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Periodic Limb Movements are NOT Associated With Disturbed Sleep
Mark W. Mahowald, M.D.
Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center, and Department of Neurology, University of Minnesota Medical
School, Minneapolis, MN
ecause our field wants periodic limb movements of sleep
(PLMs) to be a “sleep disorder,” the controversy over the
clinical importance (or lack thereof) of PLMs continues to smolder on – hanging around like a bad smell. It is intuitive: blame
PLMs for insomnia in patients with both, blame PLMs for excessive daytime sleepiness (EDS) in patients with both, or dismiss PLMs as a variant of normal in asymptomatic patients. The
clinical problem has been given a label, and we can go on to the
next case. Convenient – we have just had it all 3 ways. This approach is handy and comforting as long as we don’t let ourselves
be bothered by the pesky fact that despite extensive and exhaustive attempts, our field has failed to provide one shred of scientific
evidence that PLMs have any predictable clinical consequence.
Periodic limb movements of sleep (PLMs) are rhythmical extensions of the great toe and dorsiflexion of the ankle, knee, and
hip (and probably represent spontaneously occurring Babinski
signs or triple spinal flexion reflexes - normal phenomena during
the lighter stages of NREM sleep due to enhanced spinal cord
excitability) lasting 2-4 seconds with a frequency of one every
20-40 seconds.1 PLMs were first recorded by Lugaresi.2 Scoring
criteria were defined by Coleman in 1982,3 and later modified
by the American Sleep Disorders Association 4 and codified in
the International Classification of Sleep Disorders.5 Simply by
defining the polysomnographic (PSG) features of PLMs, a sleep
“disorder” was created.
There is a great deal of confusion between PLMs and the restless legs syndrome (RLS). Up to 90% of patients with the clinical
symptom of RLS will display the PSG observation of PLMs.6 The
converse is not true – the overwhelming majority of patients with
PLMs on PSG do not have RLS symptoms. Even in patients with
RLS who display PLMs, the severity of RLS symptoms do not
correlate with PLMs frequency.7
Arbitrarily, and without documented clinical correlation, a
PLMs index >5/hr is said to be “abnormal”. Using the arbitrarily
determined definition of “abnormality” of a PLMs index >5/hr,
30%-86% of adults aged 60 years or older are “abnormal.” Then
there are the sticky issues of the striking night-to-night variability,
and the arbitrary amplitude and sequence criteria.8-10 How many
nights of monitoring are necessary, and what are the amplitude
and frequency criteria?
It has been said that PLMs with “arousal” are clinically significant. The common misperception that the leg movements
cause arousal is erroneous; a recent study indicated that 49% of
the EEG arousals occurred before the leg movement, 31% simultaneous with, and in only 23% did the leg movement precede the
EEG arousal.11
Our field has yet to determine what constitutes an arousal, or
what arousal index may result in clinical symptoms. The American Academy of Sleep Medicine arousal criteria have never been
validated as to clinical significance.12 It may be that arousals measured by respiratory paradox or autonomic measures (increases
in blood pressure or heart rate) without EEG evidence of arousal
(by any definition) may be significant.13-20 It is likely that either/
or/or both the EEG arousals and or PLMs are the manifestations
of a common periodic central nervous system generator. PLMs
are likely a manifestation of the cyclic alternating pattern, a microstructural sleep pattern of normal arousal instability during
NREM sleep.21,22 It very well may be that the periodic arousals associated with PLMs are primary, with the PLMs being a secondary and variable accompaniment.23 Figure 1 demonstrates severe
PLMs with EEG evidence of arousal in an asymptomatic patient.
Editorial reviews of this topic have argued that no consistent
or predictable subjective or objective consequences of PLMs – in
terms of either insomnia or hypersomnia – have ever been demonstrated.24-26 Subsequent studies have buttressed that viewpoint.27-30
Based upon the fact that PLMs are not more prevalent in insomnia or hypersomnia than in controls, Montplaisir has concluded:
“...the validity of PLM disorder as a distinct nosological entity is
highly questionable and in our experience, a diagnosis of PLM
disorder has no specific utility”.31
In one recent large study 61 patients with a mean PLM arousal
index of 41.8/hr (many with PLM arousal index of >50/hr) had no
more wake/sleep complaints than the control group of 60 patients
with no PLMs. Interestingly, it was concluded that clinical data
were not predictive of PLMs, and that formal polysomnographic
evaluation was “necessary to establish the diagnosis of PLMD
in patients with insomnia or hypersomnia” – despite the fact that
those with very frequent PLMs had absolutely no clinical com-
Disclosure Statement
Dr. Mahowald has received research support from Sanofi-Aventis, Advanced
Medical Electronics Corporation, Merck, Kyowa Pharmaceuticals, Inc., and
Schwartz Biosonics.
