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Specific limb: A brief look at ‘restless legs syndrome’

Those that know me well often comment that I have a general inability to sit still and that I am a ‘fidget’. (This is not necessarily a bad thing and in fact there are some positives to fidgeting that I outlined in a previous blog on bad behaviours that are sometimes good for you). There is certainly some truth to the observation that I fidget but sometimes the fidgeting is out of my control. Every few weeks my right lower leg appears to take on a life of its own and I will get strange (uncomfortable) sensations (such as tingling, itching, and aching, and occasionally cramp-like feelings) that force me to move my right leg and foot around. It only happens when I am in a resting and relaxing state and usually lasts about 30 minutes (but can occasionally last much longer). On occasions it disrupts my work and sleep but I find that just getting up and moving around is sometimes enough to alleviate the uncomfortable feelings.

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A few years ago I Googled my ‘symptoms’ and was surprised to find that I am not the only person who appears to experience such effects and that there is a whole medical literature on what has been termed ‘restless legs syndrome’ although in my case it would be in a singular rather than plural form). I’ve had the condition for about 15 years now and it may be related to some of the medication I take for an unrelated chronic degenerative health condition that I have. According to the Wikipedia entry on restless legs syndrome (RLS):

“The first known medical description of RLS was by Sir Thomas Willis in 1672. Willis emphasized the sleep disruption and limb movements experienced by people with RLS…The term ‘fidgets in the legs’ has also been used as early as the early nineteenth century. Subsequently, other descriptions of RLS were published, including those by Francois Boissier de Sauvages (1763), Magnus Huss (1849), Theodur Wittmaack (1861), George Miller Beard (1880), Georges Gilles de la Tourette (1898), Hermann Oppenheim (1923) and Frederick Gerard Allison (1943). However, it was not until almost three centuries after Willis, in 1945, that Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, Restless legs: clinical study of hitherto overlooked disease. Ekbom coined the term “restless legs” and continued work on this disorder throughout his career. He described the essential diagnostic symptoms, differential diagnosis from other conditions, prevalence, relation to anemia, and common occurrence during pregnancy. Ekbom’s work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria”.

As well as being referred to as RLS, it is sometimes referred to as Willis-Ekbom Disease or Willis-Ekbom Syndrome. Since being ‘rediscovered’ in the 1980s, there have been a lot of scientific papers published on the phenomenon although many of these are medical case studies (I don’t think my own experiences are extreme enough or strong enough to appear in any medical textbook. The Wikipedia entry on RLS provides a good summary of what is known medically and empirically:

“Restless legs syndrome (RLS) is a disorder that causes a strong urge to move one’s legs. There is often an unpleasant feeling in the legs that improves somewhat with moving them. Occasionally the arms may also be affected. The feelings generally happen when at rest and therefore can make it hard to sleep. Due to the disturbance in sleep, people with RLS may have daytime sleepiness, low energy, irritability, and a depressed mood. Additionally, many have limb twitching during sleep. Risk factors for RLS include low iron levels, kidney failure, Parkinson’s disease, diabetes, rheumatoid arthritis, and pregnancy. A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers. There are two main types. One is early onset RLS which starts before age 45 [years], runs in families and worsens over time. The other is late onset RLS which begins after age 45 [years], starts suddenly, and does not worsen. Diagnosis is generally based on a person’s symptoms after ruling out other potential causes… Females are more commonly affected than males and it becomes more common with age…Some doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it. Others believe it is an under-recognized and undertreated disorder…An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder. Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain”.

According to a review by Dr. Richard Allen and Dr. Christopher Earley in the Journal of Clinical Neurophysiology, RLS affects 2.5-15% of the US population. In another review on sleep disorder in the journal American Family Physician, Dr. Kannan Ramar and Dr. Eric Olson reported that RLS is typically characterized by four essential features: These are:

“(1) the intense urge to move the legs, usually accompanied or caused by uncomfortable sensations (e.g., “creepy crawly,” aching) in the legs; (2) symptoms that begin or worsen during periods of rest or inactivity; (3) symptoms that are partially or totally relieved by movements such as walking or stretching; and (4) symptoms that are worse or only occur in the evening or at night”.

