795:
referred the case to Prof. Elio
Lugaresi, a well-known sleep expert, who, along with his colleagues, carried out advanced sleep analyses. As Silvano's condition quickly deteriorated, Lugaresi arranged for a postmortem neuropathological examination of the brain to be carried out by Dr. Gambetti, Lugaresi's former trainee. The collaboration of these two groups led to the 1986 publication . At the time, a prion disease was not suspected due to a lack of prion-related histpathology and frozen brain tissue for advanced analysis. However, due to the devotion of Dr. Roiter and Silvano's family, more cases were obtained, resulting in the classification of FFI as a familial prion disease tied to the 178Asn genetic mutation.
437:
531:
susceptible transgenic mice have consistently demonstrated that the same prion strain is associated with both sFI and FFI. In contrast to what has been the rule for the most common neurodegenerative disorders, sFI is rarer than its genetic counterpart. Whereas the recognized patients with FFI are numerous and belong to >50 families worldwide, only about 30 cases of CJD MM2T and a few cases with mixed MM2T and MM2C features (MM2T+C) have been recorded to date.
45:
826:
729:
565:
387:
678:(CJD). Until recently prion diseases were thought to be transmissible only by direct contact with infected tissue, such as from eating infected tissue, transfusion or transplantation; research suggests that prions can be transmitted by aerosols but that the general public is not at risk of airborne infection.
746:
of Spain, 16 family cases of the 178N mutation were seen between 1993 and 2005 related to two families with a common ancestor in the 18th century. In 2011, another family was added to the list when researchers found the first man in the
Netherlands to be diagnosed with FFI. Whilst he had lived in the
368:
The age of onset is variable, ranging from 13 to 60 years, with an average of 50. The disease can be detected prior to onset by genetic testing. Death usually occurs between 6–36 months from onset. The presentation of the disease varies considerably from person to person, even among people within the
833:
In 2011, the first reported case in the
Netherlands was of a 57-year-old man of Egyptian descent. The man came in with symptoms of double vision and progressive memory loss, and his family also noted he had recently become disoriented, paranoid and confused. Whilst he tended to fall asleep at random
633:
The real-time quaking-induced conversion (RT-QuIC), a highly sensitive assay that detects minute amounts of PrP in the cerebrospinal fluid (CSF), has been reported to have a sensitivity of 50% in FFI and sFI. However, this low sensitivity may change since the examination was based on a low number of
530:
Given its striking clinical and neuropathologic similarities with fatal familial insomnia (FFI), a genetic prion disease linked to a point mutation at codon 178 (D178N) in the PRNP coupled with methionine at codon 129, the MM2T subtype is also known as sporadic FI (sFI). Transmission studies using
834:
during daily activities, he experienced vivid dreams and random muscular jerks during normal slow-wave sleep. After four months of these symptoms, he began to have convulsions in his hands, trunk and lower limbs while awake. The person died at age 58, seven months after the onset of symptoms. An
794:
In 1986, Lugaresi and colleagues first named and described in detail the clinical and histopathological features of fatal familial insomnia (FFI) . This report was mostly based on a patient referred to as
Silvano, who was diagnosed with sleep impairment in 1983 by Dr. Ignazio Roiter. Dr. Roiter
637:
A test that measures the cerebral metabolic rate of glucose by positron emission tomography (PET), referred to as -FDG-PET, has demonstrated severe hypometabolism of the thalamus bilaterally in FFI and sFI, also in the earliest stages of the disease. This hypometabolism then spreads, eventually
816:
in an attempt to induce sleep at night and increase alertness during the day. He managed to write a book and drive hundreds of miles in this time, but nonetheless, over the course of his trials, the man succumbed to the classic four-stage progression of the illness.
2163:
2148:
1730:
Jansen C, Parchi P, Jelles B, Gouw AA, Beunders G, van
Spaendonk RM, et al. (August 2011). "The first case of fatal familial insomnia (FFI) in the Netherlands: a patient from Egyptian descent with concurrent four repeat tau deposits".
773:
129. Nonetheless, the methionine presence in lieu of the valine (Val129) is what causes the sporadic form of disease. The targeting of this mutation has been suggested as a strategy for treatment, or possibly as a cure for the disease.
1329:
Cortelli P, Perani D, Parchi P, Grassi F, Montagna P, De Martin M, et al. (July 1997). "Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein".
