Effects of Deep Brain Stimulation Surgery on Motor and Functional Outcomes in Individuals With Parkinson's Disease: An Uncontrolled Clinical Trial

Parkinson's Disease (PD) is a progressive neurodegenerative pathology characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the abnormal accumulation of alpha-synuclein, forming Lewy bodies. It was initially described by James Parkinson in 1817 as "shaking palsy," being recognized as the second most prevalent neurodegenerative disease in the world, with a higher incidence in the elderly population. According to the Global Burden of Disease Study 2016 (GBD 2016), the global prevalence of PD more than doubled in recent decades; approximately 6.1 million people worldwide have PD, and by 2040, it is estimated to reach 12.9 million. This increase is primarily associated with population aging, increased life expectancy, and the potential influence of environmental factors.

Symptoms generally begin after age 50 and affect 1% of the population over 65 and 4% to 5% of the population over 85 . Cases starting before age 40 are considered early-onset PD, and before age 21, juvenile PD. In Brazil, the disclosure of data on individuals with PD is not mandatory, making it complex to pinpoint the exact number of individuals with the disease. In a population-based study conducted in Brazil in 2006, the prevalence of idiopathic PD was 3.3%. PD threatens quality of life and is associated with significant economic costs for both the individual and society.

The etiology of PD is not yet fully understood and is considered multifactorial. Current evidence points to a complex interaction between genetic predisposition, exposure to environmental factors, and biological processes related to aging, including mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein degradation. Neuropathological evidence indicates that changes may begin years or even decades before classic motor manifestations, with early involvement of the enteric nervous system (Meissner and Auerbach myenteric plexuses), the olfactory bulb, and nuclei of the lower brainstem. As the disease progresses, involvement of the locus coeruleus, substantia nigra, basal forebrain, and limbic system structures is observed. In more advanced neuropathological stages, there is cortical dissemination of alpha-synuclein-related pathology, with the presence of Lewy bodies in associative areas, contributing to non-motor manifestations and cognitive impairment.

The cardinal motor manifestations of PD include bradykinesia, rigidity, and resting tremor. According to the Movement Disorder Society (MDS) diagnostic criteria, the presence of bradykinesia associated with at least one of the following signs-rigidity or resting tremor-is required for the clinical diagnosis of parkinsonian syndrome. In addition to motor symptoms, PD presents a broad spectrum of non-motor manifestations, often present in the prodromal phases and, in many cases, preceding motor symptoms by years. Notable among these are hyposmia, constipation, depressive disorders, and Rapid Eye Movement (REM) sleep behavior disorder, characterized by the loss of physiological atonia during this sleep phase. These manifestations reflect the early involvement of extra-striatal structures and reinforce the concept of PD as a multisystem disease.

The diagnosis of PD remains clinical, based on a detailed anamnesis and neurological examination according to MDS criteria, which require parkinsonism defined by the presence of bradykinesia associated with resting tremor or rigidity, in addition to the exclusion of alternative causes and the presence of supportive criteria. Examinations such as MRI and CT scans primarily serve to exclude differential diagnoses, while others like DAT-SPECT and PET with dopaminergic radiotracers have been increasingly studied for their diagnostic and disease stratification value. Basal ganglia dopaminergic function can be measured by radiotracers such as Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) and may assist in diagnosis.