Main goals

Sleep related movement disorders. Restless legs syndrome (RLS) and periodic limb movements (PLM).

Group members and their position

Stephany Fulda, Psy, PhD, clinical researcher
Silvia Miano, MD. Neurologist, clinical researcher
Pietro Luca Ratti, MD. Neurologist, clinical researcher
Chiara Prosperetti, MD. Neurologist, clinical researcher
Agnese Salvadè, PhD, animal researcher

Previous and current research

The pathogenesis and the treatment of RLS and PLM represent the core of our research. We deeply characterized the time structure of PLM during sleep by elaborating an automatic computer-assisted program. We demonstrated that PLM are suppressed by dopamine-agonists. We understood that D3 subtype receptors locate within the spinal cord represent the target of dopamine agonists in RLS/PLM. We analyzed the relationship between PLM, cortical EEG arousals and autonomic activation, understanding that the three oscillating systems are highly synchronized during NREM sleep but are not directly causally related each other. By studying PLM in subjects with spinal lesions we de-monstrated that the pace-maker of PLM is located within the spinal cord and is regulated by supra-spinal dopaminergic centers. We demonstrated that pregnancy is a strong transient risk factor for RLS/PLM and that iron supplementation can improve symptoms.

Future projects

To establish if PLM represents a risk factor for cardiovascular diseases. To better characterize and model the infra-slow oscillations of brain, autonomic, and motor activity during sleep. To create an animal rodent model of RLS/PLM to verify the pathogenetical role of a spinal cord disinhibition. To understand the role of iron and hypoxia in triggering RLS and PLM.

Techniques / methods

Automatic computed detection, analysis and simulation of EMG, EEG and autonomic signal during sleep in human and animal.

Equipment

Human research: Video-polysomnographic recording system. High-density (256 channels) recording system.
Animal research: Video-polysomnographic recording system. Open field paradigm. Molecular biology.

Selected publications

1. Manconi M, et al. Dissociation of periodic leg movements from arousals in restless legs syndrome. Ann Neurol. 2012 Jun;71(6):834-44.
2. Manconi M, et al. Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome. Neurology. 2011 Jul 12;77(2):110-7.
3. Cesnik E, et al. Transient RLS during pregnancy is a risk factor for the chronic idiopathic form. Neurology. 2010 Dec 7;75(23):2117-20.
4. Manconi M, et al. Restless legs syndrome and pregnancy. Neurology. 2004 Sep 28;63(6):1065-9.
5. Manconi M, et al. Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med. 2011 Jan;12(1):47-55.

Selected lectures, seminars, colloquia

Lecturer “Restless legs syndrome and pregnancy”, American Academy of Sleep Medicine.
Instructor “Psychobiology of Sleep”, course for Psychologists, Vita-Salute University of Milan, Italy.
Instructor “Neruology” course of Master School in Medicine, University of Bern, Switzerland.
Visiting Professor at the Wisconsin Medical College, Milwaukee, USA.

Funding

Swiss National Foundation.
UCB-Pharma.