Dottorato in NEUROSCIENZE CLINICO-SPERIMENTALI E PSICHIATRIA

Titolo della tesi: BRADYKINESIA IN NON-PARKINSONIAN CONDITIONS: THE EMERGING CONCEPT OF A NETWORK DISORDER

Bradykinesia (movement slowness) is one of the cardinal motor symptoms of Parkinson’s disease and atypical parkinsonism and it has hystorically been interpreted as a motor disorder due to basal ganglia dysfunction. Clinical and experimental studies, however, indicate that it may be also observed in the context of various neurological conditions not primarily characterized by parkinsonism. These conditions include hyperkinetic movement disorders, such as dystonia and chorea, as well conditions primarily characterized by tremor (e.g. essential tremor) or other nervous diseases characterized by the involvement of brain areas and network including not only the basal ganglia but also the cerebellum and upper motoneurons. Also, movement slowness may be observed in patients with neurodegenerative or inflammatory diseases of the central nervous system of various origin, like dementia or multiple sclerosis. From a pathophysiological standpoint, the observation of movement slowness in neurological conditions not primarily characterized by parkinsonism is possibly explained by a brain network dysfunction, as hypothesized in parkinsonism. In the present thesis, we will first provide an updated overview on bradykinesia in non-parkinsonian conditions and discuss major findings of clinical reports and experimental studies. In the experimental part of the present thesis, we will provide the results from three original studies, which investigated the presence of bradykinesia and its possible pathophysiological mechanisms in (i) patients with essential tremor, (ii) patients with Alzheimer’s disease and (iii) patients with amyotrophic lateral sclerosis. Finally we will provide an unifying pathophysiological interpretation of bradykinesia in non-parkinsonian conditions from a network perspective and emphasize possible terminological implications.