pii: sp- 00701-15
http://dx.doi.org/10.5665/sleep.5662
LETTERS TO THE EDITOR
Is Restless Legs Syndrome Involved in Ambulation Related to Sleepwalking? Régis Lopez, MD1,2; Yves Dauvilliers, MD, PhD1,2 1 National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sleep Disorders Center, Department of Neurology, Gui-deChauliac Hospital, CHU Montpellier, France; 2Inserm, U1061, Montpellier, France
had a primary disorder of arousal that was infrequently associated with another significant sleep disorder. On the other hand, triggering factors that increased both the frequency and severity of the parasomnia episodes were found in 60% of patients. They were mainly related to stressful events and sleep deprivation, and less frequently to drug or alcohol intake or intense evening physical activity, in agreement with previous studies.10 The median age at onset was 8 years old (range 2–42), with adult onset only in 28 patients. Moreover, 33.6% of patients reported only sleepwalking episodes, 4.7% sleep terrors or confusional arousal only, and 61.7% mixed episodes. At the time of the study, 39 patients (21.3%) had daily episodes and 129 (70.5%) at least one episode per week. Severe episodes with violent parasomnias were reported by 55.7% of patients and a positive family history by 59.7%. Insomnia symptoms (Insomnia Severity Index > 14) were found in 48.8% of patients and excessive daytime sleepiness (Epworth Sleepiness Scale > 10) in 42.8%. Twenty-six subjects had an apnea-hypopnea index (AHI) above 5/h, including five (2.9%) with AHI > 15/h, but none > 30/h. Twenty-four patients (12.4%) had RLS, but only eight reported symptoms more than twice a week (4.1%). RLS severity was moderate (median severity score = 16/40; range: 9–30) in all patients, but four. The age of RLS onset was clearly identified in 18 patients and it was after the disorder of arousal onset for all. Two patients with both sleepwalking and severe RLS were treated with pramipexole. This led to a significant RLS improvement without any change in parasomnia severity. Eleven patients with parasomnia and RLS had a PLMS index above 5/h and higher than 15/h in five of them. Demographic (age and gender) and clinical characteristics (age at onset, positive family history, sleepiness and insomnia symptoms, frequency and severity of episodes, phenotype with ambulation or not) were not significantly different between sleepwalking patients with RLS (n = 24) and without RLS (n = 169). To conclude, the RLS frequency (4.1% of patients with symptoms more than twice per week) in our large clinical cohort of well-characterized adults with disorders of arousal was not different from what previously reported in the general population.4 We found no association between RLS symptoms and sleepwalking or other parasomnia characteristics. In our experience, excessive motor restlessness driven by RLS appears infrequent in sleepwalking and cannot explain why sleepwalkers walk during pain-free episodes of parasomnia. Therefore, it is unlikely that motor restlessness, as proposed by Howell, contributes to the complex genetically-driven pathophysiology of dissociated brain activity in disorders of arousal.11
We have read with great interest the commentary “Darwin’s Predisposition and the Restlessness that Drives Sleepwalking” by Howell published in SLEEP in November 2015.1 In this editorial, the author proposed that motor restlessness, a symptom of restless leg syndrome (RLS), might explain why some individuals with a disorder of arousal get out of bed and ambulate (sleepwalking), while others stay in bed (sleep terror, or confusional arousals). Sleepwalking is a disorder characterized by arousal specifically from slow-wave sleep with dissociated brain activity, resulting in behavioral manifestations, with no conscious awareness of such actions.2 We recently reported in a crosssectional, case-controlled study that sleepwalking patients frequently complain about chronic pain, migraine and headache during wakefulness, while experiencing analgesia during severe parasomnia episodes.3 The absence of normal pain perception during parasomnia is in disagreement with Howell’s hypothesis that pain per se could predispose patients with disorder of arousal to walk at night (“motor restlessness”). RLS, also known as Willis-Ekbom