Sporadic Fatal Insomnia (A brief Guide)

In this guide, we will discuss what Sporadic Fatal Insomnia is, symptoms, causes and some additional considerations. 

Sporadic Fatal Insomnia: What is it?

Sporadic Fatal Insomnia, also known as MM2-thalamic Creutzfeldt-Jakob disease (CJD), can be defined as a sporadic prion disorder causing difficulty sleeping, motor dysfunction and subsequently, leading to death.

According to the MSD manual, Sporadic Fatal Insomnia lacks a PrP gene mutation.

“Average age at onset is slightly older and life expectancy is slightly longer than in FFI. Early symptoms include cognitive decline and ataxia. Sleep abnormalities are not commonly reported but can usually be observed during a sleep study.”

Other human prion proteins have been associated with incurable diseases classed as neurodegenerative disorders such as spongiform encephalopathies such as Parkinson’s disease, Alzheimer’s disease, Fatal Familial Insomnia, Kuru and Gerstmann-Straussler-Scheinker (GSS) syndrome. 

In contrast, Fatal Familial Insomnia is another prion disease that results from an autosomal mutation in the PrP gene.

The average onset is 40 years (from the late 20s to the early 70s). The life expectancy is said to be between 7 to 73 months.

The early symptoms include insomnia or the increasing difficulty of falling and staying asleep cognitive decline, and loss of coordinated movements.

In addition, hypertension, tachycardia, hyperthermia, and sweating can occur later. 

In addition, “Human prion diseases are rare, transmissible, invariably fatal neurodegenerative diseases that are characterized by the accumulation of a misfolded host protein, the prion protein, in brain tissue” as mentioned by Moody et al., (2011) in their study on “Sporadic Fatal Insomnia in a young woman: A diagnostic challenge: Case report”. 

Prion diseases can be classified into three groups, sporadic, acquired and genetic.

Additionally, just as Fatal Familial Insomnia, Sporadic Familial Insomnia is also characterized by atrophy of the thalamus, manifesting disrupted sleep, autonomic dysfunction, and motor abnormalities including myoclonus, ataxia, dysarthria, dysphagia, and pyramidal signs.

Even though it is not considered an infectious disease in the common definition, it can be acquired if someone ingests the contaminated brain tissue, as it is the case of Kuru disease in Papua New Guinea, since culturally they practiced a form of cannibalism as part of their funeral ritual.  

Also, other clinical features include strange or peculiar behaviors that can be confused by psychotic signs.

Due to being deprived of sleep, they can manifest symptoms such as drowsiness during the day which is usually described as hypersomnolence unless the abnormal nocturnal sleep pattern, usually recognized by electroencephalogram (EEG) and/or polysomnography (PSG). 

Signs and symptoms of SFI

Progressive insomnia is one of the main symptoms in FFI and SFI.

It is believed to start during middle age, but it can also occur earlier or later in life.

The manifestation of insomnia may initially be mild but it can become worse progressively until the person affected gets very little sleep.

The onset of insomnia usually begins suddenly and can rapidly worsen over the next couple of months.

When the person gets to finally go to sleep, vivid dreams may occur.

This lack of sleep can lead to physical and mental deterioration and the disease subsequently progresses to coma and death.

Even though insomnia is the first symptom, in most cases, some may also present with progressive dementia, in which there are worsening problems with thought, cognition, memory, language, and behavior.

According to the National Organization for Rare Disorders, “Initially, the signs may be subtle and include unintended weight loss, forgetfulness, inattentiveness, problems concentrating, or speech problems. Episodes of confusion or hallucinations can eventually occur.”

Some people may manifest the following:

  • Double vision (diplopia) or abnormal, jerky eye movements (nystagmus). 
  • Problems with swallowing (dysphagia)
  • Slurred speech (dysarthria)
  • Some individuals eventually have trouble coordinating voluntary movements (ataxia). Abnormal movements including tremors or twitchy, jerking muscle spasms (myoclonus)
  • Parkinson’s-like symptoms

Causes of SFI

FFI is caused by a gene mutation of the PRNP gene.

It is widely known that genes provide instructions for creating proteins that play a critical role in many functions of the body.

When there is a gene mutation, the resulting protein product may be faulty, inefficient, absent, or overproduced.

Depending on the particular protein, this can affect certain organs, including the brain. 

The other form of Familial insomnia can be manifested in a variation in the PRPN gene in individuals with FFI that occurs spontaneously, without having a family history of the disease or a genetic inherited link.

This is also known as “de novo” variant. 

In accordance with the National Organization for Rare Disorders, “The gene variation has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. The disorder is usually not inherited from or “carried” by a healthy parent. However, the person who has this de novo variant could pass on the variant gene to their offspring in an autosomal dominant manner.”

