Sporadic fatal insomnia (SFI) is a terrifying reality for a minute portion of the population. This incredibly rare, degenerative prion disease affects cognitive functions and causes sleep problems.
Prions are a unique type of infectious agent unlike any other. They are misfolded proteins that can transmit their abnormal shape to healthy prions in the brain. These healthy prions then refold into the same abnormal shape, creating a chain reaction. Consequently, leading to abnormal prion form, called PrPSc which is resistant to destruction and wreaks havoc on brain tissue. This is what ultimately leads to fatal brain diseases like SFI, a primary and most debilitating symptom is the progressive inability to sleep, leading to severe sleep deprivation.
However, there are other SFI symptoms, such as:
- Incoordination
- Behavioral and personality changes
- Memory loss
- Vision problems, like double vision
- Tremors
- Unusual walking pattern (gait instability)
- Fatigue
- Anxiety
- Depression
- Visual hallucinations
- Delusions
Furthermore, you may experience:
- Dementia
- Spasticity
- Weakness
- Weight loss
- Twitching of muscles in your arms, legs, and face
- Coma
Decreased Life Span of Sporadic Fatal Insomnia
At present, there is no cure for SFI. The progression of the disease is rapid, which leads to dementia, muscle wasting, and eventually coma. Life expectancy after diagnosis can range from a few months to a year. However, research is ongoing to develop new drugs, such as one monoclonal antibody that has been shown to increase the life span in mice suffering from prion.
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Sporadic Fatal Insomnia treatment
Since there is no definite cure, the treatment is mostly supportive, and the aim is to make a person feel comfortable.
Doctors may prescribe you medications to treat symptoms like anti-seizure drugs, sedatives, and other medications typically used for movement disorders, though medications that typically treat insomnia do not work for SFI.
Sporadic fatal insomnia is related to familial fatal insomnia, with a difference in FFI being genetic.
Prion Proteins and Misfolding
Normal vs. Pathogenic Prion Proteins:
Prion proteins (PrP) are present in many cells, including neurons. The normal form, denoted as PrP^C, seemed to play roles in cellular signaling and protecting cells from oxidative stress. The SFI disease occurs when prion proteins are misfolded into an apathogenic form called PrP^Sc.
Moreover, this misfolded form is resistant to proteases, which are enzymes that normally degrade proteins. The accumulation of PrP^Sc leads to neurodegenerative changes seen in prion diseases, including sporadic fatal insomnia (SFI).
Mechanism of Prion Propagation:
Prion diseases are caused by the propagation of misfolded prion proteins. So, the pathogenic prion causes the misfolding of the normal PrP^C into the same abnormal conformation. Hence, this process creates a chain reaction that leads to the progressive accumulation of PrP^Sc. The exact mechanism by which PrP^Sc converts PrP^C is unclear. However, it is known that the misfolded protein can act as a template, guiding the normal protein to adopt the abnormal structure. This conversion process disrupts cellular function and leads to the characteristic spongiform degeneration in the brain tissue.
Genetic and Sporadic Occurrence
Differences Between Sporadic and Genetic Forms:
Sporadic fatal insomnia (SFI) differs from familial fatal insomnia (FFI) primarily in the occurrence process. FFI is inherited in an autosomal dominant manner and is associated with a specific mutation in the PRNP gene, which codes for the prion protein. Furthermore, this mutation involves two substitutions on the same allele of the prion gene:
- At codon 129, aspartic acid (D) is replaced with methionine (M).
- At codon 178, aspartic acid (D) is swapped for asparagine (N).
However, SFI occurs sporadically with no known familial linkage or identifiable mutation in the PRNP gene. The exact cause of the spontaneous misfolding in SFI remains unclear, but it may arise from random conformational changes in the prion protein.
Known Mutations (if any) and Their Roles:
While SFI has no specific genetic mutation associated with its onset, understanding the mutation that caused FFI offers valuable insights into the disease mechanism. The D178N mutation in FFI, when combined with the M129 polymorphism, results in a highly pathogenic form of a prion. This mutation alters the protein’s structure, making it prone to misfolding. For SFI, the absence of a specific mutation suggests that environmental factors or other genetic variants might play a role in the sporadic misfolding events.
Brain Regions Affected
Thalamus:
The thalamus is responsible for relaying sensory and motor signals and regulating sleep, alertness, and consciousness. SFI affects the anteroventral and mediodorsal nuclei of the thalamus. These regions are important to the regulation of sleep-wake cycles. Therefore, damage to the thalamus leads to disruptions in sleep patterns, a prominent symptom of the disease. In addition, the destruction of thalamic neurons impairs the brain’s ability to regulate sleep, leading to progressive insomnia.
Other Affected Brain Regions:
The other parts of the brain that often show pathological changes are inferior olives, which often exhibit neuronal loss and gliosis (scarring). In addition, cortical atrophy (thinning of the brain’s cortex) can occur as the disease progresses, contributing to neurological symptoms such as cognitive decline. The cerebellum, involved in motor control, may also be affected, leading to ataxia and other motor disturbances. The combination of these affected areas results in the complex clinical picture seen in SFI, characterized by severe sleep disturbances, autonomic dysfunction, and progressive neurological decline.
Diagnosing Sporadic Fatal Insomnia (SFI)
Diagnosing SFI presents some significant challenges for the following reasons:
- Overlapping Symptoms: SFI shares many symptoms with other neurological orders, such as Parkinson’s disease, Alzheimer’s disease, and Lewy body dementia. So, this overlap makes it difficult to pinpoint SFI based solely on clinical presentation.
- Rarer Occurrence: The rarity of SFI also complicates its diagnosis, making it difficult for physicians when presented with a patient’s symptoms.
Overcoming these Challenges
To overcome these challenges, a thorough diagnostic approach is essential. This involves:
- Detailed Medical History: To perform an accurate diagnosis of the disease, a patient’s comprehensive medical history is required. It should contain the patient’s symptoms, their progression, and any potential risk factors. This includes family history (to rule out FFI), sleep patterns, cognitive changes, and movement difficulties.
- Neurological Examination: An in-depth neurological examination will assess the individual’s cognitive function, muscle control, reflexes, and coordination. So, this examination can help identify neurological abnormalities suggestive of SFI.
Diagnostic Tools for Sporadic Fatal Insomnia
While there is no single definitive test for SFI, several tools can aid in the diagnostic process:
- Sleep Studies (Polysomnography): This procedure records muscle activity, brain activity, breathing patterns, and oxygen levels during sleep. Therefore, this test can identify sleep disturbances characteristic of SFI, such as fragmented sleep, reduced deep sleep stages, and increased wakefulness.
- Brain Imaging Tests (MRI, PET Scan): MRI and PET scans can reveal abnormalities in brain structure and function associated with SFI. These scans may show damage in specific brain regions responsible for sleep regulation.
- Cerebrospinal Fluid Analysis (CSF) Analysis: CSF may not directly help in the diagnosis of SFI. However, it can rule out other infectious or inflammatory conditions that may look like SFI.
- Genetic Testing: It is crucial to differentiate sporadic fatal insomnia from familial fatal insomnia. So, a negative test for the FFI-associated PRNP gene mutation helps strengthen the case for SFI.
Conclusion
In conclusion, sporadic fatal insomnia (SFI) is a rare and devastating prion disease that rapidly destroys brain function. While the exact cause remains unknown, scientists believe prion misfolding plays a key role. There is currently no cure, and the disease progresses quickly, leading to coma and death. Although a definitive diagnosis is challenging, a combination of medical history, neurological examination, and various tests can help identify SFI.
