SpringerLink
Log in

Pruritus in familial Creutzfeldt–Jakob disease: a common symptom associated with central nervous system pathology

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with Creutzfeldt–Jakob disease (CJD), and its anatomical background is not well defined. The present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in CJD patients and investigate its anatomical substrate by MRI. The study group included consecutive familial and sporadic CJD patients carrying the E200K PRNP mutation followed up in a longitudinal prospective study between the years 2005 and 2008. Pruritus was prospectively screened for and diffusion-weighted imaging (DWI) was used to correlate brain diffusion abnormalities with pruritus in CJD patients. Pruritus was present in 6/31 (19.35%) patients with familial disease (fCJD) and in none of the patients with sporadic disease (sCJD). Pruritus was a presenting symptom in one patient and evolved during the course of the disease in the other five patients. The pruritus was generalized in three patients, regional in two and localized in one patient. It was transient in one patient and continued throughout the disease in five patients. DWI showed that pruritus was significantly associated with reduced diffusion in the several areas known to be affected by CJD, but most significantly in the midbrain periaqueductal grey matter. Pruritus is relatively common in patients with familial CJD carrying the E200K mutation. Our findings point to a central origin that involves damage to the inhibitory gating mechanism for itch in the periaqueductal grey matter.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Prusiner SB (1991) Molecular biology of prion diseases. Science 252:1515–1522

    Article  CAS  PubMed  Google Scholar 

  2. Eggenberger E (2007) Prion disease. Neurol Clin 25:833–842 viii

    Article  PubMed  Google Scholar 

  3. Knight RS, Will RG (2004) Prion diseases. J Neurol Neurosurg Psychiatry 75(Suppl 1):i36–i42

    Article  PubMed  Google Scholar 

  4. Goldfarb LG, Korczyn AD, Brown P, Chapman J, Gajdusek DC (1990) Mutation in codon 200 of scrapie amyloid precursor gene linked to Creutzfeldt–Jakob disease in Sephardic Jews of Libyan and non-Libyan origin. Lancet 336:637–638

    Article  CAS  PubMed  Google Scholar 

  5. Hsiao K, Meiner Z, Kahana E et al (1991) Mutation of the prion protein in Libyan Jews with Creutzfeldt–Jakob disease. N Engl J Med 324:1091–1097

    Article  CAS  PubMed  Google Scholar 

  6. Petrie L, Heath B, Harold D (1989) Scrapie: report of an outbreak and brief review. Can Vet J 30:321–327

    CAS  PubMed  Google Scholar 

  7. Wilesmith JW, Wells GA, Cranwell MP, Ryan JB (1988) Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123:638–644

    CAS  PubMed  Google Scholar 

  8. Shabtai H, Nisipeanu P, Chapman J, Korczyn AD (1996) Pruritus in Creutzfeldt-Jakob disease. Neurology 46:940–941

    CAS  PubMed  Google Scholar 

  9. Chapman J, Brown P, Goldfarb LG, Arlazoroff A, Gajdusek DC, Korczyn AD (1993) Clinical heterogeneity and unusual presentations of Creutzfeldt–Jakob disease in Jewish patients with the PRNP codon 200 mutation. J Neurol Neurosurg Psychiatry 56:1109–1112

    Article  CAS  PubMed  Google Scholar 

  10. Young GS, Geschwind MD, Fischbein NJ et al (2005) Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt–Jakob disease: high sensitivity and specificity for diagnosis. AJNR Am J Neuroradiol 26:1551–1562

    PubMed  Google Scholar 

  11. Lee H, Rosenmann H, Chapman J et al (2009) Thalamo-striatal diffusion reductions precede disease onset in prion mutation carriers. Brain 132:2680–2687

    Article  PubMed  Google Scholar 

  12. World Health Organization (1998) Human transmissible spongiform encephalopathies. Weekly Epidemiological Record 73:361–365

  13. Fulbright RK, Hoffmann C, Lee H, Pozamantir A, Chapman J, Prohovnik I (2008) MR imaging of familial Creutzfeldt–Jakob disease: a blinded and controlled study. AJNR Am J Neuroradiol 29:1638–1643

