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There are a number of genetic forms of dystonia with new discoveries being made constantly. The phenotypes of the genetic forms can be classified as those with mainly isolated dystonia and those with combined dystonia where tehre are additional features apart from dystonia. The phenotypes of isolated dystonia such as young onset dystonia related to the DYT-1 and DYT-6 (THAP-1) genes and the more recent ANO3 and GNAL which can cause early adult forms of craniocervical dystonia. In the combined forms genetic phenotypes of myoclonus dystonia (epsilon sarcoglycan gene and others), genetic forms of dystonia with parkinsonism and other combined dystonia's will be discussed including the childhood onset KMT2B causing dystonia with anarthria. An approach for the clinican to be aware of these genetic forms and follow a systematic approach to the diagnosis will be provided.

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Pathophyiology of dystonia

Alfredo Berardelli and Daniele Belvisi

Dystonia is now considered a heterogeneous condition, characterized by motor and non-motor features. Several studies have clearly demonstrated that the pathophysiology of motor symptoms in dystonia is characterized by a combination of mechanisms including loss of inhibition, maladaptative cortical plasticity and deficits in sensorimotor integration, at various levels of the central nervous system. Recent evidence, however, casts doubts on the disease-specificity of these abnormalities.

From an anatomical perspective, dystonia has been traditionally considered as a consequence of a cortico-basal ganglia-thalamo-cortical circuit dysfunction. Growing evidence suggests that also cerebellum may be involved in the pathophysiology of dystonia, either exerting a compensatory role or being involved in specific motor manifestations of dystonia, such as tremor. Dystonia has been recently modeled as a “network disorder” in which the clinical phenotype depends on an abnormal interaction among several neural pathways. In this complex scenario, idiopathic, inherited, and acquired forms of dystonia may have different pathophysiological mechanisms. In addition, different mechanisms and distinct neural structures seem to underlie the various forms of focal dystonia ( cranial, cervical and focal hand dystonia).

Patients with dystonia may also show non-motor symptoms, including cognitive, psychiatric, sleep and sensory disturbances. The pathophysiology of non-motor symptoms in patients with dystonia has been poorly investigated. The coexistence of motor and non-motor symptoms suggests that dystonia is characterized by the involvement of a wide and highly-interconnected network, that include several brain regions.

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ADVANCED TREATMENTS IN DYSTONIA

Marie VIDAILHET, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Salpetriere, Paris, France

Therapeutic strategy for dystonia can be approached in two ways: based on etiology and pathophysiology, which concerns a small number of diseases and syndromes among which some paroxysmal dystonias/abnormal movements (Glut 1 deficiency), rare genetic forms (ADCY5, L-Dopa sensitive dystonia) or diseases in which dystonia is one of the multiple clinical expressions (Wilson) or based on phenomenology and dystonia severity. In most cases, the treatment is mainly symptomatic and based on a single or combined approach with botulinum toxin-kinesitherapy/medications/deep brain stimulation. Although a long experience is being acquired with long term follow-up results. Therapeutic advances are being made as a result of new pathophysiological, imaging or physiological data, technological developments (DBS, FUS) or a better definition of the objectives and a more complete evaluation of the results, taking into account not only the motor signs but also the non-motor signs. Moreover, teams experience has expanded over the year, from pediatric forms to the long-term effects of parties who combine very long follow-up periods, with the consideration of age and long-term effects of treatments. These different elements will be discussed with clinical cases and take home messages.