Darwin's Predisposition and the Restlessness that Drives Sleepwalking

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, 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 cross-sectional 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, 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 21^st 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.

DISCLOSURE STATEMENT

Dr. Howell has indicated no financial conflicts of interest.