pii: sp-00543-15
http://dx.doi.org/10.5665/sleep.5134
EDITORIAL
Darwin’s Predisposition and the Restlessness that Drives Sleepwalking
Commentary on Lopez et al. Pain in sleepwalking: a clinical enigma. SLEEP 2015;38:1693–1698.
Michael Howell, MD, FAASM
Department of Neurology, University of Minnesota, Minneapolis, MN; University of Minnesota Medical Center, Fairview, Minneapolis, MN; Sleep
Medicine Clinic, University of Minnesota Medical Center Fairview, Minneapolis, MN, Minnesota Regional Sleep Disorders Center, Minneapolis,
MN; Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center, Minneapolis, MN
For a common condition that intrigued Hippocrates, Aristotle,
Galen, and Shakespeare, remarkably little is known about somnambulism.1 A recent surge in sleepwalking parallels the expanded use of sedative medications, most notably zolpidem.2–4
But despite the increased prevalence, sleepwalking research
has fallen behind other sleep disorders. For example, in contrast to REM sleep behavior disorder, only a few functional imaging studies have been performed on sleepwalkers and most
of these have been single case reports.5,6 Therapeutic evidence
is contradictory, and commonly recommended therapies often
exacerbate the behaviors they are trying to control.5,7–9
Prior to Broughton’s seminal 1968 publication, it was assumed that sleepwalking occurred during intense dream mentation. He demonstrated that somnambulism was not a REM
sleep phenomenon; rather sleepwalking occurred after a disorder of arousal (DOA) from NREM sleep.10 Later studies established that the predominant scalp electroencephalographic
(EEG) feature of sleepwalking episodes was fast EEG activity
with an admixture of slow waves (typically from the frontal
leads), suggesting an overlap between NREM sleep and wakefulness.11,12 These findings are identical with confusional
arousals, and thus polysomnography (PSG) does not distinguish one DOA from another. In addition, only the rare PSG
epoch during sleepwalking would qualify as sleep by AASM
scoring rules.13 Thus, the terms sleepwalking and somnambulism are misnomers, as the patients are not asleep. But the romance of old nomenclature lingers with semantic inertia and a
proposal to change Lady Macbeth’s nocturnal wondering to a
Disorder of Arousal with Ambulation (DOA-a) would be dead
on arrival.
Pressman’s 3 P model is currently used to conceptualize the
pathophysiology of a DOA.8 A predisposed patient is primed
by a condition that impairs a transition to wakefulness. Subsequently, a DOA is precipitated by an arousing stimulus.
Priming factors include sleep deprivation and sedative medications; precipitators can be endogenous pathology (e.g., sleep
disordered breathing) or environmental factors (e.g., noise).14,15
Unlike priming and precipitating factors however, we have
little insight into what predisposes patients to DOA in general,
Submitted for publication September, 2015
Accepted for publication September, 2015
Address correspondence to: Michael J. Howell, MD, FAASM University
of Minnesota, Department of Neurology, 717 Delaware Street SE, Room
510l, Minneapolis, MN 55455; Tel: (612) 624-9025; Email: howel020@
umn.edu
SLEEP, Vol. 38, No. 11, 2015
and sleepwalking in particular. Correcting the priming and
precipitating factors can sometimes resolve a DOA but the 3P
model does not answer a vexing mystery. Why do some individuals, when disoriented, arise and ambulate (sleepwalkers)
and others stay in bed (confusional arousals)?
An article in this month’s SLEEP by Lopez and colleagues16
expounds upon our knowledge and provides some intriguing
clues on who may be predisposed to sleepwalk. Using a crosssectional case-controlled design, the authors demonstrate a
relationship between pain and sleepwalking. Of note, the authors excluded patients on sedative medications or if they met
criteria for other identifiable sleep disorders. In other words,
they eliminated patients with identifiable priming and precipitating factors. These exclusions were understandable as their
stated goal was to study the role of nociception in somnambulism. However these prohibitions limit the studies immediate
clinical relevance as the majority of sleepwalkers have separate identifiable sleep disorders.5,14,17 Further, the exclusion of
patients with a certain sleep-related movement disorder may
obscure a larger insight. The authors do not speculate on how
pain could predispose an individual to walking; however, I
would suggest that the answer may be sitting (or ambulating)
right in front of us—motor restlessness.
