In a previous blog, I examined the scientific literature on fatal familial insomnia (FFI), an incredibly rare genetic sleep disorder cause caused by a genetic mutation that leads to prion disease. Today’s blog takes a brief look at another prion disease – ‘kuru’. Like FFI, kuru is also an incurable and degenerative neurological disorder (i.e., a transmissible spongiform encephalopathy) although the only people known to have experienced it are a few cannibalistic tribes in the Eastern Highlands Province of New Guinea (most notably the Fore tribe) where it is known as the ‘laughing sickness’ or the ‘laughing disease’ (that refer to one of the disease’s most noticeable symptoms – the hysterical and pathological outbursts of laughter that suffering individuals produce in the latter stages of the disease).
The disease has a relatively long incubation period (5 to 20 years, with an average of 10 to 13 years according to a study led by Dr. Jerome Huillard d’Aignaux in a 2002 issue of the journal Epidemiology. However, a study published by Dr. R.L. Klitzman and colleagues in an earlier issue of Neuroepidemiology reported that:
“Epidemiological data were collected on…65 kuru patients who died or were diagnosed between 1977 and 1981. From these…2 or more participants were exposed to the infectious agent for the first time and died within weeks or months of each other 25–30 years later. Thus, it is shown that the natural incubation period of kuru could be as long as 25–30 years”
A more recent paper by Dr. John Collinge and colleagues in The Lancet identified 11 kuru sufferers from July 1996 to June 2004 all living in the South Fore. They reported that the minimum estimated incubation periods ranged from 34 to 41 years. However, they also noted that the likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. Therefore, incubation periods could be very long.
According to Dr. Robert Will (in a 2003 issue of the British Medical Bulletin), over 2700 cases of kuru have been recorded since 1957 (in a total population within the kuru region of 36,000 people). Those infected with kuru typically die between 3 and 24 months following the first symptoms. Because of the long incubation period, it is thought that the last person to die of kuru in New Guinea was only seven years ago (i.e., 2005).
The word ‘kuru’ (not to be confused with ‘koro’, the culture bound genital retraction syndrome typically found in south-east Asia) is derived from the Fore tribe’s word ‘to shake’ (‘kuria’). Research carried out in the 1960s and 1970s demonstrated beyond doubt that kuru was transmitted from one individual to another via the cannibalistic practices of the Fore tribe (particularly the South Fore of the Okapa Subdistrict that showed the most large and notable kuru infection rates). The first recorded cases of kuru were made by a number of Australians back in the early 1950s. W.T. Brown reported that
“The first sign of impending death is a general debility which is followed by general weakness and inability to stand. The victim retires to her house. She is able to take a little nourishment but suffers from violent shivering. The next stage is that the victim lies down in the house and cannot take nourishment and death eventually ensues”.
It was in the early 1960s at the Eastern Highlands Awande Hospital that kuru sufferers underwent medical research in an effort to locate the cause of the disease. It was the pioneering work Daniel Gajdusek and Michael Alpers that led to the discovery of the causative agent of kuru. Brain tissue samples were taken from an 11-year old girl who had died of kuru and subsequently injected into a couple of chimpanzees. One of the chimps developed kuru within 24 months, and the research showed unequivocally that kuru was capable of infection cross-species. According to Dr. Robert Will, “this seminal discovery led to the successful laboratory transmission of [Creutzfeldt-Jakob disease] and initiated research into the epidemiology and pathogenesis of human prion disease”
It is now generally believed that the kuru outbreak began following the consumption of an infected human brain with sporadic Creutzfeldt-Jakob disease (CJD) by people in the Fore tribe in around 1900. Kuru then spread to other nearby tribes following inter-tribe marrying (gradually spreading to the 169 villages and hamlets according to a 2010 paper by Dr. Nils Pedersen and Dr. Else Smith in a 2010 issue of Acta Pathologica Micobiologica Et Immunologica Scandinavica). Once infected with kuru, the disease has three distinct phases (ambulant, sedentary, and terminal):
- Ambulant phase: Symptoms typically include decreased muscle and motor control leading to an unsteady gait and stance, tremors, and deterioration and slurring of speech (dysarthria).
