Kuru Clinical Presentation
- Author: Zartash Zafar Khan, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD more...
Before kuru had nearly disappeared following cessation of the ritual of endocannibalism, the disease affected only the Fore, a New Guinea highland tribe. Case histories were usually obtained with the aid of a pidgin English–speaking man of the same tribal group as the infected individuals, but, in some cases, a European linguist who spoke the appropriate language was available. Only rarely were infected individuals able to communicate in pidgin English. Kuru has not been reported outside this context. Therefore, the potential for any practitioner encountering a case of kuru in the current era is extremely remote.
Kuru is a cerebellar syndrome with a characteristic and relentless progression of neurological symptoms through well-defined clinical stages. Kuru is invariably fatal. Initially, cognition is fairly well-preserved, and the disease presentation is sufficiently distinctive to be easily recognized by patients, their relatives, and the local community. The initial clinical presentation includes a prodrome of headache and arthralgia followed by the following clinical features:[27, 28]
Involuntary movements (choreoathetosis, myoclonic jerks, fasciculations)
Euphoria, dementia, emotional liability, and a loss of grasp reflexes in advanced stages
Upon disease progression, infected individuals become sedentary and develop sensory and motor and cranial nerve deficits that lead to progressive wasting, malnutrition, and intercurrent pneumonia. Death typically follows a clinical course of 4 months to 2 years, with most patients dying within a year of symptom onset.
Compared with other prion diseases, kuru’s clinical features most closely resemble those of vCJD. Clinical symptoms of vCJD consist of behavioral, psychiatric, and peripheral sensory disturbances and cerebellar ataxia. Common early psychiatric features include depression, withdrawal, anxiety, insomnia, and apathy. The symptoms of iatrogenic CJD are similar to those of sporadic CJD, which include a prodrome of malaise, headache, and ill-defined pain. Other symptoms include cognitive deterioration, myoclonus, extrapyramidal signs, cerebellar ataxia, pyramidal signs, and cortical blindness. The median age of onset for sporadic CJD is 45-75 years, whereas the median age of onset for vCJD is 26 years.
Among the group of inherited prion diseases, GSS typically presents as a chronic cerebellar ataxia with pyramidal features, with dementia occurring much later. The clinical course is typically longer than that of classic CJD.
FFI is characterized by progressive untreatable insomnia, dysautonomia and dementia, and selective thalamic degeneration.[29, 2]
Physical findings during the initial course of kuru are characterized by ataxia and muscular weakness. This results in tremulous legs and walking difficulties that eventually necessitate dependence on sticks, crutches, or human assistance for locomotion. Slow and clumsy movements can lead to injuries sustained by falls.
In the later stages, signs of psychiatric disturbances develop, including loss of emotion control, depression, euphoria, agitation, and confusion. Dementia can also occur in individuals with kuru, but it is a relatively more common feature of CJD.[27, 2]
Neurological signs of kuru include hyperreflexia, loss of grasp reflex, strabismus, and nystagmus. Involuntary muscle jerking and twitching is observed, along with other cerebellar signs such as tremor on finger-to-nose testing, difficulty with heel-to-toe walking, and dysdiadochokinesis. Plantar responses include flexor, and hypotonia is often present in advanced cases.[27, 20]
Ptosis and oculomotor imbalance are observed in a small number of cases.
Eventually, individuals with kuru become bedridden and may even be unable to sit, raise their head, or roll over. In advanced stages, patients lose the ability to chew, swallow, or control excretory processes and become progressively wasted.
Death results from starvation, complicating pneumonia, or infected decubitus ulcers.
The signs and symptoms of vCJD commonly include disorientation, hallucinations, paranoid ideation, confabulation, impaired self-care, and multiple neurological features (eg, cerebellar signs, chorea, dystonia, myoclonus, upper motor neuron signs, visual symptoms). Classic sporadic CJD presents as a rapidly progressive multifocal dementia with myoclonus. Clinical progression to akinetic mutism occurs fairly rapidly, with a median illness duration of only 5 months. Extrapyramidal signs, cerebellar ataxia, pyramidal signs, and cortical blindness are also observed in sporadic CJD. GSS typically presents as a chronic cerebellar ataxia with pyramidal features, with dementia occurring much later in the clinical course than is typically seen in classic CJD. Fatal familial insomnia (FFI) is characterized by progressive untreatable insomnia, dysautonomia and dementia, and thalamic degeneration.
Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci. 2001. 24:519-50. [Medline].
Wadsworth JD, Collinge J. Update on human prion disease. Biochim Biophys Acta. 2007 Jun. 1772(6):598-609. [Medline].
Almond JW. Bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease. Br Med Bull. 1998. 54(3):749-59. [Medline].
Belay ED, Schonberger LB. The public health impact of prion diseases. Annu Rev Public Health. 2005. 26:191-212. [Medline].