Address correspondence to: Mark W. Mahowald, MD, Minnesota Regional
Sleep Disorders Center, Hennepin County Medical Center, 701 Park Ave.,
Minneapolis, MN 55415, Tel: (612) 872-6288; Fax: (612) 904-4207; E-mail:
[email protected]
Journal of Clinical Sleep Medicine, Vol. 3, No. 1, 2007
MW Mahowald
Figure 1—This 5-minute epoch contains 18 PLMs. The overall PLM index was 91/hr (548 PLMs over 364 minutes of total sleep time) in this
asymptomatic patient. Note numerous EEG arousals associated with PLMs. (LOC – left outer canthus, ROC – right outer canthus, A1/A2 – left/
right mastoid, C3/C4 – left/right central EEG, O1/O2 – left/right occipital EEG, chin – submental EMG, Leg/L/Leg/R – left/right anterior tibialis
plaints.32 In another study, arousals associated with PLMs were
associated with lower sleep efficiency, higher percentage of stages 1 and 2 NREM sleep, and lower percentages of stages 3 and 4
NREM and REM sleep. Although these PSG observations were
not associated with any identifiable subjective daytime symptoms, it was concluded that PLMs associated with arousal were
“markers of disturbed sleep.”33 (Disturbed sleep to the patient or
to PSG interpreter?) Oh, we want it to be so badly.
In support of the concept that PLMs are of no clinical significance is the fact that there have been no valid studies documenting that treating isolated PLMs per se improves either nighttime
sleep or daytime functioning in any condition. As a corollary, in
patients with narcolepsy, the reduction of PLMs by bromocriptine
does not improve the nocturnal sleep disruption in that disorder.34
The PLMs controversy continues to smolder because our field
wants PLMs to be significant, not because PLMs are significant.
It is an intuitive and clinically convenient diagnosis unsupported
by any scientific evidence. Most clinically significant medical
phenomena eventually declare themselves during 20 years of intensive study. (It did not take 20 years and hundreds of studies to
determine that penicillin was good for Gonorrhea.) Clinical significance of PLMs has been exhaustively sought – to no avail. It
may be time to stop looking. Despite innumerable attempts, the
clinical relevance of PLMs remains elusive. Once a diagnosis of
PLMs has been made, clinical thinking ceases, and patients may
be exposed to gratuitous medication. This is particularly true in
the pediatric population. It is likely that the only consequence of
PLMs is to the bedpartner(s).
Journal of Clinical Sleep Medicine, Vol. 3, No. 1, 2007
Bara-Jimeniz W, Aksu M, Graham B, et al. Periodic limb movements in sleep. State-dependent excitability of the spinal flexor reflex. Neurology 2000;54:1609-15.
2. Lugaresi E, Coccagna G, Tassinari CA, et al. Rilievi poligrafici
sui fenomeni motori nella sindrome delle gambe senza riposo. Riv
Neurol 1965;35:550-61.
3. Coleman RM. Periodic movements in sleep (nocturnal myoclonus)
and restless legs syndrome. In: Guillemiault C, ed. Sleeping and
waking disorders: indications and techniques. Palo Alto, CA: Addison-Wesley; 1982. p. 265-95.
4. American Sleep Disorders Association. Recording and scoring leg
movements. Sleep 1993;16:748-59.
5. American Academy of Sleep Medicine. International classification
of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005.
6. Gamaldo CE, Earley CJ. Restless legs syndrome. A clinical update.
Chest. 2006;130:1596-604.
7. Bastuji H, Garcia-Larrea L. Sleep/wake abnormalities in patients
with periodic leg movements during sleep: factor analysis on data
from 24-h ambulatory polygraphy. Sleep Res 1999;8:217-23.
8. Gschliesser V, Brandauer E, Ulmer H, et al. Periodic limb movment
counting in polysomnography: effects of amplitude. Sleep Med.
9. Hornyak M, Kopasz M, Feige B, et al. Variability of periodic movements in various sleep disorders: implications for clinical and
pathophysiologic studies. Sleep 2005;28:331-5.
