Although the ultimate therapy for FFI must address the destructive prion, present treatment of FFI is mainly palliative. FFI patients respond poorly to conventional drugs such as sedatives and benzodiazepines. Cibula and colleagues mention giving a cocktail of medications to successfully induce SWS and sleep spindles for EEG testing of an insomniac, non-FFI patient without thalamic degeneration. These investigators did not discuss their potential therapeutic use for patients with FFI. Gamma-hydroxybutyrate (GHB), an investigational drug that reliably stimulates SWS in normal and insomniac patients, resulted in 3 hours of SWS sleep in a patient with FFI of 14 months' duration (3-mg dose).
Whereas before receiving this medication, the patient was unresponsive to his environment, when he awoke from his drug-induced sleep, he was alert, attentive, and responsive to questions. The continued nightly use of this medication yielded similar positive results for an additional 2 weeks. During the third week, the patient developed fevers and restlessness, and subsequently died. Obviously, whether the medication hastened or delayed his death cannot be determined. GHB is a normally endogenous metabolite and precursor of GABA; it is found in all mammalian cells, with the greatest concentrations being found in the substantia nigra, thalamus, and hypothalamus. Known effects include increases in acetylcholine and serotonin and time-dependent changes in dopamine (DA) levels. DA suppression is followed by increased secretion of both GH and prolactin.
At appropriate doses, GHB induces sleep, lowers the body temperature, and slows the heart rate without loss of blood pressure. Indeed, many of the problems inherent to FFI are influenced by this drug. Although recreational use of GHB has been associated with adverse reactions and a few fatalities, low doses have been regarded as safe. GHB has been used for over 40 years in surgical procedures.
According to Reder (personal communication; 2005), the patient's death followed shortly after the termination of treatment trials, suggesting either that GHB administration must not be stopped abruptly or, perhaps, that the patient had reached a fatal level of degeneration and would not have survived under any circumstance. Autopsy of this patient showed that only 5% of dorsomedial and anteroventral thalamic cells were preserved. It is significant that SWS can still be induced with this very low number of cells and that cognitive function should be so markedly enhanced as a result. These findings suggest that the functional suppression is reversible and not totally a consequence of degeneration.
Efforts to treat the confusional state of FFI are not systematically made. In one patient, flumazenil (a benzodiazepine antagonist) produced a dramatic alerting reaction on 2 occasions, but the drug was not administered therapeutically.[1,45] Treatment of insomnia, even if only moderate, may positively affect the patient's symptoms and enhance the quality of the patient's remaining days. The accompanying case describes the ongoing self-initiated therapeutic efforts of a Met-Met patient, DF, whose symptoms began around March 2001 and who managed, through both conventional and nontraditional approaches, to ameliorate some of the devastating symptomatology of FFI, to achieve sporadic but substantial periods of sleep (even in the 26th month of his illness), and to enhance the quality of his life despite the ongoing ravages of his disease. The purpose of this paper is not to suggest that FFI can be cured by this approach or even that life can be extended by any appreciable amount (although DF did outlive the typical Met-Met patient). Primarily, it is to offer some suggestions for disease management and research directions, as well as to offer neuropsychological insights into the disorder.
All of DF's approaches were based on trial and error. Many worked for a short time, and some were accompanied by serious medical side effects. Some of these approaches stirred ethical concerns among the participating clinicians. To entreat compliance, DF stressed his fatal diagnosis and the interest of science. Although his good days were often punctuated with symptoms of his illness (such as fever, high blood pressure, ataxia, dysarthria, tremor, memory loss), his various strategies to promote sleep gave him months of mental clarity and productivity; during the 25th month of his illness, he was able to drive 950 miles in a single 15-hour stretch.
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Cite this: Self Management of Fatal Familial Insomnia. Part 1: What Is FFI? - Medscape - Sep 12, 2006.