790:
hospital's sleep institute. The man, known only as
Silvano, decided in a rare moment of consciousness to be recorded for future studies and to donate his brain for research in hopes of finding a cure for future victims.
803:
In an article published in 2006, Schenkein and
Montagna wrote of a 52-year-old American man who was able to exceed the average survival time by nearly one year with various strategies that included vitamin therapy and
550:
being the most severe in the latter. Given the relationship between the involvement of the thalamus in regulating sleep and alertness, a causal relationship can be drawn and is often mentioned as the cause.
506:
prion protein gene located on chromosome 20, along with the presence of the methionine polymorphism at position 129 of the mutant allele. Pathologically, FFI is characterized predominantly by
742:
In 1998 40 families were known to carry the gene for FFI globally: eight German, five
Italian, four American, two French, two Australian, two British, one Japanese and one Austrian. In the
884:
The Prion
Alliance was established by husband and wife duo Eric Minikel and Sonia Vallabh after Vallabh's mother was diagnosed with the fatal disease. They conduct research at the
52:
Cranial imaging of an FFI patient. In the MRI, there are abnormal signals in the bilateral frontoparietal subcortical area. MRA showed smaller distal branches of cerebral arteries.
2306:
583:
405:
2443:
1692:
Parchi P, Capellari S, Chin S, Schwarz HB, Schecter NP, Butts JD, et al. (June 1999). "A subtype of sporadic prion disease mimicking fatal familial insomnia".
365:, which is the state just before sleep in healthy individuals. During these stages, people commonly and repeatedly move their limbs as if they were dreaming.
2463:
2448:
732:
Hypnogram comparing the sleep pattern of a healthy control with five FFI patients, who display decreased sleep efficiency and disrupted sleep cycles.
2261:
854:
Still with unclear benefit in humans, a number of treatments have had tentative success in slowing disease progression in animal models, including
330:, during which the person becomes unresponsive or mute over the course of six months, is the final stage of the disease, after which death follows.
2337:
2274:
651:
177:
720:
Like all prion diseases, the disease is invariably fatal. Life expectancy ranges from seven months to six years, with an average of 18 months.
2360:
1382:
743:
515:
2438:
1033:
754:
As of 20 September 2022, 37 cases of sporadic fatal insomnia have been diagnosed. Unlike in FFI, those with sFI do not have the
263:). The problems with sleeping typically start out gradually and worsen over time. Eventually, the patient will succumb to total insomnia (
2178:
225:
70 families worldwide are known to carry the gene associated with the disease, 37 sporadic cases diagnosed (as of
September 20th, 2022)
1165:
947:
747:
Netherlands for 19 years, he was of Egyptian descent. Other prion diseases are similar to FFI and may be related but are missing the
2407:
601:
423:
626:
if the patient's family has a history of the disease. As with other prion diseases, the diagnosis can be confirmed only by a brain
361:. Prolonged constipation is common as well. As the disease progresses, the person becomes stuck in a state of pre-sleep limbo, or
2412:
2387:
1085:
Cortelli P, Gambetti P, Montagna P, Lugaresi E (June 1999). "Fatal familial insomnia: clinical features and molecular genetics".
659:
2392:
2417:
2355:
2327:
2301:
675:
468:
873:
In 2009, a mouse model was made for FFI. These mice expressed a humanized version of the PrP protein that also contains the
2254:
877:
FFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the
276:
638:
impacting most cortical regions. The complexity and cost of this test currently impede its use in routine diagnosis.
1128:
542:. The extent of this symptom varies between two variations of the disease, these being those presenting methionine
1282:"Clinical profile of fatal familial insomnia: phenotypic variation in 129 polymorphisms and geographical regions"
235:
1233:"Specific structuro-metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study"
369:
same family; in the sporadic form, for example, sleep problems are not commonly reported and early symptoms are
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2189:
519:
2239:
2402:
2247:
663:
436:
173:
91:
2458:
979:
169:
164:
787:
511:
1963:"Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases"
698:, as a treatment for the disease. Symptoms of fatal familial insomnia may be treated with medications.
1513:
1485:
1057:
1649:
Montagna P, Gambetti P, Cortelli P, Lugaresi E (March 2003). "Familial and sporadic fatal insomnia".
