Fatal Insomnia
A shallow dive into fatal insomnia
Having just learned about fatal insomnia in behavioral neuroscience, and already having an interest in hallucinations from another class I’m taking this semester, I decided to do a shallow dive into fatal insomnia today. What is it? How rare is it? How does it come about/work? What are some case stories of individuals with this?
Wikipedia (1) proved useful in giving a background for this disorder/disease. Fatal insomnia is a rare disease caused by mutated prions. It is most commonly familial fatal insomnia, and is caused by a rare hereditary prion that is associated with the mutation of PRNP (I didn’t know what PRNP was but it’s not really that important). FFI is characterized by four stages: 1–worsening insomnia that leads to panic attacks, paranoia, and phobias, and lasts four months, 2–hallucinations and panic attacks begin to appear, lasts about five months, 3–complete loss of sleep that results in rapid weight loss, lasts about three months, 4–person becomes mute and unresponsive, dementia, lasts about six months until death. The age of onset can be 13-60, with an average of 50 years old. According to Wikipedia, no medicine or long term treatment has proved effective, and this disease, like many prion diseases, is fatal.
Having received this general background, I turned to my tried and trusted academic search complete, and found some interesting articles:
Patel et al. (2)
A 54 year old woman came in after her family said she was struggling with memory. She came in with an Acute Mental Test of 7/10. On examination, she had spasms and tremors, and occasionally what appeared to be hypnopompic hallucinations (hallucinations involved with sleep). Her cognitive state declined rapidly, and one month after being admitted, her ACE score was 20/100.
Initial diagnosis was Creutzfeldt-Jakob disease (being the most common prion disorder) or Dementia with Lewy Bodies. Paraffin embedded tissue blot analysis showed the misshapen prion protein (the photo in the article is very interesting). Initial treatment for the supposed DLB produced no results. The patient died after being admitted, 6-7 months after the first sign of symptoms.
This case story is interesting because it draws a connection between FFI and CJD, both of which are prion diseases, with CJD being much more common (though still rare).
Habteslassie et al. (3)
A 31 year old man came to the hospital with fever and confusion. He had a functional endoscopic sinus surgery the day before, and everything had gone normally, with same day discharge. The day after the procedure, he had become erratic and confused. Many tests were done and diagnoses considered, and a detailed family history investigation showed that he had an aunt who had progressive insomnia and neurocognitive decline. Her death happened 14 months after symptom onset. Our current patient also had a 6 month previous history of memory and concentration problems, as well as sleep onset insomnia. He had behaviors consistent with REM-sleep behavior disorder, and insomnia was confirmed with an EEG.
All of these radiology findings and the clinical presentation and history led to a diagnosis of FFI. Genetic testing did confirm this diagnosis, with a substitution in the PRNP gene (for any specificities on this article, you can read it yourself or look up the definitions!).
After being discharged, progressive insomnia was reported, and death occurred 4 months after diagnosis, 10 months after illness onset.
The way diagnosis occurred in this case study was slightly different then the previous one, but still similar symptoms and tests were run. This article was published in 2021.
Hermann, et al. (4)
This article was very bio heavy and discussed the difficulties of diagnosing FFI, and how the only viable biomarker to detect it early is the thalamic hypometabolism in positron emission tomography (an imaging technology using isotopes and gamma rays), which is a really difficult process. This study wanted to see if there was a way to use information from plasma as a biomarker for FFI. Participants had PRNP mutations, and there plasma, NfL, total tau, and GFAP levels were measured. Comparisons were then made using multivariate linear regression models. Ultimately, this study indicated that it could be useful after clinical onset, but also that there is an association with plasma NfL and FFI stage and duration. So using plasma NfL can be helpful once there are already symptoms to help diagnose FFI.
This article wasn’t super helpful in giving me a general overview of FFI, but it was interesting to see what current research is being done in this area. This article was published in 2022.
Chen, et al. (5)
This article looked at differences and similarities between sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI), as well as looking at how ethnicity played into the phenotypes of sFI patients. Data on almost all patients was pulled from a literature review, with 11 participants data coming from the authors center. This article touched on the fact that symptoms and clinical features can change based on ethnicity.
Results showed that sFI has a much longer period of duration than FFI, but that the frequency of sleep related symptoms was significantly lower in sFI patients compared to FFI patients. More sFI patients had neuropsychiatric symptoms at the beginning, and had similar cluster B symptoms to CJD.
This article was also very bio heavy and more difficult to understand, but it did a good job spelling out some differences between sFI and FFI.
My conclusion to this research dive is that it was wonderful to do a little literature review into something that I will probably never research, but was still really fun to learn about. I gained knowledge, and also practiced writing a mini literature review, which was valuable experience I wouldn’t have if I just read a couple articles or did a quick google search. I already added several new topics to my research list while writing this, so I hope to be back soon with more shallow dives!
References
Patel, D., Ibrahim, H., Rankin, J., Hilton, D., Barria, M. A., Ritchie, D. L., Smith, C., & Zeman, A. (2021). Fatal insomnia: the elusive prion disease. BMJ Case Reports, 14(6). https://doi.org/10.1136/bcr-2020-241289
Habteslassie, D., McMahon, M., & Wimaleswaran, H. (2022). Can insomnia be fatal? An Australian case of fatal familial insomnia. Internal Medicine Journal, 52(4), 667–670. https://doi.org/10.1111/imj.15737
Hermann, P., Canaslan, S., Villar-Piqué, A., Bunck, T., Goebel, S., Llorens, F., Schmitz, M., & Zerr, I. (2022). Plasma neurofilament light chain as a biomarker for fatal familial insomnia. European Journal of Neurology, 29(6), 1841–1846. https://doi.org/10.1111/ene.15302
Chen, Z., Chu, M., Zhang, J., Kong, Y., Xie, K., Cui, Y., Ye, H., Liu, L., Li, J., Wang, L., & Wu, L. (2023). Clinical profiles and ethnic heterogeneity of sporadic fatal insomnia. European Journal of Neurology, 30(4), 813–822. https://doi.org/10.1111/ene.15676