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7. Dissociation of periodic leg movements from arousals in restless legs syndrome
Society Proceedings / Clinical Neurophysiology 123 (2012) e101–e114
tion: only subjects with high alpha-band FC in the stimulated area showed the expected neglect-like effect. Conversely, inhibitory cTBS applied to subjects whose right TPJ was already poorly connected before stimulation induced the inverse effect of more left-sided exploration (Fig. 2, bottom). Conclusion: Behavioural effects of cTBS are associated with changes in electrical network interactions at the stimulation frequencies. Effects are variable across subjects. An important proportion of this variability seems to depend on, and can be predicted by, network states before stimulation. Thus, FC analyses based on EEG might help optimize therapeutic cTBS in the future.
References Nyffeler T, Cazzoli D, Wurtz P, Lüthi M, von Wartburg R, Chaves S, et al. Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex. Eur J Neurosci 2008;27:1809–13.
e111
cebo. Sleep stages, Cyclic Alternating Pattern (CAP), and leg movement activity were scored according to standard criteria; symptoms of RLS were also assessed. Results: Pramipexole suppressed PLMS without affecting EEG instability (CAP) and arousals (corresponding to CAP A3 and, partially, A2 subtypes), while clonazepam did the opposite, reducing the NREM sleep EEG instability without any effects on PLMS (Fig. 1). Both drugs were effective in reducing sensory RLS symptoms. Conclusions: This study demonstrates that a selective pharmacological approach can disconnect PLMS from arousal events, suggesting an indirect relationship between each other. The results weaken the hypothesis of a direct pathological role of PLMS in sleep disruption and put into serious discussion the existence of the distinct entity called periodic limb movements disorder. Moreover, the study opens the doors to the possibility of a joint treatment for RLS, targeting sensory and motor symptoms, as well as sleep instability. doi:10.1016/j.clinph.2012.03.071
doi:10.1016/j.clinph.2012.03.070
7. Dissociation of periodic leg movements from arousals in restless legs syndrome—M. Manconi a, S. Fulda a, R. Ferri b, L. FeriniStrambi c, C.L. Bassetti a (a Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital (EOC) of Lugano, Lugano, Switzerland, b Sleep Research Centre, Department of Neurology I.C., Oasi Institute (IRCCS), Troina, Italy, c Sleep Disorders Center, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Institute and Ospedale San Raffaele, Milan, Italy) Introduction: Periodic leg movements during sleep are usually associated with cortical arousals, but the causal role of PLMS in sleep disruption is still debated. The purpose of this study was to characterize the nature of the relationship between periodic leg movements during sleep (PLMS) and cortical arousals in order to contribute to the debate of the clinical significance and treatment of PLMS. Methods: A prospective, placebo-controlled, single-blind, parallel group study was carried out including 46 drug naïve patients with idiopathic RLS. Each patient underwent two consecutive full-night polysomnographic studies. The first night was the baseline night. Prior to the second night, one group received a single oral dose of 0.25 mg pramipexole while a second group received a single oral dose of 0.5 mg clonazepam, and the remaining patients received pla-
8. Natalizumab de-escalation to interferon beta-1b in multiple sclerosis patients—C. Zecca a, D.S. Meier b, U. Candrian a, F. Cotton c,d, N. Nadarajah a, M. Sintzel e, C.R.G. Guttmann b, C. Gobbi a (a Neurocentre of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland, b Center for Neurological Imaging, Departments of Radiology and Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, c Université de Lyon, Université Lyon 1, Laboratoire d’Anatomie de Rockefeller, Lyon et Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service de Radiologie , Pierre Bénite Cedex, France, d Université de Lyon, Université Lyon 1, Villeurbanne Cedex, France, e Medical Communication Services (MCS), Küsnacht, Switzerland) Background: Natalizumab (NAT) discontinuation leads to multiple sclerosis reactivation. Objective: To explore the concept of natalizumab de-escalation to interferon beta-1b (IFNB-1b) compared to continued treatment with NAT. Methods: One year, randomized, rater-blinded, parallel-group, pilot study. RRMS patients on NAT for >12 months and clinically stable (free from relapses and disability progression for >6 months, without enhancing lesions [CEL] at baseline MRI) were randomized to NAT or IFNB-1b. Primary endpoint was time to first on-study relapse. Secondary endpoints were frequency of relapse free patients, number of relapses per patient, number of new/enlarging
Fig. 1. Examples extracted from PSG recordings after placebo, pramipexole or clonazepam.
tion: only subjects with high alpha-band FC in the stimulated area showed the expected neglect-like effect. Conversely, inhibitory cTBS applied to subjects whose right TPJ was already poorly connected before stimulation induced the inverse effect of more left-sided exploration (Fig. 2, bottom). Conclusion: Behavioural effects of cTBS are associated with changes in electrical network interactions at the stimulation frequencies. Effects are variable across subjects. An important proportion of this variability seems to depend on, and can be predicted by, network states before stimulation. Thus, FC analyses based on EEG might help optimize therapeutic cTBS in the future.