855:
2060:
1579:
44:
2220:
2167:
813:
354:
1007:
909:
1756:
1674:
1110:
86:
Progressive insomnia, ataxia, double vision, weight loss, high blood pressure, excessive sweating
81:
888:
to develop therapeutics for human prion diseases. Other research interests involve identifying
2200:
2041:
1992:
1961:
Forloni G, Tettamanti M, Lucca U, Albanese Y, Quaglio E, Chiesa R, et al. (21 May 2015).
1943:
1899:
1848:
1797:
1774:
Mehta LR, Huddleston BJ, Skalabrin EJ, Burns JB, Zou WQ, Gambetti P, et al. (July 2008).
1748:
1709:
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1378:
1347:
1311:
1262:
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499:
142:
57:
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1982:
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1701:
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1490:
1456:
1446:
1407:
1370:
1339:
1301:
1293:
1252:
1244:
1147:
1094:
712:
may be prescribed to help treat insomnia. However these drugs do not work in the long term.
539:
256:
124:
2010:
Jackson WS, Borkowski AW, Faas H, Steele AD, King OD, Watson N, et al. (August 2009).
885:
687:
623:
479:
codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the
195:
156:
2365:
2172:
2036:
2011:
1987:
1962:
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1921:
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1257:
1232:
863:
655:
74:
70:
17:
1705:
1662:
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2012:"Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice"
1744:
1098:
691:
492:
464:
460:
310:
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1760:
1678:
1411:
1114:
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178 of the prion protein gene. FFI is also invariably linked to the presence of the
766:
547:
335:
296:
1978:
1884:
2194:
2027:
1205:
867:
783:
705:
695:
615:
275:. It results in death within a few months to a few years, and there is no known
148:
132:
2205:
1817:"Sporadic fatal insomnia in a young woman: a diagnostic challenge: case report"
1248:
2157:
1815:
Moody KM, Schonberger LB, Maddox RA, Zou WQ, Cracco L, Cali I (October 2011).
1792:
1776:"Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome"
1775:
1398:
Morton AJ (May 2013). "Circadian and sleep disorder in Huntington's disease".
805:
763:
701:
543:
488:
484:
476:
362:
202:
97:
66:
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62:
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1996:
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1635:
1565:
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1419:
1315:
1266:
1217:
1106:
1351:
825:
728:
534:
In itself the presence of prions causes reduced glucose to be used by the
1343:
878:
843:
762:-prion gene; they all have a different mutation in the same gene causing
709:
619:
535:
507:
440:
358:
327:
300:
292:
272:
242:
152:
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1451:
1280:
Zhang J, Chu M, Tian Z, Xie K, Cui Y, Liu L, et al. (March 2022).
839:
835:
627:
268:
2140:
984:
Genetic and Rare Diseases Information Center (GARD) – an NCATS Program
313:
and panic attacks become noticeable, continuing for about five months.
2152:
1365:
Kostina A, Alama A, McGintya D, Alama N (2023). "Sleep homeostasis".
483:
codon at that position. The disease occurs when there is a change of
480:
370:
357:
and heart rate. The sporadic form of the disease often presents with
342:
321:
304:
739:
Fatal insomnia was first described by Elio Lugaresi et al. in 1986.
1179:
2270:
1610:"Self management of fatal familial insomnia. Part 1: what is FFI?"
1540:"Self management of fatal familial insomnia. Part 1: what is FFI?"
1231:
Xie K, Chen Y, Chu M, Cui Y, Chen Z, Zhang J, et al. (2022).
824:
770:
727:
472:
452:
317:
238:
1922:"Self-management of fatal familial insomnia. Part 2: case report"
2292:
2183:
2104:
667:
647:
495:. This has to be accompanied with a methionine at position 129.
251:
2243:
1866:
Tabaee Damavandi P, Dove MT, Pickersgill RW (September 2017).
671:
558:
380:
334:
Clinically, FFI manifests with a disordered sleep-wake cycle,
634:
cases, and the RT-QuIC technology is continuously evolving.
245:
as its hallmark symptom. The majority of cases are familial (
892:
to track the progression of prion disease in living people.
829:
Timeline of an FFI patient (same as the one above this one)
786:/sleep expert Dr Ignazio Roiter received a patient at the
674:
in some areas of the United States and Canada, as well as
614:
Diagnosis is based on symptoms and can be supported by a
2224:
2061:"One Couple's Tireless Crusade to Stop a Genetic Killer"
579:
459:. The gene, which provides instructions for making the
401:
1868:"A review of drug therapy for sporadic fatal insomnia"
1580:"Fatal familial insomnia: Everything you need to know"
338:, motor disturbances, and neuropsychiatric disorders.