    Article  CAS  PubMed  Google Scholar 

  14. Cyngiser TA (2008) Creutzfeldt–Jakob disease: a disease overview. Am J Electroneurodiagnos Technol 48:199–208

    Google Scholar 

  15. Skinningsrud A, Stenset V, Gundersen AS, Fladby T (2008) Cerebrospinal fluid markers in Creutzfeldt–Jakob disease. Cerebrospinal Fluid Res 5:14

    Article  PubMed  Google Scholar 

  16. Cohen OS, Hoffmann C, Lee H, Chapman J, Fulbright RK, Prohovnik I (2009) MRI detection of the cerebellar syndrome in Creutzfeldt–Jakob disease. Cerebellum 8:373–381

    Article  PubMed  Google Scholar 

  17. Meiner Z, Gabizon R, Prusiner SB (1997) Familial Creutzfeldt–Jakob disease Codon 200 prion disease in Libyan Jews. Medicine (Baltimore) 76:227–237

    Article  CAS  Google Scholar 

  18. Gabizon R, Rosenmann H, Meiner Z, Kahana I, Kahana E, Shugart Y, Ott J, Prusiner SB (1993) Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt–Jakob disease (CJD). Am J Hum Genet 53(4):828–835

    CAS  PubMed  Google Scholar 

  19. Ikoma A, Rukwied R, Stander S, Steinhoff M, Miyachi Y, Schmelz M (2003) Neurophysiology of pruritus: interaction of itch and pain. Arch Dermatol 139:1475–1478

    Article  PubMed  Google Scholar 

  20. Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork HE, Handwerker HO (2003) Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol 89:2441–2448

    Article  CAS  PubMed  Google Scholar 

  21. Andrew D, Craig AD (2001) Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 4:72–77

    Article  CAS  PubMed  Google Scholar 

  22. Schoene WC, Masters CL, Gibbs CJ Jr et al (1981) Transmissible spongiform encephalopathy (Creutzfeldt–Jakob disease). Atypical clinical and pathological findings. Arch Neurol 38:473–477

    CAS  PubMed  Google Scholar 

  23. Meiner Z, Halimi M, Polakiewicz RD, Prusiner SB, Gabizon R (1992) Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt–Jakob disease. Neurology 42:1355–1360

    CAS  PubMed  Google Scholar 

  24. Thomzig A, Schulz-Schaeffer W, Wrede A et al (2007) Accumulation of pathological prion protein PrPSc in the skin of animals with experimental and natural scrapie. PLoS Pathog 3:e66

    Article  PubMed  Google Scholar 

  25. Notari S, Moleres FJ, Hunter SB et al (2010) Multiorgan detection and characterization of protease resistant prion protein in a case of variant CJD examined in the United States. PLoS One 19(5):e8765

    Article  Google Scholar 

  26. Yosipovitch G, Samuel LS (2008) Neuropathic and psychogenic itch. Dermatol Ther 21:32–41

    Article  PubMed  Google Scholar 

  27. Groschup MH, Beekes M, McBride PA, Hardt M, Hainfellner JA, Budka H (1999) Deposition of disease-associated prion protein involves the peripheral nervous system in experimental scrapie. Acta Neuropathol 98:453–457

    Article  CAS  PubMed  Google Scholar 

  28. McBride PA, Schulz-Schaeffer WJ, Donaldson M et al (2001) Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75:9320–9327

    Article  CAS  PubMed  Google Scholar 

  29. Beekes M, McBride PA (2007) The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. FEBS J 274:588–605

    Article  CAS  PubMed  Google Scholar 

  30. Koeppel MC, Bramont C, Ceccaldi M, Habib M, Sayag J (1993) Paroxysmal pruritus and multiple sclerosis. Br J Dermatol 129:597–598