References Nyffeler T, Cazzoli D, Wurtz P, Lüthi M, von Wartburg R, Chaves S, et al. Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex. Eur J Neurosci 2008;27:1809–13.
e111
cebo. Sleep stages, Cyclic Alternating Pattern (CAP), and leg movement activity were scored according to standard criteria; symptoms of RLS were also assessed. Results: Pramipexole suppressed PLMS without affecting EEG instability (CAP) and arousals (corresponding to CAP A3 and, partially, A2 subtypes), while clonazepam did the opposite, reducing the NREM sleep EEG instability without any effects on PLMS (Fig. 1). Both drugs were effective in reducing sensory RLS symptoms. Conclusions: This study demonstrates that a selective pharmacological approach can disconnect PLMS from arousal events, suggesting an indirect relationship between each other. The results weaken the hypothesis of a direct pathological role of PLMS in sleep disruption and put into serious discussion the existence of the distinct entity called periodic limb movements disorder. Moreover, the study opens the doors to the possibility of a joint treatment for RLS, targeting sensory and motor symptoms, as well as sleep instability. doi:10.1016/j.clinph.2012.03.071
doi:10.1016/j.clinph.2012.03.070
7. Dissociation of periodic leg movements from arousals in restless legs syndrome—M. Manconi a, S. Fulda a, R. Ferri b, L. FeriniStrambi c, C.L. Bassetti a (a Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital (EOC) of Lugano, Lugano, Switzerland, b Sleep Research Centre, Department of Neurology I.C., Oasi Institute (IRCCS), Troina, Italy, c Sleep Disorders Center, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Institute and Ospedale San Raffaele, Milan, Italy) Introduction: Periodic leg movements during sleep are usually associated with cortical arousals, but the causal role of PLMS in sleep disruption is still debated. The purpose of this study was to characterize the nature of the relationship between periodic leg movements during sleep (PLMS) and cortical arousals in order to contribute to the debate of the clinical significance and treatment of PLMS. Methods: A prospective, placebo-controlled, single-blind, parallel group study was carried out including 46 drug naïve patients with idiopathic RLS. Each patient underwent two consecutive full-night polysomnographic studies. The first night was the baseline night. Prior to the second night, one group received a single oral dose of 0.25 mg pramipexole while a second group received a single oral dose of 0.5 mg clonazepam, and the remaining patients received pla-
8. Natalizumab de-escalation to interferon beta-1b in multiple sclerosis patients—C. Zecca a, D.S. Meier b, U. Candrian a, F. Cotton c,d, N. Nadarajah a, M. Sintzel e, C.R.G. Guttmann b, C. Gobbi a (a Neurocentre of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland, b Center for Neurological Imaging, Departments of Radiology and Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, c Université de Lyon, Université Lyon 1, Laboratoire d’Anatomie de Rockefeller, Lyon et Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service de Radiologie , Pierre Bénite Cedex, France, d Université de Lyon, Université Lyon 1, Villeurbanne Cedex, France, e Medical Communication Services (MCS), Küsnacht, Switzerland) Background: Natalizumab (NAT) discontinuation leads to multiple sclerosis reactivation. Objective: To explore the concept of natalizumab de-escalation to interferon beta-1b (IFNB-1b) compared to continued treatment with NAT. Methods: One year, randomized, rater-blinded, parallel-group, pilot study. RRMS patients on NAT for >12 months and clinically stable (free from relapses and disability progression for >6 months, without enhancing lesions [CEL] at baseline MRI) were randomized to NAT or IFNB-1b. Primary endpoint was time to first on-study relapse. Secondary endpoints were frequency of relapse free patients, number of relapses per patient, number of new/enlarging
Fig. 1. Examples extracted from PSG recordings after placebo, pramipexole or clonazepam.