846:. The latter is one of the most common signs of FFI.
2221:"AFIFF Fatal Familial Insomnia Families Association"
2130:
2378:
2346:
2320:
2290:
2281:
2134:
1486:"Airborne prions make for 100 percent lethal whiff"
662:(BSE, also known as mad cow disease) in cattle and
574:
may be too technical for most readers to understand
396:
may be too technical for most readers to understand
221:
211:
201:
191:
183:
163:
141:
131:
120:
112:
104:
90:
80:
56:
37:
1286:Journal of Neurology, Neurosurgery, and Psychiatry
842:of the frontal cortex and moderate atrophy of the
467:at position p13. Individuals with FFI or familial
1080:
1078:
498:FFI is an autosomal dominant disease caused by a
1725:
1723:
881:, and early deaths, similar to humans with FFI.
690:. There is conflicting evidence over the use of
267:), most often leading to other symptoms such as
116:Fatal familial insomnia, sporadic fatal insomnia
1915:
1913:
1058:"Dying To Sleep: Fatal Familial Insomnia (FFI)"
1012:NORD (National Organization for Rare Disorders)
914:NORD (National Organization for Rare Disorders)
1603:
1601:
704:may be prescribed to treat muscle spasms, and
455:disease that is associated with a mutation in
2255:
451:Fatal familial insomnia is a rare hereditary
8:
942:
940:
938:
936:
934:
932:
930:
255:gene, with the remainder of cases occurring
1435:"Prion diseases: immunotargets and therapy"
1367:Encyclopedia of Sleep and Circadian Rhythms
373:, cognitive impairment, and double vision.
2287:
2262:
2248:
2240:
2131:
1920:Schenkein J, Montagna P (September 2006).
1608:Schenkein J, Montagna P (September 2006).
1538:Schenkein J, Montagna P (September 2006).
1002:
1000:
974:
972:
970:
968:
147:Suspected based on symptoms, supported by
34:
2444:Transmissible spongiform encephalopathies
2035:
1986:
1937:
1893:
1883:
1842:
1832:
1791:
1625:
1555:
1460:
1450:
1305:
1256:
602:Learn how and when to remove this message
586:, without removing the technical details.
424:Learn how and when to remove this message
408:, without removing the technical details.
341:Other symptoms include profuse sweating,
307:. This stage lasts for about four months.
178:transmissible spongiform encephalopathies
1514:"The man who never slept: Michael Corke"
1154:. Vol. 217, no. 5. p. 74.
435:
345:(pinpoint pupils), sudden entrance into
2338:Variably protease-sensitive prionopathy
2307:Gerstmann–Sträussler–Scheinker syndrome
2275:transmissible spongiform encephalopathy
1733:Neuropathology and Applied Neurobiology
1166:"Fatal Insomnia - Neurologic Disorders"
948:"Fatal Insomnia – Neurologic Disorders"
901:
584:make it understandable to non-experts
406:make it understandable to non-experts
7:
1204:Khan Z, Sankari A, Bollu PC (2024).
866:. As of 2016, a study investigating
463:PrP, is located on the short arm of
324:. This lasts for about three months.
2464:Sleeplessness and sleep deprivation
650:are known. Some are transmissible (
546:at codon 129 and methionine/valine
249:), stemming from a mutation in the
1433:Burchell JT, Panegyres PK (2016).
1375:10.1016/B978-0-12-822963-7.00243-7
952:Merck Manuals Professional Edition
538:and a mild hypo-metabolism of the
25:
2449:Unsolved problems in neuroscience
2408:Transmissible mink encephalopathy
2413:Feline spongiform encephalopathy
2388:Bovine spongiform encephalopathy
1745:10.1111/j.1365-2990.2010.01126.x
1099:10.1046/j.1365-2869.1999.00005.x
660:bovine spongiform encephalopathy
563:
522:is a perplexing feature of FFI.
