Deep-Brain Stimulation for Parkinson's Disease

Okun, Michael S.

doi:10.1056/nejmct1208070

Cited by 446 publications

(343 citation statements)

References 61 publications

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“…Although attempts to transmit PD to monkeys by intracerebral inoculation were unsuccessful (37), our transmission data suggest that caution should be exercised when reusing neurosurgical instruments that have been previously used on suspected cases of MSA or PD to minimize any risk for iatrogenic transmission of the disease. Although deep brain stimulation is not commonly used to treat MSA patients, its increasingly wide use to control dyskinesias often found in many patients with advanced PD requires surgical implantation (38) and, as such, may represent a potential risk for human-to-human transmission of α-synuclein prions.…”

Section: Discussionmentioning

confidence: 99%

Transmission of multiple system atrophy prions to transgenic mice

Watts

Giles

Oehler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

396

397

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Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson's disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83 +/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83 +/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83 +/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83 +/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83 +/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.neurodegeneration | bioluminescence imaging | seeding | proteinopathies

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Section: Discussionmentioning

confidence: 99%

Transmission of multiple system atrophy prions to transgenic mice

Watts

Giles

Oehler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

396

397

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“…149 Class 1 evidence supports the use of STN DBS when compared with best medical therapy, 102,198,202 and in trials comparing the stimulation-on state versus the stimulation-off state. 150 However, several aspects of this accepted standard are in flux.…”

Section: Current Approach To Therapymentioning

confidence: 99%

Deep brain stimulation: a mechanistic and clinical update

Karas

Mikell

Christian

et al. 2013

FOC

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Deep brain stimulation (DBS), the practice of placing electrodes deep into the brain to stimulate subcortical structures with electrical current, has been increasing as a neurosurgical procedure over the past 15 years. Originally a treatment for essential tremor, DBS is now used and under investigation across a wide spectrum of neurological and psychiatric disorders. In addition to applying electrical stimulation for clinical symptomatic relief, the electrodes implanted can also be used to record local electrical activity in the brain, making DBS a useful research tool. Human single-neuron recordings and local field potentials are now often recorded intraoperatively as electrodes are implanted. Thus, the increasing scope of DBS clinical applications is being matched by an increase in investigational use, leading to a rapidly evolving understanding of cortical and subcortical neurocircuitry. In this review, the authors discuss recent innovations in the clinical use of DBS, both in approved indications as well as in indications under investigation. Deep brain stimulation as an investigational tool is also reviewed, paying special attention to evolving models of basal ganglia and cortical function in health and disease. Finally, the authors look to the future across several indications, highlighting gaps in knowledge and possible future directions of DBS treatment.

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“…Patient with adequate response to dopaminergic therapy, on-off fluctuations, dyskinesias impairing quality of life, medication-resistant tremor and reasonable cognitive function are good candidates for DBS [34]. Levodopa can be discontinued in 50% of patients of Parkinson's disease who underwent subthalamic deep brain stimulation [35].…”

Section: Deep Brain Stimulation (Dbs) Surgerymentioning

confidence: 99%

A Review on Pharmacological Treatment of Idiopathic Parkinson’s Disease

Shah¹

2017

Journal of Neurological Disorders

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Deep-Brain Stimulation for Parkinson's Disease

Cited by 446 publications

References 61 publications

Transmission of multiple system atrophy prions to transgenic mice

Transmission of multiple system atrophy prions to transgenic mice

Deep brain stimulation: a mechanistic and clinical update

A Review on Pharmacological Treatment of Idiopathic Parkinson’s Disease

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