scholarly journals Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson’s disease

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Rubens Gisbert Cury ◽  
Nicola Pavese ◽  
Tipu Z. Aziz ◽  
Joachim K. Krauss ◽  
Elena Moro ◽  
...  

AbstractGait issues in Parkinson’s disease (PD) are common and can be highly disabling. Although levodopa and deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus internus have been established therapies for addressing the motor symptoms of PD, their effects on gait are less predictable and not well sustained with disease progression. Given the high prevalence of gait impairment in PD and the limitations in currently approved therapies, there has been considerable interest in alternative neuromodulation targets and techniques. These have included DBS of pedunculopontine nucleus and substantia nigra pars reticulata, spinal cord stimulation, non-invasive modulation of cortical regions and, more recently, vagus nerve stimulation. However, successes and failures have also emerged with these approaches. Current gaps and controversies are related to patient selection, optimal electrode placement within the target, placebo effects and the optimal programming parameters. Additionally, recent advances in pathophysiology of oscillation dynamics have driven new models of closed-loop DBS systems that may or may not be applicable to gait issues. Our aim is to describe approaches, especially neuromodulation procedures, and emerging challenges to address PD gait issues beyond subthalamic nucleus and the globus pallidus internus stimulation.

2017 ◽  
Vol 45 (5) ◽  
pp. 1602-1612 ◽  
Author(s):  
Hao Xu ◽  
Feng Zheng ◽  
Boris Krischek ◽  
Wanhai Ding ◽  
Chi Xiong ◽  
...  

Objective Deep brain stimulation (DBS) for treatment of advanced Parkinson’s disease (PD) has two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). The clinical effectiveness of these two stimulation targets was compared in the present study. Methods A systematic review and meta-analysis was performed to evaluated the postoperative changes in the United Parkinson’s Disease Rating Scale (UPDRS) on- and off-phase, on-stimulation motor scores; activities of daily living score (ADLS); and levodopa equivalent dose (LED) after STN and GPI stimulation. Randomized and nonrandomized controlled trials of PD treated by STN and GPI stimulation were considered for inclusion. Results Eight published reports of eligible studies involving 599 patients met the inclusion criteria. No significant differences were observed between the STN and GPI groups in the on-medication, on-stimulation UPDRS motor score [mean difference, 2.15; 95% confidence interval (CI), −0.96–5.27] or ADLS (mean difference, 3.40; 95% CI, 0.95–7.76). Significant differences in favor of STN stimulation were noted in the off-medication, on-stimulation UPDRS motor score (mean difference, 1.67; 95% CI, 0.98–2.37) and LED (mean difference, 130.24; 95% CI, 28.82–231.65). Conclusion The STN may be the preferred target for DBS in consideration of medication reduction, economic efficiency, and motor function improvement in the off phase. However, treatment decisions should be made according to the individual patient’s symptoms and expectations.


Author(s):  
Paolo Mazzone ◽  
Peter Brown ◽  
Vincenzo DiLazzaro ◽  
Paolo Stanzione ◽  
Antonio Oliviero ◽  
...  

Neurosurgery ◽  
2008 ◽  
Vol 62 (2) ◽  
pp. 311-325 ◽  
Author(s):  
Jorge Guridi ◽  
Jose A. Obeso ◽  
Maria C. Rodriguez-Oroz ◽  
Andres M. Lozano ◽  
Miguel Manrique

Abstract OBJECTIVE To assess the impact of different surgical targets and techniques, such as ablation and deep brain stimulation, to treat patients with L-dopa-induced dyskinesia (LID), a major therapeutic complication of Parkinson's disease. METHODS This review analyzes the effects of early surgical procedures to treat hyperkinesia and the current methods and targets used to combat LID in Parkinson's disease, which are mainly thalamotomy, pallidotomy, and deep brain stimulation of the globus pallidus internus and the subthalamic nucleus. RESULTS Available information indicates that surgery of the globus pallidus internus and thalamus (the pallidal receiving area) and of the subthalamic nucleus has a pronounced antidyskinetic effect. This effect is associated with a concomitant improvement in the parkinsonian (“off”-medication) state. Although it is more profound with pallidal and subthalamic surgery, such an effect can also be observed to some extent with thalamic surgery. The latter is attributable to the fact that surgery of the ventralis intermedius is primarily effective for treating tremor. An integral pallidothalamic pathway is needed for dyskinesia to be expressed. Thus, LID is less frequent after subthalamotomy or deep brain stimulation of the subthalamic nucleus through a functional effect mediated by the physiological normalization of the motor system and by an indirect effect associated with a reduction in the daily dose of L-dopa. CONCLUSION Surgery is the only treatment available for Parkinson's disease that can predictably improve both the parkinsonian motor syndrome and LID. The exact mechanisms involved in these effects are not well understood. Pallidal and thalamic surgery affecting pallidal relays reduce LID frequency by disrupting the pallidothalamic circuit, probably eliminating the neuronal activity associated with dyskinesia. Alternatively, the antidyskinetic effect of subthalamic nucleus surgery may in part be attributable to a reduction in the L-dopa dose as well as to the stabilization of the basal ganglia circuits after the surgical procedure.


2001 ◽  
Vol 22 (1) ◽  
pp. 87-88 ◽  
Author(s):  
A. E. Scotto di Luzio ◽  
F. Ammannati ◽  
P. Marini ◽  
S. Sorbi ◽  
P. Mennonna

2013 ◽  
Vol 250 ◽  
pp. 221-227 ◽  
Author(s):  
Bogdan Neagu ◽  
Eric Tsang ◽  
Filomena Mazzella ◽  
Clement Hamani ◽  
Elena Moro ◽  
...  

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