Fatal insomnia is a very rare neurodegenerative disease characterized by progressively worsening insomnia and eventual death. In this video, I explain the symptoms of fatal insomnia as well as what happens in the brain during the disease.

TRANSCRIPT:

Fatal insomnia is a very rare terminal condition characterized by difficulty sleeping that becomes progressively worse over time. Although the disease is typically genetic in origin, some sporadic cases without a clear genetic basis have also been documented. The condition usually begins in middle age or later, and early symptoms include trouble sleeping as well as autonomic nervous system disturbances, such as increased body temperature and increased heart rate.

The disease gets worse over time as the amount of sleep patients get continues to decline. Patients will sometimes lapse into a state of unresponsiveness during which they make involuntary movements that seem to be related to acting out dreams, and they can develop a variety of additional symptoms including difficulties with balance and coordination, trouble speaking and swallowing, hallucinations, and personality changes. Eventually, most patients lose the ability to enter deep sleep at all, and fall into a stupor that it is difficult to rouse them from. This stupor sometimes leads to coma, and the disease is always fatal, with death occurring in just over 18 months on average.

Fatal insomnia is a prion disease, meaning it is associated with the conversion of a protein called prion protein into a form that cannot be broken down. The new pathological form of prion protein accumulates in the brain, and its accumulation is associated with the death of neurons and other pathological changes such as the brain taking on a spongy texture. The neuronal death eventually becomes insurmountable and is linked to the death of the patient. In fatal insomnia, the most severe neuronal loss often occurs in the thalamus and inferior olivary nuclei, but pathological changes are sometimes seen through other areas of the brain such as the cerebral cortex. Damage to the sleeppromoting regions of the thalamus is thought to be especially important to causing the insomnia that occurs in the disease.

REFERENCES:

Cracco L, Appleby BS, Gambetti P. Fatal familial insomnia and sporadic fatal insomnia. Handb Clin Neurol. 2018;153:271299. doi: 10.1016/B9780444639455.000155. PMID: 29887141.

Montagna P. Fatal familial insomnia and the role of the thalamus in sleep regulation. Handb Clin Neurol. 2011;99:98196. doi: 10.1016/B9780444520074.000187. PMID: 21056239.

Montagna P, Gambetti P, Cortelli P, Lugaresi E. Familial and sporadic fatal insomnia. Lancet Neurol. 2003 Mar;2(3):16776. doi: 10.1016/s14744422(03)003235. PMID: 12849238.