Motor restlessness underlies restless legs syndrome (RLS),
but the restrictive RLS criteria fails to identify numerous
patients who are compelled to ambulate at night.18–20 For example, patients often attribute nocturnal discomfort to some
other condition (e.g., neuropathy, disc herniation), and RLS
symptoms can be notoriously difficult to describe in English,
let alone when translated across languages. Ultimately many
patients can only state that there is some disturbance that compels movement. Additionally, commonly prescribed medications such as opioids and alpha-2 delta ligands (gabapentin,
pregabalin) may obscure restlessness. This leads RLS to have
a parallel clinical syndrome, “atypical RLS,” which may outnumber its parent disorder. Finally, for reasons not fully understood, many patients recoil from a diagnosis as they perceive
that the name, restless legs syndrome, fails to characterize the
disabling nature of their condition and trivializes their suffering.21 All of these challenges were nicely summarized in
the title of a recent RLS report, “rarely diagnosed and barely
treated.”19
As patients with RLS (typical or atypical) present to their
physicians with difficulty initiating sleep, it is not surprising
that many of them are misdiagnosed with a hypervigilant insomnia syndrome and treated with zolpidem. Subsequently,
as zolpidem inhibits executive and hippocampal function,
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Editorial—Howell
it is to be expected that it would unleash inappropriate amnestic walking behaviors in patients predisposed to ambulation.2,5,20,22–24 Lopez et al.16 cited a transcranial magnetic
stimulation study of sleepwalkers that demonstrated altered
excitability of the motor cortex (with reductions in the short
interval intracortical inhibition, the cortical silent period, and
in the short latency afferent inhibition).25 Intriguingly, these
same TMS findings have been repeatedly demonstrated in
TMS studies of RLS patients, which suggests an overlap between these two conditions.26–33
In 1796, the English Naturalist Erasmus Darwin (grandfather of Charles) wrote on sleep disorders and described sleepwalking as a voluntary exertion that served to relieve pain. He
also noted a rather profound therapeutic response to opium.1
Later in 1869, the first neurologist to practice in North America,
William Hammond, found iron to be an effective therapy in
sleepwalking.1 Of course, opioids and iron repletion are standard therapies in the contemporary management of RLS.
I suggest that Darwin’s predisposition, cryptic motor restlessness, is the answer to the mystery of why sleepwalkers
walk and explains the 21st century surge in medication-induced
somnambulism. Clearly, further studies are needed to explore
the link between sleepwalking and RLS (typical or atypical);
however, a critical review of the literature suggests a shared
pathology.
CITATION
Howell M. Darwin’s predisposition and the restlessness that
drives sleepwalking. SLEEP 2015;38(11):1667–1668.
ACKNOWLEDGMENT
The author thanks Judith Strand and Dr. Louis Kazaglis for
their assistance in proofreading this commentary.
DISCLOSURE STATEMENT
Dr. Howell has indicated no financial conflicts of interest.
REFERENCES
1. Umanath S, Sarezky D, Finger S. Sleepwalking through history:
medicine, arts, and the courts of law. J Hist Neurosci 2011;20:253–76.
2. Dolder CR, Nelson MH. Hypnosedative-induced complex behaviors:
incidence, mechanisms, and management. CNS Drugs 2008;22:1021–36.
3.American Academy of Sleep Medicine. International classification of
sleep disorders. 3rd edition. Darien, IL: American Academy of Sleep
Medicine, 2014.
4. Frauscher B, Mitterling T, Bode A, et al. A prospective questionnaire
study of 100 healthy sleepers: non-bothersome forms of recognizable
sleep disorders are still present. J Clin Sleep Med 2014;10:623–9.
5. Howell MJ. Parasomnias: an updated review. Neurotherapeutics
2012;9:753–75.
6. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder
and neurodegenerative disease. JAMA Neurol 2015;72:707–12.
7. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine
treatment of injurious parasomnias and other disorders of disrupted
nocturnal sleep in 170 adults. Am J Med 1996;100:333–7.
8. Pressman MR. Factors that predispose, prime and precipitate NREM
parasomnias in adults: clinical and forensic implications. Sleep Med
Rev 2007;11:5–30.
9. Harris M, Grunstein RR. Treatments for somnambulism in adults:
assessing the evidence. Sleep Med Rev 2009;13:295–7.
10. Broughton RJ. Sleep disorders: disorders of arousal. Enuresis,
somnambulism, and nightmares occur in confusional states of arousal,
not in “dreaming sleep.” Science 1968;159:1070–8.
SLEEP, Vol. 38, No. 11, 2015
1668
11. Schenck CH, Pareja JA, Patterson AL, Mahowald MW. Analysis
polysomnographic events surrounding 252 slow-wave sleep arousals in
thirty-eight adults with injurious sleepwalking and sleep terrors. J Clin
Neurophysiol 1998;15:159–66.