Haïk S, Brandel JP. Infectious prion diseases in humans: Cannibalism, iatrogenicity and zoonoses. Infect Genet Evol. 2014 Aug. 26C:303-312. [Medline].
Takada LT, Geschwind MD. Prion diseases. Semin Neurol. 2013 Sep. 33(4):348-56. [Medline].
Araújo AQ. Prionic diseases. Arq Neuropsiquiatr. 2013 Sep. 71(9B):731-7. [Medline].
Gajdusek DC. Unconventional viruses and the origin and disappearance of kuru. Science. 1977 Sep 2. 197(4307):943-60. [Medline].
Liberski PP, Brown P. Kuru: a half-opened window onto the landscape of neurodegenerative diseases. Folia Neuropathol. 2004. 42 Suppl A:3-14. [Medline].
Grabow JD, Campbell RJ, Okazaki H, et al. A transmissible subacute spongiform encephalopathy in a visitor to the eastern highlands of New Guinea. Brain. 1976 Dec. 99(4):637-58. [Medline].
Gajdusek DC, Zigas V, Baker J. Studies on kuru. III. Patterns of kuru incidence: demographic and geographic epidemiological analysis. Am J Trop Med Hyg. 1961 Jul. 10:599-627. [Medline].
Hornabrook RW. Kuru. Contemp Neurol Ser. 1975. 12:71-90;294. [Medline].
Collinge J, Whitfield J, McKintosh E, Beck J, Mead S, Thomas DJ, et al. Kuru in the 21st century--an acquired human prion disease with very long incubation periods. Lancet. 2006 Jun 24. 367(9528):2068-74. [Medline].
Whitfield JT, Pako WH, Collinge J, Alpers MP. Mortuary rites of the South Fore and kuru. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3721-4. [Medline].
Alpers MP. Review. The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3707-13. [Medline].
Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9. 216(4542):136-44. [Medline].
Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, et al. A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med. 2009 Nov 19. 361(21):2056-65. [Medline].
Lee HS, Brown P, Cervenakova L, et al. Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype. J Infect Dis. 2001 Jan 15. 183(2):192-196. [Medline].
Collinge J. Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry. 2005 Jul. 76(7):906-19. [Medline].
Brandner S, Whitfield J, Boone K, Puwa A, O'Malley C, Linehan JM, et al. Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3755-63. [Medline].
Chakraborty C, Nandi S, Jana S. Prion disease: a deadly disease for protein misfolding. Curr Pharm Biotechnol. 2005 Apr. 6(2):167-77. [Medline].
Collinge J. Variant Creutzfeldt-Jakob disease. Lancet. 1999 Jul 24. 354(9175):317-23. [Medline].
Collinge J. Human prion diseases and bovine spongiform encephalopathy (BSE). Hum Mol Genet. 1997. 6(10):1699-705. [Medline].
Statement by USDA Chief Veterinary Officer John Clifford Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States. United States Department of Agriculture. Available at http://usda.gov/wps/portal/usda/usdahome?contentid=2012/04/0132.xml. Accessed: April 29, 2012.
vCJD (Variant Creutzfeldt-Jakob Disease) Date: August 23, 2010. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/dvrd/vcjd/factsheet_nvcjd.htm. Accessed: April 29, 2012.
BSE (Bovine Spongiform Encephalopathy, or Mad Cow Disease). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/dvrd/bse/. Accessed: April 29, 2012.
Hornabrook RW. Kuru--a subacute cerebellar degeneration. The natural history and clinical features. Brain. 1968 Mar. 91(1):53-74. [Medline].
Mandell G, Bennett J, Dolin R. Prions and prion diseases of the central nervous system. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA: Elsevier; 2005. Vol 2: 2221.
Fiorino AS. Sleep, genes and death: fatal familial insomnia. Brain Res Brain Res Rev. 1996 Oct. 22(3):258-64. [Medline].
Ridley RM, Baker HF. The myth of maternal transmission of spongiform encephalopathy. BMJ. 1995 Oct 21. 311(7012):1071-5; discussion 1075-6. [Medline].
Collinge J. New diagnostic tests for prion diseases. N Engl J Med. 1996 Sep 26. 335(13):963-5. [Medline].
Kobayashi A, Parchi P, Yamada M, Mohri S, Kitamoto T. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases. Neuropathology. 2015 Dec 15. [Medline].
Lampert PW, Gajdusek DC, Gibbs CJ. Subacute spongiform virus encephalopathies. Scrapie, Kuru and Creutzfeldt-Jakob disease: a review. Am J Pathol. 1972 Sep. 68(3):626-52. [Medline].
Fichet G, Comoy E, Duval C, Antloga K, Dehen C, Charbonnier A, et al. Novel methods for disinfection of prion-contaminated medical devices. Lancet. 2004 Aug 7-13. 364(9433):521-6. [Medline].
