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Invasive Neurostimulation in Stroke Rehabilitation

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Neurotherapeutics

Abstract

The last decade has seen a growing interest in adjuvant treatments that synergistically influence mechanisms underlying rehabilitation of paretic upper limb in stroke. One such approach is invasive neurostimulation of spared cortices at the periphery of a lesion. Studies in animals have shown that during training of paretic limb, adjuvant stimulation targeting the peri-infarct circuitry enhances mechanisms of its reorganization, generating functional advantage. Success of early animal studies and clinical reports, however, failed to translate to a phase III clinical trial. As lesions in humans are diffuse, unlike many animal models, peri-infarct circuitry may not be a feasible, or consistent target across most. Instead, alternate mechanisms, such as changing transcallosal inhibition between hemispheres, or reorganization of other viable regions in motor control, may hold greater potential. Here, we review comprehensive mechanisms of clinical recovery and factors that govern which mechanism(s) become operative when. We suggest novel approaches that take into account a patient’s initial clinical–functional state, and findings from neuroimaging and neurophysiology to guide to their most suitable mechanism for ideal targeting. Further, we suggest new localization schemes, and bypass strategies that indirectly target peri-lesional circuitry, and methods that serve to counter technical and theoretical challenge in identifying and stimulating such targets at the periphery of infarcts in humans. Last, we describe how stimulation may modulate mechanisms differentially across varying phases of recovery- a temporal effect that may explain missed advantage in clinical trials and help plan for the next stage. With information presented here, future trials would effectively be able to target patient’s specific mechanism(s) with invasive (or noninvasive) neurostimulation for the greatest, most consistent benefit.

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Acknowledgments

Funding sources include grants from the National Institutes of Health, including NIH R01-HD061363 (AM) and K01HD069504 (EP), and American Heart Association’s 13BGIA17120055 (EP).

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Authors and Affiliations

  1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, ND20, Cleveland, OH, 44195, USA

    Ela B. Plow

  2. Department of Physical Medicine & Rehabilitation, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Ela B. Plow

  3. Center for Neurological Restoration, Department of Neurosurgery, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Andre Machado

  4. Center for Neurological Restoration, Department of Neurosurgery, Neurological Institute, Cleveland, OH, USA

    Ela B. Plow

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  1. Ela B. Plow
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Correspondence to Ela B. Plow.

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Plow, E.B., Machado, A. Invasive Neurostimulation in Stroke Rehabilitation. Neurotherapeutics 11, 572–582 (2014). https://doi.org/10.1007/s13311-013-0245-y

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