Clinical Features and Pathogenesis of FFI

The pathogenesis of FFI is evident by the progressive neuronal death (atrophy) in the limbic regions of the thalamus within the brain by the proliferation of the prion infectious agent, which turns healthy prion proteins already present in the brain into abnormal misfolded prions.

The subsequent cell death and neuronal damage results in a 'sponge-like' appearance of the brain tissue when studied under the microscope via histopathology. Due to this feature, FFI is considered to be a 'spongiform encephalopathy' or in layman's terms 'a sponge-like brain disorder.

Another pathogenic feature of FFI is the excess proliferation of the brain's supporting cells, and in particular astrocytes, which is generally restricted to the thalamus only (Ha
ïk et al. 2008). This is known as 'thalamic gliosis'.

Studies have shown that this selective cell death or 'atrophy' of the limbic region of the thalamus is generally concentrated in the anteroventral (AV) and mediodorsal (MD) regions (see diagram below), and are directly attributable to a patients inability to generate normal EEG sleep patterns, hypovigilence and circadian rhythm dysregulation, which are the major clinical features of FFI (Lugaresi et al. 1998)

Along with neuronal atrophy and thalamic gliosis, the hypothalamus is released from corticolimbic control and begins to shift towards a prevalence of deactivating rather than activating certain bodily functions including sleep, sympathetic hyperactivity and alertness: this illustrates another pathogenesis mechanism of associated with FFI.

This figure illustrates a schematic diagram of the thalamus. This is primary region of the brain which is involved with the prion disease FFI. Note the medial dorsal (MD) and the ventral anterior (VA) regions as these are primary area where neuronal atrophy occurs in patients with FFI causing the characteristic symptoms of insomnia, hypovigilence, and circadian rhythm dysregulation.

Clinical Onset and Prognosis of FFI

FFI has an interesting onset in that the patient is generally symptom free until the initial onset (usually around 50 years of age) when suddenly the characteristic symptoms associated with FFI begin to manifest themselves.

Studies have indicated that the approximate time at which the neurogenerative process associated with FFI which begins in the thalamus is between 13 and 21 months before the clinical presentation of the disease or the ‘onset’ (Cortelli et al. 2006).

The prognosis of FFI is considered to be very poor as at present there is no known cure and death usually occurs between 7-36 months after the iniatial onset of the symptoms.

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References: Clinical Features and Pathogenesis of FFI

Cortelli, P, Perani, D, Montagna, P, Gallassi, R, Tinuper, P, Provini, F, Avoni, P, Ferrillo, F, Anchisi, D, Moresco, R.M, Fazio, F, Parchi, P, Baruzzi, A, Lugaresi, E and Gambetti, P 2006, ‘Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and FDG-PET studies’, Brain, vol. 129, pp. 668-675, viewed 13 August 2009 from CINAHL database.

Haïk, S, Galanaud, D, Linguraru, M.G, Peoc’h, K, Privat, N, Faucheux, B.A, Ayache, N, Hauw, J-J, Dormont, D, Brandel, J-P 2008, ‘In Vivo Detection of Thalamic Gliosis: A Pathoradiologic Demonstration in Familial Fatal Insomnia. ’, Archives of Neurology, vol. 65, pp. 545-549, viewed 13 August 2009 from MEDLINE database.

Lugaresi, E, Tobler, I, Gambetti, P, Montagna, P 1998, ‘The Pathophysiology of Fatal Familial Insomnia’, Brain Pathology, vol. 8, pp. 521-526, viewed 23 August 2009 from Wiley InterScience database.