Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson’s Disease: Interim Results from a Randomised Double-Blind Clinical Trial

2021 ◽  
pp. 1-15
Author(s):  
Julie Bourilhon ◽  
Claire Olivier ◽  
Hana You ◽  
Antoine Collomb-Clerc ◽  
David Grabli ◽  
...  

Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results: The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.

2021 ◽  
Vol 11 (4) ◽  
pp. 500
Author(s):  
Geetanjali Gera ◽  
Zain Guduru ◽  
Tritia Yamasaki ◽  
Julie A. Gurwell ◽  
Monica J. Chau ◽  
...  

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results.


2019 ◽  
Vol 9 (3) ◽  
pp. 51 ◽  
Author(s):  
Rens Verhagen ◽  
Lo Bour ◽  
Vincent Odekerken ◽  
Pepijn van den Munckhof ◽  
P. Schuurman ◽  
...  

Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson’s disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact location relative to the neurophysiological STN, estimated by the intraoperative microelectrode recordings (MER-based STN), and contralateral motor improvement after one year. A generic STN shape was transformed to fit onto the stereotactically defined MER sites. The location of 43 electrodes (26 patients), derived from MRI-fused CT images, was expressed relative to this patient-specific MER-based STN. Using regression analyses, the relation between contact location and motor improvement was studied. The regression model that predicts motor improvement based on levodopa effect alone was significantly improved by adding the one-year active contact coordinates (R2 change = 0.176, p = 0.014). In the combined prediction model (adjusted R2 = 0.389, p < 0.001), the largest contribution was made by the mediolateral location of the active contact (standardized beta = 0.490, p = 0.002). With the MER-based STN as a reference, we were able to find a significant relation between active contact location and motor improvement. MER-based STN modeling can be used to complement imaging-based STN models in the application of DBS.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Benzi M. Kluger ◽  
Veronica Parra ◽  
Charles Jacobson ◽  
Cynthia W. Garvan ◽  
Ramon L. Rodriguez ◽  
...  

Fatigue is a common and disabling nonmotor symptom seen in Parkinson’s disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson’s Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life.


2021 ◽  
pp. 1-13
Author(s):  
Mathilde Boussac ◽  
Christophe Arbus ◽  
Helene Klinger ◽  
Alexandre Eusebio ◽  
Elodie Hainque ◽  
...  

Background: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson’s disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients’ quality of life (QoL) amelioration after DBS-STN. We hypothesized that personality dimensions might affect QoL after DBS-STN. Objective: To evaluate associations between personality dimensions and QoL improvement one year after DBS-STN. Methods: DBS-STN-PD patients (n = 303) having answered the “Temperament and Character Inventory” (TCI) before surgery and the PDQ-39 before and one year after surgery were included, from the cohort study PREDI-STIM. Linear regression models were used to evaluate associations between TCI dimensions and change in PDQ-39 scores after DBS-STN. Results: Novelty Seeking and Cooperativeness scores before surgery were positively associated with PDQ-39 scores improvement after DBS-STN (FDR-adjusted p <  0.01). Moreover, paradoxically unimproved patients with deterioration of their PDQ-39 scores after DBS-STN despite improvement of their MDS-UPDRS-IV scores had lower Cooperativeness scores, while paradoxically improved patients with amelioration of their PDQ-39 scores despite deterioration of their MDS-UPDRS-IV scores had higher Reward Dependence scores. Conclusion: Some presurgical personality dimensions were significantly associated with QoL amelioration and discrepancy between motor state and QoL changes after DBS-STN in PD. Educational programs before DBS-STN should take in account patient personality dimensions to better deal with their expectations.


2018 ◽  
Vol 129 (11) ◽  
pp. 2482-2491 ◽  
Author(s):  
Pasquale Varriale ◽  
Antoine Collomb-Clerc ◽  
Angele Van Hamme ◽  
Anaik Perrochon ◽  
Gilles Kemoun ◽  
...  

2020 ◽  
Vol 75 ◽  
pp. 7-13 ◽  
Author(s):  
Takashi Tsuboi ◽  
Janine Lemos Melo Lobo Jofili Lopes ◽  
Bhavana Patel ◽  
Joseph Legacy ◽  
Kathryn Moore ◽  
...  

Neurology ◽  
1998 ◽  
Vol 51 (3) ◽  
pp. 850-855 ◽  
Author(s):  
R. Kumar ◽  
A. M. Lozano ◽  
Y. J. Kim ◽  
W. D. Hutchison ◽  
E. Sime ◽  
...  

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e049955
Author(s):  
Sara Marceglia ◽  
Costanza Conti ◽  
Oleg Svanidze ◽  
Guglielmo Foffani ◽  
Andres M Lozano ◽  
...  

IntroductionAfter several years of brain-sensing technology development and proof-of-concept studies, adaptive deep brain stimulation (aDBS) is ready to better treat Parkinson’s disease (PD) using aDBS-capable implantable pulse generators (IPGs). New aDBS devices are capable of continuous sensing of neuronal activity from the subthalamic nucleus (STN) and contemporaneous stimulation automatically adapted to match the patient’s clinical state estimated from the analysis of STN activity using proprietary algorithms. Specific studies are necessary to assess superiority of aDBS vs conventional DBS (cDBS) therapy. This protocol describes an original innovative multicentre international study aimed to assess safety and efficacy of aDBS vs cDBS using a new generation of DBS IPG in PD (AlphaDBS system by Newronika SpA, Milan, Italy).MethodsThe study involves six investigational sites (in Italy, Poland and The Netherlands). The primary objective will be to evaluate the safety and tolerability of the AlphaDBS System, when used in cDBS and aDBS mode. Secondary objective will be to evaluate the potential efficacy of aDBS. After eligibility screening, 15 patients with PD already implanted with DBS systems and in need of battery replacement will be randomised to enter a two-phase protocol, including a ‘short-term follow-up’ (2 days experimental sessions during hospitalisation, 1 day per each mode) and a ‘long-term follow-up’ (1 month at home, 15 days per each mode).Ethics and disseminationThe trial was approved as premarket study by the Italian, Polish, and Dutch Competent Authorities: Bioethics Committee at National Oncology Institute of Maria Skłodowska-Curie—National Research Institute in Warsaw; Comitato Etico Milano Area 2; Comitato Etico IRCCS Istituto Neurologico C. Besta; Comitato Etico interaziendale AOUC Città della Salute e della Scienza—AO Ordine Mauriziano di Torino—ASL Città di Torino; De Medisch Ethisch Toetsingscommissie van Maastricht UMC. The study started enrolling patients in January 2021.Trial registration numberNCT04681534.


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