
  31. 31.
    Kallenberg K, Schulz-Schaeffer WJ, Jastrow U, Poser S, Meissner B, Tschampa HJ et al (2006) Creutzfeldt–Jakob disease: comparative analysis of MR imaging sequences. AJNR Am J Neuroradiol 27:1459–1462PubMedGoogle Scholar
  32. 32.
    Lodi R, Parchi P, Tonon C, Manners D, Capellari S, Strammiello R et al (2009) Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study. Brain 132(10):2669–2679CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Figini M, Alexander DC, Redaelli V, Fasano F, Grisoli M, Baselli G et al (2015) Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases. Neuroimage Clin 7:142–154CrossRefPubMedGoogle Scholar
  34. 34.
    Lee H, Hoffman C, Kingsley PB, Degnan A, Cohen O, Prohovnik I (2010) Enhanced detection of diffusion reductions in Creutzfeldt–Jakob disease at a higher B factor. AJNR Am J Neuroradiol 31(1):49–54CrossRefPubMedGoogle Scholar
  35. 35.
    Hyare H, Thornton J, Stevens J, Mead S, Rudge P, Collinge J et al (2010) High-b-value diffusion MR imaging and basal nuclei apparent diffusion coefficient measurements in variant and sporadic Creutzfeldt–Jakob disease. AJNR Am J Neuroradiol 31(3):521–526CrossRefPubMedGoogle Scholar
  36. 36.
    Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P (2012) Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol 11(7):618–28Google Scholar
  37. 37.
    Kong A, Kleinig T, Van der Vliet A, Bergin P, Coscia C, Ring S et al (2008) MRI of sporadic Creutzfeldt–Jacob disease. J Med Imaging Radiat Oncol 52:318–324CrossRefPubMedGoogle Scholar
  38. 38.
    Lee H, Cohen OS, Rosenmann H, Hoffmann C, Kingsley PB, Korczyn AD et al (2012) Cerebral white matter disruption in Creutzfeldt–Jakob disease. AJNR Am J Neuroradiol 33(10):1945–1950CrossRefPubMedGoogle Scholar
  39. 39.
    Galanaud D, Haik S, Linguraru MG, Ranjeva JP, Faucheux B, Kaphan E et al (2010) Combined diffusion imaging and MR spectroscopy in the diagnosis of human prion diseases. AJNR Am J Neuroradiol 31(7):1311–1318CrossRefPubMedGoogle Scholar
  40. 40.
    Kim JH, Choi BS, Jung C, Chang Y, Kim S (2011) Diffusion-weighted imaging and magnetic resonance spectroscopy of sporadic Creutzfeldt Jacob disease: correlation with clinical course. Neuroradiology 53(12):939–945CrossRefPubMedGoogle Scholar
  41. 41.
    Clarencon F, Gutman F, Giannesini C, Penicaud A, Galanaud D, Kerrou K et al (2008) MR and FDG PET/TC findings in a case of probable Heidenhain variant Creutzfeldt–Jacob disease. J Neuroradiol 35:240–243CrossRefPubMedGoogle Scholar
  42. 42.
    Krasnianski A, Kallenberg K, Collie DA, Meissner B, Schulz-Scaeffer WJ, Heinemann U et al (2008) MRI in the classical MM1 and the atypical MV2 subtypes of sporadic CJD: an inter-observer agreement study. Eur J Neurol 15:762–771CrossRefPubMedGoogle Scholar
  43. 43.
    Poon MA, Stuckey S, Storey E (2001) MRI evidence of cerebellar and hippocampal involvement in Creutzfeldt–Jakob disease. Neuroradiology 43(9):746–749CrossRefPubMedGoogle Scholar
  44. 44.
    Chang CC, Eggers SD, Johnson JK, Haman A, Miller BL, Geschwind MD (2007) Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt–Jakob disease. Clin Neurol Neurosurg 109(1):54–57CrossRefPubMedGoogle Scholar
  45. 45.