Various online articles and papers report a variety of potential treatments based on the notion that RLS might be caused by a dopamine imbalance in the body. Some medics advise a regular sleep routine (such as that advised for those with insomnia), and cutting out the drinking of alcohol and the smoking of cigarettes. Pharmacological treatments include the use of drugs that are also used in the treatment of Parkinson’s disease such as L-DOPA and pramipexole, and the use of magnesium sulphate therapy (as reported in a 2006 paper in the Journal of Clinical Sleep Medicine – magnesium is known to be a natural muscle relaxant). In a 2011 issue of the journal Sleep Medicine, In an online article about RLS, Dr Michael Platt, author of the 2014 book Adrenalin Dominance, claims that RLS sufferers can be treated using a progesterone cream:

“Excess adrenalin during the night can cause restless leg syndrome. People often have associated symptoms also resulting from elevated adrenalin, such as teeth grinding, the need to urinate, and tossing and turning, and they often awaken in the morning with low back pain. Characteristically, RLS patients have an excess of adrenaline, may toss and turn all night, be quick to anger, might be workaholics, will usually have fibromyalgia (aches and pains – low back, side of the hips, and grind their teeth), they might drink too much, and will be hypoglycemic (sleepy between 3-4 p.m. or when in a car), and so on. There is an associated over-production of insulin and an under-production of progesterone…[By using a progesterone cream] I have had 100% success with eliminating RLS by getting hormones into balance, often within the first week. Patients feel more relaxed, they can sleep at night, rage disappears, and they can focus more easily”.

Dr. Luis Marin and his colleagues reported a different treatment for RLS altogether. They reported the case of a 41-year-old male RLS sufferer who after being on medication for RLS discovered his own solution – having sex. Following sex, the man reported that all RLS symptoms would disappear. Marin and colleagues speculated that the release of dopamine following orgasm might alleviate RLS symptoms. This appears to be a reasonable speculation given the findings of research published in the Journal of Neuroscience by Dr. Gert Holstege and his colleagues who examined brain activation at the point of ejaculation. In their paper they reported the similarity between ejaculation and using heroin in terms of brain activation:

“We used positron emission tomography to measure increases in regional cerebral blood flow during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer’s female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush”.

It could well be that the increase in dopamine following ejaculation acts in a similar way to the medications that are given to RLS sufferers. Of all the treatments for RLS that I have read about, I think I know which one I would prefer!

Dr. Mark Griffiths, Professor of Behavioural Addiction, International Gaming Research Unit, Nottingham Trent University, Nottingham, UK

Further reading

Allen, R.P., & Earley, C.J. (2001). Restless legs syndrome: A review of clinical and pathophysiologic features. Journal of Clinical Neurophysiology, 18(2), 128-147.

Bartell S1, Zallek S. Intravenous magnesium sulfate may relieve restless legs syndrome in pregnancy. Journal of Clinical Sleep Medicine, 15, 187-188.

Chaudhuri, K.R., Appiah-Kubi, L.S., & Trenkwalder, C. (2001). Restless legs syndrome. Journal of Neurology, Neurosurgery & Psychiatry, 71(2), 143-146.

Ekbom, K., & Ulfberg, J. (2009). Restless legs syndrome. Journal of Internal Medicine, 266(5), 419-431.

Holstege, G., Georgiadis, J. R., Paans, A. M., Meiners, L. C., van der Graaf, F. H., & Reinders, A. S. (2003). Brain activation during human male ejaculation. Journal of Neuroscience, 23(27), 9185-9193

Leschziner, G., & Gringras, P. (2012). Restless legs syndrome. British Medical Journal, 344, e3056.

Marin, L.F., Felicio, A.C., & Prado, G.F. (2011). Sexual intercourse and masturbation: Potential relief factors for restless legs syndrome? Sleep Medicine, 12(4), 422.

Ondo, W. G. (2009). Restless legs syndrome. Neurologic Clinics, 27(3), 779-799.

