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DBS e rTMS como janelas causais para os mecanismos das discinésias na doença de Parkinson
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Resumo(s)
Parkinson's disease (PD) affects more than 6 million people worldwide and, despite therapeutic advances, remains incurable. Levodopa is the most effective drug for motor control, but its prolonged use often leads to levodopa-induced dyskinesias (LID), which affect up to 90% of patients after 10 years and significantly compromise quality of life. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective alternative in advanced stages, but it can also induce dyskinesias (SID), suggesting that the impact depends more on the modulated networks than on the anatomical position of the electrodes. At the same time, non-invasive neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), have shown promising effects in reducing dyskinesias, although with heterogeneous results. In this study, 10 patients with PD and dyskinesias who underwent STN-DBS under two conditions: parameters that contained dyskinesias and parameters that improved dyskinesias. Reconstructions of the activated tissue volume (VTA) did not reveal any relevant differences, prompting a connectivity analysis. It was observed that DBS associated with dyskinesias preferentially involved deep cerebellar nuclei, such as the dentate nucleus, suggesting hyperactivation of the dentate-thalamic-cortical circuit. In contrast, parameters that improved symptoms predominantly recruited the frontal corticopontine tract, the main cortical input pathway to the cerebellum, suggesting that GABAergic inhibitory modulation of Purkinje cells may reduce excessive activity in deep nuclei. Exploratory analyses of structural connectivity corroborated this dissociation and showed a relationship with cerebellar rTMS inhibitory protocols previously described as antidyskinetic. This hypothesis suggests that cerebellar networks play a causal role in the onset of dyskinesias and underscores the importance of circuit-guided therapeutic approaches, in which the combination of DBS and rTMS may open new opportunities for intervention, requiring validation in larger samples.
Descrição
Tese de mestrado, Engenharia Biomédica e Biofísica, 2025, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Deep Brain Stimulation Parkinson’s Disease Dyskinesia Normative Connectome Transcranial Magnetic Stimulation