In addition, some people may have developed fatal insomnia (FI) without a variation in the PRNP gene, and these are said to have sporadic fatal insomnia (SFI) and although this is a non-genetic form of FFI, the underlying trigger for its development is unknown.

As its name indicates “sporadic” occurs randomly, by chance, even rarer occurrence than Fatal Familial Insomnia.

It has been established that the PrP is toxic to the body, especially cells of the nervous system.

Misfolded PrP, in the manifestation of Fatal Familial Insomnia, is primarily found in the thalamus, which is a structure located deep within the brain that helps to regulate many functions of the body such as sleep, appetite, and body temperature, among others. 

As the misfolded PrP progresses to build in the thalamus, it results in the progressive destruction of neurons, which leads to the manifestation of the symptoms we have discussed previously.

When examining the brain tissue under the microscope, the tissue may appear as sponge-like holes or gaps, which is why prion diseases like FFI are also known as transmissible spongiform encephalopathies.

Current therapy

Although there is no cure, some treatments have been proposed to slow down the presentation of the disease. 

According to Damavandi, Dove, and Pickersgill (2017), “because symptomatic treatment with vitamins B6, B12, iron and Folic Acid has offered some improvement in the wellbeing of patients affected by SFI, vitamin supplementation remains a helpful nutritional aspect in the management of the illness.”

Additionally, they mention how dairy products and other aliments also contain those to a lower extent, however dairy products are still important due to their tryptophan content, which is also beneficial.

This has been identified to lead to a prolonged symptomatic relief and sleep restoration effects, up to 5–7 hours nightly sleep for several consecutive days, within months of therapy.

Melatonin supplements can also be used in the early stages of the disease, which is decreased dramatically when the disease progresses.

In other cases, blood tests reveal that ferritin. Hormone levels from the thyroid in these types of patients are low.

These blood tests are usually accompanied by Cerebral Spinal Fluid examinations, which normally won’t show any abnormalities in the early stages, making it difficult to diagnose. 

According to Damavandi et. al., (2017), Some drugs have been used for the treatment but they have been unsuccessful.

They include “the anti-parasitic Quinacrine, which belongs to the group of anti-protozoan and anti-amoebic compounds.

The choice of Quinacrine was linked to its reported effectiveness in vitro, but not in vivo.

Failure had been associated with induced drug resistance after Quinacrine use, accompanied by increased Pgp transporter activity across the blood-brain barrier (BBB)”. 

Additionally, withdrawal symptoms from the anti-protozoan molecule are said to be toxic and consequently generate adverse drug reactions (e.g Chlorpromazine). 

Finally, the antipsychotic drugs classed as phenothiazines are widely used in the treatment of insomnia, which seems to be successful as short term therapy.

After a few days of being unable to sleep, many patients have confirmed that Promethazine worked for 24 hours. 

Why is this blog about Sporadic Fatal Insomnia important?

Even though Sporadic Fatal Insomnia is extremely rare and there is still a lot of investigation needed to be done about this disease, it is important to be aware of what we know so far and the manifestation of the symptomatology. 

In addition, there is no cure known yet, but there are some options to slow down the presentation of the disease which are important to consider as well.

Once the disease starts showing the first symptoms it tends to progress rapidly deteriorating normal brain function until it ends up causing the death of the person, where the life expectancy can range between 7 to 73 months approximately but every case is different and it tends to vary. 

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Frequently Asked Questions (FAQs) about Sporadic Fatal Insomnia

How common is sporadic fatal insomnia?

Sporadic Fatal Insomnia (SFI) is considered extremely rare and has only been described in the medical literature in about a dozen people only.

In general terms, prion disorders can affect about 1,000,000 million people in the general population per year.

What causes fatal insomnia?

Fatal insomnia results in death within a few months to a few years.

This is a prion disease of the brain, which is usually caused by a mutation to the protein PrPC, ithas two forms: fatal familial insomnia (FFI), which is autosomal dominant and sporadic fatal insomnia (SFI) which is due to a non-inherited mutation.

What are the symptoms of fatal familial insomnia?

The symptoms of more advanced Fatal Familial Insomnia include:

– Insomnia or inability to sleep

– Cognitive and mental functioning deterioration

– Loss of coordinated movements, or ataxia

– Increased blood pressure and heart rate

– Sweating excessively

– Trouble speaking or swallowing

– Weight loss that is unexplained

– Fever 

How long can you live with fatal familial insomnia?

It has been estimated that after the symptoms of Fatal Familial Insomnia begin, the disease usually evolves and causes death within 12-18 months, with a range of a few months to several years.

How is sporadic fatal insomnia diagnosed?

The diagnosis of sporadic fatal insomnia can be confirmed through genetic testing of the familial form.

An MRI scan and measurement of 14-3-3 protein and tau in CSF are not useful, but polysomnography and PET (which shows thalamic hypometabolism) can confirm the diagnosis.

For fatal insomnia, there is only supportive treatment but there is no cure. 

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