How Fatal Familial Insomnia Works


FFI Pathology, Diagnosis and Treatment
The central nervous system is deeply affected by fatal familial insomnia.
The central nervous system is deeply affected by fatal familial insomnia.
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If you look beneath the insomnia of fatal familial insomnia, there are pathological changes inside your body that are the root of the problem. Insomnia is only a symptom of those changes. FFI causes crippling changes to your central nervous system (your brain and your spinal cord), including significant death of your anterior-ventral and medio-dorsal thalamic neurons. These are neurons in the thalamus, which is the part of your brain responsible for managing your motor functions and carrying sensory information where it needs to go. When these nervous system cells die, they unfortunately aren't replaced with new, healthy ones. Instead, your glial cells -- the support cells that help your neurons communicate and also function as a cleaning service for the central nervous system -- form scar tissue in the thalamus, which is called gliosis. Scar tissue can't perform the important functions of the neurons that have died, and without a healthy central nervous system your body begins to deteriorate.

Diagnosing FFI before symptoms appear is difficult, and involves a combination of patient-reported symptoms, family history, and genetic testing in addition to blood tests, spinal tap (to test the cells in your cerebrospinal fluid), and neurological and eye exams. Magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans of the brain are all also used to diagnose FFI. Electroencephalography (EEG) patterns, which measure the patterns of electrical activity in your brain, are also used to diagnose FFI. Researchers have discovered that the brain waves of people symptomatic with the disease don't follow normal sleep patterns (four stages of non-rapid eye movement -- NREM -- sleep, alternating with rapid-eye movement sleep -- REM). As early as a few months into the onset of the disease, FFI appears to cause the electrical activity in the brain to slow down and to skip important steps in the sleep cycle. In particular, deep REM sleep, ultimately progressing toward shorter and shorter amounts of sleep each day. None of the tests are good diagnostic tools unless used in combination with others on the list, and some, such as the EEG, are only accurate when the patient has already developed symptoms of the disease.

As of 2014, there's no cure or treatment for FFI. The best available care is palliative care, which addresses a patient's quality of life through management of the worsening and disabling symptoms rather than curing the disease. Research and clinical trials are being conducting on the effectiveness of experimental treatments, and some preliminary findings show there may be some therapies worth investigating further for their potential ability to relieve symptoms and possibly extend the lives of FFI patients, but nothing conclusive has come to light so far.

Sedatives and other traditional methods of treating sleep deprivation don't seem to have any impact against FFI, except for, possibly, the narcotic sedative (and recreational club drug) gamma-hydroxybutyrate (GHB). GHB is sometimes used as a prescription sleep-aid, and some speculate it may help induce sleep, at least a short burst, as well as additionally relieving other symptoms of sympathetic nervous system hyperactivity by decreasing both heart rate and body temperature in FFI patients [source: Schenkein]. Benzodiazepine antagonists, such as the drug flumazenil commonly used to treat tranquilizer overdoses, may also temporarily relieve the confusion and dementia that FFI causes, but as with all possible FFI treatments, additional research and clinical trials are needed.

Author's Note: How Fatal Familial Insomnia Works

Any time you're writing about a fatal disease with no known cure, it's a difficult one to get through -- both the research and the writing. Aside from the horrifying symptoms -- and name -- of this disorder, I really didn't know much at all about it. I was surprised to learn in my initial research that it's related, as a prion disease, to mad cow disease, as well as its human form, Creutzfeldt-Jakob disease.