471:(fCJD) both carry a mutation at
385:
43:
27:Prion disease of the human brain
2393:Camel spongiform encephalopathy
1412:10.1016/j.expneurol.2012.10.014
1062:www.world-of-lucid-dreaming.com
821:Egyptian man, 2011, Netherlands
510:degeneration—especially in the
491:is found instead of the normal
159:(if familial form is suspected)
2418:Exotic ungulate encephalopathy
799:Unnamed American patient, 2001
1:
1979:10.1080/19336896.2015.1027857
1885:10.1080/19336896.2017.1368937
1706:10.1016/S0304-4858(07)74572-9
1663:10.1016/S1474-4422(03)00323-5
1133:Obscura: A True Crime Podcast
778:Silvano, 1983, Bologna, Italy
646:Other diseases involving the
443:of chromosome 20 showing gene
320:is followed by rapid loss of
287:The disease has four stages:
271:, coordination problems, and
2059:Clancy K (15 January 2019).
2028:10.1016/j.neuron.2009.07.026
1484:Mosher D (13 January 2011).
1129:"Episode 25: Fatal Insomnia"
500:missense GAC-to-AAC mutation
2439:Neurodegenerative disorders
808:, different stimulants and
355:elevation of blood pressure
291:Characterized by worsening
277:disease-modifying treatment
127:, sporadic form (very rare)
2482:
1249:10.1016/j.nicl.2022.103026
1793:10.1001/archneur.65.7.971
1439:ImmunoTargets and Therapy
1212:. StatPearls Publishing.
1206:"Fatal Familial Insomnia"
1087:Journal of Sleep Research
1008:"Fatal Familial Insomnia"
980:"Fatal familial insomnia"
910:"Fatal Familial Insomnia"
676:Creutzfeldt–Jakob disease
654:, including FFI) such as
487:at position 178 in which
469:Creutzfeldt–Jakob disease
51:
42:
1834:10.1186/1471-2377-11-136
1298:10.1136/jnnp-2021-327247
724:Epidemiology and history
2403:Chronic wasting disease
2333:Sporadic fatal insomnia
2312:Fatal familial insomnia
1518:World of Lucid Dreaming
1184:Genetics Home Reference
664:chronic wasting disease
648:mammalian prion protein
261:sporadic fatal insomnia
247:fatal familial insomnia
174:frontotemporal dementia
18:Fatal familial insomnia
1400:Experimental Neurology
1148:"The Secrets of Sleep"
870:is being carried out.
830:
736:
642:Differential diagnosis
520:Phenotypic variability
448:
353:, neck stiffness, and
316:Complete inability to
165:Differential diagnosis
2109:www.prionalliance.org
1780:Archives of Neurology
1651:The Lancet. Neurology
828:
788:University of Bologna
782:In late 1983 Italian
731:
439:
234:is an extremely rare
1344:10.1212/wnl.49.1.126
1237:NeuroImage. Clinical
856:pentosan polysulfate
516:anteroventral nuclei
502:at codon 178 of the
100:later in the illness
1152:National Geographic
1146:Max DT (May 2010).
814:sensory deprivation
686:Treatment involves
170:Alzheimer's disease
96:Permanent state of
2227:on 21 October 2016
1452:10.2147/ITT.S64795
1369:. pp. 39–47.
1093:(Suppl 1): 23–29.
1032:"Fatal Insomnia".
831:
812:and even complete
737:
449:
283:Signs and symptoms
2426:
2425:
2374:
2373:
2215:
2214:
1384:978-0-323-91094-1
612:
611:
604:
434:
433:
426:
265:agrypnia excitata
236:neurodegenerative
229:
228:
143:Diagnostic method
32:Medical condition
16:(Redirected from
2471:
2381:in other animals
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2250:
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2234:
2232:
2223:. Archived from
2132:
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2105:"Prion Alliance"
2101:
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2085:. 20 August 2015
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1700:(9): 1757–1763.
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758:mutation in the
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540:cingulate cortex
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243:trouble sleeping
241:that results in
125:Genetic mutation
47:
35:
21:
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2454:Sleep disorders
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2083:Broad Institute
2079:"Sonia Vallabh"
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2009:
2008:
2004:
1960:
1959:
1955:
1919:
1918:
1911:
1865:
1864:
1860:
1819:. Case report.
1814:
1813:
1809:
1773:
1772:
1768:
1729:
1728:
1721:
1691:
1690:
1686:
1648:
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1589:
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1586:. 14 April 2020
1578:
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1173:
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1140:
1127:
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1122:
1084:
1083:
1076:
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1055:
1054:
1050:
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1038:
1031:
1030:
1026:
1016:
1014:
1006:
1005:
998:
988:
986:
978:
977:
966:
956:
954:
946:
945:
928:
918:
916:
908:
907:
903:
898:
886:Broad Institute
852:
823:
801:
780:
751:gene mutation.
