In mid-1980 Italy, a 52 year old man complains of insomnia, waking easily when he does get sleep, and loss of libido. He knows it’s close to the end for him; he has seen this in his sisters. Within a month, he has fever, starts drooling, cries for no reason. By 2 months, he starts getting out of bed at night and saluting at a hallucinated coronation. He is unable to sleep at all by 3 months.
Barbiturates and other drugs have no effect. Severe fatigue weighs him down. He would go into fugue states and reenact his dreams. His speech is slurred and incoherent. Eight months in and he has resorted to intermittently spasming and screaming. He cannot recall his dreams. His breathing has become irregular and weak. Nine months after the first symptoms, the man dies from a lung infection.
Tracing his family tree, researchers confirm that 14 family members had the same symptoms. Due to its congenital nature and its symptoms, this disease was termed Fatal Familial Insomnia. To the present day, this disease has been reported in 27 unrelated families from all over world. In most cases, symptoms start around the 5th decade of life, but some as young as 20 have succumbed to this horrible disease.
The cause was found when researchers sequenced the prion protein gene in these patients. Family members of the same family had the same mutation in the gene. This suggested that the mutated gene was being passed on from parents to children.
When they looked in the brain of deceased patients, they found the same spongy features to kuru and mad cow disease patients. However, they also saw that the thalamus (a fairly central portion of the brain) of patients was completely destroyed. The thalamus of the brain is now recognised to regulate sleep and alertness patterns.
Why these mutations in prion protein cause a specific destruction of the thalamus is not known. We also don’t know why it takes so long for patients to start displaying symptoms of the disease, even though they are born with this mutated protein. What we do know is that it’s a good candidate for Disease of the week syndrome; med students will stay up worrying about FFI, prompting more concerns of FFI.
CJD usually presents itself in patients around the 6th decade of life and can come about suddenly with extremely vague symptoms: fatigue, disordered sleep, decreased appetite, or changes in behaviour. Other times it can come about by more dramatic means: loss of vision, of movement, or of speech. However it presents, CJD quickly ravages the patients body with progressive loss of awareness and motor dysfunctions. The vast majority of the infected die within a year of the start of symptoms. As with the other prion diseases, there is no cure.
Who gets CJD? Anyone can. There’s no known preference for doctors, nurses, dentists, butchers or those working in abattoirs; people who work closely with bodily fluids. There is no bias based on sex, country, ethnicity, or diet. Each year, 0.5 – 1.5 people are diagnosed with CJD per million people
How can you get CJD? There have been incidences of environmental infections. For example, in the mid-1980s, growth hormone was made from the pituitary glands of cadavers. Over a hundred patients who were prescribed a batch of this growth hormone were diagnosed with CJD, some almost 30 years later. There have also been cases of CJD transmission through corneal transplants. Also, like FFI, CJD can be passed to patients’ children, if the mutation is in their DNA. But the majority of cases, it is completely random who is struck down with CJD.
What causes the different symptoms amongst patients with different prion diseases? The protein is the same in all cases. But, different mutations causes different outcomes: for example, which part of the brain is affected and how; how long the incubation time is; and where in the body it is located. We still don’t know how prion diseases cause such diverse symptoms.
What causes some people to get it? Is it truly random? Are some people more likely to get prion diseases than others? Obviously there are family clusters, but we don’t know whether the spontaneous forms are truly randomly distributed.
How does it relate to other diseases? And how do we cure it? Researchers have seen the protein build-up associated with prion diseases in other diseases, such as Alzheimers and punch-drunk syndrome. In the future, we may use treatments of these diseases to cure prion-based disease.
Of course, the most important question is if and how we can stop prion diseases from occurring in the first place. This question still has no answer, but, like prions, will continue to plague us into the future.
Lugaresi E, Medori R, Montagna P, Baruzzi A, Cortelli P, Lugaresi A, Tinuper P, Zucconi M, & Gambetti P (1986). Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. The New England journal of medicine, 315 (16), 997-1003 PMID: 3762620