What is Sporadic Fatal Insomnia?
Insomnia is a difficult condition for anyone to deal with at the best of times, but there is a variation of insomnia called sporadic fatal insomnia. It’s an extremely a rare condition which physically affects an individuals ability to sleep. It does this to such an extent that every known case has proven fatal.
Sporadic Fatal Insomnia (SFI) is a rare genetic disease found in humans. It is a subtype of human prion disease, whose clinical and neuropathological phenotype is very similar to Familial Fatal Insomnia (FFI), which too is a genetic and also a hereditary sleep disorder.
Technically speaking, SFI patients reported until now were all homozygous for methionine (it is a protein based amino acid that helps with metabolic function), at codon (the sequence of genetic code) 129 of PRNP with deposition of type 2 PrPres (Parchi classification) in the brain.
Huhhh… such technical jargon always goes way above our heads. But do not worry, as I will now explain it to you in more simple terms. As you are aware, all living things are made up of minute structures called cells. A cell is said to be homozygous for a particular gene when identical alleles of the gene are present on both homologous chromosomes. The cell or organism in question is called a homozygote. True breeding organisms, like human beings, are always homozygous for the traits that are to be held constant.
Something about DNA and RNA
DNA (Deoxyribonucleic Acid) is a molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses. Along with RNA (Ribonucleic Acid) and proteins, DNA is one of the three major macromolecules that are essential for all known forms of life.
In our bodies, and every other living creature, DNA is organized in large structures called chromosomes and these chromosomes are responsible for the different genetic traits that the living beings exhibit.
DNA is basically composed of proteins and when it mutates, a change in the structure of the proteins takes place. It might also happen that during this mutation a chromosome attaches a part of itself to some other chromosome.
The genetic code is the set of rules by which information encoded within genetic material (DNA or mRNA sequences) is translated into proteins (amino acid sequences) by living cells. Biological decoding is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms, and can be expressed in a simple table with 64 entries.
The genetic code defines how sequences of these nucleotide triplets, called codons, specify which amino acid will be added next during protein synthesis.
Unlike the more common type of insomnia that you or I may suffer from, Sporadic Fatal Isomnia is not caused by external influences such as stress, anxiety, diet or other difficulties. Rather, it is an internal condition caused by a deficient protein called prion.
Sporadic Fatal Insomnia (SFI) and Fatal Familial Insomnia (FFI) are very rare autosomal dominant inherited prion disease of the brain. It is almost always caused by a mutation to the protein but can also develop spontaneously in patients with a non-inherited mutation variant.
What is a Prion?
The “Oxford Dictionary” defines a prion as “an infectious agent composed primarily of protein“. These prions build up in the brain and, over time, destroy the nerve cells. Creating what are best described as sponge-like holes in the brain; prions attack the thalamus – the region of the brain that is responsible for regulating your sleep.
In the unfortunate anybody suffering from Sporadic Fatal Insomnia, he/she will be robbed of the sleep and, usually in less than a year after the onset of SFI, conditions would be life threatening for them.
Are SFI and FFI Similar?
SFI is quite similar to the other inherited condition known as Fatal Familial Insomnia. However, SFI differs only in that it affects people who do not appear to carry the genetic mutation of FFI. Instead, true to its name; it is sporadic, striking random people without warning.
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. Only eight cases of SFI have ever been diagnosed. In SFI there is no mutation in PRNP-prion gene in D178N, but all have methionine homozygosity at codon 129.
Characteristics of SFI?
Although scientists had described a probable case of SFI in 1997, the disease was definitively established in 1999 by both Mastroianni et al and Parchi et al utilizing the term Sporadic Fatal Insomnia.
The age of onset of SFI is variable, ranging from 18 to 60 years, with an average of 50. However, the disease tends to prominently occur in later years. In women, SFI primarily occurs following delivery. The disease can be detected prior to its onset by genetic testing. The presentation of the disease varies considerably from person to person, even among patients from within the same family. Death usually occurs between 7 and 36 months from onset.
Parchi and colleagues reported five such cases in subjects between the ages of 36 and 70 years (mean 50) with duration of illness ranging from 15 to 24 months (mean 17.8). An additional ten patients have been reported in the literature as suffering from SFI, expanding the age range to 30-74 and the disease duration to 13-73 months.
Diagnosis of SFI
In patients with suspected prion disease, a characteristic, change in sleep pattern can be an important clinical clue for identifying SFI or FFI; polysomnography (PSG), genetic analyst and nuclear imaging may also aid in diagnosis.
Like FFI, SFI is characterized pathologically by thalamic atrophy and clinically by disrupted sleep, autonomic dysfunction and motor abnormalities; including myoclonus, ataxia, dysarthria, dysphagia and pyramidal signs. Other clinical features consist of peculiar behaviors that can be mistaken for psychotic signs. Since the people suffering from SFI are deprived of sleep they may display drowsiness during the day, which may be described as hypersomnolence (excessive sleep during the day), unless the abnormal nocturnal sleep pattern is recognized by electroencephalogram (EEG) and /or polysomnography (PSG).
It’s unlikely that sporadic fatal insomnia will be mistaken for common insomnia. The symptoms, whilst possibly similar at first, soon show their differences. Having said that, it’s speculated that cases of dementia may have been diagnosed incorrectly, supporting the theory that there have been more cases of sporadic fatal insomnia than have been reported.
The rarity of this disease makes the diagnosis of SFI quite challenging. To pronounce it more specifically, I present the following clinical and pathological details of a patient whose SFI diagnosis had not been considered before the patient’s actual death.
The patient developed trouble walking properly, and could not swallow properly. The patient started witnessing a loss of short term memory; and also a loss of power to distinguish between reality and his/her infrequent, troubled dreams.
Different Stages of Sporadic Fatal Insomnia
SFI has four stages and it usually take 7 to 18 months to run its full 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 quite common as well.
As it would be clear from the above facts, prion diseases like SFI, have an unusual presentation. Hence, it is important to pursue a thorough sleep history when prion disease is being suspected/considered.
What Treatment Exists for SFI?
In late 1983, Italian neurologist/sleep expert Dr Ignazio Roiter received a patient at the University of Bologna 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 have his brain harvested for research in hopes of finding a cure for future victims.
As of 2013, no cure or treatment has yet been found for SFI. Gene therapy has been thus far unsuccessful. While it is not currently possible to reverse the underlying illness, there is some evidence that treatments that focus solely upon the symptoms may improve quality of life.
It has been proven that sleeping pills and barbiturates (drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia) are unhelpful. However, on the contrary, in 74% of cases they have been found to worsen the clinical manifestations and hasten the course of the disease. And hence, a lot of debate exists on their efficacy.
It has been reported that 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. He managed to write a book and drive hundreds of miles in this time but nonetheless, over the course of his trials, the patient too succumbed to the classic four-stage progression of the illness.
In the late 2000s, a mouse model was made for SFI. These mice expressed a humanized version of the PrP protein that also contains the D178N SFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to humans with SFI.
Sporadic familial insomnia is a devastating neurological condition that invariably leads over just a few months to severe disability and death. Fortunately, sporadic fatal insomnia is an extremely rare condition. Just because you have some of the symptoms of this disease, you do not necessarily have sporadic fatal insomnia.
If you find yourself deprived of sleep constantly, try finding out the root causes. You should try to control your stress and reduce anxiety. You should also include positive lifestyle changes in your daily life. If these simple things do not help in alleviating your insomnia, then you should visit your primary health provider for further consultation and advice.
Always be positive.