Ramar, K; Olson, EJ (Aug 15, 2013). Management of common sleep disorders. American Family Physician, 88, 231–238.

Satija, P., & Ondo, W. G. (2008). Restless legs syndrome. CNS Drugs, 22(6), 497-518.

Dead tired: A beginner’s guide to Fatal Familial Insomnia

For most of my life I have “suffered” from insomnia. I deliberately put the word ‘suffered’ in quotation marks as for the vast majority of the time I have always seen my lack of sleep as something positive (i.e., I had more time to do other things. In fact, when people ask me how I find the time to write so much, I usually say “Insomnia” but I don’t usually say it as a joke, it’s a matter of fact). Given my personal interest in insomnia, I’ve always enjoyed reading papers on insomnia (and no, they don’t send me to sleep!) and sexsomnia (which I looked at in a previous blog). In 1990, a Finnish man named Toimi Soini stayed awake for over 11 days (276 hours) and broke the world record for not going to sleep. However, this record no longer appears in the Guinness Book of World Records as it was withdrawn on health grounds because lack of sleep – as I’ll show in today’s blog – can lead to death.

One of the strangest (and deadliest) types of insomnia is ‘fatal familial insomnia’ (FFI). This is actually an incredibly rare genetic sleep disorder that affects around 40 families worldwide. The cause of FFI is a genetic mutation that leads to prion disease and is therefore related to bovine spongiform encephalopathy (BSE; i.e., ‘mad cow disease’), Creutzfeldt–Jakob disease (the human form of BSE), and ‘Kuru’ (the incurable and degenerative neurological disorder found in the cannibalistic tribes in New Guinea and known as the ‘laughing disease’). The (online) Medical Dictionary is a little more technical and notes:

“Fatal familial insomnia (FFI) is a very rare, autosomal dominant inherited, disease of the brain. It is caused by a mutation in a protein called prion protein (PrP): asparagine- 178 is replaced by aspartic acid. The mutation changes the shape of PrP so that it becomes a prion and makes other, normal PrP molecules change to the abnormal shape. This causes amyloid plaques in the thalamus, the region of the brain responsible for regulation of sleep patterns. The dysfunction of the thalamus results in insomnia first of all, which progresses to more serious problems over several years”

All prion diseases (known more scientifically as ‘transmissible spongiform encephalopathies’) are rare progressive neurodegenerative disorders that can affect both animals and humans. All of the prion diseases (including FFI) typically have (i) long incubation periods, (ii) a failure to induce inflammatory response, and (iii) characteristic spongiform changes that are associated with neuronal loss. The first recorded case of FFI is thought to be an Italian man who died in Venice in 1765. There are many descriptions of the disease online including case study accounts. The Wikipedia entry on FFI described the case of the American music teacher, Michael Corke from Chicago:

“He suddenly began to have trouble sleeping not long after his 40th birthday in 1991, and his health and state of mind quickly deteriorated as his sleeplessness grew worse. Eventually, he couldn’t sleep at all, and he was soon admitted to the hospital. Doctors there weren’t sure what was wrong with him, initially diagnosing multiple sclerosis; in a bid to send him to sleep in the later stages of the disease, physicians induced a coma with the use of sedatives, but they found that his brain still failed to shut down. Corke died in 1992 a month before his 41st birthday, by which time he had gone without sleep for six months”

Another 2011 online article on “bizarre brain disorders” by Anna McGann also described a family case study (which is very similar to paper published in a 2000 issue of the Journal of Neurology, Neurosurgery and Psychiatry by Dr. C. Tabernero and colleagues):

“Dr. Ignazio Rottier gained unwanted firsthand experience when he and his wife, Elisabetta, watched her family fall victim to [FFI]. First known to fall ill was Elisabetta’s grandfather. Decades later, Elisabetta’s uncle, Silviano, was 53 when he lost his ability to sleep. A few short months following initial onset, Silviano fell into a coma and died…In the 70s, an aunt of Elisabetta’s passed on, one year after her own initial onset of sleeplessness. Yet another year later, a second aunt too lost her life battling the very same affliction”.