726:
718:
688:palliative care
684:
644:
624:genetic testing
608:
597:
591:
588:
580:help improve it
577:
568:
564:
557:
528:
526:Pathophysiology
430:
419:
413:
410:
402:help improve it
399:
390:
386:
379:
295:, resulting in
285:
269:speech problems
196:Supportive care
157:genetic testing
108:45–50 years old
33:
28:
23:
22:
15:
12:
11:
5:
2479:
2478:
2475:
2467:
2466:
2461:
2456:
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2431:
2430:
2424:
2423:
2421:
2420:
2415:
2410:
2405:
2400:
2395:
2390:
2384:
2382:
2379:Prion diseases
2376:
2375:
2372:
2371:
2369:
2368:
2363:
2358:
2352:
2350:
2349:transmissible:
2344:
2343:
2341:
2340:
2335:
2330:
2324:
2322:
2318:
2317:
2315:
2314:
2309:
2304:
2298:
2296:
2285:
2282:Prion diseases
2279:
2278:
2271:Prion diseases
2269:
2267:
2266:
2259:
2252:
2244:
2238:
2237:
2213:
2212:
2209:
2208:
2197:
2186:
2175:
2160:
2144:
2139:
2138:
2136:
2135:Classification
2128:
2127:External links
2125:
2122:
2121:
2096:
2070:
2051:
2022:(4): 438–450.
2002:
1953:
1909:
1878:(5): 293–299.
1858:
1807:
1786:(7): 971–973.
1766:
1739:(5): 549–553.
1719:
1684:
1657:(3): 167–176.
1641:
1597:
1571:
1530:
1504:
1476:
1425:
1390:
1383:
1357:
1338:(1): 126–133.
1321:
1292:(3): 291–297.
1272:
1223:
1196:
1171:
1157:
1138:
1120:
1074:
1048:
1024:
996:
964:
926:
900:
899:
897:
894:
864:amphotericin B
851:
848:
838:revealed mild
822:
819:
800:
797:
779:
776:
744:Basque Country
725:
722:
717:
714:
692:sleeping pills
683:
680:
643:
640:
630:post-mortem.
610:
609:
571:
569:
562:
556:
553:
527:
524:
432:
431:
414:September 2023
393:
391:
384:
378:
375:
332:
331:
325:
314:
311:Hallucinations
308:
284:
281:
232:Fatal insomnia
227:
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199:
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167:
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145:
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137:Family history
135:
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118:
117:
114:
110:
109:
106:
102:
101:
94:
88:
87:
84:
78:
77:
75:Neuropathology
71:Sleep medicine
60:
54:
53:
49:
48:
40:
39:
38:Fatal insomnia
31:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2477:
2476:
2465:
2462:
2460:
2459:Rare diseases
2457:
2455:
2452:
2450:
2447:
2445:
2442:
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2419:
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2110:
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2100:
2097:
2084:
2080:
2074:
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2066:
2062:
2055:
2052:
2047:
2043:
2038:
2033:
2029:
2025:
2021:
2017:
2013:
2006:
2003:
1998:
1994:
1989:
1984:
1980:
1976:
1972:
1968:
1964:
1957:
1954:
1949:
1945:
1940:
1935:
1931:
1927:
1923:
1916:
1914:
1910:
1905:
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1896:
1891:
1886:
1881:
1877:
1873:
1869:
1862:
1859:
1854:
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1822:
1821:BMC Neurology
1818:
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621:
617:
606:
603:
595:
585:
581:
575:
572:This section
570:
561:
560:
554:
552:
549:
548:heterozygotes
545:
541:
537:
532:
525:
523:
521:
517:
513:
509:
505:
501:
496:
494:
493:aspartic acid
490:
486:
482:
478:
474:
470:
466:
465:chromosome 20
462:
461:prion protein
458:
454:
446:
442:
438:
428:
425:
417:
407:
403:
397:
394:This section
392:
383:
382:
376:
374:
372:
366:
364:
360:
359:double vision
356:
352:
348:
344:
339:
337:
329:
326:
323:
319:
315:
312:
309:
306:
302:
298:
297:panic attacks
294:
290:
289:
288:
282:
280:
278:
274:
270:
266:
262:
258:
254:
253:
248:
244:
240:
239:prion disease
237:
233:
224:
220:
216:
214:
210:
206:
204:
200:
197:
194:
190:
186:
182:
179:
175:
171:
168:
166:
162:
158:
154:
150:
146:
144:
140:
136:
134:
130:
126:
123:
119:
115:
111:
107:
103:
99:
95:
93:
92:Complications
89:
85:
83:
79:
76:
72:
68:
64:
61:
59:
55:
50:
46:
41:
36:
30:
19:
2332:
2311:
2229:. Retrieved
2225:the original
2199:
2188:
2177:
2162:
2147:
2112:. Retrieved
2108:
2099:
2087:. Retrieved
2082:
2073:
2064:
2054:
2019:
2015:
2005:
1973:(2): 75–79.