- Sedentary phase: Symptoms typically include deterioration of muscle coordination (ataxia) and severe tremors. Sufferers are unable to walk unaided and they suffer bouts of hysterical and uncontrolled laughter.
- Terminal phase: Symptoms typically include complete loss of muscle co-ordination, incontinence, being unable to talk or sit unaided, great difficulty in swallowing food (dysphagia) (difficulty swallowing), and the outbreak of necrotic ulcerations (sores with pus).
The early research by Michael Alpers and colleagues showed that kuru spread very rapidly as a result of the Fore tribe’s endocannibalistic practice (i.e., of eating the flesh of human beings from within the same community after the person had died and taking on that individual’s ‘life force’). Interestingly, Alper’s research also showed that kuru infection was far more prevalent in women and children (in fact, up to 9 times more prevalent). Dr. Pedersen and Dr. Smith noted that the youngest ever kuru sufferer was five years old, and that 67% of those with kuru were adult women, 23% were children and adolescents, and only 10% were adult men.
There are two reasons why kuru might be more prevalent among women and children compared to men. Firstly, men in the tribe had first choice of which parts of the infected dead tribe member to eat. Once the men had eaten the ‘choice cuts’, women and children could only eat what was left and this included the dead person’s brain (where the infected prion particles were at their most concentrated). Secondly, women and children were far more likely than men to clean the bodies of the infected dead people. If those cleaning the body had open cuts or sores on their hands, the infection may have spread through the bloodstream. The 2002 research led by Dr. Jerome Huillard d’Aignaux and colleagues also demonstrated that the incubation period in females was shorter than that in males because adult women may have been exposed to the largest doses of infectious material. However, Dr. Robert Will has noted that as time has passed, the incidence of kuru has declined and the proportion of affected adult males and females has become more similar. Research (for example by Dr. Simon Mead) has also indicated that some members of the Fore tribe were immune from catching kuru as they carried a prion-resistant factor. Dr. Will also reported that:
“No children born after 1959 have been affected and there is no evidence of vertical transmission of infectivity in kuru, despite the breast-feeding of infants by many hundreds of clinically affected mothers”.
Most recent papers on kuru (such as one by Dr. Laura Manuelidis and colleagues in a 2009 issue of Proceedings of the National Academy of Sciences) have noted that the disease has now died out due to the cessation of the endocannibalistic rituals and therefore is not created spontaneously by the human host.
Dr Mark Griffiths, Professor of Gambling Studies, International Gaming Research Unit, Nottingham Trent University, Nottingham, UK
Collinge, J., Whitfield, J.W., McKintosh, E., Beck, J., Mead, S., Thomas, D.J., & Alpers, M.P. (2006). Kuru in the 21st century—an acquired human prion disease with very long incubation periods. The Lancet, 367, 2068-2074.
Gajdusek, D.C., Gibbs, C.J. & Alpers, M. (1966). Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature, 209, 794-796.
Gajdusek, D.C & Zigas, V. (1957). Degenerative disease of the central nervous system in New Guinea. The epidemic occurrence of ‘‘Kuru’’ in the native population. New England Journal of Medicine, 257, 974-978.
Huillard d’Aignaux, J.N., Cousens, S.N., Maccario, J., Costagliola, D., Alpers, M.P., Smith, P.G., Alpérovitch, A. (2002). The incubation period of kuru. Epidemiology, 13, 402-408.
Klitzman, R.L., Alpers, M.P. & Gajdusek, D.C. (1984). The natural incubation period of kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology, 3, 3-20.
Lindenbaum, S. (1979). Kuru sorcery: Disease and danger in the New Guinea highlands. Palo Alto, CA: Mayfield.
Manuelidis, L., Chakrabarty, T., Miyazawa, K., Nduom, N. & Emmerling, K. (2009). The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents Proceedings of the National Academy of Sciences, 106, 13529-13534.
