Enhancing rehabilitation and functional recovery after brain and spinal cord trauma with electrical neuromodulation

Abstract

Purpose of review: This review discusses recent advances in the rehabilitation of motor deficits after traumatic brain injury (TBI) and spinal cord injury (SCI) using neuromodulatory techniques.

Recent findings: Neurorehabilitation is currently the only treatment option for long-term improvement of motor functions that can be offered to patients with TBI or SCI. Major advances have been made in recent years in both preclinical and clinical rehabilitation. Activity-dependent plasticity of neuronal connections and circuits is considered key for successful recovery of motor functions, and great therapeutic potential is attributed to the combination of high-intensity training with electrical neuromodulation. First clinical case reports have demonstrated that repetitive training enabled or enhanced by electrical spinal cord stimulation can yield substantial improvements in motor function. Described achievements include regaining of overground walking capacity, independent standing and stepping, and improved pinch strength that recovered even years after injury.

Summary: Promising treatment options have emerged from research in recent years using neurostimulation to enable or enhance intense training. However, characterizing long-term benefits and side-effects in clinical trials and identifying patient subsets who can benefit are crucial. Regaining lost motor function remains challenging.

Box 1

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FIGURE 1

Summary of electrical neuromodulatory approaches, publications, and ongoing clinical trials discussed in this review. (a) Schematic illustration of different neuromodulatory approaches. (b) List of publications and ongoing trials by study type, injury type, intervention, and postinjury phase with the observed facilitated or enhanced functions. eECS, Epidural electrical cortical stimulation; tDCS, transcranial direct current stimulation; DBS, deep brain stimulation; eSCS, epidural spinal cord stimulation, tSCS, transcutaneous spinal cord stimulation; TBI, traumatic brain injury; SCI, spinal cord injury; GRASSP, Graded and Redefined Assessment of Strength, Sensibility and Prehension. Phase refers to the postinjury phase. Identifier refers to ongoing studies’ ClinicalTrials.gov identifier.

FIGURE 2

Putative biological effects of epidural spinal cord stimulation on neuronal structures. (a) After large, incomplete spinal cord injury, spared reticulospinal fibers are incapable to sufficiently activate the sublesional CPGs to generate rhythmic muscle activity and locomotion. (b) With epidural stimulation of the lumbar spinal cord, the local neurons including the CPGs regain a certain level of background activity, which makes them excitable by spared reticulospinal fibers. (c) Inset summarizing putative mechanisms. (1) Stimulation changes the resting membrane potential of CPGs, either directly or by enhancing input from propriospinal sensory fibers, thereby restoring excitability (− = no stimulation; + = stimulation; orange horizontal line = threshold potential; black and green squares = membrane potential; orange vertical lines = spikes of muscle activity). (2) Plasticity markers are upregulated by electrical activity, including, for example, growth factors, c-fos, and the growth-associated protein GAP43. (3) Neurons start to sprout, to reorganize, and to adapt the local circuits to the decreased descending input of spared fibers. CPG, Central pattern generator; eSCS, epidural spinal cord stimulation; MLR, mesencephalic locomotor region; NRG, gigantocellular reticular nucleus; GAP, growth-associated protein.