disease, is a frequent chronic and disabling sleep disorder characterized by uncomfortable sensations in the legs that worsen during periods of rest, and are partially or totally relieved by movement. Symptoms occur primarily or worsen at night and are not better explained by an underlying medical or a behavioral condition.4,5 Approximately 80% of patients with RLS exhibit periodic leg movements during sleep (PLMS). Such repetitive leg movements are often associated with excessive sleep fragmentation.4,5 Based on observational studies and transcranial magnetic stimulation findings, Howell suggests that sleepwalking physiopathology shares a common underlying mechanism with typical or atypical RLS.1 Little is known about the association between RLS, PLMS and disorders of arousal. Nevertheless, RLS frequency was not different between sleepwalking patients and controls in a small-size study.6 During sleepwalking episodes, patients often talk and perform normal-looking movements that potentially require high-level planning and motor control, such as getting dressed, cooking, driving, and that not involve exclusively the legs. Moreover, somnambulism is more common in childhood than in adulthood and progressively decreases with ages, differently from RLS.4,7,8 Five studies assessed PLMS frequency in adult sleepwalkers and controls, but only one reported an increased index.9 To test the restlessness predisposition hypothesis, we analyzed the characteristics of the disorders of arousal, RLS frequency and its potential association with the phenotype in our clinic-based adult population with a disorder of arousal (n = 193 patients; 49.7% males, median age 30 years old [range 17–62]). All patients underwent video-polysomnography recording when free of psychotropic medications to confirm the diagnosis and to rule out alternative diagnoses. Most patients SLEEP, Vol. 39, No. 4, 2016
CITATION Lopez R, Dauvilliers Y. Is restless legs syndrome involved in ambulation related to sleepwalking? SLEEP 2016;39(4):955–956. 955
Letter to the Editor—Lopez and Dauvilliers
REFERENCES
9. Labelle MA, Dang-Vu TT, Petit D, Desautels A, Montplaisir J, Zadra A. Sleep deprivation impairs inhibitory control during wakefulness in adult sleepwalkers. J Sleep Res 2015;24:658–65. 10. Lopez R, Jaussent I, Scholz S, Bayard S, Montplaisir J, Dauvilliers Y. Functional impairment in adult sleepwalkers: a case-control study. Sleep 2013;36:345–51. 11. Antelmi E, Ferri R, Iranzo A, et al. From state dissociation to status dissociatus. Sleep Med Rev 2016;28:1–13.
1. Howell M. Darwin’s predisposition and the restlessness that drives sleepwalking. Sleep 2015;38:1667–8. 2. Zadra A, Desautels A, Petit D, Montplaisir J. Somnambulism: clinical aspects and pathophysiological hypotheses. Lancet Neurol 2013;12:285–94. 3. Lopez R, Jaussent I, Dauvilliers Y. Pain in sleepwalking: a clinical enigma. Sleep 2015;38:1693–8. 4. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;165:1286–92. 5. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. International Restless Legs Syndrome Study Group. Restless legs syndrome/WillisEkbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 2014;15:860–73. 6. Brion A, Flamand M, Oudiette D, Voillery D, Golmard J-L, Arnulf I. Sleep-related eating disorder versus sleepwalking: a controlled study. Sleep Med 2012;13:1094–101. 7. Hublin C, Kaprio J, Partinen M, Heikkila K, Koskenvuo M. Prevalence and Genetics of Sleepwalking A Population-based Twin Study. Neurology 1997;48:177–81. 8. Petit D, Pennestri M-H, Paquet J, et al. Childhood sleepwalking and sleep terrors: a longitudinal study of prevalence and familial aggregation. JAMA Pediatr 2015;169:653–8.
SLEEP, Vol. 39, No. 4, 2016
SUBMISSION & CORRESPONDENCE INFORMATION Submitted for publication December, 2015 Accepted for publication December, 2015 Address correspondence to: Yves A Dauvilliers, MD, PhD, Sleep Unit, Department of Neurology, Gui de Chauliac Hospital, Inserm U1061, 80 av Augustin Fliche, Montpellier, 34295 France; Tel: (33) 4-6733-6361; Fax: (33) 4-6733-7285; Email Address [email protected]
DISCLOSURE STATEMENT Dr. Dauvilliers has received funds for speaking, board engagements and travel to conferences by UCB pharma, Jazz, and Bioprojet. Dr. Lopez has indicated no financial conflicts of interest.
