What You Need to Know About Sporadic Fatal Insomnia

What is sporadic fatal insomnia?

Sporadic fatal insomnia (SFI) is a prion disease¹ or, more specifically, a neurodegenerative disease resulting from the conversion of normal prion protein into a misfolded disease-causing version. Unlike fatal familial insomnia, which can be genetically transmitted, the misfolding of prion proteins in sporadic fatal insomnia occurs spontaneously.

Sporadic fatal insomnia shares many clinical features with fatal familial insomnia, and it is, to an extent, defined as a phenocopy,² meaning they present similarly but without a shared genetic makeup.

Symptoms of sporadic fatal insomnia       

At the onset, patients may present with mainly psychiatric symptoms such as:

Cognitive impairment

• Psychiatric symptoms

• Impaired coordination/ataxia

• Muscle jerks

• Autonomic dysfunction

• Psychomotor hyperactivity

• Slurred speech/dysarthria

• Vision problems, such as double vision

• Behavioral or mood changes

• Pyramidal symptoms

• Extrapyramidal symptoms

Insomnia is not the most prominent symptom in people with sporadic fatal insomnia, despite what the name might suggest.

What causes sporadic fatal insomnia?

Like in other prion diseases, experts hypothesize that sporadic fatal insomnia occurs when the normal physiological form of prion protein found in the brain converts into a diseased form due to the prion gene mutation or contact with another diseased prion. 

Some research³ suggests that the accumulation of the misfolded prion protein may be a triggering factor in neurodegenerative conditions such as prion diseases. Imagine your proteins in the brain as a rope that needs to be carefully tied. If there’s a wrong knot, this propagates and starts accumulating as misfolded prions.

You may also get prion diseases from consuming meat products from cattle with mad cow disease.⁴

While this conversion is genetically passed down through families in the case of fatal familial insomnia, this is not necessarily the case in sporadic fatal insomnia.

How is sporadic fatal insomnia diagnosed?

The same tests carried out in diagnosing fatal familial insomnia are used to determine the presence of sporadic fatal insomnia.

To be diagnosed with the condition, one must first exhibit sleep disturbances on a sleep study and present with at least two of the following symptoms of brain degeneration.

• Cognitive impairment

• Uncontrollable muscle twitching

• Vision problems

• Sleep disturbance

• Psychiatric symptoms, such as depression, anxiety, and changes in mood and personality

A person with this condition may also show weight loss, increased heart rate, profuse sweating, and voice changes. A doctor may also collect blood tests to rule out other health issues, such as thyroid problems, as sporadic fatal insomnia is a diagnosis of exclusion.

They should also consider conducting further tests to rule out the possibility of the symptoms resulting from degenerative conditions such as Alzheimer's.

A doctor may carry out the following tests to determine whether one has the condition.

Sleep study (Polysomnography)

Doctors may request you to be the subject of a sleep study if you present with insomnia or sleep disturbances. They will record data about your brain activity and heart rate during sleep at the sleep center and observe for a decline in sleep spindles and K-complexes on the polysomnogram.

The sleep study is critical in people with sporadic fatal insomnia, as they might not realize their sleep is affected.

Brain scan

Doctors may subject the patient to a brain scan to image the structure and functioning of the brain to determine abnormalities or damage. Common scans include PET and MRI scans. These scans show decreased activity in the brain's thalamus and cerebral cortex regions in people with sporadic fatal insomnia. The decreased activity may be indicated by reduced blood flow, known as hypoperfusion in medical circles, and hypometabolism or reduced brain glucose consumption. 

While these typically occur in the thalamus region, they are likely to spread to other brain regions as the disease progresses. MRI scans do not always result in findings. Still, some patients exhibit atrophy⁵ in certain brain regions in the later stages.

MRI may also help rule out other neurological diseases. MRI and CT changes may also be nonspecific and present later in the disease progression.

Cerebrospinal fluid (CSF) analysis

Although most commonly analyzed features remain normal in these tests, some CSF prion biomarkers may yield abnormal results.

Electroencephalogram (EEG)

Periodic spike discharges common in Creutzfeldt Jakob Disease are not found in FFI or SFI, and most EEG findings in this context are nonspecific, such as slowing.

What is the treatment for sporadic fatal insomnia?

Currently, the disease is incurable. However, experts are hopeful about immunotherapy as a treatment and prevention option for SFI and similar prion diseases, which are still in the preliminary stages of research but have provided promising results in animal studies and clinical trials.