    Sureka J, Jakkani RK (1017) Clinico-radiological spectrum of bilateral temporal lobe hyperintensity: a retrospective review. Br J Radiol 2012(85):e782–e792Google Scholar
  46. 46.
    Küker W (2007) Cerebral vasculitis: imaging signs revisited. Neuroradiology 49(6):471–479CrossRefPubMedGoogle Scholar
  47. 47.
    Gomes LJ (2010) The role of imaging in the diagnosis of central nervous system vasculitis. Curr Allergy Asthma Rep 10(3):163–170CrossRefPubMedGoogle Scholar
  48. 48.
    Thurnher MM, Donovan Post MJ (2008) Neuroimaging in the brain in HIV-1-infected patients. Neuroimaging Clin N Am 18(1):93–117CrossRefPubMedGoogle Scholar
  49. 49.
    Ito H, Mori K, Kagami S (2011) Neuroimaging of stroke-like episodes in MELAS. Brain Dev 33(4):283–288CrossRefPubMedGoogle Scholar
  50. 50.
    Hegde AN, Mohan S, Lath N, Lim CC (2011) Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus. Radiographics 31(1):5–30CrossRefPubMedGoogle Scholar
  51. 51.
    Cianfoni A, Caulo M, Cerase A, Della Marca G, Falcone C, Di Lella GM et al (2013) Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities. Eur J Radiol 82(11):1964–1972CrossRefPubMedGoogle Scholar
  52. 52.
    Howard SA, Barletta JA, Klufas RA, Saad A, De Girolami U (2009) Best cases from the AFIP: osmotic demyelination syndrome. Radiographics 29(3):933–938CrossRefPubMedGoogle Scholar
  53. 53.
    Cerase A, Rubenni E, Rufa A, Vallone I, Galluzzi P, Coratti G et al (2011) CT and MRI of Wernicke’s encephalopathy. Radiol Med 116(2):319–333CrossRefPubMedGoogle Scholar
  54. 54.
    Rossi A (2008) Imaging of acute disseminated encephalomyelitis. Neuroimaging Clin N Am 18(1):149–161CrossRefPubMedGoogle Scholar
  55. 55.
    Cardaioli E, Da Pozzo P, Cerase A, Sicurelli F, Malandrini A, De Stefano N et al (2006) Rapidly progressive neurodegeneration in a case with the 7472insC mutation and the A7472C polymorphism in the mtDNA tRNA ser(UCN) gene. Neuromuscul Disord 16(1):26–31CrossRefPubMedGoogle Scholar
  56. 56.
    Reisin RC, Romero C, Marchesoni C, Napoli G, Kisinovsky I, Caceres G et al (2011) Brain MRI findings in patients with Fabry disease. J Neurol Sci 305(1–2):41–44CrossRefPubMedGoogle Scholar
  57. 57.
    Politei JM, Capizzano AA (2006) Magnetic resonance image findings in 5 young patients with Fabry disease. Neurologist 12(2):103–105CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Medical Radiology 2017

Authors and Affiliations

  • Simona Gaudino
    • 1
    Email author
  • Emma Gangemi
    • 1
  • Raffaella Colantonio
    • 1
  • Annibale Botto
    • 1
  • Emanuela Ruberto
    • 1
  • Rosalinda Calandrelli
    • 1
  • Matia Martucci
    • 1
  • Maria Gabriella Vita
    • 2
  • Carlo Masullo
    • 2
  • Alfonso Cerase
    • 3
  • Cesare Colosimo
    • 1
  1. 1.Department of Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario A. GemelliSchool of Medicine, Catholic UniversityRomeItaly
  2. 2.Institute of Neurology, Fondazione Policlinico Universitario A. GemelliSchool of Medicine, Catholic UniversityRomeItaly
  3. 3.Unit of Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Università Senese“Santa Maria alle Scotte” University and NHS HospitalSienaItaly

Personalised recommendations