Deep Brain Stimulation in Parkinson's Disease: Motor and Functional Outcomes

Overview

Introduction: Parkinson's Disease (PD) is a progressive neurodegenerative condition characterized by classic motor symptoms, such as bradykinesia, rigidity, resting tremor, and postural instability, which directly compromise the mobility and autonomy of individuals with PD. Furthermore, non-motor manifestations, including autonomic, cognitive, and emotional changes, impact the quality of life of individuals with PD. Deep Brain Stimulation (DBS) surgery is a well-established treatment to assist in improving the primary motor symptoms of PD; however, literature is scarce in describing specific results regarding physiotherapeutic aspects, such as the motor symptoms that determine better quality of life and social participation for individuals with PD. Determining whether factors amenable to improvement prior to surgery-such as bradykinesia, muscle strength, and balance-are related to better motor and functional outcomes in individuals with PD post-DBS is of great importance to ensure a better result from the surgical intervention. Objective: To compare motor outcomes (gait speed, balance, freezing of gait, fear of falling, muscle strength, functional capacity, and physical activity level) of individuals with PD after undergoing DBS, relative to the motor status previously observed in the preoperative period. Methods: This is an uncontrolled clinical trial, with data collection conducted at the Neurovida private multidisciplinary clinic and the Hospital Santa Casa in Belo Horizonte. This study will be registered at www.clinicalTrials.gov and conducted according to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. The present study will be submitted to the Research Ethics Committee of the Federal University of Minas Gerais (COEP) and will only commence after proper approval. All necessary consents for the development of the study have been obtained. The sample consists of individuals with idiopathic PD selected by a clinical neurologist specializing in movement disorders. The inclusion criteria for the present study are: having idiopathic PD diagnosed for more than five years, being under treatment with a neurologist specializing in movement disorders, and having an indication for DBS. Descriptive statistics and normality tests will be performed for all study variables. Selected variables will be compared in terms of mean difference between post- and pre-surgery measurements, considering a 95% CI. In all analyses, a significance level of α=0.05 will be considered, using the SPSS statistical package version 15.0 for Windows.

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. There is still no curative treatment for PD; its treatment is symptomatic, individualized, and multidisciplinary, based on pharmacological, neurosurgical, and physiotherapeutic approaches. Striatal dopaminergic deficiency constitutes the neurochemical basis of PD, justifying the use of levodopa as the main symptomatic therapy since the 1960s. Currently, levodopa remains the gold standard treatment for motor symptoms, especially bradykinesia and rigidity . Although it provides a significant clinical response in the early stages, prolonged use may be associated with motor fluctuations and dyskinesias. Axial symptoms tend to be less responsive, particularly in advanced stages of the disease. Drug treatment is paramount, but despite providing symptom relief, it does not reduce the functional disabilities that affect the quality of life of patients with PD. Rehabilitation complements the therapeutic improvement that is not achieved with medication. Although PD has effective symptomatic therapies, pharmacological treatment does not halt disease progression or completely prevent long-term functional decline. With clinical evolution and chronic levodopa use, most patients develop motor complications, especially fluctuations in therapeutic response and medication-induced dyskinesias. Deep Brain Stimulation (DBS) surgery has consolidated itself in recent decades as an important therapeutic option for PD patients who present motor complications refractory to optimized pharmacological treatment. The procedure consists of the stereotactic implantation of electrodes into specific targets, such as the subthalamic nucleus (STN)-the most commonly used-or the internal globus pallidus (GPi), allowing continuous, adjustable, and reversible electrical stimulation. The primary indication for DBS includes patients with motor fluctuations and levodopa-induced dyskinesias, or refractory tremor, provided they have a prior satisfactory response to levodopa and an absence of dementia or severe psychiatric comorbidities. Proper candidate selection is fundamental, as only about 20% to 30% of individuals with PD meet ideal criteria for the procedure. Furthermore, the timing of the intervention in the course of the disease directly influences functional results, and a careful multidisciplinary evaluation is recommended to maximize benefits and reduce risks. The main indication for a surgical approach in PD is the lack of a satisfactory response to conservative treatment. Among the cardinal manifestations of the disease, three show the best potential for response to surgical intervention: tremor, rigidity, and bradykinesia. Performing the L-dopa challenge test is fundamental to estimating the possible postoperative benefit. Generally, an ideal candidate is a patient who presents significant motor impairment in the "off" state (without medication), with a score greater than 30 points on Part III of the Unified Parkinson's Disease Rating Scale (UPDRS), but who demonstrates a good response in the "on" state (with medication), with a score below 30 points on the same scale. Additionally, motor complications associated with prolonged L-dopa use or medication-refractory tremor must be present). Schuepbach et al. demonstrated that patients who underwent earlier surgical intervention-that is, before comorbidities generated by the pathology-showed significant improvement in quality of life, motor performance, and maintenance of activities of daily living, in addition to a greater reduction in L-dopa-induced motor complications and increased "on" time with good mobility and without dyskinesias, when compared to those maintained on drug treatment alone. The motor and non-motor manifestations of PD result in disabilities where medical care alone is insufficient, requiring the work of multiple professionals, including physical therapy, whose role is to maximize functional capacity and minimize secondary complications within a context of education and support for the individual with PD. The physical therapist's assessment and follow-up must systematically integrate the screening and monitoring protocol for PD patients who are candidates for surgical intervention, as it allows for a detailed characterization of the functional profile before the procedure and the establishment of objective parameters for postoperative comparison. Based on the physical therapy approach to individual functionality, an analysis of gait, balance, transfers, global mobility, manual dexterity, posture, and functional capacity is performed. Thus, the physical therapist contributes to identifying limitations, risks, and rehabilitation potential, assisting in the proper selection of candidates and aligning expectations regarding motor outcomes. Furthermore, this assessment provides a basis for individualized physical therapy planning after surgery, favoring a more targeted, safe rehabilitation based on clear functional goals. Currently, pre-surgical screening is predominantly based on the Levodopa challenge test and the Unified Parkinson's Disease Rating Scale (UPDRS)-a fundamental instrument for measuring motor impairment, but one that does not deeply address specific functional aspects, such as performance in activities of daily living, mobility in real-world environments, dynamic balance, and social participation. Given that the primary expectation of patients is the improvement of functionality and independence, it is essential to expand the assessment beyond the UPDRS, incorporating more specific functional measures to guide both candidate selection and individualized post-surgical rehabilitation planning. The objective of the present study is to compare motor outcomes (gait speed, balance, freezing of gait, fear of falling, muscle strength, functional capacity, and physical activity level) in individuals with Parkinson's Disease after undergoing Deep Brain Stimulation, in relation to the motor status previously observed during the preoperative period. The expected effects of DBS surgery are solidly documented in the literature through pre- and postoperative clinical tests, such as the UPDRS with the L-dopa challenge test, which adequately predicts surgical response (Welter et al., 2002). However, motor symptoms-specifically axial symptoms, including gait, posture, and balance-are infrequently assessed, even though it is recognized that better motor and functional outcomes are among the primary expectations of patients in the postoperative period. Individuals are undergoing surgical intervention increasingly earlier to achieve a longer duration of quality of life, which reveals more favorable outcomes than in individuals operated on later in the disease course (Schuepbach et al., 2013). Such outcomes, however, focus on quality of life aspects, UPDRS scores, and reduction in medication dosage. They also include cognitive and neuropsychiatric assessment scales but fail to present specific results regarding physiotherapeutic aspects, such as the motor symptoms that determine improved quality of life and social participation for individuals with PD.