Pedersen, N.S. & Smith, E. (2010). Prion diseases: Epidemiology in man. Acta Pathologica Micobiologica Et Immunologica Scandinavica, 110, 14-22.
Will, R.G. (2003). Acquired prion disease: iatrogenic CJD, variant CJD, kuru. British Medical Bulletin, 66, 255-265.
For most of my life I have “suffered” from insomnia. I deliberately put the word ‘suffered’ in quotation marks as for the vast majority of the time I have always seen my lack of sleep as something positive (i.e., I had more time to do other things. In fact, when people ask me how I find the time to write so much, I usually say “Insomnia” but I don’t usually say it as a joke, it’s a matter of fact). Given my personal interest in insomnia, I’ve always enjoyed reading papers on insomnia (and no, they don’t send me to sleep!) and sexsomnia (which I looked at in a previous blog). In 1990, a Finnish man named Toimi Soini stayed awake for over 11 days (276 hours) and broke the world record for not going to sleep. However, this record no longer appears in the Guinness Book of World Records as it was withdrawn on health grounds because lack of sleep – as I’ll show in today’s blog – can lead to death.
One of the strangest (and deadliest) types of insomnia is ‘fatal familial insomnia’ (FFI). This is actually an incredibly rare genetic sleep disorder that affects around 40 families worldwide. The cause of FFI is a genetic mutation that leads to prion disease and is therefore related to bovine spongiform encephalopathy (BSE; i.e., ‘mad cow disease’), Creutzfeldt–Jakob disease (the human form of BSE), and ‘Kuru’ (the incurable and degenerative neurological disorder found in the cannibalistic tribes in New Guinea and known as the ‘laughing disease’). The (online) Medical Dictionary is a little more technical and notes:
“Fatal familial insomnia (FFI) is a very rare, autosomal dominant inherited, disease of the brain. It is caused by a mutation in a protein called prion protein (PrP): asparagine- 178 is replaced by aspartic acid. The mutation changes the shape of PrP so that it becomes a prion and makes other, normal PrP molecules change to the abnormal shape. This causes amyloid plaques in the thalamus, the region of the brain responsible for regulation of sleep patterns. The dysfunction of the thalamus results in insomnia first of all, which progresses to more serious problems over several years”
All prion diseases (known more scientifically as ‘transmissible spongiform encephalopathies’) are rare progressive neurodegenerative disorders that can affect both animals and humans. All of the prion diseases (including FFI) typically have (i) long incubation periods, (ii) a failure to induce inflammatory response, and (iii) characteristic spongiform changes that are associated with neuronal loss. The first recorded case of FFI is thought to be an Italian man who died in Venice in 1765. There are many descriptions of the disease online including case study accounts. The Wikipedia entry on FFI described the case of the American music teacher, Michael Corke from Chicago:
“He suddenly began to have trouble sleeping not long after his 40th birthday in 1991, and his health and state of mind quickly deteriorated as his sleeplessness grew worse. Eventually, he couldn’t sleep at all, and he was soon admitted to the hospital. Doctors there weren’t sure what was wrong with him, initially diagnosing multiple sclerosis; in a bid to send him to sleep in the later stages of the disease, physicians induced a coma with the use of sedatives, but they found that his brain still failed to shut down. Corke died in 1992 a month before his 41st birthday, by which time he had gone without sleep for six months”
Another 2011 online article on “bizarre brain disorders” by Anna McGann also described a family case study (which is very similar to paper published in a 2000 issue of the Journal of Neurology, Neurosurgery and Psychiatry by Dr. C. Tabernero and colleagues):
“Dr. Ignazio Rottier gained unwanted firsthand experience when he and his wife, Elisabetta, watched her family fall victim to [FFI]. First known to fall ill was Elisabetta’s grandfather. Decades later, Elisabetta’s uncle, Silviano, was 53 when he lost his ability to sleep. A few short months following initial onset, Silviano fell into a coma and died…In the 70s, an aunt of Elisabetta’s passed on, one year after her own initial onset of sleeplessness. Yet another year later, a second aunt too lost her life battling the very same affliction”.