    Article  CAS  PubMed  Google Scholar 

  31. Massey EW (1984) unilateral neurogenic pruritus following stroke. Stroke 15:901–903

    CAS  PubMed  Google Scholar 

  32. Andreev VC, Petkov I, Berova N, Mustakov G (1975) Isolated lymphogranulomatosis of the skin. Dermatol Monatsschr 161:209–214

    CAS  PubMed  Google Scholar 

  33. Sullivan MJ, Drake ME Jr (1984) Unilateral pruritus and Nocardia brain abscess. Neurology 34:828–829

    CAS  PubMed  Google Scholar 

  34. King CA, Huff FJ, Jorizzo JL (1982) Unilateral neurogenic pruritus: paroxysmal itching associated with central nervous system lesions. Ann Intern Med 97:222–223

    CAS  PubMed  Google Scholar 

  35. Kimyai-Asadi A, Nousari HC, Kimyai-Asadi T, Milani F (1999) Poststroke pruritus. Stroke 30:692–693

    CAS  PubMed  Google Scholar 

  36. Shapiro PE, Braun CW (1987) Unilateral pruritus after a stroke. Arch Dermatol 123:1527–1530

    Article  CAS  PubMed  Google Scholar 

  37. Yamamoto M, Yabuki S, Hayabara T, Otsuki S (1981) Paroxysmal itching in multiple sclerosis: a report of three cases. J Neurol Neurosurg Psychiatry 44:19–22

    Article  CAS  PubMed  Google Scholar 

  38. Mochizuki H, Tashiro M, Kano M, Sakurada Y, Itoh M, Yanai K (2003) Imaging of central itch modulation in the human brain using positron emission tomography. Pain 105:339–346

    Article  PubMed  Google Scholar 

  39. Mochizuki H, Sadato N, Saito DN et al (2007) Neural correlates of perceptual difference between itching and pain: a human fMRI study. Neuroimage 36:706–717

    Article  PubMed  Google Scholar 

  40. Herde L, Forster C, Strupf M, Handwerker HO (2007) Itch induced by a novel method leads to limbic deactivations a functional MRI study. J Neurophysiol 98:2347–2356

    Article  PubMed  Google Scholar 

  41. Valet M, Pfab F, Sprenger T et al (2008) cerebral processing of histamine-induced itch using short-term alternating temperature modulation—an FMRI study. J Invest Dermatol 128:426–433

    CAS  PubMed  Google Scholar 

  42. Leknes SG, Bantick S, Willis CM, Wilkinson JD, Wise RG, Tracey I (2007) Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans. J Neurophysiol 97:415–422

    Article  PubMed  Google Scholar 

  43. Chapman J, Cohen OS, Nitzan Z, Tsabari R, Prohovnik I (2007) The CJD rating scale: a new tool for evaluation of neurologic symptomatology in early CJD patients. Neurology 68(Suppl 1):A141

    Google Scholar 

Download references

Acknowledgment

The study was supported by NIH grant NS043488.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, The Sagol Center for Neuroscience, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel

    Oren S. Cohen, Joab Chapman, Zeev Nitsan & Shmuel Appel

  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Oren S. Cohen & Joab Chapman

  3. Departments of Psychiatry and Radiology, Mount Sinai Medical Center, New York, NY, USA

    Hedok Lee & Isak Prohovnik

  4. Department of Radiology, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Chen Hoffman

  5. Hadassah University Hospital, Jerusalem, Israel

    Hanna Rosenmann

  6. Sieratzki Chair of Neurology, Tel Aviv University, Tel-Aviv, Israel

    Amos D. Korczyn

Authors
  1. Oren S. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joab Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hedok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeev Nitsan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shmuel Appel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chen Hoffman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hanna Rosenmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amos D. Korczyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Isak Prohovnik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oren S. Cohen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cohen, O.S., Chapman, J., Lee, H. et al. Pruritus in familial Creutzfeldt–Jakob disease: a common symptom associated with central nervous system pathology. J Neurol 258, 89–95 (2011). https://doi.org/10.1007/s00415-010-5694-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-010-5694-1

Keywords

Search

Navigation