956
Letter to the Editor—Lopez and Dauvilliers
http://dx.doi.org/10.5665/sleep.5662
LETTERS TO THE EDITOR
Is Restless Legs Syndrome Involved in Ambulation Related to Sleepwalking? Régis Lopez, MD1,2; Yves Dauvilliers, MD, PhD1,2 1 National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sleep Disorders Center, Department of Neurology, Gui-deChauliac Hospital, CHU Montpellier, France; 2Inserm, U1061, Montpellier, France
had a primary disorder of arousal that was infrequently associated with another significant sleep disorder. On the other hand, triggering factors that increased both the frequency and severity of the parasomnia episodes were found in 60% of patients. They were mainly related to stressful events and sleep deprivation, and less frequently to drug or alcohol intake or intense evening physical activity, in agreement with previous studies.10 The median age at onset was 8 years old (range 2–42), with adult onset only in 28 patients. Moreover, 33.6% of patients reported only sleepwalking episodes, 4.7% sleep terrors or confusional arousal only, and 61.7% mixed episodes. At the time of the study, 39 patients (21.3%) had daily episodes and 129 (70.5%) at least one episode per week. Severe episodes with violent parasomnias were reported by 55.7% of patients and a positive family history by 59.7%. Insomnia symptoms (Insomnia Severity Index > 14) were found in 48.8% of patients and excessive daytime sleepiness (Epworth Sleepiness Scale > 10) in 42.8%. Twenty-six subjects had an apnea-hypopnea index (AHI) above 5/h, including five (2.9%) with AHI > 15/h, but none > 30/h. Twenty-four patients (12.4%) had RLS, but only eight reported symptoms more than twice a week (4.1%). RLS severity was moderate (median severity score = 16/40; range: 9–30) in all patients, but four. The age of RLS onset was clearly identified in 18 patients and it was after the disorder of arousal onset for all. Two patients with both sleepwalking and severe RLS were treated with pramipexole. This led to a significant RLS improvement without any change in parasomnia severity. Eleven patients with parasomnia and RLS had a PLMS index above 5/h and higher than 15/h in five of them. Demographic (age and gender) and clinical characteristics (age at onset, positive family history, sleepiness and insomnia symptoms, frequency and severity of episodes, phenotype with ambulation or not) were not significantly different between sleepwalking patients with RLS (n = 24) and without RLS (n = 169). To conclude, the RLS frequency (4.1% of patients with symptoms more than twice per week) in our large clinical cohort of well-characterized adults with disorders of arousal was not different from what previously reported in the general population.4 We found no association between RLS symptoms and sleepwalking or other parasomnia characteristics. In our experience, excessive motor restlessness driven by RLS appears infrequent in sleepwalking and cannot explain why sleepwalkers walk during pain-free episodes of parasomnia. Therefore, it is unlikely that motor restlessness, as proposed by Howell, contributes to the complex genetically-driven pathophysiology of dissociated brain activity in disorders of arousal.11
We have read with great interest the commentary “Darwin’s Predisposition and the Restlessness that Drives Sleepwalking” by Howell published in SLEEP in November 2015.1 In this editorial, the author proposed that motor restlessness, a symptom of restless leg syndrome (RLS), might explain why some individuals with a disorder of arousal get out of bed and ambulate (sleepwalking), while others stay in bed (sleep terror, or confusional arousals). Sleepwalking is a disorder characterized by arousal specifically from slow-wave sleep with dissociated brain activity, resulting in behavioral manifestations, with no conscious awareness of such actions.2 We recently reported in a crosssectional, case-controlled study that sleepwalking patients frequently complain about chronic pain, migraine and headache during wakefulness, while experiencing analgesia during severe parasomnia episodes.3 The absence of normal pain perception during parasomnia is in disagreement with Howell’s hypothesis that pain per se could predispose patients with disorder of arousal to walk at night (“motor restlessness”). RLS, also known as Willis-Ekbom