| Fatal familial insomnia |
| Classification and external resources |
| ICD-10 |
A81.9 |
| ICD-9 |
046.72 |
| OMIM |
600072 |
| DiseasesDB |
32177 |
| MeSH |
D034062 |
Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited prion disease of the brain. It is almost always caused by a mutation to the protein PrPC, but can also develop spontaneously in patients with a non-inherited mutation variant called sporadic Fatal Insomnia (sFI). FFI has no known cure and involves progressively worsening insomnia, which leads to hallucinations, delirium, and confusional states like that of dementia.[1] The average survival span for patients diagnosed with FFI after the onset of symptoms is 18 months.[1]
The mutated protein, called PrPSc, has been found in just 40 families worldwide, affecting about 100 people; if only one parent has the gene, the offspring have a 50% chance of inheriting it and developing the disease. The first recorded victim was an Italian man, deceased in Venice in the year 1765.[2]
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Contents
- 1 The prion
- 2 Sporadic Fatal Insomnia
- 3 Presentation
- 4 Treatment
- 5 Normal sleep and FFI
- 6 Related conditions
- 7 References
- 7.1 Notes
- 7.2 Bibliography
- 8 External links
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The prion
Gene PRNP that provides instructions for making the prion protein PrPC is located on the short (p) arm of chromosome 20 at position p13.[3] Both FFI patients and those with Creutzfeldt-Jakob disease carry a mutation at codon 178 of the prion protein gene. FFI is invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas CJD is linked to the presence of the valine codon at that position.[4] "The disease is where there is a change of amino acid at position 178 when an asparagine (N) is found instead of the normal aspartic acid (D). This has to be accompanied with a methionine at position 129."[5]
Sporadic Fatal Insomnia
Only eight cases of sFI have ever been diagnosed as of July 2005.[6] In sFI there is no mutation in PRNP-prion gene in D178N, but all have methionine homozygosity at codon 129. [7][8][9][10]
Presentation
The age of onset is variable, ranging from 18 to 60, with an average of 50. However the disease tends to prominently occur in later years, primarily following giving birth. The disease can be detected prior to onset by genetic testing.[11] Death usually occurs between 7 and 36 months from onset. The presentation of the disease varies considerably from person to person, even among patients from within the same family.
The disease has four stages, taking 7 to 18 months to run its course:
- The patient suffers increasing insomnia, resulting in panic attacks, paranoia, and phobias. This stage lasts for about four months.
- Hallucinations and panic attacks become noticeable, continuing for about five months.
- Complete inability to sleep is followed by rapid loss of weight. This lasts for about three months.
- Dementia, during which the patient becomes unresponsive or mute over the course of six months. This is the final progression of the disease, after which death follows.
Other symptoms include profuse sweating, pinpoint pupils, the sudden entrance into menopause for women and impotence for men, neck stiffness, and elevation of blood pressure and heart rate. Constipation is common as well.
Treatment
There is no cure or treatment for FFI. Gene therapy is so far unsuccessful. While it is not currently possible to reverse the underlying illness, there is some evidence that treatments that focus upon the symptoms can improve quality of life.[12]
Several cases have proven that sleeping pills and barbiturates do not help; they make FFI worse and actually speed up the disease. This is the case 74% of the time.[13]
One of the most notable cases is that of Michael Corke, a music teacher from Chicago, Illinois. 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.[14]
One patient was able to exceed the average survival time by nearly one year with various strategies, including vitamin therapy and meditation, using different stimulants and narcoleptics and even complete sensory deprivation in an attempt to induce sleep at night and increase alertness during the day. Nonetheless, over the course of his trials, the patient succumbed to the classic four-stage progression of symptoms.[12][15]
In the late 2000s, a mouse model was made for FFI. These mice express a humanized version of the PrP protein that also contains the D178N FFI mutation.[16] These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to people with FFI.
Normal sleep and FFI
Normal sleep. FFI–patients cannot pass stage 1.
Normal sleep has different stages that together last 90 to 100 minutes:
- REM-sleep when dreams occur.
- Non REM Stages 1 and 2: Light slow wave sleep NREM-sleep
- Non REM Stages 3 and 4: Deep sleep
REM is most important for health,[17] followed by stage 2. Most reviving and repairing processes of the body are believed to happen during these two stages. The FFI-patients cannot go past stage 1 and thus brains are not getting the rest they need to revive.[15] Prolonged REM-sleep deprivation is the eventual cause of death.[18][clarification needed]
Related conditions
There are other diseases involving the mammalian prion protein. Some are transmissible (TSEs) such as kuru, bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cows, and chronic wasting disease in American deer and American elk in some areas of the United States and Canada, as well as Creutzfeldt-Jakob disease (CJD). Until recently prion diseases were only thought to be transmissible via direct contact with infected tissue, such as from eating infected tissue, transfusion or transplantation; new research now suggests that prion diseases can be transmitted via aerosols, but that the general public is not at risk of airborne infection.[19]
References
Notes
- ^ a b Schenkein J, Montagna P (2006). "Self management of fatal familial insomnia. Part 1: what is FFI?". MedGenMed 8 (3): 65. PMC 1781306. PMID 17406188. http://www.medscape.com/viewarticle/542963.