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Sources

  • Cortelli, Pietro. "Fatal familial insomnia: clinical features and molecular genetics." Journal of Sleep Research. Vol. 8, no. S1. Pages 23-29. March 1999. (Aug. 17, 2014) http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2869.1999.00005.x/full
  • Gambetti, Pierluigi. "Prion Diseases: Fatal Insomnia." The Merck Manual. May 2013. (Aug. 17, 2014) http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/prion_diseases/fatal_insomnia.html
  • Harvard NeuroDiscovery Center. "The challenge of neurodegenerative diseases." 2014. (Aug. 17, 2014) http://www.neurodiscovery.harvard.edu/challenge/challenge_2.html
  • Johns Hopkins Medicine. "Prion Diseases." (Aug. 17, 2014) http://www.hopkinsmedicine.org/healthlibrary/conditions/nervous_system_disorders/prion_diseases_134,56/
  • Lehrer, Jonah. "The Root of Thought: What Do Glial Cells Do?." Scientific American. Oct. 27, 2009. (Aug. 17, 2014) http://www.scientificamerican.com/article/the-root-of-thought-what/
  • Mandal, Ananya. "Thalamus - What is the Thalamus?" News Medical. (Aug. 17, 2014) http://www.news-medical.net/health/Thalamus-What-is-the-Thalamus.aspx
  • Max, D.T. "Case Study: Fatal Familial Insomnia; Location: Venice, Italy; To Sleep No More." The New York Times. May 6, 2001. (Aug. 17, 2014) http://www.nytimes.com/2001/05/06/magazine/3-case-study-fatal-familial-insomnia-location-venice-italy-to-sleep-no-more.html
  • Mayo Clinic. "Autosomal dominant inheritance pattern." (Aug. 17, 2014) http://www.mayoclinic.org/autosomal-dominant-inheritance-pattern/img-20006210
  • Mayo Clinic. "Creutzfeldt-Jakob disease." Oct. 23, 2012. (Aug. 17, 2014) http://www.mayoclinic.org/diseases-conditions/creutzfeldt-jakob-disease/basics/causes/con-20028005
  • McGill University - The McGill Physiology Virtual Lab. "Biomedical Signals Acquisition: EEG." (Aug. 17, 2014) http://www.medicine.mcgill.ca/physio/vlab/biomed_signals/eeg_n.htm
  • MedicineNet.com. "Definition of Sympathetic nervous system." March 19, 2012. (Aug. 17, 2014) http://www.medterms.com/script/main/art.asp?articlekey=5607
  • Medori, R. "Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene." New England Journal of Medicine. Vol. 326, no. 7. Pages 444-449. Feb. 13, 1992. (Aug. 17, 2014) http://www.ncbi.nlm.nih.gov/pubmed/1346338
  • Montagna, P. "Clinical features of fatal familial insomnia: phenotypic variability in relationship to a polymorphism at codon 129 of the prion protein gene." Brain Pathology. Vol. 8, no. 3. Pages 515-520. July 1998. http://www.ncbi.nlm.nih.gov/pubmed/9669701
  • Moody, Karen M. "Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report." BMC Neurology. Vol. 11, no. 126. October 31, 2011. (Aug. 17, 2014) http://www.biomedcentral.com/1471-2377/11/136
  • National Center for Advancing Translational Sciences - Office of Rare Diseases Research. "genetic and Rare Diseases Information Center (GARD): Fatal Familial Insomnia." July 3, 2014. (Aug. 17, 2014) http://rarediseases.info.nih.gov/gard/6429/fatal-familial-insomnia/resources/1
  • Parchi, Piero. "Fatal familial insomnia." MedLink Neurology. July 7, 2013. (Aug. 17, 2014) http://www.medlink.com/medlinkcontent.asp
  • Schadler, Jay, and Laura Viddy. "Medical Mystery: When Sleep Doesn't Come, Death Does." ABC News. Feb. 21, 2008. (Aug. 17, 2014) http://abcnews.go.com/Health/story?id=3675223
  • Schenkein, Joyce. "Self management of Fatal Familial Insomnia. Part 1: What Is FFI?" Medscape. 2006. (Aug. 17, 2014) http://www.medscape.com/viewarticle/542963
  • Thorpy, Michael; and Shelby Freedman. "Can You Die of Insomnia?" The New York Times - Consults Blog. June 24, 2010. (Aug. 17, 2014) http://consults.blogs.nytimes.com/2010/06/24/can-you-die-of-insomnia/
  • Turner, Rebecca. "Fatal Familial Insomnia: The FFI Sleep Disorder." World of Lucid Dreaming. 2013. (Aug. 17, 2014) http://www.world-of-lucid-dreaming.com/fatal-familial-insomnia.html
  • University of California at San Francisco - UCSF Memory and Aging Center. "Types of Prion Disease." 2014. (Aug. 17, 2014) http://memory.ucsf.edu/cjd/overview/types
  • U.S. National Library of Medicine. "PRNP." January 2014. (Aug. 17, 2014) http://ghr.nlm.nih.gov/gene/PRNP

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