disease, is a frequent chronic and disabling sleep disorder characterized by uncomfortable sensations in the legs that worsen during periods of rest, and are partially or totally relieved by movement. Symptoms occur primarily or worsen at night and are not better explained by an underlying medical or a behavioral condition.4,5 Approximately 80% of patients with RLS exhibit periodic leg movements during sleep (PLMS). Such repetitive leg movements are often associated with excessive sleep fragmentation.4,5 Based on observational studies and transcranial magnetic stimulation findings, Howell suggests that sleepwalking physiopathology shares a common underlying mechanism with typical or atypical RLS.1 Little is known about the association between RLS, PLMS and disorders of arousal. Nevertheless, RLS frequency was not different between sleepwalking patients and controls in a small-size study.6 During sleepwalking episodes, patients often talk and perform normal-looking movements that potentially require high-level planning and motor control, such as getting dressed, cooking, driving, and that not involve exclusively the legs. Moreover, somnambulism is more common in childhood than in adulthood and progressively decreases with ages, differently from RLS.4,7,8 Five studies assessed PLMS frequency in adult sleepwalkers and controls, but only one reported an increased index.9 To test the restlessness predisposition hypothesis, we analyzed the characteristics of the disorders of arousal, RLS frequency and its potential association with the phenotype in our clinic-based adult population with a disorder of arousal (n = 193 patients; 49.7% males, median age 30 years old [range 17–62]). All patients underwent video-polysomnography recording when free of psychotropic medications to confirm the diagnosis and to rule out alternative diagnoses. Most patients SLEEP, Vol. 39, No. 4, 2016
CITATION Lopez R, Dauvilliers Y. Is restless legs syndrome involved in ambulation related to sleepwalking? SLEEP 2016;39(4):955–956. 955
Letter to the Editor—Lopez and Dauvilliers
REFERENCES
9. Labelle MA, Dang-Vu TT, Petit D, Desautels A, Montplaisir J, Zadra A. Sleep deprivation impairs inhibitory control during wakefulness in adult sleepwalkers. J Sleep Res 2015;24:658–65. 10. Lopez R, Jaussent I, Scholz S, Bayard S, Montplaisir J, Dauvilliers Y. Functional impairment in adult sleepwalkers: a case-control study. Sleep 2013;36:345–51. 11. Antelmi E, Ferri R, Iranzo A, et al. From state dissociation to status dissociatus. Sleep Med Rev 2016;28:1–13.
1. Howell M. Darwin’s predisposition and the restlessness that drives sleepwalking. Sleep 2015;38:1667–8. 2. Zadra A, Desautels A, Petit D, Montplaisir J. Somnambulism: clinical aspects and pathophysiological hypotheses. Lancet Neurol 2013;12:285–94. 3. Lopez R, Jaussent I, Dauvilliers Y. Pain in sleepwalking: a clinical enigma. Sleep 2015;38:1693–8. 4. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;165:1286–92. 5. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. International Restless Legs Syndrome Study Group. Restless legs syndrome/WillisEkbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 2014;15:860–73. 6. Brion A, Flamand M, Oudiette D, Voillery D, Golmard J-L, Arnulf I. Sleep-related eating disorder versus sleepwalking: a controlled study. Sleep Med 2012;13:1094–101. 7. Hublin C, Kaprio J, Partinen M, Heikkila K, Koskenvuo M. Prevalence and Genetics of Sleepwalking A Population-based Twin Study. Neurology 1997;48:177–81. 8. Petit D, Pennestri M-H, Paquet J, et al. Childhood sleepwalking and sleep terrors: a longitudinal study of prevalence and familial aggregation. JAMA Pediatr 2015;169:653–8.
SLEEP, Vol. 39, No. 4, 2016
SUBMISSION & CORRESPONDENCE INFORMATION Submitted for publication December, 2015 Accepted for publication December, 2015 Address correspondence to: Yves A Dauvilliers, MD, PhD, Sleep Unit, Department of Neurology, Gui de Chauliac Hospital, Inserm U1061, 80 av Augustin Fliche, Montpellier, 34295 France; Tel: (33) 4-6733-6361; Fax: (33) 4-6733-7285; Email Address [email protected]
DISCLOSURE STATEMENT Dr. Dauvilliers has received funds for speaking, board engagements and travel to conferences by UCB pharma, Jazz, and Bioprojet. Dr. Lopez has indicated no financial conflicts of interest.
956
Letter to the Editor—Lopez and Dauvilliers
