Editing Fatal insomnia (section)

==Pathophysiology==
Given its striking clinical and neuropathologic similarities with fatal familial insomnia (FFI), a genetic prion disease linked to a point mutation at codon 178 (D178N) in the PRNP coupled with methionine at codon 129, the MM2T subtype is also known as sporadic FI (sFI). Transmission studies using susceptible transgenic mice have consistently demonstrated that the same prion strain is associated with both sFI and FFI. In contrast to what has been the rule for the most common neurodegenerative disorders, sFI is rarer than its genetic counterpart. Whereas the recognized patients with FFI are numerous and belong to >50 families worldwide, only about 30 cases of CJD MM2T and a few cases with mixed MM2T and MM2C features (MM2T+C) have been recorded to date.

In itself the presence of prions causes reduced glucose to be used by the [[thalamus]] and a mild hypo-metabolism of the [[cingulate cortex]]. The extent of this symptom varies between two variations of the disease, these being those presenting methionine [[homozygote]]s at codon 129 and methionine/valine [[heterozygote]]s, with some evidence that hypo-metabolism is more severe in the latter.<ref>{{cite journal | vauthors = Cortelli P, Perani D, Parchi P, Grassi F, Montagna P, De Martin M, Castellani R, Tinuper P, Gambetti P, Lugaresi E, Fazio F | title = Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein | journal = Neurology | volume = 49 | issue = 1 | pages = 126–133 | date = July 1997 | pmid = 9222180 | doi = 10.1212/wnl.49.1.126 }}</ref> Given the relationship between the involvement of the thalamus in regulating sleep and alertness, a causal relationship can be drawn and is often mentioned as the cause of insomnia.<ref>{{cite book | vauthors = Kostina A, Alama A, McGintya D, Alama N  |chapter=Sleep homeostasis |title=Encyclopedia of Sleep and Circadian Rhythms |date=2023 |pages=39–47 |doi=10.1016/B978-0-12-822963-7.00243-7 |isbn=978-0-323-91094-1 }}</ref><ref>{{cite journal | vauthors = Morton AJ | title = Circadian and sleep disorder in Huntington's disease | journal = Experimental Neurology | volume = 243 | pages = 34–44 | date = May 2013 | pmid = 23099415 | doi = 10.1016/j.expneurol.2012.10.014 }}</ref>