Deep Brain Stimulation of the Internal Segment of the Globus Pallidus in Delayed Runaway Dyskinesia

Graff-Radford, John; Foote, Kelly D.; Rodríguez, Ramón; Fernández, Hubert H.; Hauser, Robert A.; Sudhyadhom, Atchar; Rosado, Christian; Sanchez, Justin C.; Okun, Michael S.

doi:10.1001/archneur.63.8.1181

Cited by 26 publications

(13 citation statements)

References 12 publications

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“…Herzog et al 7 reported one dyskinetic patient with bilateral fetal mesencephalic grafts who improved following GPi DBS, but no MER data were described. Graff-Radford et al 8 described spontaneous GPi discharge in one patient with OFF-period dyskinesias and worsening parkinsonian symptoms, 11 years after grafting in the open label University of South Florida pilot study 39. They reported a mean GPi neuronal firing rate of 74 s/s (n=5 units), which is only slightly lower than most reported values for PD patients in the OFF state, but is higher than the mean GPi discharge rate in the grafted patient in our study.…”

Section: Discussioncontrasting

confidence: 78%

“…They reported a mean GPi neuronal firing rate of 74 s/s (n=5 units), which is only slightly lower than most reported values for PD patients in the OFF state, but is higher than the mean GPi discharge rate in the grafted patient in our study. In the University of South Florida patient, postoperative graft-induced improvement was sustained only for 1–2 years,8 suggesting that a lack of dramatic effect of transplantation on GPi firing rates reflected the poor functional integration of the graft in that case.…”

Section: Discussionmentioning

confidence: 98%

“…We are aware of only two prior reports of DBS for graft-induced dyskinesia/dystonia 7 8. Herzog et al 7 reported one dyskinetic patient with bilateral fetal mesencephalic grafts who improved following GPi DBS, but no MER data were described.…”

Section: Discussionmentioning

confidence: 99%

“…Deep brain stimulation (DBS) of the internal globus pallidus (GPi) has been employed to provide relief for patients with severe symptoms of GID 7 8. In these cases, microelectrode-guided mapping (MER) for DBS following cell transplantation offers an opportunity to study graft-induced alterations in basal ganglia electrophysiology in humans.…”

Section: Introductionmentioning

confidence: 99%

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Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

Richardson

Freed

Shimamoto

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

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Analysis of firing rate, bursting discharge and oscillatory activity showed that the graft corrected some, but not all, of the abnormalities associated with the off-medication state. Additionally, in the transplanted patient, voluntary hand movement produced a marked reduction in pallidal discharge rate at multiple GPi recording sites, which was not observed during active movement in other patients. These findings are consistent with a persistent effect of transplanted dopamine cells on basal ganglia outflow and suggest a mechanism for the graft-induced dystonic phenotype.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

Richardson

Freed

Shimamoto

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

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“…These dyskinesias can be effectively treated with DBS in the globus pallidus [34,35]. Until now, the occurrence of GIDs and their unclear underlying mechanisms have stopped the clinical activities with cell therapy in PD.…”

Section: Adverse Effects Are Few With Dopaminergic Grafts Except Dysmentioning

confidence: 99%

Cell Therapeutics in Parkinson's Disease

Lindvall

Björklund

2011

Neurotherapeutics

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The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process longterm after implantation. Mechanisms underlying graftinduced dyskinesias, which constitute the only significant adverse event observed after neural transplantation, and how they should be prevented and treated are described. We summarize the attempts to generate DA neurons from stem cells of various sources and patient-specific DA neurons from fully differentiated somatic cells, with particular emphasis on the requirements of these cells to be useful in the clinical setting. The rationale for the new clinical trial with transplantation of fetal mesencephalic tissue is described. Finally, we discuss the scientific and clinical advancements that will be necessary to develop a competitive cell therapy for PD patients.

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Long-term Clinical Outcome of Fetal Cell Transplantation for Parkinson Disease

et al. 2014

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IMPORTANCE Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation. OBSERVATIONS Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy. CONCLUSIONS AND RELEVANCE The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.

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Deep Brain Stimulation of the Internal Segment of the Globus Pallidus in Delayed Runaway Dyskinesia

Cited by 26 publications

References 12 publications

Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

Cell Therapeutics in Parkinson's Disease

Long-term Clinical Outcome of Fetal Cell Transplantation for Parkinson Disease

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