12. Zadra A, Pilon, Joncas S, Rompre S, Montplaisir J. Analysis of
postarousal EEG activity during somnambulistic episodes. J Sleep Res
2004;13:279–84.
13. Berry RB, Brooks R, Gamaldo CE, Harding SM, Marcus CL, Vaughn
BV, for the American Academy of Sleep Medicine. The AASM manual
for the scoring of sleep and associated events: rules, terminology and
technical specifications, version 2.0. www.aasmnet.org. Darien, IL:
American Academy of Sleep Medicine, 2012.
14. Guilleminault C, Kirisoglu C, Bao G, Arias V, Chan A, Li KK. Adult
chronic sleepwalking and its treatment based on polysomnography.
Brain 2005;128:1062–9.
15. Pilon M, Montplaisir J, Zadra A. Precipitating factors of somnambulism:
impact of sleep deprivation and forced arousals. Neurology
2008;70:2284–90.
16. Lopez R, Jaussent I, Dauvilliers Y. Pain in sleepwalking: a clinical
enigma. Sleep 2015;38:1693–8.
17. Espa F, Dauvilliers Y, Ondze B, Billiard M, Besset A. Arousal reactions
in sleepwalking and night terrors in adults: the role of respiratory events.
Sleep 2002;25:871–5.
18.Allen RP. Controversies and challenges in defining the etiology and
pathophysiology of restless legs syndrome. Am J Med 2007;120:S13–21.
19. Gupta R, Lahan V, Goel D. Restless Legs Syndrome: a common disorder,
but rarely diagnosed and barely treated—an Indian experience. Sleep
Med 2012;13:838–41.
20. Howell MJ. Restless eating, restless legs, and sleep related eating
disorder. Curr Obes Rep 2014;3:108–113.
21. International Restless Legs Syndrome Study Group. DiscussionRestless Legs Syndrome or Willis-Ekbom Syndrome. SLEEP, San
Antonio 2010 Jun 6.
22. Lauerma H. Nocturnal wandering caused by restless legs and shortacting benzodiazepines. Acta Psychiatr Scand 1991;83:492–3.
23. Tsai MJ, Tsai YH, Huang YB. Compulsive activity and anterograde
amnesia after zolpidem use. Clin Toxicol (Phila) 2007;45:179–81.
24. Howell MJ, Schenck CH. Restless nocturnal eating: a common feature
of Willis-Ekbom Syndrome (RLS). J Clin Sleep Med 2012;8:413–9.
25. Oliviero A, Della Marca G, Tonali PA, et al. Functional involvement of
cerebral cortex in adult sleepwalking. J Neurol 2007;254:1066–72.
26. Entezari-Taher M, Singleton JR, Jones CR, Meekins G, Petajan JH,
Smith AG. Changes in excitability of motor cortical circuitry in primary
restless legs syndrome. Neurology 1999;53:1201–5.
27. Stiasny-Kolster K, Haeske H, Tergau F, Muller HH, Braune HJ, Oertel
WH. Cortical silent period is shortened in restless legs syndrome
independently from circadian rhythm. Suppl Clin Neurophysiol
2003;46:381–9.
28. Scalise A, Pittaro-Cadore I, Golob EJ, Gigli GL. Absence of postexercise and delayed facilitation of motor cortex excitability in
restless legs syndrome: evidence of altered cortical plasticity? Sleep
2006;29:770–5.
29. Kutukcu Y, Dogruer E, Yetkin S, Ozgen F, Vural O, Aydin H.
Evaluation of periodic leg movements and associated transcranial
magnetic stimulation parameters in restless legs syndrome. Muscle
Nerve 2006;33:133–7.
30. Gorsler A, Liepert J. Influence of cabergoline on motor excitability
in patients with restless legs syndrome. J Clin Neurophysiol
2007;24:456–60.
31. Scalise A, Pittaro-Cadore I, Janes F, Marinig R, Gigli GL. Changes
of cortical excitability after dopaminergic treatment in restless legs
syndrome. Sleep Med 2010;11:75–81.
32. Rizzo V, Arico I, Liotta G, et al. Impairment of sensory-motor
integration in patients affected by RLS. J Neurol 2010;257:1979–85.
33. Lanza G, Cantone M, Lanuzza B, et al. Distinctive patterns of cortical
excitability to transcranial magnetic stimulation in obstructive
sleep apnea syndrome, restless legs syndrome, insomnia, and sleep
deprivation. Sleep Med Rev 2015;19:39–50.
Editorial—Howell