Preoperative Levodopa Response Research Articles

Long-term motor outcomes of deep brain stimulation of the globus pallidus interna in Parkinson's disease patients: Five-year follow-up

BackgroundDeep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied. ObjectiveWe investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS. MethodsWe retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed. ResultsForty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04–1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39–17.89; p = 0.014, respectively). ConclusionsGPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients.

The effect of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation in Parkinson's disease patients.

Previous studies have reported the effects of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation (STN-DBS) of Parkinson's disease (PD) patients. However, available data involving these issues are not consistent. In particular, the effect of age and disease duration on the initial efficacy of STN-DBS has not been established. A total of 51 patients with PD treated with bilateral STN-DBS were involved in the present study. They received clinical symptom evaluation during the preoperative, initial, and chronic stages of surgery. The correlations between age when undergoing surgery/age at disease onset/disease duration and outcomes of STN-DBS were measured. The preoperative levodopa response was negatively associated with age. During the initial stage, the age when undergoing surgery and age at disease onset were negatively correlated with the effect on bradykinesia, with better symptom control of general symptoms in long-term disease patients. Similarly, patients with an early time of surgery and disease onset and long-term disease duration showed better control of bradykinesia and axial symptoms at the chronic stage. Furthermore, a long-term disease duration and early disease onset benefited from an increase of therapeutic efficacy in general, rigid, and axial symptoms with STN-DBS after a long period. Nevertheless, patients with late disease onset achieved a better relief of stigma. Age and disease durations played a unique role in controlling the symptoms of PD patients treated with STN-DBS. These results may contribute to patient selection and adjustments of expectations of surgery, based on the age, disease duration, and different symptoms.

Preoperative Levodopa Response and Deep Brain Stimulation Effects on Motor Outcomes in Parkinson's Disease: A Systematic Review.

The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson's disease (PD) is lacking. To address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS. We used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted. The STN-DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS-III at both 6- and 12-month follow-ups (P < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow-up times. For the sub-scores of UPDRS-III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor (P = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS-III total score at a median follow-up of 12 months (P = 0.030). The current study confirmed the value of preoperative levodopa responsiveness for prediction of the short-term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short-term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long-term motor outcomes were highlighted by this study.

Predictors of Long-Term Outcome of Subthalamic Stimulation in Parkinson Disease.

This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). All consecutive PD patients who underwent bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short-term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long-term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores compared to the baseline off-medication scores. As a secondary objective, potential predictors of short-term motor outcome after STN-DBS were assessed by performing univariate and multivariate linear regression analyses. In the long-term analyses (mean follow-up = 8.4 ± 6.26 years, median = 10 years, range = 1-17 years), 138 patients were included. Preoperative higher frontal score and off-medication MDS-UPDRS part III scores predicted a better long-term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1-year follow-up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off-medication MDS-UPDRS part III scores predicted the short-term motor outcome. Frontal lobe dysfunction, disease severity in the off-medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long-term motor STN-DBS effects. ANN NEUROL 2021;89:587-597.

Clinical and Kinematic Correlates of Favorable Gait Outcomes From Subthalamic Stimulation.

Objective: Gait and freezing of gait (FoG) are highly relevant to the outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Previous studies pointed to variable response to combined dopaminergic and STN-DBS treatment. Here, we performed a prospective exploratory study on associations of preoperative clinical and kinematic gait measures with quantitative gait and FoG outcomes after STN-DBS implantation.Methods: We characterized 18 consecutive PD patients (13 freezers) before and after STN-DBS implantation. The patients received preoperative levodopa challenges (MedOff vs. MedOn) and a postoperative reassessment at 6 months from surgery in MedOn/StimOn condition. We correlated the FoG outcome, calculated as improvement of Freezing of Gait Assessment Course (FoG-AC) from baseline MedOff to 6-month follow-up MedOn/StimOn, with the levodopa response of preoperative clinical and kinematic gait measures. We considered measures with significant correlations for a multiple regression model.Results: We found that the postoperative gait and FoG outcomes were associated with the preoperative levodopa response of clinical and kinematic gait measures. In particular, preoperative levodopa sensitivity of FoG showed high correlation with a favorable quantitative FoG outcome. Among kinematic measures, preoperative levodopa response of stride length and range of motion showed high correlation with favorable FoG outcome. In addition, the preoperative levodopa sensitivity of FoG predicted postoperative FoG outcome with high accuracy (R2 = 0.952; 95% CI: 0.95–1.29; P < 0.001).Conclusions: Preoperative clinical and kinematic measures correlated with favorable postoperative gait and FoG outcomes. The findings should be reproduced in larger and independent cohorts to verify their predictive value.