1970:
1966:
1956:
1929:
1925:
1875:
1871:
1861:
1824:
1820:
1810:
1783:
1779:
1769:
1736:
1732:
1697:
1693:
1687:
1654:
1650:
1644:
1617:
1613:
1588:. Retrieved
1583:
1574:
1547:
1543:
1533:
1521:. Retrieved
1517:
1507:
1495:. Retrieved
1489:
1479:
1442:
1438:
1428:
1403:
1399:
1393:
1366:
1360:
1335:
1331:
1324:
1289:
1285:
1275:
1240:
1236:
1226:
1209:
1199:
1187:. Retrieved
1183:
1174:
1160:
1151:
1141:
1132:
1123:
1090:
1086:
1065:. Retrieved
1061:
1051:
1039:. Retrieved
1035:Merck Manual
1034:
1027:
1015:. Retrieved
1011:
987:. Retrieved
983:
955:. Retrieved
951:
919:21 September
917:. Retrieved
913:
904:
883:
874:
872:
853:
832:
802:
793:
781:
767:homozygosity
759:
755:
753:
748:
741:
738:
733:
719:
700:
696:barbiturates
694:, including
685:
672:American elk
666:in American
645:
636:
632:
613:
598:
589:
573:
533:
529:
512:medio-dorsal
503:
497:
456:
450:
444:
420:
411:
395:
367:
340:
336:dysautonomia
333:
286:
264:
260:
257:sporadically
250:
246:
231:
230:
217:Always fatal
133:Risk factors
29:
1590:27 February
1180:"PRNP gene"
868:doxycycline
784:neurologist
706:eszopiclone
616:sleep study
544:homozygotes
149:sleep study
105:Usual onset
2433:Categories
2291:inherited/
2231:26 January
2201:DiseasesDB
2114:21 January
2089:21 January
1512:Turner R.
1243:: 103026.
1210:StatPearls
1056:Turner R.
896:References
890:biomarkers
806:meditation
764:methionine
702:Clonazepam
682:Treatments
489:asparagine
485:amino acid
477:methionine
363:hypnagogia
203:Medication
184:Prevention
98:hypnagogia
67:Psychiatry
2347:acquired/
2321:sporadic:
2284:in humans
1932:(3): 66.
1926:MedGenMed
1694:Neurology
1620:(3): 65.
1614:MedGenMed
1550:(3): 65.
1544:MedGenMed
1445:: 57–68.
1406:: 34–44.
1332:Neurology
860:mepacrine
810:hypnotics
716:Prognosis
592:June 2024
555:Diagnosis
351:impotence
347:menopause
222:Frequency
213:Prognosis
192:Treatment
63:Neurology
58:Specialty
2046:19709627
1997:25996399
1948:17406189
1904:28976233
1853:22040318
1802:18625868
1761:30722366
1753:20874730
1714:10371520
1679:20822956
1671:12849238
1636:17406188
1566:17406188
1471:27529062
1420:23099415
1316:34667102
1267:35504222
1218:29489284
1189:22 March
1115:24399165
1107:10389103
1067:22 March
879:thalamus
850:Research
844:thalamus
710:zolpidem
620:PET scan
536:thalamus
508:thalamic
447:location
441:Idiogram
328:Dementia
301:paranoia
293:insomnia
273:dementia
176:, other
153:PET scan
82:Symptoms
2398:Scrapie
2195:D034062
2037:2775465
1988:4601344
1939:1781276
1895:5639864
1844:3214133
1827:: 136.
