Pedunculopontine Nucleus Stimulation Improves Gait Freezing in Parkinson Disease

Thevathasan, Wesley; Coyne, Terry; Hyam, Jonathan A.; Kerr, Graham; Jenkinson, Ned; Aziz, Tipu Z.; Silburn, Peter A.

doi:10.1227/neu.0b013e31822b6f71

Cited by 151 publications

(133 citation statements)

References 23 publications

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“…Vim receives strong inputs from the cerebellum, and the effectiveness of tremor control with DBS at this location is a strong argument in favor of cerebellar involvement in the pathophysiology of tremor. PPN DBS [226][227][228][229][230][231][232][233][234][235][236][237][238][239], alone or in combination with STN or GPi DBS, is currently under study for patients with advanced PD who develop levodopaunresponsive freezing of gait, balance impairments, and falls. DBS of the PPN has been shown to be most effective at low stimulation frequencies [240].…”

Section: Use Of Dbs In Pdmentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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Section: Use Of Dbs In Pdmentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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“…However, it should be noted in this context that although high-frequency stimulation is most commonly applied, at some targets, low frequencies may be beneficial for treating movement disorders. Indeed, DBS at the pedunculopontine nucleus (PPN; a brainstem nuclei intimately connected with the basal ganglia and cerebellum) may alleviate parkinsonian symptoms of postural instability or freezing of gait, with therapeutic outcomes occurring at low frequencies (e.g., 35 Hz) (Follett and Torres-Russotto, 2012;Thevathasan et al, 2011). A small number of imaging studies have examined regional neural modulation by lowfrequency PPN-DBS (Ceravolo et al, 2011;Schweder et al, 2010;Stefani et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

Albaugh

Shih²

2013

Brain Connectivity

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Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field.

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“…In a recent study of 5 patients, who had severe freezing of gait, postural instability and frequent falls that persisted despite being on dopaminergic medications, bilateral PPN stimulation was performed. These patients were administered a specific Gait and Falls Questionnaire, which improved significantly at 24 months; however, the gait and posture scores on the UPDRS III scale revealed no improvements [95]. The authors of this study suggested that the gait and posture items on the UPDRS III scale are likely insensitive to treatment effects and may not be appropriate for outcome assessment with PPN stimulation.…”

Section: Brain Targets For Dbs In Pd: a Constant Evolutionmentioning

confidence: 78%

“…They also suggested that stimulation of the caudal pedunculopontine region, which has predominantly cholinergic neurons and undergoes degeneration in PD, may be a better target for control of gait and freezing [95].…”

Section: Brain Targets For Dbs In Pd: a Constant Evolutionmentioning

confidence: 99%

Surgical Treatment of Parkinson's Disease: Patients, Targets, Devices, and Approaches

Shukla

Okun

2014

Neurotherapeutics

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Surgical treatment for Parkinson's disease (PD) has evolved from ablative procedures, within a variety of brain regions, to implantation of electrodes into specific targets of the basal ganglia. Electrode implantation surgery, referred to as deep brain stimulation (DBS), is preferred to ablative procedures by many experts owing to its reversibility, programmability, and the ability to be safely performed bilaterally. Several randomized clinical studies have demonstrated the effectiveness of DBS surgery for control of PD symptoms. Many brain targets, including the subthalamic nucleus and the globus pallidus internus, have emerged as potentially effective, with each target being closely associated with important pros and cons. Selection of appropriate PD candidates through a methodical interdisciplinary screening is considered a prerequisite for a successful surgical outcome. Despite recent growth in DBS knowledge, there is currently no consensus on the ideal surgical technique, the best surgical approach, and the most appropriate surgical target. DBS is now targeted towards treating specific PD-related symptoms in a given individual, and not simply addressing the disease with one pre-defined approach. In this review we will discuss the historical aspects of surgical treatments, the selection of an appropriate DBS candidate, the current surgical techniques, and recently introduced DBS-related technologies. We will address important pre-and postoperative issues related to DBS. We will also discuss the lessons learned from the randomized clinical studies for DBS and the shifting paradigm to tailor to a more patient-centered and symptom-specific approach.

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Pedunculopontine Nucleus Stimulation Improves Gait Freezing in Parkinson Disease

Cited by 151 publications

References 23 publications

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

Surgical Treatment of Parkinson's Disease: Patients, Targets, Devices, and Approaches

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