Things That Go Bump in the Night, Part 1

For the latter half of October I have opted to do undertake (pun intended) a 3-part series on scary sleep disorders. If all goes as scheduled, I shall deliver the final installment of this terrifying trilogy just in time for Halloweekend. And now, we begin our journey into darkness with a topic that is sure to keep you up all night…

Humans divide their time between 3 main conscious states. Wakefulness, slow-wave non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM).* Generally these states are experienced sequentially, and all is well. However, the absence or mixing of any of the states can be disorienting, debilitating and even deadly

Insomnia is the most frequently reported sleep disorder in the general population. It is defined as the inability to obtain enough sleep in order to feel rested, which can mean insufficient quantity or quality of sleep, or both. Its causes are diverse, ranging from physical problems such as obstructive sleep apnea † and restless leg syndrome‡ to social and psychological ones like night shift work and anxiety. Sometimes there is no traceable cause. As a lifelong poor sleeper, insomnia is a familiar experience that I would describe as frustrating to maddening, depending on severity. I was, however, surprised to learn that the condition could also be completely incapacitating and ultimately lethal. Such is the fate of those afflicted with fatal familial insomnia (FFI), a genetic disease as disturbing as it is rare.

FFI is, in fact, extremely rare. So much so that the mere diagnosis of a new case is often deemed worthy of its own journal article. The conditional was first described in a 1986 New England Journal of Medicine article and is believed to affect only about 40 families in the world today. It is a prion disease with autosomal dominant inheritance.§ This means that it requires only one gene with the disease-causing mutation from either parent. As with other lethal dominantly-inherited diseases, such as Huntingtons, FFI was able to persist because its symptoms generally do not manifest until after childbearing age. A parent who carries the problematic gene has a 50% chance of passing it on to any one of his or her children, but may appear to be in perfect health until things go dreadfully awry somewhere in middle to late adulthood.

Prion diseases cause degeneration within the central nervous system. FFI does its damage to the thalamus, a region of the brain that is involved, among other things, with the regulation of sleep and wakefulness. The clinical presentation of FFI begins with a progressive inability to sleep. Patients may also exhibit weight loss, difficulties with focus and memory, loss of coordination of muscles and muscle twitching. Gradually they become completely incapable of achieving slow-wave or REM sleep. During this process another curious set of symptom appears – hallucinations and the enactment of dreams during wakefulness. It is as though the dreams normally experienced during REM sleep begin to intrude into the waking state. Patients live in a gloomy, clouded limbo, neither fully asleep nor fully awake. Eventually coma and death arrive to turn off the lights. The course of this entire nightmare varies from about 8 month to 2 years. It is a long time to go without a good night’s sleep.

The name fatal familial insomnia may be a bit misleading, as it implies that its victims actually die from insomnia. Since the inability to sleep present in FFI is caused by the destruction of the thalamus, insomnia could just as easily be viewed as another byproduct of the disease. A symptom rather than a cause. It’s one of those tricky chicken-or-the-egg questions. Scientists are pretty good at designing experiments in which animals drop dead after being forcibly kept awake for weeks, but they have a harder time determining what exactly killed them. Examinations of the animals after they die tend to turn up healthy organs and no clear signs as to what physically went wrong. Sleep is a nebulous field. There is little debate that we need it, but no solid proof as to why we need it. So cherish the sleep that you can fit in to your busy schedule, lest it be brutally taken from you by a rare genetic illness.**

* REM sleep is the stage in which dreaming occurs. During REM sleep the brain is active but the body’s voluntary muscles are paralyzed, theoretically to protect the sleeper from acting out dreams.

† Obstructive sleep apnea is the blocking of airways during sleep, which leads to multiple brief awakenings during the night to obtain more air (up to 100 per hour of sleep). Sufferers may not even realize that they are losing sleep at night as they will not recall these episodes and experience their symptoms mostly in the form of daytime sleepiness. The condition also causes snoring.

‡ Restless leg syndrome was recently mocked (by me) in another article. It is a real malady, it is just not as prevalent as the pharmaceutical industry would have you believe. It is characterized by uncomfortable creepy-crawling feelings in the legs and a subsequent urge to move them. These symptoms worsen during inactive periods, for example – lying down and attempting to go to sleep.

§ A prion is a mis-folded protein that replicates itself using healthy cells, not unlike a virus. You have likely read about prions before, as they are also the culprit behind bovine spongiform encephalopathy, aka mad cow disease.

** There is no actual causal relationship between these two things. I’m just being dramatic. It’s October.

Who told you this?

Mahowald, M.W. and Schenck, C.H. 2005. “Insight From Studying Human Sleep Disorders.” Nature 437: 1279-1285.

Raggi, A. et al. 2008. “The behavioral features of fatal familial insomnia: A new Italian case with pathological verification.” Sleep Medicine 10: 581-585.

Krasnianski, A. et al. 2008. “Fatal Familial Insomnia: Clinical Features and Early Identification.” Annals of Neurology 63: 658-661.

Gallassi, R. et al. 1996. “Fatal familial insomnia: Behavioral and cognitive features.” Neurology 46: 935-939.

Medori, R. et al. 1992. “Fatal familial insomnia: A prion disease with a mutation at codon 178 of the prion protein gene.” The New England Journal of Medicine 326: 444-449.

Special thanks to Elizabeth, who first alerted me to the existence of this ailment during an evening of dancing and karaoke.