Dottorato in NEUROSCIENZE CLINICO-SPERIMENTALI E PSICHIATRIA

Titolo della tesi: Neurophysiological and Kinematic analysis in Inherited Movement Disorders: toward a quantitative assessment of movements to improve phenotypical characterization in rare disorders.

Over the last years, next-generation sequencing analysis have significantly increased the knowledge of the movement disorders genetic landscape, revealing a great complexity in the genotype-phenotype correlations. Complexity in clinical-genetic correlations have consequences for diagnosis, treatment, and genetic counseling, and to deal with this issue, clinicians are asked to perform an accurate phenotypical characterization. Despite the advance of instrumental, biochemical, and genetic examination, the diagnosis of movement disorders still relies on clinical criteria and is based on the phenomenological evaluation (or the description and classification) of the motor phenotype. A critical issue in this process is that phenomenological evaluation is based on visual observation, and thus on the clinician’s judgement and experience. This approach has some limits, as clinical judgement is subjective and in different occasions clinicians have a low inter-rater agreement in the definition of the same motor phenotype. Furthermore, a simple visual observation is not sufficient to gather information about movement characteristics, that can be useful to monitor patients over time and that can provide insight into the underlying pathophysiological mechanisms of movement disorders. The aim of this thesis is to demonstrate as neurophysiological and kinematic analysis can provide objective and quantitative measurements, offering complementary information to the clinical examination, that can significantly improve the assessment of movement disorders. We examined through different neurophysiological and kinematic analysis the motor phenotype of individuals with Progressive Myoclonus Ataxia, Inherited Monoamine Neurotransmitter Disorders, and Neurodevelopmental disorders, obtaining information that were not appreciated on a clinical level. Clinical Neurophysiology and Kinematic analysis are valuable tools that can improve phenotypical characterization in individuals with movement disorders due to genetic causes, and this will ultimately improve their recognition, classification, and management.