Periodic leg movements during sleep and cerebral hemodynamic changes detected by NIRS Fabio Pizza a,b , Martin Biallas c , Martin Wolf c , Philipp O. Valko a , Claudio L. Bassetti a, * a Department of Neurology, University Hospital Zürich, Switzerland b Department of Neurological Sciences, University of Bologna, Italy c Clinic of Neonatology, University Hospital Zürich, Switzerland article info Article history: Accepted 13 May 2009 Available online 18 June 2009 Keywords: Periodic leg movements during sleep Near infra-red spectroscopy Arousal Cyclic alternating pattern Hemodynamics abstract Objective: Periodic leg movements during sleep (PLMS) have been shown to be associated with changes in autonomic and hemispheric activities. Near infrared spectroscopy (NIRS) assesses hemodynamic changes linked to hemispheric/cortical activity. We applied NIRS to test whether cerebral hemodynamic alterations accompany PLMS. Methods: Three PLMS patients underwent nocturnal polysomnography coupled with cerebral NIRS. EEG correlates of PLMS were scored and NIRS data were analysed for the identification of correspondent hemodynamic changes. Results: PLMS were constantly associated with cerebral hemodynamic fluctuations that showed greater amplitude when associated to changes in EEG and were present also in absence of any visually detectable arousal or A phase in the EEG. Conclusion: This is the first study documenting cerebral hemodynamic changes linked to PLMS. Significance: The clinical relevance of these observations remains to be determined. Ó 2009 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. 1. Introduction Periodic leg movements during sleep (PLMS) can be associated with primary sleep disturbances (e.g. restless legs syndrome, RLS) and are frequently accompanied by arousals. Recently, spec- tral EEG and autonomic correlates of the arousal response to PLMS have been disclosed: a cardiovascular activation (rise of heart rate and blood pressure) coupled with an increase in delta EEG activity followed by a transition to faster EEG bands activities (Sforza et al., 2002; Pennestri et al., 2007). Moreover, an increased cardiovascu- lar risk has been associated to RLS, potentially connecting the repetitive nocturnal changes in autonomic function to cardiovas- cular consequences (Winkelman et al., 2008). Near infra-red spectoscopy (NIRS) is a non-invasive technique based on the properties of NIR light (approximately 600–1000 nm), that is poorly absorbed by common biological substances (e.g. water) and penetrates several centimetres into the tissue. Given the absorption spectra of oxygenated and deoxy- genated haemoglobin within the optical NIR window (isosbestic point), these two substances can be quantified separately by using two or more different light wavelengths. Thus, NIRS detects tissue oxygen saturation, oxygenated, deoxygenated and total haemoglo- bin concentrations (StO 2 ,O 2 Hb, HHb and tHb), offering the unique opportunity to study cortical hemodynamics in different condi- tions (Wolf et al., 2007). Under the assumption of neurovascular coupling between neuronal activity, metabolism and blood flow, NIRS detects brain activation comparably to other neuroimaging techniques. Functional studies associating NIRS and BOLD f-MRI disclosed hemodynamic correlates of cortical activation: an in- crease in O 2 Hb mirrored by a decrease in HHb, due to increased cerebral blood flow (i.e. tHb in NIRS literature) leading to focal hyperoxygenation (Toronov et al., 2001). A single study evaluated hemodynamic correlates of cortical deactivation, showing an opposite pattern of increased HHb and decreased O 2 Hb, leading to focal hypooxygenation (Wenzel et al., 2000). Aim of the current report is to test whether cerebral hemody- namic modifications accompany PLMS investigating the cerebral microvascular counterpart of the arousal response by means of NIRS. 2. Patients and methods Three PLMS patients underwent videopolysomnography (VPSG), with C 3 ,C 4 ,O 1 and O 2 EEG montage, coupled with NIRS recording (ISS OxiplexTS Ò ). Patient 1 was a 46-year-old man with hypertrophic cardiomy- opathy and RLS symptoms. On VPSG a PLM index of 44/h with an 1388-2457/$36.00 Ó 2009 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. doi:10.1016/j.clinph.2009.05.009 * Corresponding author. Address: Department of Neurology, Universitätsspital Zürich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland. Tel.: +41 044 255 5503; fax: +41 044 255 4649. E-mail address: claudio.bassetti@usz.ch (C.L. Bassetti). Clinical Neurophysiology 120 (2009) 1329–1334 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph