- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07567599
Deep Brain Stimulation in Parkinson's Disease: Motor and Functional Outcomes
Effects of Deep Brain Stimulation Surgery on Motor and Functional Outcomes in Individuals With Parkinson's Disease: An Uncontrolled Clinical Trial
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Minas Gerais
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Belo Horizonte, Minas Gerais, Brasilien, 30110-017
- Clínica NeuroVida
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion Criteria:
- Individuals with PD who have been evaluated by a clinical neurologist specializing in movement disorders and have a medical indication for DBS surgical treatment. These individuals will undergo surgical screening, which includes prior neurological, speech-language pathology, neuropsychological, and physical therapy assessments.
Exclusion Criteria:
- Individuals who do not wish to undergo surgery; those with severe cardiovascular or orthopedic comorbidities that pose a risk during the surgical procedure; and those presenting with dementia or severe psychiatric disorders that could be exacerbated by the surgery.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Deep Brain Stimulation
Deep brain stimulation (DBS) surgery has consolidated itself in recent decades as an important therapeutic option for PD patients presenting with 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 for 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 demonstrate a prior satisfactory response to levodopa and an absence of dementia or severe psychiatric comorbidities (Artusi et al., 2020; Hariz et al., 2022).
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Deep Brain Stimulation (DBS) is a stereotactic surgical technique used for the control and management of motor complications arising from L-dopa treatment.
DBS consists of neural modulation through implanted electrodes connected to a neurostimulator (SHARMA et al., 2020).
The fundamental criterion for surgical indication is refractoriness to conservative treatment.
Of the four cardinal manifestations presented, three are suitable for surgical treatment: tremor, rigidity, and bradykinesia.
The levodopa challenge test allows for an approximate assessment of the improvement that can be achieved with surgery; the ideal candidate is one who is severely impaired in the 'off' state and presents motor complications related to levodopa treatment or refractory tremor (HAMANI et al., 2008; FONOFF, 2012).
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Gait Speed
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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Gait speed will be assessed using the 6-Meter Walk Test (6MWT).
The 6MWT is a simple, low-cost, and reliable test, performed on a flat surface without the use of sophisticated equipment, and it does not require specialized training on the part of the evaluator.
In individuals with Parkinson's disease (PD), this test has been used to assess gait speed (Canning et al., 2006).
During the test, the individual is instructed to walk at their usual speed for six meters along the walkway.
The total time taken to complete the test will be recorded (Lam et al., 2010; Lyons et al., 2015).
The literature indicates that there is no need to include acceleration and deceleration phases in the assessment of individuals with PD, nor to perform repeated measurements (Lindholm et al., 2018).
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Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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Balance
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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Balance will be assessed using the Mini-BESTest (Franchignoni et al., 2010), which includes sections 4 to 6 of the BESTest (anticipatory postural adjustment, postural responses, sensory orientation, and gait stability) (King et al., 2012).
It consists of 14 items, each scored from zero to two, with a maximum score of 28 and a minimum of zero, where a higher score indicates better balance.
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Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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Freezing of gait
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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For the assessment of freezing of gait (FOG), the Freezing of Gait Questionnaire (FOG-Q) (APPENDIX B) will be administered. Freezing typically occurs at gait initiation, during turning, when passing through narrow spaces, and/or immediately before reaching a destination (Baggio et al., 2012). Freezing of gait, which is a type of akinesia, is a phenomenon of unknown origin and is considered the most disabling motor symptom of Parkinson's disease (PD), as well as a significant predictor of falls (Kerr et al., 2010). The FOG-Q is a questionnaire designed to assess and quantify the degree of difficulty in walking directly related to freezing of gait. It consists of 6 items, each scored on a 5-point scale ranging from 0 (absence of symptoms) to 4 (most severe stage). The total score ranges from 0 to 24 points, with higher scores indicating greater severity. The questionnaire should be administered during the "on" medication phase. |
Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups
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Fear of falling
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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In 1990, Tinetti, Richman, and Powell developed the first scale to assess falls, called the Falls Efficacy Scale (FES). Based on this scale, the European falls prevention network developed a modified version, the Falls Efficacy Scale International (FES-I), which includes six additional items. The FES-I is a scale used to assess fear of falling and demonstrates excellent test-retest reliability (ICC = 0.96) and internal consistency (Cronbach's alpha = 0.96) (Camargos et al., 2010; Jonasson et al., 2017; Fasano et al., 2017). |
Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Muscle strength
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Muscle strength will be assessed using a Hand-Held Dynamometer test. The following muscle groups will be measured: trunk extensors, bilateral quadriceps, and bilateral plantar flexors. The hand-held dynamometer is essential for the functional assessment of individuals and is widely used in clinical practice for various purposes, including functional diagnosis to monitor improvement or deterioration over time, as well as a predictive or prognostic measure for the occurrence of falls and limitations in activities of daily living (Bohannon, 1986; Andrews et al., 1996). The device must always be stabilized by the same examiner at the appropriate location for applying resistance for each muscle group test. After stabilization, the individual will be verbally encouraged by the examiner, using a standardized verbal command, to perform a maximal isometric contraction for 5 seconds while the examiner resists the movement, keeping the segment static. A rest period of 15 seconds will be allowed. |
Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Functional capacity
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Functional capacity will be assessed using the Duke Activity Status Index (DASI) (APPENDIX B), a questionnaire originally developed in English (Hlatky et al., 1989) and translated into Portuguese (Coutinho-Myrrha et al., 2014), with the aim of evaluating metabolic cost capacity (METs) in individuals with cardiovascular diseases.
The final score ranges from 0 to 58.2 points, with higher scores indicating better functional capacity.
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Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Physical activity level
Tidsramme: Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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The level of physical activity will be assessed using the Human Activity Profile (HAP). It has previously been used (Goulart et al., 2004) as a measure of functional performance and physical activity level in individuals with Parkinson's disease (PD) in stages 1 to 3 of the Hoehn and Yahr (HY) scale. The results indicated that individuals in the early to moderate stages of PD tend to reduce their level of physical activity more rapidly than asymptomatic individuals of the same age. In addition, it was shown that low physical fitness is present in the early and moderate stages of the disease, and not only in the advanced stage (Goulart et al., 2004). |
Participants will be evaluated prior to Deep Brain Stimulation and at three- and six-month postoperative follow-ups.
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Samarbejdspartnere og efterforskere
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Synukleinopatier
- Neurologiske manifestationer
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Neurodegenerative sygdomme
- Bevægelsesforstyrrelser
- Parkinsonlidelser
- Basal Ganglia Sygdomme
- Dyskinesier
- Patologiske tilstande, tegn og symptomer
- Tegn og symptomer
- Parkinsons sygdom
- Hypokinesi
- Terapeutik
- Kirurgiske procedurer, operative
- Elektrisk stimuleringsterapi
- Dyb hjernestimulering
Andre undersøgelses-id-numre
- CAAE: 96607826.0.0000.5149
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Data will be available upon reasonable request to the corresponding author, beginning after publication of the primary results and ending five years thereafter. Requests will be evaluated based on scientific merit and must include a data use agreement to ensure participant confidentiality.
No personally identifiable information will be shared. Supporting documents such as the study protocol, statistical analysis plan, and informed consent form may also be made available upon request.
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