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Spinal cord stimulation in Parkinson's disease: a review of the preclinical and clinical data and future prospects.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disease with an incidence of 0.1 to 0.2% over the age of 40 and a prevalence of over 1 million people in North America. The most common symptoms include tremor, bradykinesia, rigidity, pain, and postural instability, with significant impact in quality of life and mortality. To date there is ongoing research to determine the optimum therapy for PD. In this review we analyze the current data in the use of spinal cord stimulation (SCS) therapy for treatment for Parkinsonian symptoms. We specifically address waveform pattern, anatomic location and the role of spinal cord stimulation (SCS) as a salvage therapy after deep brain stimulation (DBS) therapy. We also outline current experimental evidence from preclinical research highlighting possible mechanisms of beneficial effects of SCS in this context. Though the use of SCS therapy is in its infancy for treatment of PD, the data points to an exciting area for ongoing research and exploration with positive outcomes from both cervical and thoracic tonic and BURSTDR spinal cord stimulation.

SUBMITTER: Cai Y

PROVIDER: S-EPMC7098258 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Spinal cord stimulation in Parkinson's disease: a review of the preclinical and clinical data and future prospects.

Cai Yi Y Reddy Rajiv D RD Varshney Vishal V Chakravarthy Krishnan V KV

Bioelectronic medicine 20200316

Parkinson's disease (PD) is a progressive neurodegenerative disease with an incidence of 0.1 to 0.2% over the age of 40 and a prevalence of over 1 million people in North America. The most common symptoms include tremor, bradykinesia, rigidity, pain, and postural instability, with significant impact in quality of life and mortality. To date there is ongoing research to determine the optimum therapy for PD. In this review we analyze the current data in the use of spinal cord stimulation (SCS) the ...[more]

PMID: 32232113

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Project description:Spinal cord stimulation (SCS) is used clinically to limit chronic pain, but fundamental questions remain on the identity of axonal populations recruited. We developed an ex vivo adult mouse spinal cord preparation to assess recruitment following delivery of clinically analogous stimuli determined by downscaling a finite element model of clinical SCS. Analogous electric field distributions were generated with 300-µm × 300-µm electrodes positioned 200 µm above the dorsal column (DC) with stimulation between 50 and 200 µA. We compared axonal recruitment using electrodes of comparable size and stimulus amplitudes when contacting the caudal thoracic DC and at 200 or 600 ?m above. Antidromic responses recorded distally from the DC, the adjacent Lissauer tract (LT), and in dorsal roots (DRs) were found to be amplitude and site dependent. Responses in the DC included a unique component not seen in DRs, having the lowest SCS recruitment amplitude and fastest conduction velocity. At 200 ?m above, mean cathodic SCS recruitment threshold for axons in DRs and LT were 2.6 and 4.4 times higher, respectively, than DC threshold. SCS recruited primary afferents in all (up to 8) caudal segments sampled. Whereas A and C fibers could be recruited at nearby segments, only A fiber recruitment and synaptically mediated dorsal root reflexes were observed in more distant (lumbar) segments. In sum, clinically analogous SCS led to multisegmental recruitment of several somatosensory-encoding axonal populations. Most striking is the possibility that the lowest threshold recruitment of a nonprimary afferent population in the DC are postsynaptic dorsal column tract cells (PSDCs) projecting to gracile nuclei.NEW & NOTEWORTHY Spinal cord stimulation (SCS) is used clinically to control pain. To identify axonal populations recruited, finite element modeling identified scaling parameters to deliver clinically analogous SCS in an ex vivo adult mouse spinal cord preparation. Results showed that SCS first recruited an axonal population in the dorsal column at a threshold severalfold lower than primary afferents. These putative postsynaptic dorsal column tract cells may represent a previously unconsidered population responsible for SCS-induced paresthesias necessary for analgesia.

Project description:BackgroundTranscutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials.MethodsA systematic search for studies published until May 2021 was made of the following databases: EMBASE, Medline (Ovid) and Web of Science. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of included trials. The electrical characteristics of stimulation were summarised to allow for comparison across studies. In addition, the surface electromyography (EMG) recording methods were evaluated.ResultsA total of 3753 articles were initially screened, of which 25 met the criteria for inclusion. Studies were divided into those using tSCS for neurophysiological investigations of reflex responses (n = 9) and therapeutic investigations of motor recovery (n = 16). The overall quality of evidence was deemed to be poor-to-fair (10.5 ± 4.9) based on the Downs and Black Quality Checklist criteria. The electrical characteristics were collated to establish the dosage range across stimulation trials. The methods employed by included studies relating to stimulation parameters and outcome measurement varied extensively, although some trends are beginning to appear in relation to electrode configuration and EMG outcomes.ConclusionThis review outlines the parameters currently employed for tSCS of the cervicothoracic and thoracolumbar regions to produce motor responses. However, to establish standardised procedures for neurophysiological assessments and therapeutic investigations of tSCS, further high-quality investigations are required, ideally utilizing consistent electrophysiological recording methods, and reporting common characteristics of the electrical stimulation administered.

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Spinal cord stimulation in Parkinson's disease: a review of the preclinical and clinical data and future prospects.

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Spinal cord stimulation in Parkinson's disease: a review of the preclinical and clinical data and future prospects.

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