Evolução clínica e desafios terapêuticos na doença de Parkinson em fase avançada: uma revisão sistemática.

Vollständiger Abstract

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Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder predominantly characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the resulting dysfunction of basal ganglia circuits. Although traditionally associated with motor manifestations such as bradykinesia, resting tremor, and rigidity, its progression involves a broad spectrum of non-motor symptoms, including cognitive, autonomic, psychiatric, gastrointestinal, and sleep disturbances. In the advanced stage, disease progression is marked by increased clinical complexity, characterized by the emergence of motor fluctuations, dyskinesias, wearing-off phenomena, unpredictable OFF periods, gait alterations, postural instability, recurrent falls, and a progressive loss of functional autonomy. At this stage, despite levodopa remaining the primary agent for controlling motor symptoms, its conventional administration may become insufficient. This study aimed to analyze, through a systematic literature review, the clinical evolution of advanced Parkinson's disease and the main challenges associated with its treatment, including pharmacological therapies, continuous infusions, and deep brain stimulation. The review was structured following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, encompassing studies related to clinical progression, motor and non-motor complications, advanced therapies, and quality of life. The analyzed evidence indicates that the management of advanced PD requires an individualized approach, as the benefits of different interventions depend on levodopa responsiveness, cognitive and psychiatric profiles, presence of comorbidities, functional status, surgical risk, and caregiver support. Therapies such as deep brain stimulation, continuous levodopa/carbidopa infusion, apomorphine, and foslevodopa/foscarbidopa demonstrate the ability to reduce OFF periods and increase ON time without troublesome dyskinesias in selected patients. However, no single strategy can halt neurodegenerative progression or fully control non-motor manifestations. In conclusion, the treatment of advanced Parkinson's disease must go beyond the isolated control of motor symptoms, prioritizing the preservation of autonomy, functionality, and quality of life through a multidisciplinary, patient-centered approach.