Effects of Deep Brain Stimulation of the Subthalamic Nucleus on the Postoperative Levodopa Response: One Year Follow Up.

To investigate the effect of preoperative levodopa responsiveness to clinical outcomes in the first postoperative year, and to evaluate the changes in the postoperative levodopa responsiveness in patients undergoing subthalamic nucleus (STN) deep brain stimulation (DBS). Forty-nine Parkinson?s Disease (PD) patients undergoing bilateral DBS of the STN were included in this study. Their clinical motor symptoms were assessed preoperatively by UPDRS Part III score in both OFF and ON medication states. Postoperatively, the assessments were obtained in three consecutive conditions. Preoperatively and postoperatively, the percentage difference between these two scores was evaluated as levodopa response. Mean age was 54.6 ± 9 years (27?70). Levodopa response significantly decreased postoperatively by 56% a year. Compared with preoperative med on and postoperative stim on / med on scores, the clinical results of the first year were obtained and an improvement of 25% on the UPDRS 3 score was observed. Compared with preoperative levodopa response and clinical outcomes, better clinical results were obtained in patients with higher preoperative levodopa response (p < 0.05). In this study, we confirm that the response of L-dopa decreases after DBS of the STN. The reasons for this finding are not clear. However, DBS of the STN allows for the reduction of PD medications and improvement of daily life activities, motor function, motor fluctuations, and dyskinesia.

Effect of Age and Disease Duration on the Levodopa Response in Patients with Advanced Parkinson's Disease for Deep Brain Stimulation of the Subthalamic Nucleus.

Deep brain stimulation (DBS) has become a preferred option for the treatment of motor symptoms in patients with advanced Parkinson's disease (PD). A good levodopa response (LR) is considered the most important criterion in determining the suitability of a patient for DBS. However, the effect of age and disease duration (DD) on the LR is still a subject of discussion. Here, we investigated the effect of age and DD on the preoperative LR in PD patients to be selected for DBS. From August 2011 to May 2015, 54 consecutive patients (29 men and 25 women) with advanced PD were evaluated for DBS of the STN and included in this retrospective study. Thirty-seven patients were found suitable for DBS of the STN and 29 of them underwent bilateral surgery. We found no significant correlation between DD and the LR. However, there was a significant negative correlation between the patients' age and the LR. The results indicate that the patients' age, rather than DD, has a negative effect on the LR. The study, therefore, indicates that PD patients with an advanced age and with a poor LR are not good candidates for DBS of the STN.

Factors Related to Outcomes of Subthalamic Deep Brain Stimulation in Parkinson's Disease

ObjectiveSubthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment of choice for patients with advanced idiopathic Parkinson's disease (PD) who have motor complication with medication. The objectives of this study are to analyze long-term follow-up data of STN DBS cases and to identify the factors related to outcomes.MethodsFifty-two PD patients who underwent STN DBS were followed-up for more than 3 years. The Unified Parkinsons Disease Rating Scale (UPDRS) and other clinical profiles were assessed preoperatively and during follow-up. A linear regression model was used to analyze whether factors predict the results of STN DBS. We divided the study individuals into subgroups according to several factors and compared subgroups.ResultsPreoperative activity of daily living (ADL) and the magnitude of preoperative levodopa response were shown to predict the improvement in UPDRS part II without medication, and preoperative ADL and levodopa equivalent dose (LED) were shown to predict the improvement in UPDRS part II with medication. In UPDRS part III with medication, the magnitude of preoperative levodopa response was a predicting factor.ConclusionThe intensity of preoperative levodopa response was a strong factor for motor outcome. And preoperative ADL and LED were strong factors for ADL improvement. More vigorous studies should be conducted to elucidate how levodopa-induced motor complications are ameliorated after STN DBS.

Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants

Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinson's disease. Prospective studies have shown that although the beneficial effects of this procedure are maintained at 5 years, axial motor features and cognitive decline may occur in the long term after the implants. In order to address some unsolved questions raised by previous studies, we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years. The overall motor improvement reported at 5 years (55.5% at Unified Parkinson's Disease Rating Scale-motor part, P < 0.001 compared with baseline) was only partly retained 3 years later (39%, P < 0.001, compared with baseline; -16.5%, P < 0.01, compared with 5 years), with differential effects on motor features: speech did not improve and postural stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle worsening of motor features, a dramatic impairment in functional state (-56.6% at Unified Parkinson's Disease Rating Scale-Activities of Daily Living, P < 0.01) emerged after the fifth year of stimulation. The present study did not reveal a predictive value of preoperative levodopa response, whereas few single features at baseline (such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose) could predict long-term motor outcome. A decline in verbal fluency (slightly more pronounced than after 5 years) was detected after 8 years. A significant but slight decline in tasks of abstract reasoning, episodic memory and executive function was also found. One patient had developed dementia at 5 years with further progression at 8 years. Executive dysfunction correlated significantly with postural stability, suggesting interplay between axial motor deterioration and cognition. Eight years after surgery, no significant change was observed on scales assessing depression or anxiety when compared with baseline. At 8 years, there was no significant increase of side-effects when compared with 5-year follow-up. In conclusion, deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up. However, the global benefit partly decreases later in the course of the disease, due to progression of Parkinson's disease and the appearance of medication- and stimulation-resistant symptoms.

Prognostic Factors of Subthalamic Stimulation in Parkinson’s Disease: A Comparative Study between Short- and Long-Term Effects

Background/Aims: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have long-term benefits in Parkinson’s disease (PD). Through analyzing different variables, this study identified prognostic factors for the short- and long-term effects of STN-DBS. Methods: Thirty-six PD patients underwent bilateral STN-DBS. Clinical evaluations were performed 1 month before and 3 months after surgery, with additional follow-up examinations for a mean of 31.3 months. Results: There was a trend for long-term STN-DBS-induced improvements in the Unified Parkinson’s Disease Rating Scale (UPDRS) part II and part III measures to be greater in younger patients. Preoperative levodopa responsiveness only led to consistent UPDRS part III improvement from STN-DBS at 3 months, and this predictive value did not exist in the long term. The preoperative levodopa response of tremor and axial symptoms in motor disability predicted long-term DBS effect only. Preoperative cognitive function positively correlated with postoperative improvement from DBS in UPDRS part III during long-term follow-up only. Conclusions: The prognostic factors for STN-DBS benefit were different for short- and long-term follow-ups. Good prognostic factors for long-term STN-DBS for PD patients were good cognitive function and tremor dominance. Poor prognostic factors were related to older age and non-dopaminergic-responsive axial disability.

Levodopa response in long‐term bilateral subthalamic stimulation for Parkinson's disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is effective in advanced Parkinson's disease (PD), but its effects on the levodopa response are unclear. We studied the levodopa response after long-term STN-DBS, STN-DBS efficacy and predictive value of preoperative levodopa response to long-term DBS benefit in 33 PD patients with bilateral STN-DBS. Patients were assessed using the Unified Parkinson's Disease Rating Scale preoperatively (with and without medications) and postoperatively (without medications or stimulation, with only medications or stimulation, and with both medications and stimulation). Levodopa response significantly decreased postoperatively by 31.1% at 3 years and 32.3% at 5 years, possibly related to the reduction in medication requirement, direct STN stimulation effect or PD progression. STN-DBS alone significantly improved motor scores (37.2% at 3 years and 35.1% at 5 years) and activities of daily living scores (27.1% at 3 years and 19.2% at 5 years). Anti-PD drugs were significantly reduced by 47.9% at 3 years and 39.8% at 5 years. However, the magnitude of the preoperative response to levodopa did not predict DBS benefit at 3 and 5 years.