Idiopatic Isolated Focal Dystonia: from Impaired Inhibition to Modulation of Dystonic Activity During Sleep

Dystonia is a movement disorder causing abnormal movements and postures. Dystonia is the result of a network disorder, largely linked to abnormal inhibition affecting several levels of the central nervous system. The PhD thesis at issue explores different aspects of dystonia pathophysiology in prospective cohorts of patients with isolated idiopathic cervical dystonia. Indeed, the dissertation reports on the assessment of cerebellar functioning in patients affected with cervical dystonia, by applying the cerebellar classical conditioning paradigm. Results showed that cerebellar abnormalities segregated with the presence of tremor in patients with dystonia, accounting for a discrete role of cerebellum in generating dystonic tremor (Chapter 2). Along with the cerebellum, also the role of sensory system has been evaluated (Chapter 3), by means of an extensive paradigm aiming at testing markers of reduced inhibition within the somatosensory system and to assess their role in affecting temporal discrimination time in dystonia, which has been lately recognized as an endophenotypic trait of dystonia. The results showed impaired inhibition affecting several levels of the somatosensory system. However, only measurements of local (intracortical) inhibition correlated with abnormal temporal processing in dystonia. Finally, the thesis repots on the study of the pattern of muscles activity through all the night along with the objective evaluation of sleep quality by means of polysomnography in cervical dystonia (Chapter 4). The study showed the virtual disappearance of dystonia during sleep, leading to suppose that sleep might preserve a homeostatic role in these patients. However, architecture of sleep turned to be affected. Abnormal sleep structure did not correlated with motor descriptors and therefore seems to be a discrete feature of dystonia and to deserve a specific consideration. To improve the knowledge of pathogenic pathways in dystonia will hopefully lead to the discovery of new therapeutic targets in this condition.