Research has also shown that the condition (in a few cases) can result from a non-inherited genetic mutation that has been called ‘sporadic fatal insomnia’ (sFI). Less than 10 cases of sFI have ever been documented in the medical literature. As the conditions worsen, sufferers experience a wide range of symptoms including delirium, hallucinations (auditory, visual and tactile), elevated heart rate and blood pressure, hyperhidrosis (i.e., excess sweating), hyperthermia, hypertension, impotence (in men), amenorrhea (cessation of periods) and early menopause (in women), constipation, and dementia. Treating the symptoms (via vitamin therapy, meditation, use of narcoleptics) may extend the quality of life (but as noted above, there is no known cure and most interventions are purely palliative). The disease typically has four stages, and takes between half a year and a year and a half to run its course:

  • Stage 1 (typically four months): Symptoms include insomnia, paranoia, phobias and panic attacks.
  • Stage 2 (typically five months): Symptoms include severe hallucinations and increasing panic attacks.
  • Stage 3 (typically three months): Symptoms include permanent insomnia, limited mental functioning, and rapid weight loss.
  • Stage 4 (typically six months): Symptoms include dementia and general non-responsiveness leading to death.

Writing in a 2006 issue of the Medscape General Medicine journal, Dr. Joyce Schenkein outlined the etiology and characteristics of FFI. She noted that it often begins in middle age (average age of onset being 50 years) and has no cure (even ‘gene therapy has been unsuccessful to date). Unfortunately, the prognosis following initial diagnosis is poor with FFI sufferers’ only living for an average of about a year and a half (with Dr. Schenkein noting that survival ranged from 7 to 36 months from diagnosis of FFI). It originates in the form of unexplained sleeplessness before rapidly developing into a fatal insomnia. Writing in an issue of the Journal of Clinical Neuroscience, Dr. S. Collins and colleagues in a paper on prion diseases (including FFI) concluded:

“FFI [is] likely [to] remain, [a] very rare disease, [and] will be increasingly recognised as heightened clinical awareness prompts appropriate confirmatory genetic and other testing. Similarly, continued molecular biological and allied research of these less common prion diseases will undoubtedly provide fundamental insights into the pathogenesis of this group of disorders in general, disproportionate to their numerical frequency”.

Dr Mark Griffiths, Professor of Gambling Studies, International Gaming Research Unit, Nottingham Trent University, Nottingham, UK

Further reading

Collins, S., McLean, C.A. & Masters, C.L. (2001). Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. Journal of Clinical Neuroscience, 8, 387–397.

McGann, A. (2011). 5 bizarre brain disorders. Suite 101, November 25. Located at: http://suite101.com/article/5-bizarre-brain-disorders-a397906

Moody, K.M., Schonberger, L.B., Maddox, R.A., Zou, W.Q., Cracco, L., & Cali, I. (2011). Sporadic fatal insomnia in a young woman: a diagnostic challenge: case report. BMC Neurology, 11, 136.

Schenkein, J. (2006). Self-management of fatal familial insomnia. Part 1: What Is FFI? Medscape General Medicine, 8(3), 65.

Schenkein, J. & Montagna, P (2006). Self-management of fatal familial insomnia. Part 2: Case report. Medscape General Medicine, 8(3), 66.

Tabernero, C., Polo, J.M., Sevillano, M.D., Muñoz, R., Berciano, J., Cabello, A., Báez, B., Ricoy, J.R., Carpizo, R., Figols, J., Cuadrado, N., Claveria, L.E. (2000). Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family. Journal of Neurology, Neurosurgery and Psychiatry, 68, 774–777.

Turner, R. (2012). Fatal Familial Insomnia: 
The FFI Sleep Disorder. World of Lucid Dreaming. Located at: http://www.world-of-lucid-dreaming.com/fatal-familial-insomnia.html

Wikipedia (2012). ‪Fatal familial insomnia‬. Located at: http://en.wikipedia.org/wiki/Fatal_familial_insomnia