- ^ The Family That Couldn't Sleep.
- ^ PRNP-gene
- ^ PRPC gene mutation.
- ^ http://perpetualsummer.co.uk/diseasemotifs/prion/ffi.html[dead link]
- ^ Discovery-channel: "My Shocking Story-Dying to Sleep"
- ^ Fatal Familial Insomnia at Merck Manual of Diagnosis and Therapy Home Edition
- ^ Parchi P, Capellari S, Chin S, et al. (June 1999). "A subtype of sporadic prion disease mimicking fatal familial insomnia". Neurology 52 (9): 1757–63. PMID 10371520. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=10371520.
- ^ Mehta LR, Huddleston BJ, Skalabrin EJ, et al. (July 2008). "Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome". Arch. Neurol. 65 (7): 971–3. DOI:10.1001/archneur.65.7.971. PMID 18625868. http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=18625868.
- ^ Moody KM, Schonberger LB, Maddox RA, Zou WQ, Cracco L, Cali I (2011). "Sporadic fatal insomnia in a young woman: a diagnostic challenge: case report". BMC Neurol 11: 136. DOI:10.1186/1471-2377-11-136. PMC 3214133. PMID 22040318. http://www.biomedcentral.com/1471-2377/11/136.
- ^ Max, D.T. (May 2010). "The Secrets of Sleep". National Geographic Magazine: p. 74.
- ^ a b Schenkein J, Montagna P (2006). "Self-management of fatal familial insomnia. Part 2: case report". MedGenMed : Medscape general medicine 8 (3): 66. PMC 1781276. PMID 17406189. http://www.medscape.com/viewarticle/542964.
- ^ Turner, Rebecca. "The Man Who Never Slept: Michael Corke". World Of Lucid Dreaming. http://www.world-of-lucid-dreaming.com/the-man-who-never-slept.html. Retrieved May 20, 2011.
- ^ http://health.howstuffworks.com/human-body/parts/10-things-peoples-brains-have-done9.htm
- ^ a b Dying Without Sleep: Insomnia and its Implications
- ^ Jackson W, et al. (2009). "Spontaneous Generation of Prion Infectivity in Fatal Familial Insomnia Knockin Mice". Neuron 63 (4): 438–450. DOI:10.1016/j.neuron.2009.07.026. PMC 2775465. PMID 19709627. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2775465.
- ^ Prazosin modulates rapid eye movement sleep deprivation-induced changes in body temperature in rats
- ^ Types of sleep deprivation
- ^ Mosher, Dave (January 13, 2011). "Airborne Prions Make for 100 Percent Lethal Whiff". Wired. http://www.wired.com/wiredscience/2011/01/airborne-prions-disease/. Retrieved May 20, 2011.
Bibliography
- Akroush, Ann M.. "Fatal Familial Insomnia". University of Michigan. http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997%20Case%20Studies/AAkroush.html.
- Online 'Mendelian Inheritance in Man' (OMIM) Fatal Familial Insomnia; FFI -600072
- Montagna P, Gambetti P, Cortelli P, Lugaresi E (2003). "Familial and sporadic fatal insomnia". Lancet Neurol 2 (3): 167–76. DOI:10.1016/S1474-4422(03)00323-5. PMID 12849238.
- Almer G, Hainfellner JA, Brücke T, et al. (1999). "Fatal familial insomnia: a new Austrian family". Brain 122 (1): 5–16. DOI:10.1093/brain/122.1.5. PMID 10050890. http://brain.oxfordjournals.org/cgi/content/full/122/1/5.
External links
- "The Family that Couldn't Sleep" book by D.T. Max, NPR Interview
- Schadler, Jay; Viddy, Laura. "Medical Mystery: When Sleep Doesn't Come, Death Does". ABC News. http://abcnews.go.com/Health/story?id=3675223&page=1.
- Fatal Familial Insomnia Families Association website
- FFI Mutation D178N
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Infectious diseases – Prion diseases / Transmissible spongiform encephalopathy (A81, 046)
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| Prion diseases in humans |
inherited/PRNP: fCJD · Gerstmann–Sträussler–Scheinker syndrome · Fatal familial insomnia
sporadic: sCJD
acquired/transmissible: Kuru · vCJD
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| Prion diseases in animals |
Bovine spongiform encephalopathy · Scrapie · Chronic wasting disease · Transmissible mink encephalopathy · Feline spongiform encephalopathy · Exotic ungulate encephalopathy
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