Antibody-based immunotherapies

Antibody immunotherapies, i.e., passive immunization, work by binding or eliminating toxins or disease-causing antigens in the body. There are passive and active immunization strategies to clear the elements in the misfolded prion protein responsible for sporadic fatal insomnia. 

Passive immunization

Passive immunization is provided to individuals who are yet to develop the condition, with antibodies aimed at inhibiting misfolding of the proteins. Passive immunotherapies may, thus, be helpful to populations at risk of developing the disease.

Active immunization

On the other hand, active immunization is delivered upon diagnosis to induce an immune response against the attack. In the case of prion diseases such as sporadic fatal insomnia, this strategy has proved effective in mice.

However, it would pose a challenge in the case of humans, as it is challenging to diagnose the condition until it is too late, as well as since these are physiologically occurring proteins that are misfolded; self-tolerance is an issue. 

Some animal studies have also noted the paradoxical acceleration⁶ of prion diseases. The effectiveness of active immunization of such an intervention would rely on early detection of the prion disease.

DC is the short form for dendritic cells, whose function is to present foreign substances or toxins to the white blood cells in a form they can recognize to fight them. 

To treat sporadic fatal insomnia, researchers aim to deliver specifically created dendritic cells to help the immune system identify the disease-causing prions and to help induce the immune system to fight against them. Self-tolerance resulting from the body's inability to identify these harmful elements is one of the reasons antibodies don't fight this disease. This intervention seeks to overcome that challenge.

Adoptive transfer of disease-fighting T-cells

Another alternative entails delivering CD4+ lymphocytes into the body intramuscularly. These white blood cells are programmed and sensitized to note and respond against disease-causing elements lodged on the misfolded prion proteins. They have provided promising results in mice with prion diseases.

There are, however, challenges to these immunotherapy options.

Antibody immunotherapies for prion diseases such as sporadic fatal insomnia may not work because the immune system does not recognize "rogue" prion proteins. Adoptive transfer of disease-fighting cells to the affected brain regions has also proved challenging because these immune cells and antibodies cannot generally cross the blood-brain barrier.

Thus, it is hard to effectuate a successful immune response in the CNS.

Still, researchers are working on overcoming these challenges and, in the meantime, suggest the following interventions to provide relief and ease symptoms in patients.

• Melatonin supplementation: Melatonin is a sleep hormone, and its levels fall in patients with the condition. An intake of melatonin supplements can help promote proper sleep in such individuals.

• Vitamin supplementation: An intake of B6, B12, iron, and folic acid can bolster well-being in patients with SFI. These vitamins can be acquired from fish, fruits, and vegetables, and to a lesser extent, dairy products.

• Discontinuation of certain medications: Patients should keep off drugs that may exacerbate existing symptoms.

• Doxycycline:⁷ Italian researchers are also trying to see if doxycycline will help.

When to see a doctor

Sporadic fatal insomnia is very rare, and prion diseases occur in one in a million people⁸ in the general population annually. The chances of you suffering the condition are thus extremely low. However, you should still see a doctor if you present with sleep disturbance, cognitive impairment, or other symptoms hinting at a neurodegenerative condition. 

If you have a family member diagnosed with a prion disease, then you should consult a doctor as some of these conditions, such as fatal familial insomnia, are genetically transmissible, and some forms such as Kuru or BSE can be transmitted via food.

The lowdown

Sporadic fatal insomnia is a prion disease occurring due to the spontaneous conversion of prion proteins into scrapie isoforms of the prion protein. Some experts suggest that misfolded protein accumulation is responsible for prion diseases and other neurodegenerative conditions. However, the jury is still out there on whether that is the case. 

Sporadic fatal insomnia can be diagnosed through neuroimaging brain scans such as PET and SPECT scans that point out decreased brain activity in the thalamus region and is typically a diagnosis of exclusion. While MRI scans are not always conclusive, they can help rule out other conditions or show brain atrophy that may be evidence of sporadic fatal insomnia.

Doctors may also carry out a sleep study to monitor sleep disturbances evidenced by decreased sleep spindles and K-complexes on the polysomnogram. Cerebrospinal fluid analysis may also serve to allay any fears of the disease.

While the disease has no cure at present, research outcomes on the effectiveness of immunotherapy options such as antibody and DC vaccines and adoptive transfer of disease-fighting cells have been positive, indicating that there is still hope for a cure in the near future.

Meanwhile, individuals with the condition can adopt management strategies such as melatonin and vitamin supplementation to relieve and alleviate symptoms of sporadic fatal insomnia.