10. Allen RP. Is one night enough for measurement of periodic limb
movements in sleep or restless legs patients? Sleep 2005;28:296-7.
11. Karadeniz D, Ondze B, Besset A, et al. EEG arousals and awakenings in relation with periodic leg movements during sleep. J Sleep
PLMs are NOT Associated With Disturbed Sleep
Res 2000;9:273-7.
12. American Sleep Disorders Association Atlas Task Force. EEG
arousals: scoring rules and examples. Sleep 1992;15:173-84.
13. Martin SE, Wraith PK, Deary IJ, et al. The effect of nonvisible sleep
fragmentation on daytime function. Am J Respir Crit Care Med
14. Mendelson WB. Sleep fragmentation and daytime wakefulness. Am
J Respir Crit Care Med 1997;155(1499-1500).
15. O’Donnell CP, Ayuse T, King ED, et al. Airway obstruction during sleep increases blood pressure without arousal. J Appl Physiol
16. Eaton EJ, Hume KI, Stone PA, et al. Respiratory paradox as an indicator of arousal from non-REM sleep. Sleep. 1999;22:1059-65.
17. Lofaso F, Goldenberg F, d’Ortho MP, et al. Arterial blood pressure
response to transient arousals from NREM sleep in nonapneic snorers with sleep fragmentation. Chest 1998;113:985-91.
18. Pitson DJ, Stradling JR. Autonomic markers of arousal during sleep
in patients undergoing investigation for obstructive sleep apnoea,
their relationship to EEG arousals, respiratory events and sleepiness. J Sleep Res 1998;7:53-9.
19. Sforza E, Jouny C, Ibanez V. Cardiac activation during arousal in
humans: further evidence for hierarchy in the arousal response. Clin
Neurophysiol 2000;111:1611-19.
20. Togo F, Cherniack NS, Natelson BH. Electroencephalogram characteristics of autonomic arousals in normal men. Clin Neurophysiol
21. Parrino L, Boselli M, Buccino GP, et al. The cyclic alternating pattern plays a gate-control on periodic limb movements during nonrapid eye movement sleep. J Clin Neurophysiol 1996;13:314-23.
22. Droste DW, Krauss JK, Hagedorn G, et al. Periodic leg movements
are part of the B-wave rhythm and the cyclic alternating pattern.
Acta Neurol Scand 1996;94:347-52.
23. Haba-Rubio J, Staner L, Macher JP. Periodic arousals or periodic
limb movements during sleep? Sleep Med 2002;3:517-20.
24. Mahowald MW. Assessment of periodic leg movements is not an
essential component of an overnight sleep study. Am J Respir CritiCare Med 2001;164:1340-2 (editorial).
25. Mahowald MW. Hope for the PLMs quagmire? Sleep Med
26. Mahowald MW. Does size or frequency really matter? Sleep Med
2006;7:205-7 (editorial).
27. Carrier J, Frenette S, Montplaisir J, et al. Effects of periodic leg
movements during sleep in middle-aged subjects without sleep
complaints. Mov Disord 2005;20:1127-32.
28. Morrish E, King MA, Pilsworth SN, et al. Periodic limb movement
in a community population detected by a new actigraphy technique.
Sleep Med 2002;3:489-95.
29. Sforza E, Haba-Rubio J. Night-to-night variability in periodic leg
movements in patients with restless legs syndrome. Sleep Med
30. Hornyak M, Riemann D, Voderholzer U. Do periodic leg movements influence patients’ perception of sleep quality? Sleep Med
31. Montplaisir J, Michaud M, Denesle R, et al. Periodic leg movements
are not more prevalent in insomnia or hypersomnia but are specifically associated with sleep disorders involving a dopaminergic impairment. Sleep Med 2000;1:163-7.
32. Hilbert J, Mohsenin V. Can periodic limb movement disorder be
diagnosed without polysomnography? A case-control study. Sleep
Med 2003;4:35-41.
33. Claman DM, Redline S, Blackwell T, et al. Prevalence and correlates of periodic limb movements in older women. J Clin Sleep Med
34. Boivin DB, Lorraine D, Montplaisir J. Effects of bromocriptine
on periodic limb movements in human narcolepsy. Neurology
Journal of Clinical Sleep Medicine, Vol. 3, No. 1, 2007