Research has also shown that the condition (in a few cases) can result from a non-inherited genetic mutation that has been called ‘sporadic fatal insomnia’ (sFI). Less than 10 cases of sFI have ever been documented in the medical literature. As the conditions worsen, sufferers experience a wide range of symptoms including delirium, hallucinations (auditory, visual and tactile), elevated heart rate and blood pressure, hyperhidrosis (i.e., excess sweating), hyperthermia, hypertension, impotence (in men), amenorrhea (cessation of periods) and early menopause (in women), constipation, and dementia. Treating the symptoms (via vitamin therapy, meditation, use of narcoleptics) may extend the quality of life (but as noted above, there is no known cure and most interventions are purely palliative). The disease typically has four stages, and takes between half a year and a year and a half to run its course:
- Stage 1 (typically four months): Symptoms include insomnia, paranoia, phobias and panic attacks.
- Stage 2 (typically five months): Symptoms include severe hallucinations and increasing panic attacks.
- Stage 3 (typically three months): Symptoms include permanent insomnia, limited mental functioning, and rapid weight loss.
- Stage 4 (typically six months): Symptoms include dementia and general non-responsiveness leading to death.
Writing in a 2006 issue of the Medscape General Medicine journal, Dr. Joyce Schenkein outlined the etiology and characteristics of FFI. She noted that it often begins in middle age (average age of onset being 50 years) and has no cure (even ‘gene therapy has been unsuccessful to date). Unfortunately, the prognosis following initial diagnosis is poor with FFI sufferers’ only living for an average of about a year and a half (with Dr. Schenkein noting that survival ranged from 7 to 36 months from diagnosis of FFI). It originates in the form of unexplained sleeplessness before rapidly developing into a fatal insomnia. Writing in an issue of the Journal of Clinical Neuroscience, Dr. S. Collins and colleagues in a paper on prion diseases (including FFI) concluded:
“FFI [is] likely [to] remain, [a] very rare disease, [and] will be increasingly recognised as heightened clinical awareness prompts appropriate confirmatory genetic and other testing. Similarly, continued molecular biological and allied research of these less common prion diseases will undoubtedly provide fundamental insights into the pathogenesis of this group of disorders in general, disproportionate to their numerical frequency”.
Dr Mark Griffiths, Professor of Gambling Studies, International Gaming Research Unit, Nottingham Trent University, Nottingham, UK
Collins, S., McLean, C.A. & Masters, C.L. (2001). Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. Journal of Clinical Neuroscience, 8, 387–397.
McGann, A. (2011). 5 bizarre brain disorders. Suite 101, November 25. Located at: http://suite101.com/article/5-bizarre-brain-disorders-a397906
Moody, K.M., Schonberger, L.B., Maddox, R.A., Zou, W.Q., Cracco, L., & Cali, I. (2011). Sporadic fatal insomnia in a young woman: a diagnostic challenge: case report. BMC Neurology, 11, 136.
Schenkein, J. (2006). Self-management of fatal familial insomnia. Part 1: What Is FFI? Medscape General Medicine, 8(3), 65.
Schenkein, J. & Montagna, P (2006). Self-management of fatal familial insomnia. Part 2: Case report. Medscape General Medicine, 8(3), 66.
Tabernero, C., Polo, J.M., Sevillano, M.D., Muñoz, R., Berciano, J., Cabello, A., Báez, B., Ricoy, J.R., Carpizo, R., Figols, J., Cuadrado, N., Claveria, L.E. (2000). Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family. Journal of Neurology, Neurosurgery and Psychiatry, 68, 774–777.
Turner, R. (2012). Fatal Familial Insomnia: The FFI Sleep Disorder. World of Lucid Dreaming. Located at: http://www.world-of-lucid-dreaming.com/fatal-familial-insomnia.html
Wikipedia (2012). Fatal familial insomnia. Located at: http://en.wikipedia.org/wiki/Fatal_familial_insomnia