1627:1781306
1557:1781306
1462:4970640
1352:9222180
1307:8862016
1258:9065920
840:atrophy
836:autopsy
628:autopsy
578:Please
400:Please
305:phobias
2184:600072
2173:046.72
2044:
2034:
2016:Neuron
1995:
1985:
1946:
1936:
1902:
1892:
1851:
1841:
1800:
1759:
1751:
1712:
1677:
1669:
1634:
1624:
1564:
1554:
1523:20 May
1497:20 May
1469:
1459:
1418:
1381:
1350:
1314:
1304:
1265:
1255:
1216:
1113:
1105:
1017:17 May
989:17 May
957:17 May
862:, and
481:valine
371:ataxia
343:miosis
322:weight
303:, and
121:Causes
2206:32177
2158:A81.9
2065:Wired
1967:Prion
1872:Prion
1757:S2CID
1675:S2CID
1491:Wired
1111:S2CID
1041:4 May
875:D178N
771:codon
756:D178N
749:D178N
473:codon
453:prion
377:Cause
318:sleep
113:Types
2366:Kuru
2361:vCJD
2356:iCJD
2328:sCJD
2302:fCJD
2293:PRNP
2273:and
2233:2013
2190:MeSH
2179:OMIM
2168:9-CM
2116:2019
2091:2019
2042:PMID
1993:PMID
1944:PMID
1900:PMID
1849:PMID
1798:PMID
1749:PMID
1710:PMID
1667:PMID
1632:PMID
1592:2023
1562:PMID
1525:2011
1499:2011
1467:PMID
1416:PMID
1379:ISBN
1348:PMID
1312:PMID
1263:PMID
1214:PMID
1191:2018
1103:PMID
1069:2018
1043:2018
1019:2019
991:2019
959:2019
921:2022
760:PRNP
670:and
668:deer
656:kuru
652:TSEs
622:and
618:, a
514:and
504:PRNP
457:PRNP
445:PRP
252:PRNP
207:None
187:None
155:and
2164:ICD
2149:ICD
2032:PMC
2024:doi
1983:PMC
1975:doi
1934:PMC
1890:PMC
1880:doi
1839:PMC
1829:doi
1788:doi
1741:doi
1702:doi
1659:doi
1622:PMC
1552:PMC
1457:PMC
1447:doi
1408:doi
1404:243
1371:doi
1340:doi
1302:PMC
1294:doi
1253:PMC
1245:doi
1095:doi
769:at
708:or
582:to
404:to
349:or
2435::
2204::
2193::
2182::
2171::
2156::
2153:10
2107:.
2081:.
2063:.
2040:.
2030:.
2020:63
2018:.
2014:.
1991:.
1981:.
1969:.
1965:.
1942:.
1928:.
1924:.
1912:^
1898:.
1888:.
1876:11
1874:.
1870:.
1847:.
1837:.
1825:11
1823:.
1796:.
1784:65
1782:.
1778:.
1755:.
1747:.
1737:37
1735:.
1722:^
1708:.
1698:52
1696:.
1673:.
1665:.
1653:.
1630:.
1616:.
1612:.
1600:^
1582:.
1560:.
1546:.
1542:.
1516:.
1488:.
1465:.
1455:.
1441:.
1437:.
1414:.
1402:.
1377:.
1346:.
1336:49
1334:.
1310:.
1300:.
1290:93
1288:.
1284:.
1261:.
1251:.
1241:34
1239:.
1235:.
1208:.
1182:.
1150:.
1131:.
1109:.
1101:.
1089:.
1077:^
1060:.
1010:.
999:^
982:.
967:^
950:.
929:^
912:.
858:,
658:,
518:.
299:,
279:.
172:,
151:,
73:,
69:,
65:,
2295::
2263:e
2256:t
2249:v
2235:.
2166:-
2151:-
2141:D
2118:.
2093:.
2067:.
2048:.
2026::
1999:.
1977::
1971:9
1950:.
1930:8
1906:.
1882::
1855:.
1831::
1804:.
1790::
1763:.
1743::
1716:.
1704::
1681:.
1661::
1655:2
1638:.
1618:8
1594:.
1568:.
1548:8
1527:.
1501:.
1473:.
1449::
1443:5
1422:.
1410::
1387:.
1373::
1354:.
1342::
1318:.
1296::
1269:.
1247::
1220:.
1193:.
1168:.
1135:.
1117:.
1097::
1091:8
1071:.
1045:.
1021:.
993:.
961:.
923:.
734:.
605:)
599:(
594:)
590:(
576:.
427:)
421:(
416:)
412:(
398:.
259:(
20:)
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