Rogez-Kreuz C, Yousfi R, Soufflet C, Quadrio I, Yan ZX, Huyot V, et al. Inactivation of animal and human prions by hydrogen peroxide gas plasma sterilization. Infect Control Hosp Epidemiol. 2009 Aug. 30(8):769-77. [Medline].
Greenlee JJ, Nicholson EM, Hamir AN, Noyes GP, Holtzapple MT, Kehrli ME Jr. Ablation of prion protein immunoreactivity by heating in saturated calcium hydroxide. BMC Res Notes. 2008 Oct 28. 1:99. [Medline]. [Full Text].
Gajdusek DC, Gibbs CJ Jr, Alpers M. Transmission and passage of experimental "kuru" to chimpanzees. Science. 1967 Jan 13. 155(759):212-4. [Medline].
Brown P, Will RG, Bradley R, et al. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns. Emerg Infect Dis. 2001 Jan-Feb. 7(1):6-16. [Medline].
Brown P, Bradley R. 1755 and all that: a historical primer of transmissible spongiform encephalopathy. BMJ. 1998 Dec 19-26. 317(7174):1688-92. [Medline].
Carp RI, Kascsak RJ, Wisniewski HM, et al. The nature of the unconventional slow infection agents remains a puzzle. Alzheimer Dis Assoc Disord. 1989 Spring-Summer. 3(1-2):79-99. [Medline].
Collinge J, Whitfield J, McKintosh E, Frosh A, Mead S, Hill AF, et al. A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3725-39. [Medline].
Gajdusek DC. Kuru: an appraisal of five years of investigation. Eugen Q. 1962 Mar. 9:69-74. [Medline].
Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea; the endemic occurrence of kuru in the native population. N Engl J Med. 1957 Nov 14. 257(20):974-8. [Medline].
Gardash'ian AM. [Kuru]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1969. 69(5):767-72. [Medline].
Hadlow WJ. Scrapie and Kuru. Lancet. 1959. 2:289-290.
Keohane C. The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance. Clin Exp Pathol. 1999. 47(3-4):125-32. [Medline].
Lessons from kuru. Lancet. 2006 Jun 24. 367(9528):2034. [Medline].
Liberski PP, Brown P. Kuru: its ramifications after fifty years. Exp Gerontol. 2009 Jan-Feb. 44(1-2):63-9. [Medline].
Lindenbaum S. Review. Understanding kuru: the contribution of anthropology and medicine. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3715-20. [Medline].
Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Beck J, et al. Genetic susceptibility, evolution and the kuru epidemic. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3741-6. [Medline].
Miller MW, Williams ES. Chronic wasting disease of cervids. Curr Top Microbiol Immunol. 2004. 284:193-214. [Medline].
Mocsny N. The spongiform encephalopathies: prion diseases. J Neurosci Nurs. 1998 Oct. 30(5):302-6. [Medline].
Nutr Rev. Nutrition and infection: cannibalism. Nutr Rev. 1971 Oct. 29(10):226-7. [Medline].
Polo JM. [The history and classification of human prion diseases]. Rev Neurol. 2000 Jul 16-31. 31(2):137-41. [Medline].
Serpell LC, Sunde M, Blake CC. The molecular basis of amyloidosis. Cell Mol Life Sci. 1997 Dec. 53(11-12):871-87. [Medline].
Simpson NE. The map of chromosome 20. J Med Genet. 1988 Dec. 25(12):794-804. [Medline].
Sy MS, Gambetti P, Wong BS. Human prion diseases. Med Clin North Am. 2002 May. 86(3):551-71, vi-vii. [Medline].
Toledano-Gasca A. Hypotheses concerning the aetiology of Alzheimer's disease. Pharmacopsychiatry. 1988 Aug. 21 Suppl 1:17-25. [Medline].
Tyler KL. Prions and prion diseases of the central nervous system. Curr Clin Top Infect Dis. 1999. 19:226-51. [Medline].
Verdrager J. Kuru and "new variant" CJD. Southeast Asian J Trop Med Public Health. 1997 Sep. 28(3):535-40. [Medline].
Wadsworth JD, Joiner S, Linehan JM, Asante EA, Brandner S, Collinge J. Review. The origin of the prion agent of kuru: molecular and biological strain typing. Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27. 363(1510):3747-53. [Medline].
Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996 Apr 6. 347(9006):921-5. [Medline].
Wojtowicz S. Multiple sclerosis and prions. Med Hypotheses. 1993 Jan. 40(1):48-54. [Medline].
Zigas V, Gajdusek DC. Kuru: clinical study of a new syndrome resembling paralysis agitans in natives of the Eastern Highlands of Australian New Guinea. Med J Aust. 1957 Nov 23. 44(21):745-54. [Medline].